Poor predictive value of cytomegalovirus (CMV)-specific T cell assays for the development of CMV retinitis in patients with AIDS.

BACKGROUND: We examined the potential clinical utility of using a cytomegalovirus (CMV)-specific T cell immunoassay to determine the risk of developing new-onset CMV retinitis (CMVR) in patients with acquired immunodeficiency syndrome (AIDS). METHODS: CMV-specific T cell assays were performed by multiparameter flow cytometry using stored peripheral blood mononuclear cells that had been obtained in an observational study 2-6 months before new-onset CMVR was diagnosed in case patients (at a study visit during which a dilated ophthalmologic examination revealed no evidence of CMVR) and at the same study visit in control subjects (matched by absolute CD4(+) T cell count at entry) who did not subsequently develop retinitis during 1-6 years of study follow-up. RESULTS: There were no significant differences in CMV-specific CD4(+) or CD8(+) T cell interferon-gamma or interleukin-2 expression in peripheral blood mononuclear cells from case patients and control subjects. Although there were trends toward lower percentages and absolute numbers of CMV-specific, cytokine-expressing CD8(+) T cells with a "late memory" phenotype (CD27(-)CD28(-)) as well as with an "early memory" phenotype (CD27(+)CD28(+)CD45RA(+)) in case patients than in control subjects, these differences were not statistically significant. CONCLUSIONS: Many studies have reported that CMV-specific CD4(+) and CD8(+) T cell responses distinguish patients with active CMVR (i.e., who lack CMV-protective immunity) from those with inactive CMVR after immune restoration by antiretroviral treatment (i.e., who have CMV-protective immunity). However, the multiple CMV-specific immune responses we measured do not appear to have clinical utility for predicting the risk for patients with AIDS of developing new-onset CMVR with sufficient accuracy to be used in guiding therapeutic management.     

Chronic telogen effluvium in a man

Chronic telogen effluvium is a recently described condition, in which there is persistent excessive hair shedding. Hairs are replaced as quickly as they shed, so patients never become bald. This condition is found primarily in women. We describe chronic telogen effluvium in a man; the diagnosis may have only become obvious because of his long hair.     

Testosterone in men with advanced liver disease: Abnormalities and implications

Serum testosterone is reduced in up to 90% of men with cirrhosis, with levels falling as liver disease advances. Testosterone is an important anabolic hormone, with effects on muscle, bone, and hematopoiesis. Many of the features of advanced liver disease are similar to those seen in hypogonadal men, including sarcopenia, osteoporosis, gynecomastia, and low libido. However, the relative contribution of testosterone deficiency to the symptomatology of advanced liver disease has not been well established. More recently, it has been demonstrated that low testosterone in men with cirrhosis is associated with increased mortality, independent of the classically recognized prognostic factors, such as the Model for End‐Stage Liver Disease score. Only several small clinical trials have examined the role of testosterone therapy in men with cirrhosis, none of which have resolved the issue of whether or not testosterone is beneficial. However, in men with organic hypogonadism due to structural hypothalamic–pituitary–testicular axis disease, testosterone therapy has been shown to improve muscle mass and bone mineral density, increase hemoglobin, and reduce insulin resistance. Despite initial concerns linking testosterone with hepatocellular carcinoma, more recent data suggest that this risk has been overstated. There is, therefore, now a strong rationale to assess the efficacy and safety of testosterone therapy in cirrhosis in well‐designed randomized controlled trials.     

