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Postuar nga Pashai_1987 datë 22 Dhjetor 2006 - 13:42:

Citim:
Po citoj ato që tha NS-6

beh,konsidero faktin qe ato qe do te te bejne analizen nuk eshte qe e bejne per here te pare ate gje keshtu qe atyre u duket e lehte per ta bere ...pastaj mendo nese do te ta benin gogol ate analize personave qe duhet ta bejne...do ta kishte bere kush deri me sot?thjesht merre si procedure te nevojshme qe mjeku e ka konsideru qe mund te te jape nje pergjigje per dhimbjen e kokes qe ke!gjithsesi,per cdo dyshim,mjeku qe po te kuron mund te te sqaroje shume me mire!
ishallah analiza te tregon se cfare ke,keshtu qe te fillosh nje kure sa me te sakte
te uroj nje sherim te shpejte nga ajo dhimbje koke!


faleminderit eshte shum e sjelshme nga ty qe mer mundimin dhe pergjigjesh sinqerisht un e vlersoj shum qe ne mund te diskutojm keshtu
un nuk eshte se ndjek ndonje kur sepse dhimbjet qe kam nuk jan per tu shqetesuar shum por ato çka mjeket shofin ne foto-scanner ne truruin tim -jan disa njolla te bardha por as nuk ikin as nuk shtohen- nuk eshte normale dhe qe kur ato me than kete un kam me shum dhimbje koke sepse ky fakt me shqeteson
faleminderit NS-6


Postuar nga NS-6 datë 06 Shkurt 2007 - 23:57:

Newly Diagnosed Myeloid Leukemia Responds to Imatinib

Cod. A07022007

In a 5-year follow-up of patients with newly diagnosed CML, imatinib was superior to interferon-{alpha} plus cytarabine.

The dramatic efficacy of imatinib (Gleevec) in chronic myeloid leukemia (CML) patients has made it a paradigm for targeted cancer therapies. Researchers now provide 5-year follow-up data on patients who were treated in the phase III, industry-sponsored, IRIS study. Eleven hundred six patients with newly diagnosed CML were randomized to daily oral imatinib or the combination of interferon-{alpha} plus cytarabine. The primary endpoint was event-free survival; secondary endpoints were complete hematologic, cytogenetic, and molecular responses. Crossover was allowed for inadequate response to or toxicity of originally assigned therapy; 65% of patients crossed over to imatinib, whereas only 3% crossed over to interferon-{alpha} plus cytarabine. As a result, very few patients received long-term interferon, and this report focused on the imatinib-treated patients.

By 12 months, 96% of imatinib patients achieved complete hematologic responses, and 69% achieved complete cytogenetic responses; these rates were 98% and 87%, respectively, at 5 years. At 5 years, 89% of patients were alive, and 83% had experienced no disease-related events. The estimated annual rates of progression to accelerated phase or blast crisis decreased over time: 1.5% in year 1, 1.8% in year 2, 1.6% in year 3, 0.9% in year 4, and 0.6% in year 5. All patients who achieved complete cytogenetic responses and molecular responses (defined as >3 log reduction in BCR-ABL transcripts) survived at 5 years, without progression to accelerated phase or blast crisis. No difference in survival was noted between patients who were assigned initially to imatinib and those who crossed over to imatinib. Side effects of imatinib therapy included edema, muscle cramps or joint pain, diarrhea, and rash. One patient developed heart failure.

Comment: Only 7% of imatinib-treated patients progressed to accelerated phase or blast crisis. Risk for progression decreased over time and was <1% in years 4 and 5 of imatinib therapy; overall survival of imatinib-treated patients was 89%. These impressive results confirm imatinib as standard therapy for initial treatment of CML patients. As noted by the authors, the current recommendation is to continue therapy indefinitely, because relapses occur in some patients when treatment is discontinued. Ongoing questions relate to administration of higher initial doses of imatinib and integration of next-generation kinase inhibitors (i.e., dasatinib and nilotinib) into treatment algorithms. Safety and toxicity of long-term therapy still require assessment, especially in view of recent reports of cardiomyopathy and congestive heart failure in a small subset of patients.

— Michael E. Williams, MD

Published in Journal Watch Oncology and Hematology December 6, 2006


Postuar nga NS-6 datë 20 Shkurt 2007 - 22:20:

How Valuable Is the PPI Test for Diagnosing GERD?

Cod. A20022007

How Valuable Is the PPI Test for Diagnosing GERD?

Measuring symptom response to empirical PPI therapy is of little value in distinguishing primary care patients who have GERD.

Clinicians sometimes diagnose gastroesophageal reflux disease by evaluating symptom response to empirical therapy with a proton-pump inhibitor (PPI), but is this so-called "PPI test" reliable?

To evaluate the test’s usefulness in primary care settings, Dutch investigators studied 74 adults with symptoms suggestive of GERD; all were recruited through primary care practices or advertisements. At baseline, each participant underwent a 24-hour pH study to determine the likelihood of a temporal association between symptoms and reflux. If the likelihood of an association was greater than 95%, the patient was considered to have GERD.

Each study participant then underwent a PPI test (receiving esomeprazole, 40 mg daily) for 13 days. If the subject reported overall symptom relief, the test was considered positive for GERD. Researchers then calculated the sensitivity and specificity of the PPI test on each of the 13 days, using the pH study results as the gold standard. The pH results were not revealed to the patient or treating physician until after completion of the PPI test. The study was supported by the maker of esomeprazole.

The results of the pH studies indicated that 70% of the study population had GERD. The mean sensitivity of the PPI test during the 13-day treatment period was 91% (95% CI, 78%–96%), but the mean specificity was only 26% (95% CI, 10%–49%). The positive likelihood ratio for the test was 1.2 (95% CI, 0.9–1.6) and varied little during the treatment period.

Comment: Sensitivity and specificity are relatively poor measures of the value of a diagnostic test, because they vary with disease prevalence in the population. Obviously, any test for GERD in a population of patients selected for symptoms would have high sensitivity and low specificity. A much more robust measure of the value of a test is the likelihood ratio, which measures whether a positive test influences the odds that a patient has the disease. In this study, the positive likelihood ratio was constant at 1.2 throughout 13 days, suggesting that the PPI test was of very little value in distinguishing patients who had GERD from those who did not in this selected population.

— David J. Bjorkman, MD, MSPH (HSA), SM (Epid.)

Published in Journal Watch Gastroenterology February 9, 2007

Citation(s):

Aanen MC et al. Diagnostic value of the proton pump inhibitor test for gastro-oesophageal reflux disease in primary care. Aliment Pharmacol Ther 2006 Nov 1; 24:1377-84.


Postuar nga Fajtori datë 20 Shkurt 2007 - 22:32:

Kjo duhet spjeguar mire NS. Tashme kane dale rezultate skandaloze per besueshmerine e disa testeve.

Psh. nese ben testin per kancerin ne gjoks dhe del pozitiv mundesia qe te jete e vertete eshte 7.8 %. Ndersa kur ben testin e AIDS dhe del pozitiv ka vetem 50% mundesi qe ta kesh ne realitet.

Llogarite jane shume te thjeshta dhe do linin me goje hapur secilin. Po ju jap disa shifra se nuk kam kohe te bej gjithe llogarite tamam:

Nese 100 veta kane kancer testi do nxjerre 80% tamam dhe 20% gabim.
Nderkohe nese 100 veta nuk kane kancer testi do nxjerre 91% tamam (pa kancer) dhe 9% gabim (me kancer).

Ne pamje te pare duket sikur testi eshte goxha i sakte, por nese behen llogarite duke u bazuar tek epidemiologjia reale e semundjes, zbulon se testi nuk eshte aspak afidabel. Klecka qendron pikerisht tek ai 9% qe del me kancer kur nuk e ka. Duket gabim i vogel por popullsia qe s'ka kancer eshte shume e madhe dhe 9% jane jashtezakonisht shume. Si rrjedhoje perfundon qe shumica e atyre qe dalin pozitive jane efektivisht te shendetshem dhe vetem 7.8% e kane vertet.


Postuar nga NS-6 datë 20 Shkurt 2007 - 23:08:

kjo eshte mbi graden e specificitetit dhe sensibilitetit qe ka nje test dhe se keto 2 faktore jane te nderlidhur njeri me tjetrin.dmth sa me shume rrit aftesite e njerit aq me shume ul te tjetrit.ato ndjekin grafikun e Gaussit dhe jane ato pjese te deviancave qe perben problemin sepse nese ti tenton te shkosh ne drejtimin qe te shtosh sensibilitetin duke spostuar parametrat,ti ul specificitetin e asaj analize.nese ti thua qe ke nje sensibilitet 91% atehere ai test arrin ne 91% te rasteve te gjeje personat qe kane semundjen dhe mund te cilesohet sidoqofte i nje grade te mire si aftesi diagnostikuese.eshte normale qe per nje semundje me te perhapur,ajo grade gjithsesi eshte e ulet.por nga ana tjeter nje specificitet i ulet te ben qe ti te kesh edhe nje numer pacientesh qe gjithsesi ate semundje nuk e kane por diagnostikohen per te tille!

nje rast te mire per ceshtjen e sensilibitetit dhe specificitetit te ulet ke per markatoret tumorale qe edhe pse perdoren si markatore per tumore te ndryshme kane nje sensibilitet dhe specificitet te ulet,qe i ben te mos jene diagnostikues per kanceret.dhe prandaj,pervec PSA,sot per sot ato perdoren me shume si analiza per follow up te kancereve te ndryshem.

per testin e AIDS-it sot per sot ka analiza qe kapin graden e sensibilitetit te gati 100% sic eshte kerkimi i antigjenit viral p24


Postuar nga NS-6 datë 28 Shkurt 2007 - 16:25:

2 New Drugs Offer Options in H.I.V. Fight

Cod. A28022007

February 28, 2007

By LAWRENCE K. ALTMAN and ANDREW POLLACK

LOS ANGELES, Feb. 27 — Two new AIDS drugs, each of which works in a novel way, have proved safe and highly successful in large studies, a development that doctors said here on Tuesday would significantly expand treatment options for patients.

The two drugs, which could be approved for marketing later this year, would add two new classes of drugs to the four that are available to battle H.I.V., the AIDS virus. That would be especially important to tens of thousands of patients in the United States whose treatment is failing because their virus has become resistant to drugs already in use.

“This is really a remarkable development in the field,” Dr. John W. Mellors of the University of Pittsburgh said at a news conference here at the 14th Annual Conference on Retroviruses and Opportunistic Infections.

Dr. Mellors, who was not involved in the studies but has been a consultant to the manufacturers of the drugs, said he “wouldn’t be going out on a limb” to say the new results were as exciting as those from the mid-1990s, when researchers first discovered that cocktails of drugs could significantly prolong lives.

Dr. Scott Hammer, chief of infectious diseases at Columbia University Medical Center, who also was not involved in the studies but has been a consultant to the manufacturers, agreed that the new drugs “will provide extended years of meaningful survival to patients.”

One drug, maraviroc, was developed by Pfizer, which has already applied for approval to sell it. The Food and Drug Administration has scheduled an advisory committee meeting on April 24 to discuss the application.

The other drug, raltegravir, was developed by Merck, which has said it will apply in the second quarter for approval.

Experts said the new drugs would be used in combination with older drugs. Both drugs stem from scientific findings made a decade or more ago that have peeled back the intricate molecular process used by H.I.V. to infect human immune system cells and to replicate themselves.

While there are now more than 20 approved drugs to treat H.I.V. and AIDS, there are only four different mechanisms by which the drugs work. In many patients, the virus develops resistance to one or more drugs, usually because patients do not take their drugs on time as prescribed.

And if the virus develops resistance to one drug in a class, it often becomes resistant to others in that class and sometimes in other classes. So AIDS experts have said there is an urgent need for drugs that work by new mechanisms.

The two new drugs would represent the first new classes since 2003, when an injectable drug called Fuzeon was approved. They would be the first new classes of oral H.I.V. drugs in a decade.

Merck’s drug works by inhibiting the action of integrase, an enzyme produced by the virus that incorporates the virus’s genetic material into the DNA of a patient’s immune cell. Once incorporated, the viral DNA commandeers the cell to make more copies of the virus.

In two Merck studies involving a total of 700 patients, virus levels dropped to below 50 copies per milliliter of blood, an amount considered undetectable, in about 60 percent of patients who received raltegravir. That compared with about 35 percent of those who received a placebo.

The patients in the two Phase 3 trials, typically the last stage of testing before approval, were resistant to at least one drug in each of three classes of antiretroviral drugs. All the patients also received a combination of older drugs that their doctors deemed to be the most appropriate. The results reported here were after 16 weeks, in a study that is continuing so it is possible that longer-term side effects might yet arise.

Other integrase inhibitors, like one from Gilead Sciences, are also under development. Gilead’s drug is 18 months to 2 years behind Merck’s.

Pfizer’s drug works by blocking a protein on human immune system cells that H.I.V. uses as a portal to enter and infect the cell. It would be the first drug that targets the human body rather than the virus.

The portal, known as CCR5, was discovered in 1996 by several groups of scientists, and there has been a race to develop drugs to block it.

In two Phase 3 studies sponsored by Pfizer involving 1,049 patients, more than 40 percent of patients who received maraviroc had undetectable levels of virus after 24 weeks of a 48-week study. That was about twice the rate of those who received placebo. As in the Merck trials, patients were resistant to three classes of drugs and were receiving an optimized combination of older drugs.

Some experts said they were a bit cautious about maraviroc, in part because it blocks a human protein instead of a viral one, with possible unknown long-term effects. One CCR5 inhibitor that was being developed by GlaxoSmithKline was dropped because it caused liver toxicity, and a second being developed by Schering-Plough appeared to possibly raise the risk of blood cancers.

But in Pfizer’s study there was no increased incidence of cancers. In one study there was a higher rate of death among those who took the drug, but Pfizer said the deaths were not associated with the drug.

Experts are also encouraged that about 1 percent of Caucasians have a particular mutation in both copies of their CCR5 gene that knocks out its function. These people are resistant to H.I.V. infection and apparently live otherwise normal lives.

Yet another issue is that some viruses use a different entry portal called CXCR4. Before getting maraviroc, patients will have to be tested to see which portal their virus uses, which would make the drug an early example of “personalized medicine” tailored to the patient.

The test, which will probably take two weeks for results, was developed by Monogram Biosciences of South San Francisco, Calif. It is expected to cost as much as $1,000, or more.

About 85 percent of newly infected patients have a virus that uses CCR5 while only about half of highly drug-resistant viruses use that portal. There has been some concern that blocking CCR5 would encourage the development of viruses that use the alternative portal — and those viruses seem to be associated with worse outcomes.

But that has not proven so far to be a big problem, according to Edward A. Berger of the National Institute of Allergy and Infectious Diseases, who played a key role in the discovery of the two portals.

Government, academic and industry experts said there was no reliable estimate of the number of people who would need one of the new drugs. But the number is declining as more and better AIDS drugs become available.

“The numbers are not what they used to be six years ago,” said Norbert Bischofberger, executive vice president for research and development at Gilead, which makes some widely used AIDS drugs.

Both Merck and Pfizer say they are conducting studies testing their drugs for use as initial treatments. They would not say how much their drugs would cost.


Postuar nga cremaster datë 08 Mars 2007 - 06:48:

the most up to date, from uptodate.com

Cod. B08032007

Initial antiretroviral therapy for HIV infection

John G Bartlett, MD

UpToDate performs a continuous review of over 375 journals and other resources. Updates are added as important new information is published. The literature review for version 15.1 is current through December 2006; this topic was last changed on January 9, 2007. The next version of UpToDate (15.2) will be released in June 2007.

INTRODUCTION — The battle against the human immunodeficiency virus (HIV) has been revolutionized by highly active antiretroviral therapy. Use of these regimens has resulted in substantial reductions in mortality, progression to AIDS, opportunistic infections (OIs), and hospitalizations in patients who respond to therapy, particularly those with an adequate lowering in HIV-1 RNA levels [1,2].

The newer regimens have also brought a host of new concerns including expense, side effects, drug interactions, difficulties in adhering to complicated regimens, emergence of drug resistance, and variations in response. There are now 22 FDA-approved antiretroviral drugs, with additional investigational agents in testing.

The management of antiretroviral therapy (ART) is complex and is best when delivered by providers with specific training. Multiple studies have shown that provider experience correlates with patient outcome [3-6]. US guidelines recommend that providers of HIV care have at least 25 active HIV-infected patients [7].

Indications for initiating antiretroviral therapy in treatment-naive patients, appropriate patient evaluation prior to initiation of therapy, and recommendations for ART regimens and monitoring are discussed here. Modification of ART regimens and their use in treatment-experienced patients, and the use of ART to treat acute HIV are discussed separately. (See "Modifying HIV antiretroviral therapy regimens" and see "Primary HIV-1 infection: Diagnosis and treatment"). Also discussed separately are an overview of the protease inhibitors and major clinical trials of various regimens. (See "HIV protease inhibitors" and see "Clinical trials of HIV antiretroviral therapy").

ABBREVIATIONS USED — The following abbreviations are used in this topic for the various antiretroviral agents:

* ZDV: zidovudine; also known as AZT
* 3TC: lamivudine; also known as Epivir
* FTC: emtricitabine; also known as Emtriva
* Combivir: zidovudine (ZDV) plus lamivudine (3TC) in one pill
* d4T: stavudine; also known as Zerit
* ddI: didanosine
* ABC: abacavir; also known as Ziagen
* Trizivir: combines ZDV, 3TC, and ABC in one pill
* TDF: tenofovir; also known as Viread
* Truvada: combines TDF with FTC in one pill
* NVP: nevirapine; also known as Viramune
* EFV: efavirenz; also known as Sustiva
* DLV: delavirdine; also known as Rescriptor
* NLF: nelfinavir; also known as Viracept
* SAQ: saquinavir; also known as Invirase
* IND: indinavir; also known as Crixivan
* RTV: ritonavir; also known as Norvir
* LPV/RTV: lopinavir/ritonavir; also known as Kaletra
* FOS: fosamprenavir; also known as Lexiva
* ATZ: atazanavir; also known as Reyataz
* TPV: tipranavir; also known as Aptivus
* DRV: darunavir; also known as Prezista
* T-20; enfuvirtide; also known as Fuzeon

GOALS OF THERAPY — The following are goals when administering ART:

* Suppress HIV viral load to less than 50 copies/mL for as long as possible

* Improve quality of life

* Preserve future therapeutic options

* Restore immune function (as indicated by CD4 cell count)

IMPACT OF THERAPY — The introduction of highly active ART was accompanied by a dramatic decrease in the morbidity and mortality related to HIV infection. Death rates in the United States fell by 42 percent between 1996 and 1997, and an additional 15 percent from 1998 to 2000 [8]. National hospital discharge data show admissions for HIV-related complications decreased 30 percent in 1998 compared with 1995. A report from HIV clinics in eight cities in the United States conducted by the HIV Outpatient Study (HOPS) showed that the mortality of patients with a CD4 cell count below 100 cells/microL declined from 29.4 per 100 person-years in 1995 to 8.8 per 100 person-years in 1997 (show figure 1) [9]. Statistics from Europe are comparable [10,11]. The EuroSIDA cohort showed a dramatic decline in mortality from 23.3 per 100 patient-years in 1994 to 4.1 per 100 patient-years in 1998 [12]. A subsequent analysis has shown that treatment of HIV has added an average of 13 years of life to patients with HIV infection [13]. (See "Factors affecting HIV progression").

