HIV and Clinical Manifestations of Accelerated Aging

As HIV-infected patients live longer, more are developing chronic diseases typical of aging — but they appear to be doing so earlier and at a higher rate than the general population.

Since the advent of potent antiretroviral therapy (ART), the primary causes of morbidity and mortality among HIV-infected patients have shifted from AIDS-related illnesses to the chronic noncommunicable conditions typically associated with aging. Two research groups recently described the epidemiology of these conditions in HIV-infected patients.

Guaraldi and colleagues evaluated the prevalence of noninfectious comorbidities among 2854 HIV-infected patients receiving ART in Italy (mean age, 46; 71% with undetectable viral loads; median duration of infection, 16 years; median nadir CD4 count, 170 cells/mm3; median current CD4 count, 520 cells/mm3) and 8562 HIV-uninfected controls matched for age and sex. Compared with the controls, the HIV-infected patients had a higher prevalence of renal failure, bone fracture, and diabetes in every age range evaluated (40, 41–50, 51–60, and >60), as well as a higher prevalence of cardiovascular disease and hypertension at ages 60. They were also more likely, across all age strata, to have at least two of these conditions simultaneously (which the authors describe as “polypathology”). Of note, the HIV-infected patients appeared to develop polypathology at a younger age than controls, such that a 40-year-old HIV-infected patient had a risk similar to that of a 55-year-old HIV-uninfected person. Among HIV-infected patients, polypathology was significantly associated with increasing age, male gender, nadir CD4 count <200 cells/mm3, lipoatrophy, and lipohypertrophy.

In a separate study, Hasse and colleagues evaluated the incidence of AIDS-related and non–AIDS-related events among 8444 patients who were followed in the Swiss HIV Cohort Study between 2008 and 2010 (median age, 45; median nadir CD4 count, 190 cells/mm3; median current CD4 count, 528 cells/mm3). Approximately 30% of study participants were female, 23% had a prior AIDS diagnosis, and 69% had undetectable viral loads. During follow-up, there were 100 new AIDS-related events in the cohort versus 994 new non-AIDS events, including 39 strokes, 55 myocardial infarctions, 70 cases of diabetes, 115 non–AIDS-defining malignancies, and 160 fractures. Each of these non-AIDS conditions was significantly more common after age 50, even after adjustment for factors related to HIV disease progression and the development of comorbidities.

Comment: Many people still believe that HIV infection is confined to young adults, but the patients in these two cohorts were decidedly middle-aged — and experiencing all the same chronic conditions as their uninfected peers, though perhaps at a younger age and greater frequency. Soon, more than half of our HIV-infected patients will be older than 50, which means that as HIV clinicians, we’ll be spending an increasing amount of time providing primary care. As Hecht and colleagues noted back in 1999 , “optimal care of HIV infection requires a combination of disease-specific expertise and primary care skills and organization.” Now may be the time for many of us to take a refresher course in primary care for the HIV provider.

Source: Journal Watch HIV/AIDS Clinical Care


The Demise of EC-IC Bypass Surgery

Extracranial-intracranial bypass plus medical therapy for symptomatic carotid occlusion was no more effective than medical therapy alone at preventing stroke and early mortality in a randomized trial.

During the 1980s, a large trial showed that extracranial-to-intracranial (EC-IC) arterial bypass surgery was ineffective for stroke prevention. A lingering question was whether patients with objective evidence of hemispheric hypoperfusion would benefit from surgery. The Carotid Occlusion Surgery Study (COSS) was undertaken to study patients with symptomatic carotid occlusion and evidence on positron emission tomography of increased oxygen extraction ipsilateral to the occlusion, a marker of hemodynamic cerebral ischemia. Participants were randomized to optimal medical therapy with or without EC-IC surgery. The primary outcome was the composite of stroke or death within 30 days after either surgery or randomization, and ipsilateral stroke within 2 years of randomization.

