Bisher AKIL, MD

Archive for September, 2013|Monthly archive page

It is not always the medicine.

In HIV on September 24, 2013 at 6:38 pm

When patients fail (high virus load) their initial (first line) antiretroviral therapy, we are often confronted with the question: was the failure due to poor choice of medication (weak combo? did we miss a mutation although the resistance testing shows no resistance?) or was it because the patient did not take the medications as often as they were prescribed?

In a retrospective cohort analysis conducted in South Africa, investigators used stored specimens from patients with treatment failure on first-line ART to determine the contributions of resistance and nonadherence to failure or success with second-line regimens. From among 417 patients switching to second-line ART with viral loads >400 copies/mL, 122 had samples for genotyping, drug-concentration measurement, or both (73 had both, 42 had genotyping only, and 7 had drug-concentration measurements only). Overall, 83 of the 122 (68%) achieved viral suppression on second-line ART. Patients with ≥1 nucleoside reverse transcriptase inhibitor drug-resistance mutation (DRM) before switching regimens were more likely to achieve viral suppression than those with no DRMs. Moreover, patients with subtherapeutic first-line ART drug concentrations who had no major DRMs were less likely to achieve suppression than those with major DRMs or those with therapeutic first-line drug concentrations. Overall, patients with subtherapeutic first-line ART and no major DRMs were the least likely to achieve viral suppression with second-line ART, followed by those with subtherapeutic first-line ART and major DRMs, and, finally, those on therapeutic first-line ART.

Citation(s):Johnston V et al. Viral suppression following switch to second-line antiretroviral therapy: Associations with nucleoside reverse transcriptase inhibitor resistance and subtherapeutic drug concentrations prior to switch. J Infect Dis 2013 Sep 13;

Appeared in NEJM Journal watch on 9/23/2013.

Comment: Although this is a retrospective study, it points to adherence, or lack of it, as the main cause for failure of first regimen; it also predicts the success of the second regimen!  Medicine in bottles do not work_BA

Not all statins are equal

In General Health, Heart on September 13, 2013 at 7:57 pm

Because statins lower the incidence of adverse cardiovascular and cerebrovascular events — even in low-risk patients — they are used broadly. Statins’ reported adverse effects include myalgias (muscle pain) , myopathy(muscle disease), rhabdomyolysis (muscle damage / breakdown), transaminitis (elevated liver enzymes) , and diabetes mellitus. In a meta-analysis of 135 randomized trials (247,000 participants) that involved seven statins (atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin [Crestor], simvastatin, and pitavastatin [Livalo]), investigators evaluated adverse effects associated with statins overall and individually. The overall rate of statin discontinuation owing to adverse effects was low (6%) for all statins combined. Statins as a class caused no more medication discontinuations, myalgias, creatinine kinase elevations, myopathy, rhabdomyolysis, or cancer than placebo. However, statins significantly increased relative risk for transaminase elevations (by 50%; baseline incidence, 1%) and diabetes (by 9%) compared with placebo. Simvastatin( Zocor)  and pravastatin(Pravachol)  were associated with best overall tolerability and lowest discontinuation rates. Compared with controls, atorvastatin( Lipitor) and rosuvastatin (Crestor)  were associated with the highest discontinuation rate because of adverse events; whereas atorvastatin (lipitor) and fluvastatin( LesCol)  were associated with higher risks for transaminase elevations (odds ratios, 2.6 and 5.2, respectively). Higher doses of all statins were associated with higher risk for transaminase elevations. Although low doses of simvastatin (Zocor) appeared to be safest, daily doses >40 mg significantly raised risk for creatinine kinase elevation (OR, 4.1) and transaminase elevation (OR, 2.8).

Appeared in NEJM Journal Watch

Source: Naci H et al. Comparative tolerability and harms of individual statins: A study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials. Circ Cardiovasc Qual Outcomes 2013 Jul; 6:390. –

Comments: Useful analysis; choosing the safest statin is exceedingly important, particularly when we have significant side effects such as diabetes and elevated liver enzymes, and muscle problems. Unfortunately, we are often obligated to use other than the safest statins to achieve the desired effect on lipids, leading to the choice of the lesser of the two evils; this is certainly a discussion to have with the PCP _BA

Dude, you need Estrogen.

In General Health on September 13, 2013 at 7:32 pm
Androgen deficiency reduces muscle mass and strength in men; estrogen deficiency is associated with increase in fat mass; and deficiencies in both impair sexual function, according to an industry-supported study in the New England Journal of Medicine. Some 200 healthy men aged 20 to 50 years first received goserelin acetate for suppression of estradiol and testosterone. They were then randomized to various doses (0-10 g) of daily 1% testosterone gel for 16 weeks. Another cohort of 200 men were similarly treated and also given anastrozole daily to inhibit the aromatization of testosterone to estrogen, leading to an estrogen-deficient state.In the first cohort, patients who received low doses of testosterone saw increases in body fat percentages and reductions in lean mass. In the second cohort, the percentage of body fat increased in all groups as aromatization was blocked. In both cohorts, sexual desire declined and erectile dysfunction worsened with lower doses of testosterone.Source: Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men; N Engl J Med 2013; 369:1011-1022September 12, 2013DOI: 10.1056/NEJMoa1206168Comments: We should measure both hormones, firstly because they are related chemically, and now they appear to have separate functions.BTW Goserelin acetate (Zoladex) is an injectable gonadotropin releasing hormone superagonist (GnRH agonist), also known as a luteinizing hormone releasing hormone (LHRH) agonist.  Goserelin acetate is used to suppress production of the sex hormones (testosterone and estrogen), particularly in the treatment of breast and prostate cancer.(from Wikipedia)