Rates of clinical progression were examined according to initial treatment regimen in a multicenter prospective study of ART-naive patients [14]. In an analysis of 17,666 patients with an HIV RNA level >1000 copies/mL who started therapy after January 1996, 1617 new AIDS events and 395 deaths were analyzed with the following observations:

* Compared with EFV, the adjusted hazard ratio (HR) for AIDS/death was 1.28 for NVP (95 percent CI, I.03-1.60), 1.31 for RTV (95 percent CI, 1.01-1.71), and 1.45 for RTV-boosted PIs (95 percent CI, 1.15-1.81).

* For death, the adjusted HR for NVP was 1.65 (95 percent CI, 1.16-2.36).

* The adjusted HR for death for the combination of d4T/3TC was 1.35 (95 percent CI, 1.14-1.59) compared with ZDV/3TC.

Since the outcomes were observational, the results may be affected by bias due to confounding [14]; however, this study raises questions regarding use of short-term surrogate endpoints in randomized trials, such as changes in CD4 cell counts and HIV RNA, as indicators of clinical outcomes, such as disease progression or death [15].

A major impact has been the decline in the three major opportunistic infections Pneumocystis pneumonia, Mycobacterium avium bacteremia, and disseminated cytomegalovirus infections; these declined during this period from 21.9 to 2.3 per 100 person-years [9].

Virologic outcomes — The likelihood of achieving suppression of HIV as measured by HIV viral load depends on viral susceptibility and on patient adherence to an ART regimen. Overall, the probability of attaining an HIV viral load below 50 copies/mL one year after starting HAART in a patient who has not previously received ART ranges from 50 to 90 percent in various studies [16,17].

EVALUATION PRIOR TO INITIATION OF ANTIRETROVIRAL THERAPY

History and physical examination — The history and physical examination in patients being considered for treatment with ART should focus on looking for evidence of symptomatic HIV disease (an indication for therapy), evidence of opportunistic infections that could initially flare with the immune reconstitution seen after starting ART, and any conditions likely to be exacerbated by specific ART medications.

Patients should be asked about prior opportunistic infections, weight loss, fevers, malaise, diarrhea, cognitive problems, neuropathy, visual problems, oral lesions, skin rashes or lesions, and any chronic complaints. Patients who have experienced a slow decline in function with HIV infection may not recognize their symptoms or may attribute them to normal aging, so careful questioning is important.

A careful physical examination should be performed with attention to oral and skin lesions, cognitive changes, and evidence of peripheral neuropathy. In patients with a very low CD4 cell count (below 50 cells/microL), a dilated fundoscopic exam performed by an ophthalmologist may be useful to detect asymptomatic cytomegalovirus retinitis.

Psychosocial evaluation — A careful psychosocial history is a vital part of the evaluation of patients in whom ART is considered. Psychosocial factors can have a strong influence on patient adherence [18], and adherence is probably the most important factor in determining the success of an initial ART regimen.

Issues to consider include:

* Substance abuse: Substance abuse contributes to a disordered lifestyle and may lead to inadvertent missed medications doses.

* Psychiatric disorders: Depression, bipolar disorder, and other psychiatric disorders may interfere with a patient's ability or desire to adhere to a medication regimen.

* Housing: Patients with an unstable housing situation (such as the homeless) may have difficulties keeping medications available, remembering to take medications, and dealing with side effects such as diarrhea. However, many homeless patients can successfully take ART. As an example, in a prospective 12-month study of 148 homeless and marginally housed adults in San Francisco, 69 percent of patients continued to receive ART and average adherence in that group was 74 percent; 55 percent of those continuing ART had undetectable viral loads (below 400 copies/mL) [19].

* Support: Friends and family can be helpful in reminding patients to take ART medications. Patients who are trying to keep their HIV status from their close acquaintances may have difficulties, particularly with regimens that require frequent dosing.

* Work: Patients with irregular work schedules may have difficulty taking medications at prescribed times. Certain jobs also provide limited access to bathrooms and this can be an issue with medication side effects. The cognitive side effects seen with efavirenz in some patients can also interfere with job performance or safety.

* Ability to afford medications: Depending on where patients live, their economic resources, and their insurance, affordability of medications may be a major constraint in some cases.

Laboratory testing — Screening laboratory testing in HIV infected patients is discussed in detail elsewhere. (See "Screening laboratory tests in HIV-infected patients").

All patients being considered for ART should have the following laboratory tests:

* Two measurements of the CD4 cell count, preferably at times when the patient is not acutely ill. (See "Techniques and interpretation of measurement of the CD4 cell count in HIV-infected patients").

* Measurement of the HIV viral load. (See "Techniques and interpretation of HIV-1 RNA quantitation").

* Complete blood count with differential.

* Electrolytes, BUN, creatinine, and glucose.

* Liver function tests and amylase.

* A lipid profile including triglycerides.

* Urinalysis

* Toxoplasmosis IgG

* VDRL

* Chest x-ray: this is considered optional but should be obtained in any patient with pulmonary symptoms or a positive PPD

* Serologic testing for hepatitis B and hepatitis C virus.

HIV resistance testing — Resistance mutations to antiretroviral medications can be found in some treatment-naive patients. In a study of 1082 newly diagnosed adult patients seen in 10 US cities during 1997 to 2001, 8.3 percent had reverse transcriptase or major protease mutations associated with reduced antiretroviral susceptibility (mutations affecting NRTI susceptibility, 6.4 percent; NNRTI susceptibility 1.7 percent; PI susceptibility 1.9 percent) [20]. The prevalence of mutations was higher among men who had sex with men than among women or heterosexual men (11.6, 6.1, and 4.7 percent respectively), and was higher among whites than among African Americans or Hispanics (13.0, 5.4, and 7.9 percent respectively). Among patients whose partners reportedly took ART, the prevalence of mutations was 15.2 percent. Similar results have been found in other studies [21,22].

The percentage of patients with resistance mutations in these studies likely underestimated the actual number of patients with resistant virus as some mutations can be expected to revert to wild type over time. In addition, the data are relatively dated, reflecting the epidemiology of resistance from a number of years ago, and resistance patterns are continually changing. (See "Drug resistance testing in the clinical management of HIV infection", section on Interpretation of resistance testing).

We recommend routine HIV resistance testing prior to initiation of ART in all patients with a HIV RNA level >1000 copies/mL [7]. Most important will be detection of a K103N mutation which excludes utility of NNRTIs.

Recommendations for resistance testing in patients with primary HIV infection are discussed separately. (See "Primary HIV-1 infection: Diagnosis and treatment").

INDICATIONS FOR ANTIRETROVIRAL THERAPY — The major factors used to indicate a need for initiation of antiretroviral therapy in patients who are felt to be willing and able to take ART are the presence of symptomatic HIV disease and the CD4 count [23]. In an analysis of 13 cohort studies including 12,574 HIV-infected patients followed for 24,310 patient-years, the CD4 count proved to be the most important indictor of progression to an AIDS-defining complication or death [24]. There is general agreement that patients with symptomatic HIV disease should receive ART [7,23].

For patients without symptoms, therapy should be initiated at some point after the CD4 cell count declines below 350/microL, but before it reaches 200/microL [23]. This decision should be influenced by the viral load, the CD4 slope or rate of decline, and patient readiness for treatment. Thus, a viral load >100,000 copies/mL, a CD4 decline of >100 cells/mm3 per year and a CD4 count of 220 cells (instead of 320/mm3, for example) would indicate more urgency [23].

There is less agreement about initiating therapy in other patient subgroups. Retrospective analyses of cohorts show that therapy in a patient with a CD4 cell count >200/microL has either no, or only a modest benefit [25-27], while others show substantial benefit [28]. No study has shown convincing evidence of benefit for treatment initiated when the CD4 count is >350/microL. In patients with a CD4 count between 200 and 350/microL, clinicians must consider the potential risks and benefits of treatment since current drugs have short- and long-term toxicity [29]. There is also the concern about increasing rates of drug resistance in HIV with consequences to both the patient and to society [30]. Other factors may also need to be considered, such as concurrent tuberculosis or chronic hepatitis C. (See "Treatment of tuberculosis in HIV-infected patients" and see "Epidemiology; natural history; and diagnosis of hepatitis C in the HIV-infected patient", section on "Effect of HIV on the natural history of HCV").

The viral load plays an uncertain role in the decision to treat HIV infection. The viral load correlates with the rate of CD4 decline, and in one study the CD4 decline was 4 percent per year for each log10 copies/mL [31]. Viral load is also an independent prognostic indicator [32]. Extremely high viral loads (>100,000 copies/mL) correlate with a poor prognosis [24,33,34] and viral load influences the probability of developing an opportunistic infection, which, for unclear reasons, appears to be unusual with viral loads 400 cells/microL or women with a CD4 count >250 cells/microL. (See "Side effects" below and see "Other considerations" below).

PI versus NNRTI-based HAART — The major question confronting physicians and patients has been the relative merits of boosted PI-based HAART versus NNRTI-based HAART. ACTG 5142 compared the efficacy of EFV with two NRTIs versus LPV/r/ with two NRTIs versus EFV/LPV/r in 753 participants with a 96-week follow-up [52]. Viral suppression ( d4T > ddI > ZDV. ZDV use is associated with nausea, headache and bone marrow suppression. (See "Mitochondrial toxicity of HIV nucleoside reverse transcriptase inhibitors").

* Among the NNRTIs, rash is common with NVP and is also seen with EFV. EFV commonly causes neurocognitive side effects including unusual dreams when it is taken at bedtime. These side effects often resolve over time [55]. NVP is associated with a high rate of hepatotoxicity, especially in women with a baseline CD4 cell count above 250/microL [56]. This may be a fulminant hepatitis with hepatic necrosis and hepatic failure. NVP should not generally be used as initial therapy in women with a CD4 cell count above 250/microL. Men with CD4 cell counts above 400/microL who are started on NVP may also be at increased risk for asymptomatic aminotransferase elevations [57], however most patients are not initiated on ART at CD4 cell counts this high. It is not known whether switching a patient from efavirenz to nevirapine after the CD4 cell count has risen constitutes the same risk.

Risk of resistance with poor adherence — Multiple mutations are typically needed for HIV to develop resistance to the PIs and most of the NRTIs. Resistance to the entire class of NNRTIs can occur with a single mutation and this may be a consideration in patients who are felt to be unlikely to adhere to their ART regimen. Resistance to 3TC and FTC can also occur with a single mutation, however this mutation may decrease the reproductive fitness of HIV and it appears to enhance activity AZT, d4T and TDF. (See "Drug resistance testing in the clinical management of HIV infection").

Other considerations — Efavirenz use requires adequate contraception in women of child-bearing potential given its teratogenic risk in the first trimester of pregnancy. (See "Antiretroviral treatment during pregnancy").

NVP is recommended as the NNRTI component for women who are pregnant or may become pregnant and have a CD4 count less than 250 cells/microL.

Drug interactions also need to be carefully considered before initiating any antiretroviral therapy regimen.

Summary — Given the 20 antiviral drugs approved for use by the US FDA, a large number of potential regimens can be created. There is no one regimen that is considered most appropriate for all patients and experienced HIV care providers generally individualize regimens from the full menu of available options. Some of the specific considerations include:

* Of the NNRTIs, EFV is preferred due to its consistent efficacy and toxicity profile and low pill burden [39,40,43,47-51]. Disadvantages include a high rate of central nervous system toxicity during the first two to three weeks of therapy, and a single resistance mutation (K103N) confers high level resistance to this agents and other NNRTIs. It should not be used in women during the first trimester of pregnancy and should be avoided or used with great caution in women with child-bearing potential.

* NVP is recommended as the NNRTI component for women who are pregnant or may become pregnant or in men and women who have significant central nervous system side effects secondary to EFV. NVP should not be used in men or women with a CD4 count >400 cells and 250 cells, respectively.

* LPV/r-based regimens are popular because they have proven superior to others in clinical trials [41,42], durability has been shown with a five year follow-up, there is no evidence of PI resistance mutations with virologic failure when used as the initial PI, and the combination is available as a single coformulation. However, it has never been compared to EFV, although a trial is underway. Disadvantages of LPV/r include the need to take the medication with food, the need for twice daily dosing, gastrointestinal side effects with high rates of diarrhea, and lipid effects.

* ATV-based regimens may be the preferred choice in some patients. Advantages include potency comparable to EFV [43], low pill burden with once daily dosing, good boosting with RTV, negligible effects on lipids, and a unique resistance mutation (150L) that does not impact the activity of other PIs [58].

* The triple nucleoside regimen AZT/3TC/ABC is virologically inferior to EFV-based ART [59], and is not recommended for initial therapy. However, it may be the only good option for some patients. Other nucleoside regimens are significantly less potent, presumably due to the need to include a thymidine analogue [7,23].

* NVP should not be used for initial therapy in women with a baseline CD4 cell count above 250 cells/microL, given high rates of symptomatic hepatitis and cases of fatal hepatic necrosis even with careful monitoring of hepatic function and prompt discontinuation of NVP [56].

REGIMENS — As discussed, a typical HAART regimen consists of a backbone of two NRTIs plus a base of a PI or NNRTI.

Expert guidelines — Groups such as the International AIDS Society-USA Panel (IAS-USA) [23], and the US Department of Health and Human Services (DHHS) [7] (see "Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents; 2005") have published guidelines for initial ART.

The 2006 IAS-USA guidelines for initial ART recommend either of two basic three-drug regimens:

* EFV plus two NRTIs

OR

* A ritonavir-boosted protease inhibitor (LPV, ATZ, FOS or SAQ) plus two NRTIs

The IAS-USA guidelines recommend any of the following choices as the NRTI backbone:

* TDF and FTC
* ZDV and 3TC
* ABC and 3TC

The 2006 DHHS guidelines indicate preference for one of the following regimens for initial treatment selected on the basis of demonstrated potency in clinical trials, relatively low frequency of serious adverse reactions, substantial clinical experience, and a requirement for dosing no more than twice daily:

* LPV/r plus ZDV plus (either 3TC or FTC)
* EFV plus (either TDF or ZDV) plus (either 3TC or FTC)

Antiretroviral combinations to avoid — Certain combinations of antiretroviral medications that might appear to fit into a standard pattern should be avoided either because of toxicity or lack of efficacy:

* AZT and d4T should not be used together as their actions are antagonistic.

* 3TC and FTC are similar drugs and should not be used together.

* The use of EFV and NVP together produces more side effects and is less efficacious than either drug alone [40]. (See "Clinical trials of HIV antiretroviral therapy"). While awaiting further studies, regimens should not combine NNRTIs outside of clinical trials.

* ddI should not be used in combination with d4T due to overlapping toxicities peripheral neuropathy, pancreatitis, and lipodystrophy [23,60-62].

* The three drug combination of abacavir, lamivudine, and tenofovir should not be used based on results from a randomized, multicenter study, which demonstrated high rates of virologic failure and resistance [63,64]. (See "Clinical trials of HIV antiretroviral therapy").

* Reports from several studies have suggested that the combination of TDF and ddI may have a high rate of early virologic failure [65-68]. Additionally, even in patients with viral suppression on such a regimen, CD4 cell counts may not show as much recovery as with other regimens or may actually decline [69-71].

* The NRTI ddC is generally not used, because of high rates of toxicity. The NNRTI delavirdine is also rarely used, and there are few data about its efficacy in ART regimens.

Recommendations in typical patients — Appropriate initial ART regimens can be constructed using the above expert guidelines. Taking into consideration efficacy, ease of dosing, and toxicity, regimens constructed with an NNRTI base of EFV or a PI base of LPV/r or ATV/r are currently preferred by many experts. The following are examples of such regimens that may be appropriate in many patients:

* EFV 600 mg daily plus TDF/FTC (300 mg/200 mg) daily

When constructed with the combination medication Atripla, the above regimen requires only one pill taken once daily. EFV should not be used in women who are pregnant or are likely to become pregnant (see "Pregnancy" below).

* ATV 300 mg daily plus RTV 100 mg daily plus TDF/FTC (300 mg/200 mg) daily

* LPV/r (400 mg/100 mg) twice daily plus TDF/FTC (300 mg/200 mg) daily

The use of ZDV/3TC (300 mg/150 mg) twice daily in place of the TDF/FTC backbone is also appropriate in many patients, as is substituting 3TC 300 mg daily for FTC 200 mg daily in combination with TDF.

Considerations in selected clinical settings

Pregnancy — The dual goals of antiretroviral therapy during pregnancy are to provide therapy for the mother and decrease perinatal transmission. Some recommend a delay in the initiation of therapy in the first trimester, but there is no consensus on this and no data to support it on the basis of cohort studies or the pregnancy registry [23]. All pregnant women should receive antiretroviral therapy in the third trimester, regardless of CD4 count, to decrease HIV transmission to the neonate. The selection of medication regimens is discussed elsewhere. (See "Antiretroviral treatment during pregnancy")

Women who are pregnant or potentially pregnant need to avoid EFV during the first trimester based on its teratogenic effects in primates and at least four cases of reported neural tube defects in exposed infants [7,72-74]. (See "Antiretroviral treatment during pregnancy"). NVP should not be started in women with a CD4 cell count above 250 cells/microL due to high rates of severe hepatotoxicity [56].

The recommended regimens based on clinical experience and pharmacokinetics during pregnancy are NFV (1250 mg BID) and SQV/r (1000 mg/BID); each of these should be combined with two nucleosides, preferably AZT/3TC. LPV/r is under investigation using standard dose but may require a higher dose in the third trimester. TDF should be avoided due to concerns about fetal bone formation.

Methadone recipients — Drug interactions may be an important consideration in patients receiving methadone maintenance. The NNRTIs EFV and NVP can cause significant reductions in methadone levels which may result in opiate withdrawal symptoms [7]. The patient must be carefully monitored for withdrawal symptoms with appropriate dose adjustment of methadone. PIs also may reduce methadone levels, but the effect is less significant. Methadone decreases ddI concentrations a mean of 60 percent; thus, the ddI dose may need to be increased in methadone recipients who are also given ddI [75]. Drug interactions with buprenophine are less well studied.