The study was terminated early for futility, when 195 patients had been randomized. At the time of the study’s termination, there was only a 2% chance for surgery to be proven effective if the trial were carried to completion. The primary outcome occurred in 21.0% of the surgical group and 22.7% of the nonsurgical group, a nonsignificant difference. Thirty-day rates of ipsilateral stroke were 14.4% in the surgical group and 2.0% in the nonsurgical group. Graft patency was 98% at 30 days and 96% at last follow-up.

Comment: In planning the study, the investigators expected a 40% rate of stroke in the nonsurgical group. The fact that the actual rate was about half that is consistent with a recent study of optimal medical therapy for intracranial stenosis  in which the medically treated group did better than expected.

The current findings reinforce the need for aggressive medical therapy for optimal stroke prevention. Only 71% of the nonsurgical group had an LDL level <100 mg/dL at final follow-up, suggesting that a stroke rate even lower than that observed in these medically treated patients is achievable. This study should also stimulate a new trial to investigate aggressive medical therapy for extracranial carotid stenosis. For EC-IC bypass surgery, the door should be closed, with a padlock this time.

Source:Journal Watch Neurology


Exercise Referral Schemes Have Marginal Benefits for Sedentary Patients

Patients exercised more, but body-mass index, blood pressure, and lipid levels remained unchanged.

General practitioners are well-positioned to advise sedentary patients to exercise more and to refer them to exercise programs. In this meta-analysis, investigators assessed the effect of exercise referral schemes (the identification and referral of sedentary individuals to third-party providers who prescribe and monitor exercise programs tailored to individual needs) on physical activity and health.

Eight randomized trials with 5200 sedentary primary care patients (follow-up range, 2–12 months) were included. Compared with usual care (simple exercise advice or no intervention), exercise referral schemes resulted in a 16% relative increase in the number of participants who achieved 90 to 150 minutes of moderately intense physical activity weekly but did not result in lower body-mass index (BMI) or body fat. No between-group differences were noted in blood pressure, lipid levels, or respiratory function. However, exercise referral schemes resulted in significantly fewer patients with depression.

Comment: In this meta-analysis, exercise referral schemes increased physical activity and lowered the incidence of depression, but did not affect BMI, blood pressure, or lipid levels in sedentary primary care patients. An editorialist points out that simple exercise advice, which control-group participants in these trials received, has a small salutary effect on increasing physical activity — “similar to advice to stop smoking.” Therefore, we can reasonably continue to advise sedentary patients to increase their physical activity, bearing in mind that the benefits of referring such patients to exercise programs appear to be marginal.

source: Journal Watch General Medicine

Protein insight into spread of vCJD to brain

 The study could lead to treatments to stop vCJD spreading to the brain

Scientists have discovered that blocking the production of proteins in the immune system could prevent the spread of a disease that destroys nerve cells.

Researchers at Edinburgh University’s Roslin Institute said vCJD occurs when proteins known as prions accumulate in the spleen, lymph nodes and tonsils.

They then spread to the brain, causing a disease that can destroy nerve cells.

The study could lead to treatments to stop vCJD spreading to the brain.

The team said a study showed that blocking the production of a protein, PrPC, in one type of immune cell could stop the spread of prions.

Stopping these cells from expressing this protein did not affect the regular function of the immune system, they said.

The researchers found that when the follicular dendritic cells expressed PrPC, prions were able to replicate on the surface of these cells and spread throughout the body.

However, when the cells were prevented from producing PrPC, the prions were not able to multiply and were destroyed by other cells in the immune system.

Neil Mabbott, of the Roslin Institute, said: “If we can find a way of stopping this protein from being expressed by specific immune cells then we could potentially block the spread of the disease to the brain.

“We also want to understand how cells are infected with vCJD in the first place, so that we can look at ways of stopping this from happening and find ways to diagnose the disease at its early stages.”

The study, funded by the Biotechnology and Biological Sciences Research Council (BBSRC), has been published in the PLoS Pathogens journal.