Insulin resistance: a risk marker for disease and disability in the older person

Clinical metabolic studies have demonstrated that insulin action declines progressively with age in humans. In addition to its close association with Type 2 diabetes, which reduces life expectancy in older people, age‐related insulin resistance is implicated in pathogenesis of several highly prevalent disorders for which ageing is a major risk factor. These include atherosclerotic cardiovascular disease, dementia, frailty and cancer. Accordingly, insulin resistance may be viewed as biomarker of age‐related ill health and reduced lifespan. The rapidly rising number of older people, coupled with a high prevalence of insulin resistance resulting from obesity and sedentary lifestyles, presents unprecedented public health and societal challenges. Studies of centenarians have shown that preserved whole‐body sensitivity to insulin is associated with longevity. The mechanisms through which insulin action is associated with age‐related diseases remain unclear. Changes in body composition, i.e. sarcopenia and excess adiposity, may be more potent than age per se. Moreover, the impact of insulin resistance has been difficult to disentangle from the clustering of vascular risk factors that co‐segregate with the insulin resistance–hyperinsulinaemia complex. Potentially modifiable mediators of age‐related changes in insulin sensitivity include alterations in adipocytokines, impaired skeletal myocyte mitochondrial function and brown fat activity. The hypothesis that improving or maintaining insulin sensitivity preserves health and extends lifespan merits further evaluation. Practical non‐pharmacological interventions directed against age‐related insulin resistance remain underdeveloped. Novel metabolically active pharmacological agents with theoretical implications for some age‐related disorders are entering clinical trials. However, recent adverse experiences with the thiazolidinediones suggest the need for a cautious approach to the use of insulin sensitizing drugs in older people. This could be particularly important in the absence of diabetes where the risk to benefit analysis may be less favourable.     

Sociodemographic Differences in the Comprehension of Nutritional Labels on Food Products

ObjectiveTo examine comprehension of nutrition labels across sociodemographic groups using a measure of health literacy.MethodsCross-sectional survey of a community sample of adults including an adapted version of the Newest Vital Sign for Canadian Nutrition Facts table on prepackaged grocery products, including numerical conversion questions for calorie content and percent daily value.ResultsApproximately two thirds of participants were able to correctly identify calorie content and percent daily value from the nutrition label. Participants with higher education and higher income, those aged ≤ 64 years, and those who look at nutritional facts or calories were significantly more likely to estimate the correct calorie content. Participants were significantly more likely to correctly identify percent daily value if they reported higher education, higher income, and white ethnicity.Conclusions and ImplicationsApproximately one third of participants could not comprehend basic information on Canadian nutrition labels. Lower socioeconomic status was associated with poorer performance.     

Demystifying buprenorphine misuse: Has fear of diversion gotten in the way of addressing the opioid crisis?

Buprenorphine is considered one of the most effective treatments for opioid use disorder and significantly reduces risk of overdose death. However, concerns about its diversion and misuse have often taken center stage in public discourse and in the design of practices and policies regarding its use. This has been to the detriment of many vulnerable patient populations, especially those involved in the criminal justice system. Policies that restrict access to buprenorphine in criminal justice and other settings due to concerns of diversion do not accurately reflect the relative risks and safety profile associated with it, creating unnecessary barriers that drive an illicit market of this much-needed medication. Although proper regulation of all controlled medications should be a priority, in most instances the benefits of buprenorphine highly outweigh its risks. In the midst of a national crisis, efforts should be focused on expanding, and not restricting, access to this lifesaving treatment.     

Diabetes and dementia in older people: a Best Clinical Practice Statement by a multidisciplinary National Expert Working Group

Both dementia and diabetes mellitus are long‐term disabling conditions and each may be a co‐morbidity of the other. Type 2 diabetes is associated with a 1.5‐ to 2‐fold higher risk of dementia. Diabetes also may occur for the first time in many individuals with mental ill health, including cognitive impairment and dementia, and this may complicate management and lead to difficulties in self‐care. Case finding is often poor for cognitive impairment in medical settings and for diabetes in mental health settings and this needs to be addressed in the development of care pathways for both conditions. Many other deficiencies in quality care (both for dementia and diabetes) currently exist, but we hope that this Best Clinical Practice Statement will provide a platform for further work in this area. We have outlined the key steps in an integrated care pathway for both elements of this clinical relationship, produced guidance on identifying each condition, dealt with the potentially hazardous issue of hypoglycaemia, and have outlined important competencies required of healthcare workers in both medical/diabetes and mental health settings to enhance clinical care.