Patients with TB — Patients with active tuberculosis (TB) should always initiate treatment for TB immediately. HIV therapy is usually delayed at least two months to avoid simultaneous initiation of seven or eight medications, to avoid drug interactions with rifamycins, and to avoid the immune reconstitution inflammatory syndrome (see "Immune reconstitution inflammatory syndrome"). Patients with very low CD4 cell counts may be an exception, however due to an increased risk of mortality. This topic is discussed in detail elsewhere (See "Treatment of tuberculosis in HIV-infected patients").

Hepatitis — Patients with chronic viral hepatis are at increased risk for drug-associated hepatotoxicity. In patients with chronic hepatitis B, there can also be flares of aminotransferases secondary to exacerbations of disease activity, immune reconstitution related to ART, the onset of resistance to antiretroviral drugs with dual HIV and HBV activity, or the discontinuation of drugs with anti-HBV activity (eg, 3TC, FTC, or TDF). This topic is discussed in detail elsewhere. (See "Treatment and prevention of hepatitis B in the HIV-infected patient").

Patients who require treatment with ribavirin for hepatitis C may need to consider drug interactions with ddI, and enhanced marrow toxicity with ZDV. (See "Management and treatment of hepatitis C in the HIV-infected patient").

Cardiovascular disease — In patients with known CVD or at high risk for CVD, it makes sense to choose medications such as EFV, NVP, and ATV that are least likely to have a prominent effect on lipids.

Thymidine analogues (AZT, ddl and D4T) also effect blood lipids (as demonstrated in clinical trials ACTG 384, Gilead 903, and Gilead 934). The medication with the greatest impact, especially on tryglyceride levels, is d4T. Preferred NRTI pairings are TDF/FTC or 3TC/ABC.

Renal insufficiency — TDF is generally well-tolerated, but should be used with caution, or avoided, in patients with preexisting renal insufficiency [23]. Dose modification is required in patients with a creatinine clearance 95 percent of prescribed pills in order to have an 80 percent probability of achieving a viral load of 48 oz per day) especially with pill ingestion. Must take on an empty stomach unless the drug is combined with RTV for boosting. Warn of sicca syndrome (dry eyes, skin, and mouth).

* Lamivudine (3TC) — no serious side effects.

* Lopinavir (LPV) — take with meals and warn of diarrhea that is usually managed with loperamide.

* Nelfinavir (NFV) — take with high fat meal and warn of diarrhea that usually responds to loperamide or calcium.

* Nevirapine (NVP) — warn of hepatotoxicity with need to monitor liver function tests, especially during the first 12 weeks. Major concern is hepatic necrosis with fever and rash. Also has a high rate of rashes including toxic epidermal necrolysis and Stevens-Johnson syndrome.

* Ritonavir (RTV) — GI intolerance is a major problem and is dose-related. Patients may also note perioral tingling. Side effects are much less when RTV is used at "boosting" doses.

* Saquinavir (SQV) — Invirase and Fortovase are formulations; both are often accompanied by GI intolerance, Fortovase more than Invirase.

* Stavudine (d4T) — warn of peripheral neuropathy and pancreatitis. Long-term complications include relatively high rates of lipoatrophy and lactic acidosis, especially when combined with ddI. Must warn patient about the long-term cosmetic changes that result from loss of buccal fat.

* Tenofovir (TDF) — take with meals; well tolerated but need to monitor for renal toxicity.

* Darunavir — warn of GI intolerance and rash.

* Tipranavir (TPV) — take with meals; can cause serious liver toxicity

* Zidovudine (ZDV) — GI intolerance is common and may improve if given with meals or more frequent smaller doses. Also may cause headaches and asthenia. Main side effects are anemia and neutropenia. May cause lactic acidosis, increased triglycerides and facial fat atrophy, but the associated risk is less than with d4T.

MONITORING THERAPY

Visit frequency — Patients who are started on ART should generally have follow-up within one to two weeks to ask patients about symptoms related to HIV infection, adverse effects of drugs, adherence to the regimen, and prevention of transmission.

Visits for this purpose should then be scheduled at least once every four to six weeks thereafter until stable. Once patients are stable on an ART regimen (typically after three to six months) visit frequency can decrease to every three months.

Laboratory monitoring — Monitoring of the CD4 count and HIV viral load is discussed below. Specific ART medications may indicate a need for specific laboratory monitoring (show table 7), however the following battery of tests performed at the same time as the CD4 count and viral load may be simpler than trying to tailor the testing to the specific regimen:

* Complete blood count with differential
* BUN and creatinine
* Liver transaminases

Patients receiving IND should have periodic urine analyses, and patients receiving NVP should have liver transaminases monitored more frequently initially (at baseline, two weeks, four weeks, eight weeks, twelve weeks, and then every three months).

Lipid and glucose levels should be monitored at baseline, three months, six months, and then yearly.

Patients who have abnormalities on any of the monitoring tests that are not severe enough to warrant a change in therapy will generally require more frequent monitoring.

Virologic response — The HIV viral load should be measured at four weeks after initiating HAART, again at eight to twelve weeks, and approximately every 12 weeks until the viral load is undetectable on standard assays (50 copies/mL (see "Virologic failure" below).

Blips — This term refers to intermittent periods of "detectable viremia" meaning viral loads >50 copies/mL. These are common and usually indicate a lab error [23,82]. They do not require intervention with a new regimen unless the viral load is sustained at >50 copies/mL or perhaps >400 copies/mL [7]. (See "Modifying HIV antiretroviral therapy regimens", section on Blips).

Virologic failure — Virologic failure is defined as the failure to achieve a viral load 50 copies/mL [23]. The expected response with sequential viral load determinations are shown in the table (show table 6). The ability to achieve specific viral load thresholds is dependent to a large extent on the baseline viral load. However, the expectation is that the initial antiretroviral regimen will achieve the goal of a viral load 1000 copies/mL and expertise in interpretation. (See "Drug resistance testing in the clinical management of HIV infection").

Evaluation of patients who are failing ART and modification of ART regimens is discussed in detail separately. (See "Modifying HIV antiretroviral therapy regimens").

Immune response — The CD4 cell count should be measured approximately four weeks after starting therapy and then every three to four months, in tandem with HIV RNA levels.

Good viral suppression is usually accompanied by an increase in CD4 cell count of greater than or equal to50 cells/microL at four to eight weeks followed by a slower incremental increase of 50 to 100 cells/microL per year [90]. (See "Immune reconstitution inflammatory syndrome", section on Immunobiology and pathogenesis). The increase in CD4 cells may be slower in older patients [91].

Discordant results are seen in approximately 20 percent of patients and are usually unexplained [92]. However, in pooled data from cohorts, there is a consistent direct correlation between the CD4 slope and the decrease in viral load [90,92,93]. In patients who have discordant results, most authorities make therapeutic decisions based upon virologic results [7,94].

Immune reconstitution inflammatory syndrome — Patients who initiate HAART in the setting of a low CD4 count (typically below 50 cells/microL) may develop an immune reconstitution inflammatory syndrome that has two forms:

* The most common form is a worsening of clinical manifestations related to a OI in the setting of immune reconstitution.

* The second form, which is less common, is de novo presentation of an OI that was presumably subclinical at the time HAART was initiated. This clinical presentation is seen most commonly with mycobacterial lymphadenitis (TB in resource-limited countries and M. avium in the US and Europe), cryptococcal meningitis, and CMV retinitis.

In some cases it may be difficult to distinguish immune reconstitution inflammatory syndrome from ART toxicity; the symptoms of abacavir hypersensitivity in particular may be similar to those with immune reconstitution. The diagnosis and management of immune reconstitution inflammatory syndrome is discussed in detail elsewhere. (See "Immune reconstitution inflammatory syndrome").

INDICATIONS FOR CHANGING THERAPY — There are four common indications for changing the antiretroviral regimen:

* Virologic failure. (See "Virologic failure" above)
* Toxicity
* Difficulty adhering to the regimen
* Current antiretroviral regimen is suboptimal

Modification of ART regimens is discussed in detail separately. (See "Modifying HIV antiretroviral therapy regimens").

SUMMARY AND RECOMMENDATIONS

* Antiretroviral therapy (ART) has revolutionized the management of HIV infection with decreases in opportunistic infections and mortality rates.

* ART is complex, and, when possible, providers with training and expertise in HIV infection should initiate and manage ART.

* Prior to initiating ART, patients should undergo a careful history and physical examination with particular emphasis on evidence of symptomatic HIV disease as well as psychosocial factors that might interfere with adherence to an ART regimen.

* Laboratory testing prior to ART should include two measurements of the CD4 cell count, preferably at times when the patient is not acutely ill; measurement of the HIV viral load; a complete blood count with differential; electrolytes, BUN, creatinine, glucose; liver function tests; amylase; a lipid profile (including triglycerides); and serologic testing for syphilis, toxoplasmosis, hepatitis B and hepatitis C.

* Indications for therapy include symptomatic HIV disease (eg, an AIDS-defining diagnosis, wasting, or thrush). In asymptomatic patients, therapy should be initiated after the CD4 cell count declines below 350/microL, but before it reaches 200/microL. Providers should discuss the risks and benefits of ART with patients. The urgency to treat depends on the viral load and CD4 count decline.

* Many appropriate initial regimens can be constructed using published expert guidelines from the DHHS (show table 8) or the IAS-USA. Standard treatment consists of three active drugs against HIV including a dual nucleoside backbone and a third agent. For the third agent most experts currently would choose a regimen based on EFV 600 mg daily, ATV/r 300 mg/100 mg daily, LPV/r 400 mg/100 mg daily or FOS/r 1400 mg/200 mg daily. An NRTI backbone of TDF/FTC 300 mg/200 mg once daily, ZDV/3TC 600 mg/300 mg twice daily, or ABC/3TC 600 mg/300 mg once daily are commonly used.

* Adherence to a regimen (taking more than 95 percent of prescribed doses) is crucial to the success of ART and to preventing the development of HIV resistance. Patients should be advised of the importance of taking all or none of their ART medications.

* Patients should undergo frequent monitoring both with provider visits and laboratory testing after initiating ART. Patients who do not have the expected drop in HIV viral load after initiation of ART (show table 6) may be experiencing failure of the regimen and should be managed aggressively. (See "Virologic failure" above).

* Indications for changing therapy are virologic failure, toxicity, inability to comply with the regimen, or a suboptimal regimen. (See "Modifying HIV antiretroviral therapy regimens").


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55. Clifford, DB, Evans, S, Yang, Y, et al. Impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals. Ann Intern Med 2005; 143:714.
56. Maternal Toxicity With Continuous Nevirapine in Pregnancy: Results From PACTG 1022. J Acquir Immune Defic Syndr 2004; 36:772.
57. Stern, JO, Robinson, PA, Love, J, et al. A comprehensive hepatic safety analysis of nevirapine in different populations of HIV infected patients. J Acquir Immune Defic Syndr 2003; 34 Suppl 1:S21.
58. Colonno, RJ, Thiry, A, Limoli, K, Parkin, N. Activities of atazanavir (BMS-232632) against a large panel of human immunodeficiency virus type 1 clinical isolates resistant to one or more approved protease inhibitors. Antimicrob Agents Chemother 2003; 47:1324.
59. Gulick, RM, Ribaudo, HJ, Shikuma, CM, et al. Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection. N Engl J Med 2004; 350:1850.
60. Falco, V, Rodriguez, D, Ribera, E, et al. Severe nucleoside-associated lactic acidosis in human immunodeficiency virus-infected patients: report of 12 cases and review of the literature. Clin Infect Dis 2002; 34:838.
61. Cote, HF, Brumme, ZL, Craib, KJ, et al. Changes in mitochondrial DNA as a marker of nucleoside toxicity in HIV-infected patients. N Engl J Med 2002; 346:811.
62. Carr, A, Cooper, DA. Adverse effects of antiretroviral therapy. Lancet 2000; 356:1423.
63. Landman, R, Peytavin, G, Descamps, D, et al. Low genetic barrier to resistance is a possible cause of early virologic failures in once-daily regimen of abacavir, lamivudine, and tenofovir: The Tonus study.11th Conference on Retroviruses and Opportunstic Infections, February 2004, San Francisco.
64. Gallant, JE, Rodriguez, AE, Weinberg, WG, et al. Early Virologic Nonresponse to Tenofovir, Abacavir, and Lamivudine in HIV-Infected Antiretroviral-Naive Subjects. J Infect Dis 2005; 192:1921.
65. Podzamczer, D, Ferrer, E, Gatell, JM, et al. Early virologic failure with a combination of tenofovir, didanosine and efavirenz. Antiviral Therapy 2004 9:S172. Poster 156 presented at the 13th International HIV Drug Resistance Workshop; June 2004; Tenerife Sur, Spain.
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67. Maitland, D, Moyle, G, Hand, J, et al. Early virologic failure in HIV-1 infected subjects on didanosine/tenofovir/efavirenz: 12-week results from a randomized trial. AIDS 2005; 19:1183.
68. Leon, A, Mallolas, J, Martinez, E, et al. High rate of virological failure in maintenance antiretroviral therapy with didanosine and tenofovir. AIDS 2005; 19:1695.
69. Barrios, A, Rendon, A, Negredo, E, et al. Paradoxical CD4+ T-cell decline in HIV-infected patients with complete virus suppression taking tenofovir and didanosine. AIDS 2005; 19:569.
70. Lacombe, K, Pacanowski, J, Meynard, JL, et al. Risk factors for CD4 lymphopenia in patients treated with a tenofovir/didanosine high dose-containing highly active antiretroviral therapy regimen. AIDS 2005; 19:1107.
71. Negredo, E, Bonjoch, A, Paredes, R, et al. Compromised immunologic recovery in treatment-experienced patients with HIV infection receiving both tenofovir disoproxil fumarate and didanosine in the TORO studies. Clin Infect Dis 2005; 41:901.
72. Watts, DH. Management of human immunodeficiency virus infection in pregnancy. N Engl J Med 2002; 346:1879.
73. Fundaro, C, Genovese, O, Rendeli, C, et al. Myelomeningocele in a child with intrauterine exposure to efavirenz. AIDS 2002; 16:299.
74. De Santis, M, Carducci, B, De Santis, L, et al. Periconceptional exposure to efavirenz and neural tube defects. Arch Intern Med 2002; 162:355.
75. Rainey, PM, Friedland, G, McCance-Katz, EF, et al. Interaction of methadone with didanosine and stavudine. J Acquir Immune Defic Syndr 2000; 24:241.
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81. Lalezari, JP, Henry, K, O'Hearn, M, et al. Enfuvirtide, an HIV-1 Fusion Inhibitor, for Drug-Resistant HIV Infection in North and South America. N Engl J Med 2003; 348:2175.
82. Sungkanuparph, S, Overton, ET, Seyfried, W, et al. Intermittent episodes of detectable HIV viremia in patients receiving nonnucleoside reverse-transcriptase inhibitor-based or protease inhibitor-based highly active antiretroviral therapy regimens are equivalent in incidence and prognosis. Clin Infect Dis 2005; 41:1326.
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85. Demeter, LM, Hughes, MD, Coombs, RW, et al. Predictors of Virologic and Clinical Outcomes in HIV-1-Infected Patients Receiving Concurrent Treatment with Indinavir, Zidovudine, and Lamivudine. AIDS Clinical Trials Group Protocol 320. Ann Intern Med 2001; 135:954.
86. Rousseau, MN, Vergne, L, Montes, B, et al. Patterns of resistance mutations to antiretroviral drugs in extensively treated HIV-1-infected patients with failure of highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2001; 26:36.
87. Alexander, CS, Dong, W, Chan, K, et al. HIV protease and reverse transcriptase variation and therapy outcome in antiretroviral-naive individuals from a large North American cohort. AIDS 2001; 1501.
88. Eron, JJ, Haubrich, R, Lang, W, et al. A phase II trial of dual protease inhibitor therapy: amprenavir in combination with indinavir, nelfinavir, or saquinavir. J Acquir Immune Defic Syndr 2001; 26:458.
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Postuar nga NS-6 datë 08 Mars 2007 - 22:43:

HIV Transmission During Early Infection

Cod. A08032007

HIV Transmission During Early Infection

Nearly half of HIV transmission occurs less than 6 months after seroconversion.

The early stages of HIV infection are characterized by a high viral burden in blood and semen, which increases the risk for viral transmission. Knowing the proportion of HIV transmission that occurs during early infection is important for developing prevention strategies. Investigators in Quebec recently used comparative phylogenetic analysis to explore HIV transmission patterns among 593 patients with early HIV infection (<6 months after seroconversion) and 795 patients with chronic HIV infection.

Of 593 early infections, 293 (49.4%) segregated into one of 75 transmission clusters, with 2 to 17 infections per cluster. Half of these clusters included a mean of 2.7 infections; the other half, a mean of 8.8 infections. In contrast, only 21 of 660 treated chronic infections (3.2%) were clustered, with a mean cluster size of 3.1. HIV isolates from untreated and treated chronic infections co-clustered with early-infection HIV isolates in only 1% and 2.7% of cases, respectively. Analysis revealed that 49.4% of transmissions were attributable to early infections. Drug-resistance mutations were present in 14.7% of clustered transmissions at early stages of disease.

Comment: These findings confirm that a large proportion of HIV transmission occurs during early infection. Prompt detection of persons newly infected with HIV, followed by counseling to reduce high-risk behavior, is essential for reducing future transmission. Whether antiretroviral therapy during early infection benefits patients remains controversial, but as editorialists argue, reduction of transmission risk, through reduction of viral load, should also be considered a potential benefit of such treatment.

— Daniel J. Diekema, MD, MS

Published in Journal Watch Infectious Diseases March 7, 2007


Postuar nga NS-6 datë 12 Mars 2007 - 22:56:

Do Corticosteroids Improve Outcome in Kawasaki Disease?

Cod. A12032007


Intravenous methylprednisolone is not indicated for the primary treatment of acute KD in children.

Kawasaki disease (KD) is a mucocutaneous vasculitis apparently triggered by an unknown infectious agent in infants and young children with a genetic predisposition. It is the leading cause of acquired heart disease in children. In Japan, KD affects 1 in every 185 children. In the multiethnic U.S., that figure is about 25 children per 100,000 (5000 new cases annually). Diagnosis rests on a constellation of clinical signs that often emerge over time, including rash, fever, conjunctivitis, erythema of the lips and oral mucosa, and cervical lymphadenopathy. There is no single diagnostic test. Untreated, KD leads to coronary artery aneurysms in up to 25% of children. Standard therapy is intravenous immunoglobulin (IVIG) and high-dose aspirin given within the first 10 days of illness. Even with early treatment, approximately 5% of children develop coronary artery aneurysms, 1% develop giant aneurysms, and some develop recurrent KD.