Scientists said that any treatments would only be viable if the condition was diagnosed in its early stages.



Liking a lie-in in people’s Genes.

The study involved more than 10,000 people in a number of European countries

People who like a lie-in may now have an excuse – it is at least partly down to their genes, according to experts.

Experts, who studied more than 10,000 people across Europe, found those with the gene ABCC9 need around 30 minutes more sleep per night than those without the gene.

The gene is carried by one in five Europeans, they say in their study, published in Molecular Psychiatry.

The researchers said the finding could help explain “sleep behaviour”.

Over 10,000 people took part, each reporting how long they slept and providing a blood sample for DNA analysis.

People from the Orkney Isles, Croatia, the Netherlands, Italy, Estonia and Germany took part in the study.

When the researchers from the University of Edinburgh and Ludwig Maximilians University in Munich compared these figures with the results of the genetic analysis, they found those with a variation of a gene known as ABCC9 needed more sleep than the eight-hour average.

They then looked at how the gene works in fruit flies, who also have it and found flies without ABCC9 slept for three hours less than normal.

The gene ABCC9 is involved in sensing energy levels of cells in the body.

They say this opens up a new line of research in sleep studies, and it is hoped that future work could establish exactly how this gene variant regulates how long people sleep for.

Dr Jim Wilson, from the University of Edinburgh’s centre for population health sciences, said: “Humans sleep for approximately one-third of their lifetime.

“A tendency to sleep for longer or shorter periods often runs in families despite the fact that the amount of sleep people need can be influenced by age, latitude, season and circadian rhythms.

“These insights into the biology of sleep will be important in unravelling the health effects of sleep behaviour.”

Sleep expert Neil Stanley said around half a dozen genes had been linked to sleep patterns.

He added: “It’s interesting to know about these genes, but in a way our genes are an irrelevance unless you were actually to obey them – but none of us do that.”


Vaccine developed against Ebola

Around 1,200 people have died of Ebola virus infection since 1976.

Scientists have developed a vaccine that protects mice against a deadly form of the Ebola virus.

First identified in 1976, Ebola fever kills more than 90% of the people it infects.

The researchers say that this is the first Ebola vaccine to remain viable long-term and can therefore be successfully stockpiled.

The results are reported in the journal Proceedings of National Academy of Sciences.

Ebola is transmitted via bodily fluids, and can become airborn. Sufferers experience nausea, vomiting, internal bleeding and organ failure before they die.

Although few people contract Ebola each year, its effects are so swift and devastating that it is often feared that it could be used against humans in an act of terroism.

All previously developed vaccines have relied on injecting intact, but crippled, viral particles into the body.

Long-term storage tends to damage the virus, paralysing the vaccine’s effectiveness.

The new vaccine contains a synthetic viral protein, which prompts the immune system to better recognise the Ebola virus, and is much more stable when stored long-term.

The vaccine protects 80% of the mice injected with the deadly strain, and survives being “dried down and frozen,” said biotechnologist Charles Arntzen from Arizona State University who was involved in its development.

He said the next step is to try the vaccine on a strain of Ebola that is closer to the one that infects humans.



Staging Liver Fibrosis in Hepatitis C: A Challenge for This Decade

The limitations of and the invasive nature of liver biopsy has spurred extensive interest in the development of non-invasive tests to measure liver fibrosis in patients with chronic hepatitis C. Clinically applicable non-invasive tests, including radiological studies, elastography, and serum markers, all of which perform extremely well in excluding significant disease and diagnosing cirrhosis. FibroScan and acoustic radiation force impulse elastography are two elastography-based tests that show promise. In this new era of increased cure rates with newly Food and Drug Administration-approved drugs and the availability of multiple non-invasive tests of liver fibrosis, we anticipate a decreasing need for liver biopsies in the management of chronic hepatitis C.