Until now, studies of the value of adding systemic corticosteroids to the standard treatment have been inconclusive. Investigators in the Pediatric Heart Network performed a multicenter, randomized, placebo-controlled, double-blind trial to see if IV methylprednisolone added to conventional IVIG and aspirin therapy would reduce coronary artery abnormalities in children with acute KD. Children seen between days 4 and 10 of fever who met other strict diagnostic criteria were enrolled. Those with previous IVIG therapy, recent systemic corticosteroid treatment, or previous KD were excluded. Over 2 years, 199 of the 589 children diagnosed with KD were enrolled. All patients received IVIG and high-dose aspirin; in addition, half received 30 mg/kg of IV methylprednisolone and half received placebo.

Compared with the placebo group, the corticosteroid group had shorter initial hospitalization and lower erythrocyte sedimentation rates at 1 week, but both groups had similar coronary dimensions at weeks 1 and 5. In addition, the total number of days of hospitalization, days of fever, incidences of IVIG retreatment, and number of adverse events did not differ between groups. The authors conclude that intravenous methylprednisolone therapy is not indicated in the primary treatment of acute KD in children.

Comment: The number of KD patients collected over a mere 2 years is staggering, especially given the broad exclusion criteria. As stated in the accompanying editorial, "the failure of corticosteroids to benefit these patients underscores the difference between KD and other chronic vasculitides." More prospective, randomized, controlled studies of other therapies are needed to improve outcomes in patients with KD, especially those who do not respond to IVIG therapy. Studies by a multicenter international genotyping consortium are currently examining the genetic component of KD.

— Mary Wu Chang, MD

Published in Journal Watch Dermatology February 14, 2007


Postuar nga NS-6 datë 17 Mars 2007 - 00:23:

Cardiopulmonary resuscitation by bystanders with chest compression only

Cod. A17032007

hmmm,i found an article published by The Lancet talking about cardiopulmonary resuscitation...seems interesting...

here is the abstract because the full article was to be paid

Cardiopulmonary resuscitation by bystanders with chest compression only (SOS-KANTO): an observational study

Summary

Background
Mouth-to-mouth ventilation is a barrier to bystanders doing cardiopulmonary resuscitation (CPR), but few clinical studies have investigated the efficacy of bystander resuscitation by chest compressions without mouth-to-mouth ventilation (cardiac-only resuscitation).

Methods
We did a prospective, multicentre, observational study of patients who had out-of-hospital cardiac arrest. On arrival at the scene, paramedics assessed the technique of bystander resuscitation. The primary endpoint was favourable neurological outcome 30 days after cardiac arrest.

Findings
4068 adult patients who had out-of-hospital cardiac arrest witnessed by bystanders were included; 439 (11%) received cardiac-only resuscitation from bystanders, 712 (18%) conventional CPR, and 2917 (72%) received no bystander CPR. Any resuscitation attempt was associated with a higher proportion having favourable neurological outcomes than no resuscitation (5·0% vs 2·2%, p<0·0001). Cardiac-only resuscitation resulted in a higher proportion of patients with favourable neurological outcomes than conventional CPR in patients with apnoea (6·2% vs 3·1%; p=0·0195), with shockable rhythm (19·4% vs 11·2%, p=0·041), and with resuscitation that started within 4 min of arrest (10·1% vs 5·1%, p=0·0221). However, there was no evidence for any benefit from the addition of mouth-to-mouth ventilation in any subgroup. The adjusted odds ratio for a favourable neurological outcome after cardiac-only resuscitation was 2·2 (95% CI 1·2–4·2) in patients who received any resuscitation from bystanders.

Interpretation
Cardiac-only resuscitation by bystanders is the preferable approach to resuscitation for adult patients with witnessed out-of-hospital cardiac arrest, especially those with apnoea, shockable rhythm, or short periods of untreated arrest.

The Lancet 2007; 369:920-926


Postuar nga NS-6 datë 19 Mars 2007 - 23:21:

FDA Clears Rapid Test for Meningitis

Cod. A19032007

(March 16, 2007)
The U.S. Food and Drug Administration (FDA) today cleared for marketing a test that uses molecular biology to quickly detect the presence of viral meningitis.

The Xpert EV test, when used in combination with other laboratory tests, will help physicians distinguish between viral meningitis and the less-common, but more severe, version of meningitis caused by bacteria.

Meningitis is an infection of the cerebrospinal fluid surrounding a person's spinal cord and brain, causing inflammation of the tissues in these areas. The illness is diagnosed by testing the fluid obtained from a patient during a spinal tap. Typically, diagnostic tests for meningitis can take up to a week to get results. But results from the Xpert EV test are available in two and one-half hours.

"Because this test is significantly faster than existing methods for diagnosing meningitis, it could minimize delays in treating patients. Swift recognition of the cause and appropriate treatment is critical to patient recovery," said Daniel Schultz, M.D., director of the Center for Devices and Radiological Health. "Since bacterial meningitis can be deadly within as little as two days, patients who have viral meningitis are frequently treated with antibiotics as a safeguard against the more dangerous bacterial meningitis. This test should help physicians manage patients appropriately and prevent unnecessary treatment with antibiotics."

Knowing whether the meningitis is viral or bacterial is imperative to early effective treatment. But distinguishing between the two types of infection is difficult because of similar symptoms. Patients with viral meningitis usually recover within two weeks without any medical intervention. Bacterial meningitis, however, can lead to brain damage, hearing loss and even death if not treated properly.

For patients over two years of age, symptoms of meningitis include fever, severe headache, stiff neck, nausea, sleepiness, confusion, and sensitivity to bright lights or seizures. These symptoms may be absent or difficult to detect in newborns and small infants who may only appear slow or inactive, or be irritable, have vomiting or feed poorly.

The Xpert EV test is the first fully-automated medical diagnostic test that isolates and amplifies viral genetic material present in a patient's cerebrospinal fluid by a process called reverse transcription-polymerase chain reaction(RT-PCR). The test identifies infection resulting from a class of viruses known as Enterovirus, which are responsible for approximately 90 percent of all viral meningitis cases.

The Xpert EV test is performed by adding the sample directly to a disposable, single-use cartridge. The cartridge is loaded into the GeneXpert DX instrument which then conducts all the necessary laboratory procedures in a one-step, easy-to-use format that helps minimize errors.

The accuracy of the Xpert EV test was confirmed in a multi-site study at six institutions. A total of 255 patient samples were tested and demonstrated that 96 percent of patients who tested positive did have viral meningitis, and that 97 percent of patients who tested negative did not have viral meningitis.

The Xpert EV test was developed by Cepheid, a company located in Sunnyvale, Calif.


Postuar nga NS-6 datë 17 Prill 2007 - 11:12:

Changes in Lung Function with Inhaled Insulin

Cod. A17042007

Inhaled insulin is the new method of somministration of insulin that should avoid the problems of injections and make its somministration easier. Studies are trying to find out whether this method is more reliable or not and whether this method has any collateral effect or not in order to pay attention in the future.
I'm bringing here an article concerning a study with inhaled insulin and its side effects on the respiratory functions!
-------------------
Changes in Lung Function with Inhaled Insulin

A small initial decline in function did not appear to progress beyond 3 months.

In previous short-term studies, inhaled insulin caused small declines in lung function. In this industry-sponsored trial, researchers assessed longer-term respiratory effects of inhaled insulin.

Nearly 600 adults with type 1 diabetes were randomized to receive premeal inhaled insulin (Exubera) or premeal subcutaneous short-acting insulin; both groups also received long-acting basal insulin. At 3 months, mean FEV1 had declined by 0.05 liters in the inhaled insulin group and 0.03 liters in the subcutaneous insulin group, a small but statistically significant difference. However, after 3 months (and through 24 months), FEV1 declined at the same rate in both groups. For diffusing capacity, the same pattern was noted — a small initial decline, but no further separation between groups during months 3 to 24. Inhaled-insulin recipients reported cough more frequently than subcutaneous-insulin recipients (38% vs. 13%). Glycemic control was similar in the two groups.

Comment: This study demonstrates that inhaled insulin induces small changes in pulmonary function shortly after the start of treatment. On average, however, the changes do not appear to progress after 3 months. Patients are advised to have spirometry before starting inhaled insulin, after 6 months of treatment, and annually thereafter. Inhaled insulin is not recommended for patients with underlying lung disease and is contraindicated in smokers.

— Allan S. Brett, MD

Published in Journal Watch General Medicine March 29, 2007

Citation(s):

Skyler JS et al. Two-year safety and efficacy of inhaled human insulin (Exubera) in adult patients with type 1 diabetes. Diabetes Care 2007 Mar; 30:579-85.


Postuar nga NS-6 datë 18 Prill 2007 - 14:43:

FDA Approves First U.S. Vaccine for Humans Against the Avian Influenza Virus H5N1

Cod. A18042007
The Avian Influenza scared the world all over,remembering to the people that the influence viruses may become virulent in every moment and in order to prevent this,new defensive weapons should be discovered.Today i got an email and inside that email,an article,announcing the discovery of a vaccine against the Avarian Influenza virus H5N1. It seems that all the effort made to discover any way to protect ourselves,are giving the first results...and most probably they won't stop at this point
-----------------
FDA Approves First U.S. Vaccine for Humans Against the Avian Influenza Virus H5N1

April 17,2007

The U.S. Food and Drug Administration (FDA) today announced the first approval in the United States of a vaccine for humans against the H5N1 influenza virus, commonly known as avian or bird flu.

The vaccine could be used in the event the current H5N1 avian virus were to develop the capability to efficiently spread from human to human, resulting in the rapid spread of the disease across the globe. Should such an influenza pandemic emerge, the vaccine may provide early limited protection in the months before a vaccine tailored to the pandemic strain of the virus could be developed and produced.

"The threat of an influenza pandemic is, at present, one of the most significant public health issues our nation and world faces," said Andrew C. von Eschenbach, M.D., Commissioner of Food and Drugs. "The approval of this vaccine is an important step forward in our protection against a pandemic."

The H5N1 virus is one version of the influenza A virus commonly found in birds. Unlike seasonal influenza, where infection ranges from mild to serious symptoms in most people, the disease caused by H5N1 is far more severe and happens quickly, with pneumonia and multi-organ failure commonly seen.

While there have been no reported human cases of H5N1 infection in the United States, almost 300 people worldwide have been infected with this virus since 2003 and more than half of them have died. To date, H5N1 influenza has remained primarily an animal disease but should the virus acquire the ability for sustained transmission among humans, people will have little immunity to this virus and the potential for an influenza pandemic would have grave consequences for global public health.

"The timing and severity of an influenza pandemic is uncertain, but the danger remains very real," said Jesse L. Goodman, M.D., M.P.H., Director of FDA's Center for Biologics Evaluation and Research. "We are working closely with other government agencies, global partners and the vaccine industry to facilitate the development, licensure and availability of needed supplies of safe and effective vaccines to protect against the pandemic threat."

The vaccine was obtained from a human strain and is intended for immunizing people 18 through 64 years of age who could be at increased risk of exposure to the H5N1 influenza virus contained in the vaccine. H5N1 influenza vaccine immunization consists of two intramuscular injections, given approximately one month apart. The manufacturer, sanofi pasteur Inc., will not sell the vaccine commercially. Instead, the vaccine has been purchased by the federal government for inclusion within the U.S. Strategic National Stockpile for distribution by public health officials if needed. The vaccine will be manufactured at sanofi pasteur's Swiftwater, Pa., facility.

A clinical study was conducted to collect safety information and information on recipient's immune responses and to determine the appropriate vaccine dose. A total of 103 healthy adults received a 90 microgram dose of the vaccine by injection followed by another 90 microgram dose 28 days later. In addition, there were approximately 300 healthy adults who received the vaccine at doses lower than 90 micrograms and a total of 48 who received a placebo injection.

The vaccine was generally well tolerated, with the most common side effects reported as pain at the injection site, headache, general ill feeling and muscle pain. The study showed that 45 percent of individuals who received the 90 microgram, two-dose regimen developed antibodies at a level that is expected to reduce the risk of getting influenza. Although the level of antibodies seen in the remaining individuals did not reach that level, current scientific information on other influenza vaccines suggests that less than optimal antibody levels may still have the potential to help reduce disease severity and influenza-related hospitalizations and deaths. Additional information on this H5N1 influenza vaccine is being collected on safety and effectiveness in other age groups and will be available to FDA in the near future.

With the support of FDA, the U.S. National Institutes of Health and other government agencies, sanofi pasteur and other manufacturers are working to develop a next generation of influenza vaccines for enhanced immune responses at lower doses, using technologies intended to boost the immune response. Meanwhile, the approval and availability of this vaccine will enhance national readiness and the nation's ability to protect those at increased risk of exposure.

The U.S. Strategic National Stockpile is maintained by the U.S. Centers for Disease Control and Prevention. It contains large quantities of medicine and medical supplies to protect the American public if there is a public health emergency, which can be delivered to any state in the United States within 12 hours. For more information on the government's preparedness efforts, visit: www.pandemicflu.gov.


Postuar nga NS-6 datë 27 Prill 2007 - 00:23:

The Helium Donald Duck Effect

Cod. A27042007

The human voice originates when the stream of air flowing up the trachea undergoes pressure modulations as it passes between the vibrating vocal chords in the larynx. The sound produced consists of a fundamental frequency, which determines the voice's pitch, and harmonics (integral multiples) of this frequency. For adult males and females the average frequencies of the fundamentals are 130 hertz and 205 hertz, respectively. The amplitudes of the harmonics for vowel sounds vary approximately as the inverse of the 1.5 power of the order of the harmonic.

The sound that exits the mouth is the result of selective transmission by the configuration of the vocal tract (throat, mouth, and nasal cavities) produced by the tongue and lip constrictions. For any cavity, sound waves bouncing back and forth within it will interfere constructively for certain frequencies (the resonance frequencies) to produce a loud sound. The cavities in the vocal tract have such resonances, and the maxima in the sound transmission curve correspond to the resonance frequencies. Those harmonics near a resonance frequency of the vocal tract will be strongly transmitted, while the other harmonics will be damped. The lowest-frequency peak in the transmission curve is referred to as the fundamental, while the regions at the other peaks are called formants.

The fundamental frequency of a resonating cavity is directly proportional to the speed of sound in the gas occupying the cavity. But from the kinetic theory of gases, as well as direct measurements, we know that the speed of sound in an ideal gas (such as dry air) is proportional to the square root of the ratio T/M, where T is the absolute temperature of the gas and M is its molecular weight. For a fixed temperature and cavity volume, it is clear, therefore, that the speed of sound will be greatest for gases with the smallest molecular weights. For example, the speed of sound in dry air (M=28.964) at 0 degrees Celsius is 331.3 m/s. At this temperature in helium (M=4.003) the speed is 891.2 m/s. The resonance frequencies of the vocal tract, and hence the formants, are therefore almost 2.7 times higher for helium than for air. At a pressure of one atmosphere, with pure helium in your vocal tract instead of air, the pitch of your voice will be about two and a half octaves higher than usual (like Donald Duck's). For a helium-oxygen mixture containing 68% helium by volume, the pitch increase is only one and a half octaves.

REFERENCES:

E. G. Richardson, "Technical Aspects of Sound" (Elsevier, New York, 1953), Chapter 10.

F. Reif, "Fundamentals of statistical and thermal physics" (McGraw-Hill, New York), Chapter 5.


Postuar nga amor alucius datë 17 Maj 2007 - 09:26:

Penn and Russian doctors explore a cool surgical procedure

Cod. A17052007

Penn and Russian doctors explore a cool surgical procedure(artikull i 1998 mgjth vazhdon te jete aktual)

--------------------------------------------------------------------------------

A team of Russian physicians visited the Medical Center this month with news about an open-heart surgical procedure that leaves patients cold. The news and the team were warmly received by their Penn anesthesia department hosts, who have received a University grant to begin a collaborative research project with the Russian doctors.
A Siberian patient is iced prior to open-heart surgery as Russian doctors Dmitri Guvanov and Vladimir Lomivorotov and Assistant Anesthesia Professor Stuart Weiss observe. Guvanov is currently a research fellow in Penn's anesthesia department.


The physicians hailed from the Novosibirsk Institute of Circulatory Pathology, where for years doctors have been conducting open-heart surgery without heart-lung bypass machines. Vladimir Lomivorotov, M.D., the institute's chief cardiothoracic anesthesiologist, explained through a translator, "The procedure is quite different from the conventional approach to providing cardiothoracic surgery" in the rest of the world.

In order to operate on the heart, doctors must stop it so they can make the precise incisions needed to repair heart defects. Doing so, however, cuts off the blood flow and oxygen supply to other organs, which can cause permanent damage and even death. "The brain will only survive for three to five minutes at most without blood flow," said Assistant Professor of Anesthesia Albert Cheung.

To prevent this, one of two things must happen: either blood must keep flowing or the body's need for oxygen must be reduced.

Heart surgeons in the West have traditionally opted for the former by using a heart-lung machine, which may cause blood clotting or inflamation. The Novosibirsk method takes the latter approach: it cools the patient's body temperature until it enters suspended animation, a condition known as hypothermia.

By encasing the brain in an ice-filled helmet and covering the patient with ice prior to surgery, the Novosibirsk doctors lower body temperature from 98.6° to about 75°, and brain temperature to 60 to 65°. The doctors then clear the ice from around the body, stop the heart and operate.

"The temperature of the patient's brain is so low that it actually allows you to stop the heart for a sufficient time -- up to an hour and 30 minutes -- to restore the heart defect, restore the circulation afterwards, and restore the full functioning of the brain," Lomivorotov said.

Lomivorotov first described the procedure to Penn anesthesiologists in a talk last October. "The results of the procedure are comparable to what we routinely do here using heart-lung machines," but at a lower cost, Cheung said.

The procedure was actually first used in Japan and England more than 40 years ago, but was largely abandoned after the introduction of bypass machines. Novosibirsk Institute Executive Director Alexandr Karaskov explained that his institute was the only center in the world that continued to actively use and refine the procedure.

"We have refined [it] to the point where it can be safely done without damaging the patient," he said.

The Russians also hope to learn from their American counterparts. The Novosibirsk Institute plans to refashion itself as an academic medical center similar to Penn's Health System, and the delegation included an economist, Larissa Shkhrko, Ph.D., who is studying aspects of the American health system that could be adapted to Russia's changing health-care environment


Postuar nga ~Enigme~ datë 17 Maj 2007 - 15:31:

Shume interesant artikulli qe permenden kryerjen e operacionit te zemres.
Per nje gje nuk isha e qarte. Kerkimi eksperimental midis repartit te anestize dhe doktoreve ruse ka nisur tani apo ne '98?