Source:Nature Gastroenterology

Statins Are Associated With a Reduced Risk of Gastric Cancer: A Population-Based Case–Control Study

Experimental studies have shown that statins have potential protective effects against cancer. The aim of this study was to investigate whether the use of statins was associated with gastric cancer risk.


We conducted a population-based case–control study in Taiwan. Data were retrospectively collected from the Taiwan National health Insurance Research Database. Cases consisted of all patients who were aged ≥50 years and had a first-time diagnosis of gastric cancer for the period between 2005 and 2008. The controls were matched to cases by age, sex, and index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multiple logistic regression.


We examined 337 gastric cancer cases and 1,348 controls. We found that ever-use of any statin was associated with a significant decrease in gastric cancer risk (OR=0.68, 95% CI=0.49–0.95). Compared with no use of statins, the adjusted ORs were 0.90 (95% CI=0.60–1.36) for the group having been prescribed statins with cumulative defined daily doses (DDDs) <134.25 and 0.49 (95% CI=0.30–0.79) for the group with cumulative statin use of ≥134.25 DDDs. Also, there was a significant trend toward decreasing gastric cancer risk with increasing cumulative dose (χ2 for linear trend=7.42, P=0.006).


The results of this study are the first to suggest that statins may reduce the risk of gastric cancer.

 source:Nature gastroenterology

Once-Daily Dosing vs. Conventional Dosing Schedule of Mesalamine and Relapse of Quiescent Ulcerative Colitis: Systematic Review and Meta-Analysis

Maintenance therapy with 5-aminosalicylates (5-ASAs) is recommended in patients with quiescent ulcerative colitis (UC), but compliance rates are low. Once-daily dosing may improve adherence, but impact on the relapse of disease activity is unclear as no previous meta-analysis has studied this issue.


MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through April 2011). Eligible randomized controlled trials (RCTs) recruited adults with quiescent UC, and compared once-daily dosing of 5-ASAs with a more frequent dosing schedule of an identical total daily dose of the same 5-ASA drug. Minimum treatment duration was 6 months. Trials reported a dichotomous assessment of relapse of disease activity at last point of follow-up. Data concerning non-compliance and adverse events were extracted, where reported. Effect of once-daily vs. more frequent dosing schedule was reported as relative risk (RR) of relapse with a 95% confidence interval (CI).


The search identified 3,061 citations, and seven RCTs containing 2,745 patients were eligible. All RCTs used mesalamine. Relapse rates were not significantly different between once-daily and conventional dosing schedules for mesalamine (RR of relapse=0.94; 95% CI: 0.82–1.08). Non-compliance (RR=0.87; 95% CI: 0.46–1.66) and adverse events were no more likely with once-daily dosing (RR=1.08; 95% CI: 0.97–1.20).


Once-daily dosing with mesalamine is as effective as conventional dosing schedules for the prevention of relapse of quiescent UC, although there is no definitive evidence that compliance with once-daily dosing is better. Adverse events occur at a similar frequency.

source:Nature Gastroenerology

Improved Fitness Linked to Reduced Mortality in Men, Regardless of BMI AC

Men who maintain or improve their cardiorespiratory fitness have lower mortality risks than those who become less fit — regardless of changes in BMI — a Circulation study finds.

Some 14,000 men underwent clinical exams at baseline (mean age, 44) and again roughly 6 years later. Cardiorespiratory fitness was measured in metabolic equivalents (METs) during both exams, and mortality was assessed until 11 years after the last examination.

Among the findings:

  • Maintaining or improving cardiorespiratory fitness between the two exams conferred lower mortality risk, even after controlling for BMI changes.
  • For each 1-MET increase in fitness, the risks for all-cause and CVD mortality dropped by 15% and 19%, respectively.
  • BMI changes did not independently predict mortality.

The authors conclude: “The long-term effect of fitness change, primarily resulting from increasing physical activity, is likely to be at least as important as weight loss for reducing premature mortality.”

source: circulation