Postuar nga NS-6 datë 17 Maj 2007 - 18:10:

perderisa artikulli daton vitin 1998 do te thote qe kerkimet kane filluar me perpara dhe me sa shoh per here te pare qenka kryer rreth 40 vjet me para por vetem ruset paskan qene qe paskan vazhduar me ngulm ta permirsojne si teknike. rreth kesaj teme me kujtohet qe ka qene nje shkrim edhe tek revista "Le Scienze" (i ketyre 2 viteve te fundit eshte) dhe trajtonte pikerisht kete lloj operacioni. materiali qe kerkonin te perdornin per te ftohur trupin ishte nje xhel qe ishte prodhuar nga nje firme japoneze per qellime te tjera por pastaj u pa qe mund te kishte dobi ne keto lloj operacionesh. eksperimentet e kryera tek kafshet treguan qe teknika e ftohjes ishte mjaft e mire edhe per ecurine pas operacionit te pacientit. per momentin nuk kam te reja te tjera per kete ceshtje


Postuar nga ~Enigme~ datë 17 Maj 2007 - 19:20:

NS-6 faleminderit per shtimin.
Nuk e di pse nuk me ka dale modifikimi i mesazhit. Por ajo qe doja te percillja me mesazhin tim eshte se nqs keto kerkime eksperimentale kane nisur qe ne 98 atehere do te isha e interesuar te dija me shume burimet e ketyre materialeve per te shtrire pak horizontin ne kete ceshtje, duhen shfletuar journals se nga interneti asnjehere nuk i gjej me tekstet e plota.


Postuar nga NS-6 datë 17 Maj 2007 - 21:22:

Neuroprotective Effect of Mild Hypothermia in Coronary Artery Surgery

Cod. C17042007

ketu po sjell nje abstract mbi nje artikull te publikuar tani ne Maj ne Journal of Thoracic and Cardiovascular Surgery (artikulli i plote ishte me leke).gjithsesi ky shkrim vlereson me shume efektet ne distance 5 vjetesh te nje operacioni te kryer ne hipotermi mbi trurin.

Neuroprotective Effect of Mild Hypothermia in Patients Undergoing Coronary Artery Surgery With Cardiopulmonary Bypass: Five-Year Follow-up of a Randomized Trial
(J Thorac Cardiovasc Surg. 2007 May;133(5):1206-11)

Objective: In a randomized trial of 223 patients undergoing coronary artery surgery with cardiopulmonary bypass, we have reported a neuroprotective effect of mild hypothermia. To determine whether the beneficial effect of mild hypothermia was long-lasting, we repeated the psychometric tests in 131 patients after 5 years.

Methods: Patients were cooled to 32 degrees C during aortic crossclamping and then randomized to rewarming to either 34 degrees C or 37 degrees C, with no further rewarming until arrival in intensive care unit. Cognitive function was measured preoperatively and 1 week and 5 years postoperatively with a battery of 11 psychometric tests interrogating verbal memory, attention, and psychomotor speed and dexterity.

Results: Patients who had greater cognitive decline 1 week after surgery showed poorer performance 5 years later. The magnitude of cognitive decline over 5 years was modest. The incidence of deficits defined as a 1 standard deviation [SD] decline in at least 1 of 3 factors was not different between temperature groups. Fewer patients in the hypothermic group had deficits that persisted over the 5 years, but this difference did not attain statistical significance (RR = 0.64, P = .16).

Conclusions: The effect of surgery on cognitive function observed early after surgery is an important predictor of cognitive performance 5 years later. Although there was evidence of a neuroprotective effect of mild hypothermia early after surgery in the original cohort, the results after 5 years were inconclusive. In general, the magnitude of cognitive changes over 5 years was modest. We believe that further trials investigating the efficacy of mild hypothermia in patients having cardiac surgery are warranted.

do kishte qene interesante te gjehej artikulli i plote per faktin se mund te kontrolloheshin edhe referencat sepse me shume mundesi ka edhe shkrime te tjera qe do kene te bejne me temen...gjithsesi...
ndonje gje tjeter?


Postuar nga NS-6 datë 19 Maj 2007 - 12:23:

Focused Readings: Acute Stroke

Cod. A19052007

there was an article in Journal Watch website concerning the advancement on stroke. here is the main article and 2 other articles cited inside.
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Focused Readings: Acute Stroke

Recent studies address advances in acute stroke care.

Few areas in emergency medicine have changed as rapidly, or with as much controversy, as the care of acute stroke. Systemic fibrinolysis, once vilified as dangerous and unproven, has emerged as the standard of care for a highly select patient population, with proven outcome benefit. Imaging modalities have evolved, but the clear superiority of magnetic resonance imaging is often negated by lack of access to this imaging study. Here, we present several recent studies of acute stroke. They address the incidence of acute stroke, validation of a score (ABCD2) to help identify patients at high risk, the role of imaging in the decision to administer systemic lytic therapy, functional outcomes at stroke centers, and performance of systemic lytic therapy in "real life."

The bottom line? Emergency departments should have a tightly organized system of care for acute stroke patients, with access to prompt imaging and protocols for administration of acute lytic therapy.

--------------
ARTICLE 1
Declining Risk and Incidence of Clinical Stroke

Age-adjusted incidence of first stroke has decreased during the past 50 years.

Stroke is the third leading cause of death and the number-one etiology of long-term neurologic disability in the U.S. Researchers prospectively examined the Framingham Study cohorts during three intervals (1950–1977, 1978–1989, and 1990–2004) to ascertain trends in stroke incidence, severity, 30-day mortality, and risk. The authors defined clinical stroke as "rapidly developing signs of focal neurologic disturbance of presumed vascular etiology, lasting more than 24 hours."

The age-adjusted incidence of first stroke per 1000 person-years decreased in each of the three intervals both in men (7.6, 6.2, and 5.3, respectively) and in women (6.2, 5.8, and 5.1). The 10-year risk at age 65 decreased significantly in men (from 19.5% to 14.5%) but not in women (from 18.0% to 16.1%). Similarly, 30-day mortality decreased significantly in men (from 23% to 14%) but not in women (from 21% to 20%). Assessment of risk factors at age 65 demonstrated significant reductions in mean systolic blood pressure, total cholesterol, prevalence of hypertension, and prevalence of current smoking as well as an increase in the proportion of persons receiving antihypertensive treatment. However, the prevalence of atrial fibrillation in men and the mean body-mass index in both sexes increased. Overall, the Framingham Stroke Risk Profile, a validated instrument, improved significantly for both men and women. The proportion of strokes that were moderate or severe did not change significantly in men or women.

Comment: The good news is that the annual incidence of clinical stroke has declined during the past 50-plus years for men and women, as has the 10-year risk for stroke for people aged 65. The bad news is that stroke severity has not declined and that 30-day mortality has dropped only in men. The latter finding could be due to older age at stroke onset and greater stroke severity in women. The need for primary prevention continues.

— John A. Marx, MD, FAAEM, FACEP

Published in Journal Watch Emergency Medicine February 2, 2007

Citation(s):

Carandang R et al. Trends in incidence, lifetime risk, severity, and 30-day mortality of stroke over the past 50 years. JAMA 2006 Dec 27; 296:2939-46.
----------------------
ARTICLE 2
Who’s at Risk for Stroke After TIA?

A risk-stratification system is effective for determining a patient's risk for stroke within 2 days.

From 4% to 20% of patients with transient ischemic attacks (TIAs) progress to stroke within 90 days, half within the first 48 hours. How do we identify patients at greatest risk? Researchers first validated two recently developed prognostic scores — the California score (designed to predict stroke within 90 days) and the ABCD score (designed to predict stroke within 7 days; see Journal Watch Emergency Medicine Aug 23 2005) — and then combined the two systems and validated the resulting new score, termed ABCD2 (designed to predict stroke within 2 days).

The scores were derived in two groups of patients (totaling 1916) and validated in four groups of patients (totaling 2893) from emergency departments, clinics, and population-based cohorts in California and Oxford, England.

The ABCD2 score assigns 0 to 7 points based on Age (≥60 years, 1 point), Blood pressure at presentation (≥140/90 mm Hg, 1 point), Clinical features (unilateral weakness, 2 points; speech disturbance without weakness, 1 point), Duration of symptoms (≥60 minutes, 2 points; 10–59 minutes, 1 point), and Diabetes (1 point).

Strokes occurred in 3.9% of patients within 2 days, 5.5% within 7 days, 7.5% within 30 days, and 9.2% within 90 days. When applied to the validation groups, the ABCD2 score stratified 21% of patients as high risk (score, 6–7), 45% as moderate risk (score, 4–5), and 34% as low risk (score, 0–3). The 2-day risks for stroke in the high-, moderate-, and low-risk groups were 8.1%, 4.1%, and 1.0%, respectively.

An editorialist suggests that the ABCD2 system is the best available method for determining which patients are at short-term risk for stroke after TIA but notes that the score should be used as an adjunct to, rather than a replacement for, clinical judgment and data from other sources, such as imaging.

Comment: TIAs are like angina of the brain, and symptoms lasting longer than 1 hour are highly likely to represent stroke (see Journal Watch Emergency Medicine Mar 12 2003). The ABCD2 prediction score helps us to risk-stratify patients. Patients with a score of less than 4 might be suitable for discharge on aspirin therapy with close follow-up, but most patients with new-onset TIA should be admitted to a hospital.

— Kristi L. Koenig, MD, FACEP

Published in Journal Watch Emergency Medicine February 23, 2007

Citation(s):

Johnston SC et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet 2007 Jan 27; 369:283-92.
Medline abstract (Free)

Kernan WN. Stroke after transient ischaemic attack: Dealing in futures. Lancet 2007 Jan 27; 369:251-2.
Medline abstract (Free)


Postuar nga NS-6 datë 25 Maj 2007 - 00:50:

Could Early and Continuous HIV Therapy Achieve Eradication?

Cod. B25052007

one of the main reasons why HIV therapy fails is the persistence of the virus in unknown viral reservoirs. there are still unknown reservoirs , and the effect the drugs might have on these reservoirs is not well understood.however research continues to give new clues concerning these reservoirs and probable drug effect! the following article is a result of these efforts to eradicate this virus

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The decay rate of the HIV reservoir in patients treated early in infection raises the question of whether eradication is possible with prolonged continuous therapy.

Eradication of HIV infection has not been possible, even with potent combination antiretroviral therapy (ART), because the virus persists in resting CD4 cells and other viral reservoirs. Estimates of the half-life of such viral reservoirs vary widely, but most of the relevant studies have involved patients who initiated ART during chronic infection.

Investigators from the NIH and the University of Washington now report results from a longitudinal study of seven patients who had initiated ART 0.3–4.4 months (mean, 2.7 months) after the onset of symptoms of primary HIV infection. The patients had received ART for 31.1–54.0 months (mean, 40.4 months) and had achieved maximal viral suppression. Throughout therapy, the researchers performed serial measurements on each patient to determine the number of circulating resting CD4 cells carrying replication-competent HIV.

The number of latently infected CD4 cells declined rapidly in each patient, with the half- life of the viral reservoir estimated to be 1.9–8.7 months (mean, 4.6 months). Assuming 106 latently infected CD4 cells at baseline, the projected time to complete elimination of HIV in the resting CD4-cell reservoir would be 3.1–14.5 years (mean, 7.7 years).

Comment: The short half-life of latently infected resting CD4 cells in this study raises the question of whether viral eradication is possible. However, if HIV populates reservoirs other than circulating CD4 cells early in infection, or if the decay rate slows over time, viral eradication might not be possible, at least until more-potent ART or new strategies to purge the reservoir are available.

— Daniel J. Diekema, MD, MS

Published in Journal Watch Infectious Diseases May 23, 2007


Postuar nga NS-6 datë 26 Maj 2007 - 10:23:

More Support for Fecal Immunochemical Testing

Cod. A26052007
one of the main,noninvasive test performed to find any suspect for colorectal masses is the guaiac test (a fecal occult blood detecting test). the problem with this test is that it is affected by many variables that may produce false positives and false negatives. the presence of non human hemoglobin, rehydration may produce false positives meanwhile hemoglobin degradation or vitamin C may produce false negatives. however the rate of these false results depend on the bleeding site. to prevent these false results,new methods are developed and their efficiency is getting analysed. the following article talks about one of these. it mainly concerns the usage of these methods in detecting colorectal cancers

also, i'd like to recommend you a review article present in the New England Journal of Medicine (NEJM 1999; 341: 38-46) that analysis the main fecal occult blood detecting test. i found it very interesting and i hope you find it the same
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More Support for Fecal Immunochemical Testing

Immunochemical testing is emerging as superior to guaiac-based testing for colorectal cancer screening.

Many studies have indicated that immunochemical testing is superior to guaiac-based testing for detecting fecal occult blood. Adding to this evidence base is a French study, in which 10,673 average-risk adults completed both standard guaiac-based testing (nonrehydrated Hemoccult II) and quantitative immunochemical testing (Immudia/RPHA). Of the 886 study participants who had positive results on one or both tests, 644 underwent colonoscopy. Of these, 294 had adenomas or cancer.

The immunochemical test outperformed the guaiac-based test at every evaluated hemoglobin threshold. At the usual threshold of 20 ng/mL, the immunochemical test identified 50% more cancers and 256% more high-risk adenomas than did the guaiac-based test. However, the increased sensitivity resulted in lower specificity, such that 47 false-positive results would be required to detect 1 extra case of invasive colorectal cancer, and 2.2 false-positive results would be required to detect 1 extra advanced adenoma. With a threshold of 50 ng/mL, the immunochemical test detected 2.3 times as many advanced neoplasias as the guaiac-based test did, with no loss of specificity. At a threshold of 75 ng/mL, the overall rate of positive results on the immunochemical test was similar to that of the guaiac-based test (2.4%), with a 90% gain in sensitivity and an actual improvement in specificity (a 33% reduction in false positives).

Comment: The time has come to replace guaiac-based testing for colorectal cancer with fecal immunochemical testing wherever possible. One powerful advantage of the quantitative testing method is that the performance characteristics can be adjusted to meet the goals of specific screening programs by altering the threshold level for a positive test.

— Douglas K. Rex, MD

Published in Journal Watch Gastroenterology May 25, 2007

Citation(s):

Guittet L et al. Comparison of a guaiac based and an immunochemical faecal occult blood test in screening for colorectal cancer in a general average risk population. Gut 2007 Feb; 56:210-4.


Postuar nga NS-6 datë 03 Qershor 2007 - 12:30:

Reducing the Intensity of Treatment in Mild Asthma

Cod. B03062007

Two randomized trials demonstrate the feasibility of step-down therapy in patients whose asthma is well controlled.

Many patients with mild asthma take standard daily doses of inhaled corticosteroids indefinitely. Two new industry-supported, placebo-controlled, randomized trials — each with about 500 participants whose mild asthma was controlled with twice-daily inhaled steroids — show that "step-down" therapy may be reasonable for such patients.

One study compared twice-daily inhaled steroid therapy with once-daily oral or inhaled alternatives. Patients received one of three treatments: inhaled fluticasone (Flovent Diskus, 100 µg), twice daily; combined fluticasone/salmeterol (Advair Diskus, 100/50 µg), once daily in the evening; or oral montelukast (Singulair), once daily. At 16 weeks, treatment failure (an endpoint that included several clinical and spirometric outcomes) had occurred in 20% of patients in each inhaled-therapy group and in 30% of montelukast patients, a significant difference. This difference reflected primarily spirometric outcomes, and not differences in need for systemic steroids or urgent asthma care.

The second study examined the relatively novel idea that as-needed inhaled steroids might be as effective as daily maintenance therapy. Patients received one of four treatments: twice-daily inhaled beclomethasone (250 µg) with as-needed albuterol; twice-daily combined beclomethasone/albuterol, with as-needed albuterol; the same beclomethasone/albuterol combination, but only as needed; and as-needed albuterol only. At 6 months, the primary outcome — morning peak expiratory flow rate — was similar in the twice-daily beclomethasone and the as-needed beclomethasone/albuterol groups, and was significantly higher in both groups than in the as-needed albuterol group. Both twice-daily beclomethasone and as-needed beclomethasone/albuterol were associated with fewer exacerbations than as-needed albuterol.

Comment: These important trials demonstrate the feasibility of step-down therapy in patients whose mild persistent asthma is well controlled with standard twice-daily inhaled corticosteroids. An objective of this research is to minimize cumulative lifetime exposure to inhaled steroids, which may have systemic effects after years of use. The first trial shows that once-daily montelukast or a once-daily combination of an inhaled steroid plus salmeterol are both reasonable alternatives (although treatment failures occurred somewhat more frequently with montelukast). In the second trial, symptom-driven inhaled corticosteroids worked as well as daily therapy in patients with mild asthma.

— Allan S. Brett, MD
---------------
the studies mentioned in the article have been published in the New England Journal of Medicine. if any of you have any access or need to browse those articles for any interest,here are the citations :

-The American Lung Association Asthma Clinical Research Centers. Randomized comparison of strategies for reducing treatment in mild persistent asthma. N Engl J Med 2007 May 17; 356:2027-39.

-Papi A et al. Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma. N Engl J Med 2007 May 17; 356:2040-52.


Postuar nga NS-6 datë 27 Qershor 2007 - 00:43:

Stimulating Platelet Production

the progress in understanding the way stem cells get transformed in blood cells brought to life the concept of growth factors synthesis.they can play the same role as the factors produced by the body. this concept may bring great benefit in diseases where there is placelet destruction or lack of production increasing so the risk of hemorrhages due to lack of placelets. the following article considers the recent progresses in this research and analysis the benefit of the new placelet production stimulators (NS-6)
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New megakaryocyte-stimulating agents might allow patients with thrombocytopenia to avoid drug toxicity.

Three classes of agents that stimulate platelet production are being developed. These all bind to and stimulate the thrombopoietin (TPO) receptor: TPO peptide mimetics (e.g., AMG 531), TPO nonpeptide mimetics (e.g., AKR-501, eltrombopag), and TPO-agonist antibodies (genetically modified to create small bivalent fragments called minibodies; Blood 2007; 109:4607). All of the agents raise platelet counts in animal models; two, AMG 531 and eltrombopag, are currently in clinical development. AMG 531, when injected weekly for 6 weeks, significantly increased platelet counts in 12 of 16 patients with immune thrombocytopenic purpura (ITP; N Engl J Med 2006; 355:1672).

In a phase 1 dose-finding study of eltrombopag, conducted by industry employees, the drug (range, 5–75 mg) was given orally once daily for 10 days to 73 healthy men. Plasma samples were collected through day 28. Platelet counts increased by more than 20% above baseline in 6 of 9 men who received 30 mg, and in all 19 men who received 50 mg or 75 mg. The largest increase, 50% above baseline, was seen in men who received 75 mg daily. The platelet count began rising by day 8, peaked at day 16, and returned to baseline by day 22. The half-life of the drug was longer than 12 hours, and drug accumulated in the plasma at the higher dose levels. No consistent clinical or laboratory adverse effects were noted.

In a meeting abstract from a previous study of eltrombopag in patients with ITP, researchers reported that 86% of patients had increases in platelet counts to greater than 50,000/µL at a daily dose of 75 mg for 6 weeks. A trend toward less bleeding was seen, and no significant adverse effects manifested (Blood 2006; 108:abstract 475).

Comment: Most of the treatments that are recommended for patients with ITP (steroids, splenectomy, anti-D antibodies, cytotoxic agents, and, more recently, rituximab) are directed toward limiting the platelet destruction that occurs in this disease. However, although marrow megakaryocytes usually are increased in patients with ITP, they might not be producing platelets maximally. As demonstrated by these trials of megakaryocyte-stimulating agents, additional platelet production to raise platelet counts can be achieved in some of these patients. This new approach could allow patients to avoid some of the more toxic drugs that currently are prescribed for ITP. Furthermore, these agents could be useful in the management of thrombocytopenia that occurs in some patients with myelodysplasia, in whom megakaryocytes are present but platelet production is suboptimal. Some experts speculate that one or more of these new agents will be clinically available by the end of 2008. Whether these agents are indicated mainly for patients with refractory thrombocytopenia or also as a first-line therapy is still unclear.

— David Green, MD, PhD

(June 25, 2007)

Citation(s):

Jenkins JM et al. Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood 2007 Jun 1; 109:4739-41.


Postuar nga NS-6 datë 07 Korrik 2007 - 00:19:

Mending Broken Hearts (part 1)

Cod. A07072007

By Jennifer Kahn
Foto: Robert Clark

As heart disease reaches epidemic proportions worldwide, researchers are moving away from the old "clogged-pipes" model to search for triggers lurking in our genes.

Cheeseburgers, smoking, stress, the rise of the couch potato: These are the usual suspects on the list of risk factors for heart disease, a malady reaching global epidemic proportions. Now discoveries about genetic triggers may help us spot trouble before it starts.

Gloria Stevens is lying on her back, sedated but alert, staring at an image of her own beating heart. Metaphorically, Gloria's heart is the very core of her emotional self—not to be worn on the sleeve, much less displayed on an overhead monitor. More literally, it is a blood-filled pump about the size of a clenched fist whose rhythmic contractions have kept Gloria alive for 62 years, and with a little tinkering will keep her going for an indeterminate number more.

At this moment, her doctor is threading a thin catheter up through her femoral artery from an incision in her groin, on into the aorta, and from there into one of the arteries encircling Gloria's heart. At the tip of the catheter is a small balloon. The doctor gently navigates the tip to a spot where plaque has narrowed the artery's channel by 90 percent. With a quick, practiced movement he inflates the balloon to push back the artery wall, deflates the balloon, then inserts an expandable stent—it looks like a tiny tube of chicken wire—that will keep the passage open. As Gloria watches on the monitor, the crimp in her artery disappears, and a wide laminar flow gushes through the vessel, like a river in flood.

The procedure is over. It has lasted only half an hour. In all likelihood, Gloria will be able to go home the next day. So will a few thousand other patients in the United States undergoing such routine angioplasty—more than a million of them a year. Pipe fixed, patient cured, right?

Wrong.

Because of her treatment, Gloria's quality of life will likely improve. She'll breathe easier and maybe live longer. But she is hardly cured. Her coronary atherosclerosis—a hardening and narrowing of the arteries that supply the heart with oxygen-rich blood—still leaves her vulnerable to future blockages and coronary heart disease.

Although hearts suffer many maladies—valves leak, membranes become inflamed—coronary heart disease, which can lead to heart attack and ultimately to heart failure, is the number one killer of both men and women in the United States, where 500,000 die annually. Worldwide, it kills 7.2 million people every year. Exacerbated by the export of Western lifestyle—motorized transport, abundant meat and cheese, workdays conducted from the comfort of a well-padded chair—incidence of the disease is soaring.

To help stem this lethal tide, cardiologists can prescribe such cholesterol-lowering drugs as statins to help keep arteries clear. They can advise patients to change their habits, or they can operate to fix an immediate problem. Angioplasty is one procedure, and surgery to bypass the diseased arteries is another—each year more than 400,000 bypasses are performed in the U.S. Transplants can replace severely damaged hearts, and artificial ones can keep people alive while they wait for a donor heart. But in the face of an impending global epidemic, none of these stopgap measures addresses the essential question: Who gets heart attacks and why?

The human heart beats 100,000 times a day, propelling six quarts of blood through 60,000 miles (97,000 kilometers) of vessels—20 times the distance across the U.S. from coast to coast. The blood flows briskly, surging out of a ten-ounce (0.3 kilograms) heart so forcefully that large arteries, when severed, can send a jet of blood several feet into the air. Normally the relentless current helps keep blood vessels clean. But where an artery bends, tiny eddies form, as in a bend in a river. This is where bits of sticky, waxy cholesterol and fat can seep into the artery wall and oxidize, like butter going rancid. Other matter piles up too. Eventually, the whole mass calcifies into a kind of arterial stucco, or plaque.

Until recently, cardiologists approached heart disease as a plumbing problem. Just as mineral deposits restrict the flow of water through a pipe, an accretion of plaque impedes the flow of blood through an arterial channel. The more crud in the system, the greater likelihood that a dammed artery will trigger a heart attack. Doctors now dismiss this "clogged-pipes model" as an idea whose time has passed. It's just not that simple.

Most heart attacks are caused by plaque embedded within the artery wall that ruptures, cracking the wall and triggering the formation of a blood clot. The clot blocks the flow of blood to the heart muscle, which can die from lack of oxygen and nutrients. Suddenly, the pump stops pumping.

Contrary to the clogged pipes model, heart attacks generally occur in arteries that have minimal or moderate blockage, and their occurrence depends more on the kind of plaque than on the quantity. Scientists have been struggling to figure out what type is most responsible. Paradoxically, findings suggest that immature, softer plaques rich in cholesterol are more unstable and likely to rupture than the hard, calcified, dense plaques that extensively narrow the artery channel. But understanding the root cause of the disease will require much more research. For one thing, human hearts, unlike plumbing fixtures, are not stamped from a mold. Like the rest of our body parts, they are products of our genes.


Postuar nga NS-6 datë 07 Korrik 2007 - 00:21:

Mending Broken Hearts (part 2)

Don Steffensen was putting duck-hunting decoys out on a small lake one fall afternoon in southwestern Iowa when his heart attack hit. The infarction was massive and unexpected. It's likely that Steffensen survived only because a buddy was carrying nitroglycerin tablets and quickly slipped one under his friend's tongue. Nitroglycerin is used to make dynamite; in the body, a heavily diluted form releases nitric oxide, which signals the smooth muscle cells in veins and arteries to relax, dilating the vessels.

The Steffensen clan is enormous: more than 200 relatives spread over three generations, many of the youngest are now dispersed from Iowa to New York and beyond. Although heart trouble is common in the family, it had never struck anyone as unusual. "I attributed it to diet," shrugs Tina, a slim 38-year-old and the family's only vegetarian.

It was a reasonable conclusion. The Steffensens were raised on the kind of farm food that the state is famous for—ham balls, meatloaf, pie, macaroni and cheese—and still popular even as careers have moved indoors. Driving north through cornfields to meet some of the family in Buffalo Center, I dined at a restaurant offering deep-fried sandwiches. A single ham and cheese hoagie—dunked in hot fat and served sizzling—seemed capable of stopping a heart all on its own.

But could the high incidence of heart trouble among the Steffensens be related to something else besides high-fat diets? Eleven years after Don's attack, his wife, Barbara, happened to overhear a doctor describing a study about the genetics of heart attacks.

Curious, Don and 20 of his relatives each sent a vial of blood to the Cleveland Clinic, where the research was being conducted. Eric Topol, a cardiologist and genetics researcher at the clinic, spent a year studying their DNA. Each person's genome comes with millions of individual variations, but Topol was looking for something distinctive—and shared only by the members of the clan with heart trouble. The mutation he and his team finally spotted, in a gene called MEF2A, produced a faulty protein. "We knew we had something," Topol says. "But the question was: How does this sick protein, present at birth, lead to heart attacks 50 years later in life?"

Topol himself is as lean as a greyhound and weathered in a cowboyish way. He talks slowly and eats minimally: salads for dinner and high-fiber cereal for breakfast. He doesn't eat lunch at all. Like almost every cardiologist I've talked to, he takes statins preventively, and his cholesterol count is a low 135. His children, 22 and 25, also eat uncommonly well for their ages. "People have looked at the cadavers of men in their 20s who died in car accidents or as casualties of war, and nearly all had arterial cholesterol deposits," Topol said as we walked to his lab. "This disease starts much earlier than people realize."

Using endothelial cells (which line the inside of the artery wall) grown in culture, Topol set about figuring out what the MEF2A mutation does. He and his coworkers created some cells carrying the Steffensen variant, and others with the normal form of the protein. Both cell proteins were tagged fluorescent green so their locations could be visualized on a computer screen. The resulting images revealed a striking difference.

In a normal cell, all the MEF2A protein was inside the nucleus; on the screen, the cell resembled a fried egg with a fluorescent green yolk. But in the cells carrying the mutated version, the nucleus did not glow; instead the cell membrane was edged by a thin, luminous green line: a layer of MEF2A protein, trapped where it cannot serve its usual purpose. Topol believes that this defect affects the integrity of the coronary artery walls, rendering them more vulnerable to cracking when the plaque embedded in them ruptures. And each crack brings an increased chance of a heart attack.

Since this discovery, the Steffensens have become famous, appearing on shows like 60 Minutes II. Their mutant gene turns up in a Robin Cook novel titled Marker, about a health insurance company in New York that secretly screens patients for the MEF2A mutation and then kills them to preempt future medical-care payouts. Lively reading, but the Steffensen gene is an unlikely target for an insurance company, in part because it is an uncommon genetic defect.

Topol's study did find that although dysfunctional MEF2A is very rare, the chance of heart disease in those carrying it may approach 100 percent. Most other genetic variations identified thus far increase the risk by much less. As it turns out, Topol himself carries a bum gene: apoE4, which affects inflammation in the arteries. Unlike MEF2A, it is common; every fourth person has it.

"Heart disease is not a one- or two-gene problem," says Steven Ellis, a Cleveland Clinic cardiologist who oversees a 10,000-person genetic study known as GeneBank that collects DNA samples from patients who enter hospitals with atherosclerosis. Ellis, like most cardiac researchers, suspects that dozens of genes end up contributing to a predisposition: Some affect arterial integrity, others inflammation (which both causes and exacerbates arterial cracks), and still others the processing of lipids (the fats and cholesterol that turn into plaques). Of the several dozen genes, each may contribute just one percent to a person's total risk—an amount that may be compounded, or offset, by outside factors like diet. As one doctor told me, any person's heart attack risk is "50 percent genetic and 50 percent cheeseburger."

The point of tracking down all these small mutations, Ellis explains, is to create a comprehensive blood test—one that could calculate a person's genetic susceptibility by adding up the number of risky (and, eventually, beneficial) variables. Combined with other important factors, such as smoking, weight, blood pressure, and cholesterol levels, doctors could decide which patients need aggressive treatment, such as high-dose statins, and which ones are likely to benefit from exercise or other lifestyle changes. Some genes already can predict whose cholesterol level will respond strongly to dietary changes and whose won't. Assessing risk is crucial, Ellis says, because heart disease is often invisible. In fact, 50 percent of men and 64 percent of women who die of heart disease die suddenly, without experiencing any previous symptoms.

Although standard tests can detect atherosclerosis, they aren't foolproof. They may reveal plaques, but give no indication whether or not they are life-threatening. Tests like angiography, for example, where doctors inject a dye into the bloodstream and track it with x-rays, can show how much blood is flowing through an artery, but not discern the plaques embedded inside the artery wall—often the culprit in a heart attack.

Researchers have been working to solve this problem with scanners that provide pictures of the arterial wall itself, but it's a tricky task. Normal cardiac artery walls are about a millimeter thick. Coronary arteries move with every beat of the heart, 70 times a minute. It's tough to get a clear image of something so small in constant motion.

Difficult, but not impossible. As I walk through the basement of the Cleveland Clinic, I pass a room containing a large, blue, plastic doughnut as tall as I am, with a woman's legs sticking out of the middle. The doughnut is a computed tomography (CT) scanner, a kind of three-dimensional x-ray machine that's also used for imaging tumors. The scanner, aided by medications that reduce a patient's heart rate and an injectable dye that highlights the arteries, can produce startlingly clear pictures.


Postuar nga NS-6 datë 07 Korrik 2007 - 00:22:

Mending Broken Hearts (part 3)

Scrolling through images on his computer monitor, Mario Garcia, the clinic's director of cardiac imaging, retrieves one that looks like a black-and-white landscape photographed from a plane, with a single, large river running through it. As Garcia zooms in on the river, a series of white lumps appears on the bank—hard plaques bright with calcium. But there is also a tiny black smudge. "That's the type we believe causes a heart attack," he says with satisfaction, pointing to the smudge of soft plaque. "It's a rare opportunity to see that."

Scrolling through images on his computer monitor, Mario Garcia, the clinic's director of cardiac imaging, retrieves one that looks like a black-and-white landscape photographed from a plane, with a single, large river running through it. As Garcia zooms in on the river, a series of white lumps appears on the bank—hard plaques bright with calcium. But there is also a tiny black smudge. "That's the type we believe causes a heart attack," he says with satisfaction, pointing to the smudge of soft plaque. "It's a rare opportunity to see that."

As compelling as the CT scan is, it's still an imperfect tool for predicting heart disease. It's expensive, for one, and the dose of radiation from the x-rays makes it ill suited for use in healthy-patient annual exams. And although it sees arterial plaques, even soft plaques inside arterial walls, it can't reveal whether those plaques are likely to crack and cause a heart attack.


Postuar nga NS-6 datë 07 Korrik 2007 - 00:24:

Mending Broken Hearts (part 4)

Until there are tests, genetic or otherwise, that give a clearer measure of risk, everyone would be advised to exercise, watch their diet, and take statins for elevated cholesterol—the same advice doctors gave when the clogged-pipes model of heart disease reigned unchallenged.

At the Cleveland Clinic, cardiologist Stephen Nissen has conducted several studies on statins such as Lipitor, which reduce the amount of LDL ("bad" low-density lipoprotein) cholesterol made by the liver. Nissen is an advocate of lowering cholesterol by any means necessary. Does he take a statin? "You bet!" he says. "I have no intention of dying of the disease I treat." His LDL level is a paltry 51. Of eight cardiologists I spoke with, all but one were taking the medication. (Some studies now seem to show that lowering even normal cholesterol levels has a protective effect.) HDL ("good" high-density lipoprotein) cholesterol is another story. Nissen calls it the "arterial-wall garbage barge" because of its ability to remove cholesterol from clogged arteries. Not all HDL can do this; some is dysfunctional. But tests have shown that raising the HDL level in genetically engineered lab mice can shrink their arterial plaques.

A drug that could raise functional HDL levels in humans would likely become the next multibillion-dollar blockbuster, and a few are in various stages of testing. However, the trial of a Pfizer drug called torcetrapib ended in failure. Torcetrapib had been shown, in combination with Lipitor, to raise HDL levels 44 to 66 percent with a once-a-day pill. But the increase was not necessarily in functional HDL, and the drug was also associated with elevated blood pressure. In December, when data showed a 60 percent higher death rate in patients taking torcetrapib with Lipitor than in those taking Lipitor alone, Pfizer abruptly ended the trial.

It's not clear whether the problem lay with one drug or an entire class of drugs. Until further research is completed, the several different statins on the market will remain the most prescribed class of drugs in the world, with 11.6 million prescriptions filled monthly in the U.S. alone. Pfizer's Lipitor may be the best-selling drug ever made, with 12 billion dollars in annual worldwide sales.

But statins, like any drug, carry the risk of side effects: Muscle aches are a well-known effect, and periodic blood tests to check liver function are recommended. The fact is, many of us just like to eat cheeseburgers, watch television, and get around in cars. And it's hard, says Leslie Cho, director of the Cleveland Clinic's Women's Cardiovascular Center, for a person to worry about a disease that hits ten years down the road—particularly since heart patients, unlike cancer patients, can't easily observe the progress of their disease. "You've done damage over years, and it will take years to undo that damage," she says. "That's a very hard thing to sell to Americans. We do what we can, but then people go home."

The good news is that genetic research continues to thrive. Should we want to, we will soon be able to know the state of our hearts—and our genes—in ever growing detail. That knowledge, and what we do with it, could make the difference between dying at 65 and living until 80. The choice, increasingly, will be ours.

(National Geographic)

Think Again


Postuar nga NS-6 datë 26 Korrik 2007 - 15:25:

A Controlled Clinical Trial of Steroids for Bronchiolitis

Cod. C26072007

One dose of oral dexamethasone was no different from placebo.

Bronchiolitis is the leading cause of hospitalization of infants in the U.S. Use of steroids for infants with bronchiolitis remains controversial because of the lack of high-quality, sufficiently powered studies. In a multisite, double-blind clinical trial, researchers randomized 600 infants (age range, 2–12 months) who presented to the emergency department with no prior history of wheezing and a clinical picture consistent with moderate-to-severe bronchiolitis to receive either a single dose of oral dexamethasone (1 mg/kg) or placebo. The primary outcome was hospitalization 4 hours after drug administration.

The admission rate was virtually identical in the steroid and placebo groups (39.7% and 41.0%, respectively). No differences emerged in subgroup analyses of infants who were positive for respiratory syncytial virus, those younger than 6 months, or those with a history of eczema or a family history of asthma. Mean length of stay for hospitalized infants and subsequent admissions during the 7 days after the intervention were similar in the two groups.

Comment: This study likely represents the definitive study on the use of steroids for infants with bronchiolitis in the ambulatory care setting — steroids convey no benefit. However, infants with a prior history of wheezing were excluded. I am sure some clinicians will continue to administer steroids to infants who are admitted with bronchiolitis despite the lack of compelling evidence. I do not believe that steroids have a role in the treatment of bronchiolitis.

— Howard Bauchner, MD

Published in Journal Watch Pediatrics and Adolescent Medicine July 25, 2007

Citation(s):

Corneli HM et al. A multicenter, randomized, controlled trial of dexamethasone for bronchiolitis. N Engl J Med 2007 Jul 26; 357:331-9.


Postuar nga NS-6 datë 06 Shtator 2007 - 23:03:

FDA Approves Novel Antiretroviral Drug

Cod. A07092007

August 6, 2007

The U.S. Food and Drug Administration (FDA) today approved maraviroc, an antiretroviral drug for use in adult HIV patients. Maraviroc, sold under the trade name Selzentry, is the first in a new class of drugs designed to slow the advancement of HIV and received priority review by the FDA.

Maraviroc is approved for use in combination with other antiretroviral drugs for the treatment of adults with CCR5-tropic HIV-1, who have been treated with other HIV medications and who have evidence of elevated levels of HIV in their blood (viral load). Rather than fighting HIV inside white blood cells, maraviroc prevents the virus from entering uninfected cells by blocking the predominant route of entry, the CCR5 co-receptor. CCR5 is a protein on the surface of some types of immune cells. Among patients who have previously received HIV medications, approximately 50 percent to 60 percent have circulating CCR5-tropic HIV-1. "This is an important new product for many HIV-infected patients who have not responded to other treatments and have few options," said Steven Galson, M.D., M.P.H., director of FDA's Center for Drug Evaluation and Research.

The product label includes a boxed warning about liver toxicity (hepatoxicity) and a statement in the Warnings/Precautions section about the possibility of heart attacks. The FDA's approval of maraviroc is based on safety and effectiveness data from two double-blind, placebo-controlled studies. The 1,076 clinical trial participants were selected because they still showed evidence of HIV-1 in their blood, despite treatment with other HIV medications. A blood test for CCR5 tropic HIV-1 was used during clinical trials to identify patients appropriate for treatment with maraviroc.

The safety and effectiveness of maraviroc have not been established in adult and pediatric patients who have never been treated with any other HIV drug. Additionally, the drug has not been tested or studied in pregnant women. The FDA recommends that HIV positive women should not breast feed, whether or not they are on antiretroviral medications.

The most common adverse events reported with maraviroc were cough, fever, upper respiratory tract infections, rash, musculoskeletal symptoms, abdominal pain, and dizziness.

Maraviroc is distributed by New York-based Pfizer Inc.


Postuar nga NS-6 datë 03 Tetor 2007 - 14:49:

A Link Between Eosinophilic Esophagitis and Celiac Disease?

Cod. B03102007

Eosinophilic esophagitis (EoE) is an inflammatory disorder that is characterized by severe, isolated eosinophilic infiltration of the esophagus; it is associated with a variety of clinical findings, including dysphagia, food impaction, vomiting, chest pain, and weight loss. Although its causes are unknown, EoE has been linked to food hypersensitivity, particularly among children. In fact, the primary approach for treating pediatric EoE is elimination diets, which typically exclude cow’s milk, soy, wheat, eggs, peanuts, and seafood. Now, investigators describe a possible association between EoE and celiac disease.

During a 21-month period at a single center in Italy, 17 children (age, <10 years) met the established clinical and histologic criteria for EoE diagnosis. All had presenting complaints of dysphagia, epigastric pain, or regurgitation or vomiting; none had presenting complaints of diarrhea, failure to thrive, anemia, or anorexia. During evaluation, celiac disease — established by serologic testing (anti–tissue transglutaminase and antiendomysial antibodies) with histologic confirmation by duodenal biopsies — was diagnosed in six of the patients. These patients all switched to gluten-free diets, whereas the remaining 11 patients switched to restricted diets based on allergy-testing results.

During an average follow-up of 6 months, all six patients with celiac disease had complete resolution of their presenting EoE complaints, and repeat endoscopy demonstrated complete resolution of esophageal eosinophilia in the three who underwent the procedure. In contrast, only 7 of the 11 patients without celiac disease had moderate improvement in their presenting complaints; repeat endoscopy in 7 patients showed improvement, but not resolution, of esophageal eosinophilia.

Comment: Food antigens have been implicated in both EoE and celiac disease, but this report is the first to demonstrate a potential association between the two conditions. The clinical and histologic improvements in EoE seen among patients with celiac disease in this study were impressive. Whether this finding reflects a real association or a selection bias clearly warrants further evaluation in both pediatric and adult patients with EoE.

— David A. Johnson, MD

Published in Journal Watch Gastroenterology September 21, 2007

the origin of the article:
Quaglietta L et al. Eosinophilic oesophagitis and coeliac disease: Is there an association? (Aliment Pharmacol Ther 2007 Aug 1; 26:487).

per celiakine me shume mund te shihni:
-celiakia (Cod. A 22092007)
- pronjoza e celiakise (Cod. B 22092007)


Postuar nga MARSMED datë 08 Tetor 2007 - 23:49:

Hip Size of Mothers Linked to Breast Cancer in Daughters

Cod. A09102007

Hip Size of Mothers Linked to Breast Cancer in Daughters



Postuar nga NS-6 datë 16 Tetor 2007 - 00:06:

FDA Approves Raltegravir Tablets, First-in-Class Oral HIV-1 Integrase Inhibitor

Cod. B16102007

FDA Approves ISENTRESS™ (raltegravir) Tablets, First-in-Class Oral HIV-1 Integrase Inhibitor

WHITEHOUSE STATION, N.J., Oct. 12, 2007 - Merck & Co., Inc., announced today that the U.S. Food and Drug Administration (FDA) granted ISENTRESS™ (raltegravir) tablets accelerated approval for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced adult patients who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.

This indication is based on analyses of plasma HIV-1 RNA levels up through 24 weeks in two controlled studies of ISENTRESS [pronounced i-sen-tris]. These studies were conducted in clinically advanced, three-class antiretroviral [nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)] treatment-experienced adults. The use of other active agents with ISENTRESS is associated with a greater likelihood of treatment response. The safety and efficacy of ISENTRESS have not been established in treatment-naïve adult patients or pediatric patients. There are no study results demonstrating the effect of ISENTRESS on clinical progression of HIV-1 infection. Longer term data will be required before the FDA can consider traditional approval for ISENTRESS.

ISENTRESS is the first medicine to be approved in a new class of antiretroviral drugs called integrase inhibitors. ISENTRESS works by inhibiting the insertion of HIV DNA into human DNA by the integrase enzyme. Inhibiting integrase from performing this essential function limits the ability of the virus to replicate and infect new cells. There are drugs in use that inhibit two other enzymes critical to the HIV replication process - protease and reverse transcriptase - but ISENTRESS is the only drug approved that inhibits the integrase enzyme.

The FDA's decision was based on a 24-week analysis of clinical trials in which ISENTRESS in combination with optimized background therapy (OBT) in treatment-experienced patients, provided significant reductions in HIV RNA viral load and increases in CD4 cell counts.

"The development of ISENTRESS is a significant milestone in the history of HIV/AIDS therapy because we now have a drug that's potent against another key enzyme essential for viral replication," said Joseph J. Eron Jr., M.D., professor of medicine, Division of Infectious Diseases, UNC Chapel Hill School of Medicine. "It's important for physicians to know that ISENTRESS should always be used in combination with other active agents."

Data from two ongoing Phase III multi-center, double-blind, randomized, placebo-controlled studies (BENCHMRK-1 and BENCHMRK-2) in 699 treatment-experienced adult patients with documented resistance to at least one drug in each of three classes (NRTIs, NNRTIs and PIs) of antiretroviral therapies showed that ISENTRESS 400 mg dosed twice daily in combination with OBT was significantly more effective at both reducing levels of HIV viral RNA and increasing CD4 cell counts in these patients living with HIV, when compared to a regimen of placebo plus OBT.

Pooled analyses from the two Phase III studies showed that after 24 weeks of therapy, 75.5 percent of patients (216 out of 286) receiving ISENTRESS in combination with OBT achieved HIV viral RNA load reduction to below 400 copies/mL compared to 39.3 percent of patients (59 out of 150) receiving placebo plus OBT. In addition, after 24 weeks of therapy, 62.6 percent of patients (179 out of 286) receiving ISENTRESS plus OBT achieved viral load reduction to below 50 copies/mL compared to 33.3 percent of patients (50 out of 150) receiving placebo plus OBT. After 24 weeks of therapy, increases in CD4 cell counts from baseline were 89 and 35 cells/mm3 for patients receiving ISENTRESS plus OBT and for those receiving placebo plus OBT, respectively.

Important safety information about ISENTRESS
ISENTRESS does not cure HIV or AIDS and does not prevent passing HIV to others. Healthcare providers should know that immune reconstitution syndrome has been reported in patients treated with antiretroviral therapy, which may necessitate further evaluation and treatment.

The most commonly reported adverse experiences of any severity (mild, moderate or severe) regardless of drug relationship were diarrhea (16.6 percent vs. 19.5 percent), nausea (9.9 percent vs. 14.2 percent), headache (9.7 percent vs. 11.7 percent) and fever (4.9 percent vs. 10.3 percent) for ISENTRESS plus OBT and placebo plus OBT, respectively.

Creatine kinase elevations were observed in subjects who received ISENTRESS. Myopathy and rhabdomyolysis have been reported; however, the relationship of ISENTRESS to these events is not known. ISENTRESS should be used with caution in patients at increased risk of myopathy or rhabdomyolysis, such as patients receiving concomitant medication known to cause these conditions.

Safety and tolerability profile of ISENTRESS
Results from pooled safety analyses from three separate studies in treatment-experienced patients taking 400 mg of ISENTRESS dosed twice daily plus OBT or placebo plus OBT showed that after 24 weeks of therapy the rates of discontinuation of therapy due to adverse experiences were 2.0 percent in patients receiving ISENTRESS plus OBT and 1.4 percent in patients receiving placebo plus OBT. In addition, drug-related clinical adverse events of moderate to severe intensity occurring in greater than or equal to 2.0 percent of patients were diarrhea (3.7 percent vs. 4.6 percent), nausea (2.2 percent vs. 3.2 percent) and headache (2.4 percent vs. 1.4 percent) for ISENTRESS plus OBT and placebo plus OBT, respectively.

Drug interactions
Based on the results of drug interaction studies and the clinical trials data, no dose adjustment of ISENTRESS is required when coadministered with other antiretroviral agents. Also, preclinical studies show that ISENTRESS is not metabolized by cytochrome P450 enzymes. Caution should be used when coadministering ISENTRESS with strong inducers of uridine diphosphate glucuronosyltransferase (UGT) 1A1 (e.g., rifampin) due to reduced plasma concentrations of ISENTRESS.

About ISENTRESS
ISENTRESS is a single 400 mg tablet taken twice daily without regard to food. ISENTRESS does not require boosting with ritonavir.

Merck has worked closely with the HIV community regarding the price of ISENTRESS. The wholesale acquisition cost (WAC) of ISENTRESS will be $27 per day, comparable to the price of several available ritonavir-boosted protease inhibitors.

To help patients in the United States who cannot afford treatment with ISENTRESS, the SUPPORT™ program is available. The SUPPORT program is a patient assistance program to help patients who have been prescribed ISENTRESS by providing personalized support and patient advocacy regarding individual reimbursement issues. In addition, Merck also participates in the Partnership for Prescription Assistance program, a single point of access to more than 475 public and private patient assistance programs. ISENTRESS will be available in pharmacies in approximately two weeks. For more information on ISENTRESS, visit www.isentress.com.

Expanded access program
ISENTRESS is currently available worldwide to qualified patients through an expanded access clinical research program, EARMRK. This global program provides early access to ISENTRESS for patients failing current therapy whose HIV is resistant to drugs in three existing classes (NRTIs, NNRTIs, PIs) of antiretroviral medications. Information about the program can be found at www.benchmrk.com.

Merck HIV research
Merck is committed to developing innovative therapies that offer advances in the treatment of infectious diseases - including HIV. Merck's efforts to develop investigational treatments for HIV/AIDS have been under way for more than 20 years and continue today. Merck began its HIV integrase inhibitor research in 1993 and was the first to demonstrate inhibition of HIV integrase in vitro and in vivo.

Prevalence of HIV/AIDS
In 2006, over one million Americans were living with HIV/AIDS and it is estimated that approximately 40,000 new cases of HIV/AIDS are diagnosed each year in the United States. Worldwide, an estimated 40 million people are infected with HIV/AIDS, and more than four million new infections occurred in 2006.

"As the AIDS crisis continues, new drugs like ISENTRESS are needed, which target the virus in unique ways," said Ben Cheng, deputy director, Forum for Collaborative HIV Research. "The HIV Advocacy Community is really excited and encouraged by this new treatment."

About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.

Forward-looking statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2006, and in its periodic reports on Form 10-Q and Form 8-K, which the company incorporates by reference.

ISENTRESS™ is a trademark of Merck & Co., Inc.
SUPPORT™ is a trademark of Merck & Co., Inc.


Postuar nga NS-6 datë 20 Dhjetor 2007 - 00:07:

Anastrozole VS Tamoxifen

Cod. A20122007

Source : The Lancet Oncology
Date of Publication : 15 dicember 2007

Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial

Background

Little data exist on whether efficacy benefits or side-effects persist after 5 years of adjuvant treatment with an aromatase inhibitor. We aimed to study long-term outcomes in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial that compares anastrozole with tamoxifen after a median follow-up of 100 months.

Methods

We analysed postmenopausal women with localised invasive breast cancer. The primary endpoint disease-free survival (DFS), and the secondary endpoints time to recurrence (TTR), incidence of new contralateral breast cancer (CLBC), time to distant recurrence (TTDR), overall survival (OS), and death after recurrence were assessed in the total population (intention to treat; ITT: anastrozole, n=3125; tamoxifen, n=3116; total 6241) and the hormone-receptor-positive subpopulation, the clinically important subgroup for which endocrine treatment is now known to be effective (84% of ITT: anastrozole, n=2618; tamoxifen, n=2598; total 5216). After treatment completion, fractures and serious adverse events continued to be collected blindly (safety population: anastrozole, n=3092; tamoxifen, n=3094; total 6186). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN18233230.

Findings

At a median follow-up of 100 months (range 0–126), DFS, TTR, TTDR, and CLBC were improved significantly in the ITT and hormone-receptor-positive populations. For hormone-receptor-positive patients: DFS hazard ratio (HR) 0·85 (95% CI 0·76–0·94), p=0·003; TTR HR 0·76 (0·67–0·87), p=0·0001; TTDR HR 0·84 (0·72–0·97), p=0·022; and CLBC HR 0·60 (0·42–0·85), p=0·004. Absolute differences in time to recurrence increased over time (TTR 2·8% [anastrozole 9·7% vs tamoxifen 12·5%] at 5 years and 4·8% [anastrozole 17·0% vs tamoxifen 21·8%] at 9 years) and recurrence rates remained significantly lower on anastrozole compared with tamoxifen after treatment completion (HR 0·75 [0·61–0·94], p=0·01). The fewer deaths after recurrence (anastrozole 245 vs tamoxifen 269) was not significant (HR 0·90 [0·75–1·07], p=0·2), and no effect was noted for OS (anastrozole 472 vs tamoxifen 477) HR 0·97 [0·86–1·11], p=0·7). Fracture rates were higher in patients receiving anastrozole than in those receiving tamoxifen during active treatment (number [annual rate]: 375 [2·93%] vs 234 [1·90%]; incidence rate ratio [IRR] 1·55 [1·31–1·83], p<0·0001), but were not different after treatment was completed (off treatment: 146 [1·56%] vs 143 [1·51%]; IRR 1·03 [0·81–1·31], p=0·79). We did not note any significant difference in risk of cardiovascular morbidity or mortality between anastrozole and tamoxifen treatment groups.

Interpretation

These data show long-term safety findings and establish clearly the long-term efficacy of anastrozole compared with tamoxifen as initial adjuvant treatment for postmenopausal women with hormone-sensitive, early breast cancer, and provide statistically significant evidence of a larger carryover effect after 5 years of adjuvant treatment with anastrozole compared with tamoxifen.


Postuar nga NS-6 datë 02 Janar 2008 - 19:37:

Revised AHA Guidelines for Prevention of Infective Endocarditis

Cod. A02012008

The 2007 guidelines reflect questions about the effectiveness of antimicrobial prophylaxis for IE associated with dental, GI, or GU tract procedures.

[Sponsoring Organizations: American Heart Association, American Dental Association, Infectious Diseases Society of America, Pediatric Infectious Diseases Society]

Background and Purpose: Morbidity and mortality associated with infective endocarditis (IE) remain high despite great advances in medicine and surgery. Prevention of IE has therefore been a priority for the American Heart Association for more than 50 years. The 2007 document updates the AHA’s guidelines, last revised in 1997. The key rationale for the current revision is to address the persistent question of whether antimicrobial prophylaxis effectively prevents IE associated with dental, gastrointestinal, or genitourinary (GU) tract procedures.

Key Points:
1. Prophylactic antibiotics based on a patient’s lifetime risk for acquiring IE are no longer recommended for dental, GI, or GU tract procedures. This recommendation follows from the observation that most cases of IE result from bacteremia caused by routine activities such as chewing food, brushing teeth, and flossing. Moreover, no published data clearly indicate that prophylaxis prevents IE from invasive procedures.

2. Dental disease may increase IE risk, but emphasis should shift from antibiotic prophylaxis for dental procedures to improved dental care and oral health in patients with conditions that carry the highest risk for IE.

3. IE prophylaxis is reasonable (Class IIb, level of evidence C) for dental procedures that involve gingival tissues or the periapical region of a tooth and for procedures that perforate the oral mucosa, in patients with cardiac conditions associated with the highest risk for adverse outcomes from IE:

* prosthetic cardiac valve
* previous IE
* unrepaired congenital heart disease (including palliative shunts and conduits)
* completely repaired congenital heart defect with prosthetic material or device, during the first 6 months after the procedure
* repaired congenital heart disease with residual defects at the site or adjacent to the site of a prosthetic patch or device
* cardiac transplantation recipients who develop cardiac valvulopathy

4. IE prophylaxis is no longer recommended for patients with mitral valve prolapse.

5. If administered, antibiotics should be given in a single dose before the procedure. The preferred antibiotic is amoxicillin (2 g in adults and 50 mg/kg in children).

6. IE prophylaxis is not strongly recommended for respiratory tract procedures and not recommended at all for bronchoscopy, unless incision of the respiratory tract mucosa is necessary.

7. IE prophylaxis is not recommended for GU or GI procedures.

Comment: These guidelines represent a marked change in approach to IE prevention, limiting the situations in which antimicrobial prophylaxis is considered reasonable and eschewing strong endorsement of prophylaxis in any setting (the guidelines contain no Class I recommendations). The shift is away from antibiotics and toward dental health. The authors also called for further studies so that future recommendations may be built on a stronger evidence base.

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology May 30, 2007


Postuar nga NS-6 datë 24 Shkurt 2008 - 22:32:

Insurance Fears Lead Many to Shun DNA Tests

Cod. A24022008

Source : New York Times
Published : 24/02/2008
Author : Amy Harmon

Victoria Grove wanted to find out if she was destined to develop the form of emphysema that ran in her family, but she did not want to ask her doctor for the DNA test that would tell her.

She worried that she might not be able to get health insurance, or even a job, if a genetic predisposition showed up in her medical records, especially since treatment for the condition, alpha-1 antitrypsin deficiency, could cost over $100,000 a year. Instead, Ms. Grove sought out a service that sent a test kit to her home and returned the results directly to her.

Nor did she tell her doctor when the test revealed that she was virtually certain to get it. Knowing that she could sustain permanent lung damage without immediate treatment for her bouts of pneumonia, she made sure to visit her clinic at the first sign of infection.

But then came the day when the nurse who listened to her lungs decided she just had a cold. Ms. Grove begged for a chest X-ray. The nurse did not think it was necessary.

“It was just an ongoing battle with myself,” recalled Ms. Grove, of Woodbury, Minn. “Should I tell them now or wait till I’m sicker?”

The first, much-anticipated benefits of personalized medicine are being lost or diluted for many Americans who are too afraid that genetic information may be used against them to take advantage of its growing availability.

In some cases, doctors say, patients who could make more informed health care decisions if they learned whether they had inherited an elevated risk of diseases like breast and colon cancer refuse to do so because of the potentially dire economic consequences.

Others enter a kind of genetic underground, spending hundreds or thousands of dollars of their own money for DNA tests that an insurer would otherwise cover, so as to avoid scrutiny. Those who do find out they are likely or certain to develop a particular genetic condition often beg doctors not to mention it in their records.

Some, like Ms. Grove, try to manage their own care without confiding in medical professionals. And even doctors who recommend DNA testing to their patients warn them that they could face genetic discrimination from employers or insurers.

Such discrimination appears to be rare; even proponents of federal legislation that would outlaw it can cite few examples of it. But thousands of people accustomed to a health insurance system in which known risks carry financial penalties are drawing their own conclusions about how a genetic predisposition to disease is likely to be regarded.

As a result, the ability to more effectively prevent and treat genetic disease is faltering even as the means to identify risks people are born with are improving.

“It’s pretty clear that the public is afraid of taking advantage of genetic testing,” said Dr. Francis S. Collins, director of the National Human Genome Research Institute at the National Institutes of Health. “If that continues, the future of medicine that we would all like to see happen stands the chance of being dead on arrival.”

Caught in a Bind

For Ms. Grove, 59, keeping her genetic condition secret finally became impossible. When her symptoms worsened she was told to come back to the clinic before antibiotics would be prescribed. But there had been a snowstorm that day, and she could not summon the strength to drive.

“I have alpha-1,” she remembers sobbing into the phone. “I need this antibiotic!”

The clinic called in the prescription.

Ms. Grove, who does freelance accounting from home and has health insurance through her husband’s employer, allowed herself to be identified here because she said she felt an obligation to others — including some in her own family — to draw attention to the bind she sees herself in.

“Something needs to be done so that you cannot be discriminated against when you know about these things,” she said. “Otherwise you are sicker, your life is shorter and you’re not doing what you need to protect yourself.”

Employers say discrimination is already prohibited in the workplace by the Americans with Disabilities Act and existing laws governing privacy of medical records. But employee rights advocates say nothing in those laws explicitly prevents employers hard-pressed to pay for mounting health care costs from trying to screen out employees they know are more likely to get sick.

Courts have yet to rule on the subject. When the Equal Employment Opportunities Commission sued the Burlington Northern Santa Fe Railway for secretly testing the blood of employees who had filed compensation claims for carpal-tunnel syndrome in an effort to discover a genetic cause for the symptoms, the case was settled out of court in 2002.

And in 2005 when Eddy Curry, then the center for the Chicago Bulls, refused a genetic test to learn if he was predisposed to a heart ailment, the team traded him to the New York Knicks.

Insurers say they do not ask prospective customers about genetic test results, or require testing. “It’s an anecdotal fear,” said Mohit M. Ghose, a spokesman for America’s Health Insurance Plans, whose members provide benefits for 200 million Americans. “Our industry is not interested in any way, shape or form in discriminating based on a genetic marker.”

Still, a recent study by the Georgetown University Health Policy Institute found otherwise. In 7 of 92 underwriting decisions, insurance providers evaluating hypothetical applicants said they would deny coverage, charge more for premiums or exclude certain conditions from coverage based on genetic test results.

The Medical Cost

Regardless of whether discrimination actually occurs, many health care professionals say the pervasive anxiety over it demands legislative action. Geneticists complain that discrimination fears prevent them from recruiting research participants, delaying cures and treatments for disease. At Memorial Sloan-Kettering Cancer Center in New York, the same concern is a leading reason people cancel appointments for tests that detect cancer risk.

“We are dealing with potential lifesaving interventions,” said Dr. Kenneth Offit, chief of the center’s clinical genetics service. “It’s a tragedy that people are being scared off by this.”

The Genetic Information Nondiscrimination Act, which passed the House of Representatives by a wide margin last year, would prohibit insurers from using genetic information to deny benefits or raise premiums for both group and individual policies. (It is already illegal to exclude individuals from a group plan because of their genetic profile.) The bill would also bar employers from collecting genetic information or using it to make decisions about hiring, firing or compensation. But it has yet to reach the Senate floor.

Meanwhile, a $300 genetic test for prostate cancer risk announced last month immediately drew callers to a public radio station in Washington that was discussing the test, voicing fears of insurance discrimination. Dr. Karim Kader, who made the test possible with his discovery that men who carry certain DNA variants are four to five times likelier to develop prostate cancer, assured one caller that the test would be “very private.”

For some, that is not good enough.

Linda Vahdat, director of the breast cancer research program at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, estimates that 20 percent of her patients choose to pay for the DNA test for inherited breast cancer risk with cash, to avoid submitting insurance claims.

And last year, hundreds of customers paid the start-up company DNA Direct for tests that range in cost from $175 to $3,456 to ensure that no third party, not even a doctor, had access to their results. Mary, a freelance camera assistant in Brooklyn, for instance, sent a swab of her cheek cells to DNA Direct to find out if her extreme fatigue was caused by hemochromatosis, a genetic condition in which the body retains too much iron.

“I would rather not lay out the $200 myself,” said Mary, who requested that her last name be withheld for the same reason she paid for her own test. “But it seemed safer.”

Treatment for hemochromatosis typically involves removing a unit of blood twice-weekly by phlebotomy. But that would mean disclosing the condition to a doctor, so Mary is planning on becoming a frequent blood donor.

Kathy, a financial analyst in Houston who would like to know if she, like her two sisters, has a genetic predisposition to breast cancer, said she was not going to take even an anonymous test. “Then,” she said, “I’m just in a position of having to lie.”

The culture of secrecy around genetic information is stronger in the United States, some experts say, than in countries where people are guaranteed health care. Among Americans at risk for Huntington’s disease, an incurable brain disorder, only 5 percent take the DNA test to determine if they will develop it, compared with 20 percent of Canadians in the same position, according to Michael R. Hayden, a professor of human genetics at the University of British Columbia in Vancouver.

Here, doctors often feel obligated to inform patients of the potential financial downside.

“I always warn them,” said Dr. Stephen Moll, director of the Thrombophilia Program at the University of North Carolina, who uses a genetic test to determine the best treatment for patients with blood clots. “Especially if they are self-employed, I don’t want it to be a surprise if their health insurance premium goes up.”

Unknown Risks

After receiving a similar warning from her doctor, Katherine Anderson’s parents did not allow her to be tested for Factor V Leiden, a genetic condition she might have inherited from her father that increases the risk of blood clots.

But last year, with nothing in Ms. Anderson’s record to indicate reason for concern, a gynecologist prescribed a birth control pill to regulate her uneven periods. Six weeks later, Ms. Anderson, then 16, developed a clot that stretched from her knee to her abdomen. The pill, combined with the gene she had indeed inherited, had increased her clotting risk by 30-fold.

Now largely recovered, her primary concern is whether she will be viewed as a health insurance liability for the future.

“I don’t want to have to work for a big business just to get insurance,” she said. “This could be determining what I can do for my whole life.”

For Judith Berman Carlisle, the price of privacy was forgoing the DNA test that would have convinced her not to have surgery. Ms. Carlisle, 48, who was setting up her own therapy practice, was afraid testing positive for the high-risk breast and ovarian cancer gene that runs in her family would prevent her from buying health insurance.

But her sister had developed ovarian cancer the year before, an aunt had died of it, and Ms. Carlisle was desperate not to get it herself. Her doctor agreed to remove her ovaries based on her family history — the way such decisions were commonly made before a genetic test was available.

Ms. Carlisle was convinced the surgery would be less damning than proof that she carried a defective BRCA1 gene, which also confers a very high chance of developing breast cancer.

“There’s a big difference between someone saying, ‘I have a strong family history,’ ” Ms. Carlisle said, “and saying, ‘I only have a 13 percent chance of not getting breast cancer during the time you’re insuring me.’ ”

Last fall, after the surgery to remove her ovaries, she began to consider a double mastectomy to remove any chance of breast cancer, the disease her grandmother and another aunt had died of. Having secured health insurance, she took the test for the BRCA1 mutation. It came back negative.

“The first thing they said to me,” Ms. Carlisle said, “is that I have no higher risk than anyone on the street.”


Postuar nga NS-6 datë 03 Prill 2008 - 09:41:

Warfarin Dose Modification by Genotyping

Cod. A03042008

Prescribing a therapy is not always as easy as it seems! You have to keep in mind a lot of variables in order to prevent any possible complication and at the same time be ready to act when that complication becomes evident,in order to avoid major problems.
Yet, a lot of complications occur. Most probably this is due to a incomplete understanding of the mechanisms of a drug or its target and because it is given based on statistical data that show its efficacy . Up to now we are still far away from what medicine should be: an individual based medicine. However,as the knowledge on human body function grows, therapies change in order to get closer to that aim.
The following script analysis one of the new frontiers of prescribing drugs: Genetic based prescription! (NS-6)
------------------

Decisions about initial dosing of warfarin are influenced by patient age, concurrent medications, diet, and comorbid diseases. Despite dose modifications based on these considerations, many patients receive initial dosing that is too high or too low and can experience serious consequences, such as bleeding or new thrombi. During the past few years, researchers have reported that polymorphisms in the genes whose products interact with warfarin can have marked clinical effects. For example, vitamin K epoxide reductase C1 (VKORC1) is critical for the formation of functional clotting factors and is inhibited by warfarin, and cytochrome P-2C9 (CYP2C9) degrades warfarin.

To assess the effects of these genetic variations on warfarin management, investigators from Vanderbilt University School of Medicine genotyped 297 patients who were beginning warfarin therapy. Patients’ ages, sex, racial or ethnic backgrounds, indications for warfarin therapy, target international normalized ratio (INR) ranges, initial warfarin doses, and concomitant medications were noted at baseline. Subsequent INR values and warfarin doses, frequency of monitoring, and bleeding events were recorded for as long as 168 days (median, 43 days).

Target INRs for most patients were 2 to 3, and the average warfarin dose was 4.8±0.8 mg. About 12% of white patients and no black patients were homozygous for polymorphisms in VKORC1 (VKORC1-A). INRs rose into the therapeutic range 2.4x faster and became excessively high (>4) 2.5x times faster in VKORC1-A homozygotes than in non-A–haplotype patients (P=0.02 and P=0.003, respectively). INRs were above the therapeutic range for a greater percentage of time in VKORC1-A homozygotes (18.8% vs. 9.1%; P=0.02). VKORC1-A heterozygotes also had higher risk for having INRs >4 than did non-A–haplotype patients. Among all patients, 12% and 4.8% had polymorphisms for CYP2C9 type *2 and type *3, respectively. Whereas CYP2C9 genotype did not affect the time needed for INRs to rise into the therapeutic range, patients with *2 or *3 alleles did reach INRs >4 more rapidly than did those without CYP2C9 mutations (P=0.03); CYP2C9 mutations also were associated with more time above the therapeutic INR range, although this did not reach significance (P=0.09). Eight major and five minor bleeding events occurred, but these were not limited to patients with the genetic polymorphisms and were not significantly higher in any one group.

Comment: Recently, the FDA recommended that the labeling of warfarin include a statement about initial lower doses for patients with genetic variations in the CYP2C9 or the VKORC1 gene. The results of the present study confirm that people with these mutations are more sensitive to the effects of warfarin and that VKORC1 mutations have a greater effect than do mutations in CYP2C9. However, whether lowering warfarin doses will lower the incidence of bleeding is unknown and will be difficult to demonstrate, because even people whose INRs are within the therapeutic range occasionally bleed. The National Heart, Lung, and Blood Institute currently is supporting a large, multicenter, double-blind, randomized trial of genotype-guided warfarin therapy designed to determine whether this strategy improves patient outcomes.

David Green, MD, PhD
Published in Journal Watch Oncology and Hematology April 1, 2008

Citations:
Schwarz UI et al. Genetic determinants of response to warfarin during initial anticoagulation. N Engl J Med 2008 Mar 6; 358:999


Postuar nga NS-6 datë 11 Qershor 2008 - 14:54:

Why Is Warfarin Such a Dangerous Drug?

Many patients who receive warfarin would have been excluded from the trials in which the drug’s efficacy versus safety was assessed.

Despite having a propensity to cause bleeding, vitamin K antagonists (VKAs) such as warfarin have been used widely to prevent thrombosis in patients with atrial fibrillation, venous thromboembolism, or cardiovascular disease. This practice is supported by the results of many randomized, controlled trials showing that benefits of thrombus prevention trump risks for bleeding. However, many patients who receive VKAs experience major hemorrhages, an outcome that has led investigators to question whether the populations in these pivotal trials accurately represent patients usually seen in practice.

To determine whether the type of patient seen in ordinary practice was excluded from clinical trials of VKA because of comorbidities or concurrent therapies and whether patient-exclusion criteria might have inadvertently skewed the risk-benefit ratios to favor VKA usage, Dutch researchers performed a 4-year case-control study. Cases consisted of approximately 1000 patients (mean age, 67; 57% male) who were admitted to a university hospital with VKA-associated bleeding (mean duration of VKA therapy, 3.2 years). Bleeding was categorized as gastrointestinal (60%), intracranial (15%), urogenital (15%), and other (10%). Controls, matched by age, sex, and VKA-therapy duration, had no hemorrhages and were hospitalized for respiratory or urinary tract infections. Compared with the control group, the case group had a significantly higher mean international normalized ratio (INR; 4.1 vs. 2.9), a higher incidence of INRs >5 (30% vs. 4.5%), higher mean creatinine levels (5.9% vs. 2.7%), and a higher incidence of liver failure (2.4% vs. 1.0%).

A greater proportion of cases than controls (40% vs. 23%) met at least one exclusion criterion: Unsuitability for anticoagulation therapy and use of restricted medications (such as aspirin, nonsteroidal anti-inflammatory drugs, and clopidogrel) were most common, followed by cardiac comorbidity, previous stroke, cancer, and risk factors for thrombosis. As such, these patients likely would not have been eligible for the trials of the pertinent indication for VKA therapy. Moreover, compared with patients who met no exclusion criteria, those who met one exclusion criterion had 3-fold higher risk for bleeding, and those who met three or more criteria had 15-fold higher risk. The authors concluded that, for patients who deviated from those in the pivotal VKA trials, the balance between risks and benefits of VKA therapy was shifted toward a less-favorable safety profile.

Comment: Evidence-based medicine supports the use of VKAs for management of patients with a variety of disorders. However, as this report indicates, each patient must be evaluated carefully for risk factors related to bleeding, such as renal failure and concurrent antithrombotic medications. The danger of VKAs lies in their use in patients for whom risks for bleeding exceed benefits of thrombus prevention. Careful assessment of each patient is essential, and the risks involved should be discussed fully with patients before therapy is initiated.

— David Green, MD, PhD

Published in Journal Watch Oncology and Hematology June 10, 2008

Citation(s):

Levi M et al. Bleeding in patients receiving vitamin K antagonists who would have been excluded from trials on which the indication for anticoagulation was based. Blood 2008 May 1; 111:4471.


Postuar nga ESHI datë 11 Qershor 2008 - 23:23:

Re: Insurance Fears Lead Many to Shun DNA Tests

[QUOTE]Po citoj ato që tha NS-6
[B]Cod. A24022008

Still, a recent study by the Georgetown University Health Policy Institute found otherwise. In 7 of 92 underwriting decisions, insurance providers evaluating hypothetical applicants said they would deny coverage, charge more for premiums or exclude certain conditions from coverage based on genetic test results.


Kjo eshte mese e vertete.
Kjo eshte politika e sigurimeve shendetesore ketu ne USA.
NS6 nuk e di sa i informuar je ne lidhje me sigurimet ketu ne US, nqse ke info te mjaftueshme per te krijuar nje opinion mbi rrolin e sigurime shendetesore ketu , do kisha shume interres ti ndanim mendimet dhe opinionet per aq sa dime.

FLM dhe Pershendetje .


Postuar nga NS-6 datë 11 Qershor 2008 - 23:44:

me te thene te drejten per sigurimet shendetsore ne Amerike di pak dhe kryesisht jane gjera qe kam lexuar neper shkrime si ai qe kam paraqitur me siper si dhe ne ato qe kam pare ne televizion...sic mund te jete dokumentari i Michael Moore "Sicko"...gjithsesi,cdo info nga ana jote do ishte i mirpritur!


Postuar nga ESHI datë 12 Qershor 2008 - 00:19:

Arsyeja perse te pyeta eshte pasi une kam krijuar opinionin tim ne lidhje me keto,qe vijon. Sigurimet shendetesore ketu ne amerike jane nje "Big Lie". Keto nuk i sherbejne asnjeriu (nenkuptoj:njerezit qe paguajne per te pasur keto sherbime) perveqse lobeve te tyre. usa eshte i vetmi shtet qe lejon spitale per profit,,,dhe gjithcka rrotullohet rreth keti fakti. Ketu eshte ndertuar nje network i tille ku sherbimet shendetesore kontrollojne dhe jane ne dijeni te per te gjitha , dhe ne baze te historise se shendetit tend ato vendosin te te pranojne ty si perfitues i ketyre sherbimeve apo jo. Prite Zot te kesh nje semundje serioze, s'ka ishurence te te pranoje ne planet e veta. They cure,treat ... you but the system kills you on the other side, with bills.
Dicka te tille kisha shprehur ne nje detyre kursi ktu ,,, oboobob vetem ta shikoje rreagimin e presoreshes, I am so sorry I am giving you that impression. Please let me know any question you may have so, you have a different opinion about this, because it isn't really like what you think. Pasi e qetesova qe kete peshtypje nuk e kisha krijuar nga teorite e saj por nga experienca personale dhe krahasimi i sistemit shendetesor ketu me ate te europes perendimore nuk e kuptova perse nuk e vazhdoi biseden me tej.
Kjo ishte dhe arsyeja perse isha e interresuar per mendimin e te tjereve rreth kesaj.

Te falenderoj per durimin dhe materialet interresante qe sjell ketu.


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