Eric M. Hecht

Alpha-2 receptor antagonist add-on therapy in the treatment of schizophrenia; a meta-analysis

INTRODUCTION Reduced dopaminergic activity in the pre-frontal cortex may partially explain the negative symptoms of schizophrenia. Animal models have shown that adding an alpha-2 adrenergic receptor antagonist to a D2 antagonist can efflux dopamine into the frontal cortex increasing dopaminergic activity. Trials of alpha-2 antagonist add-on therapy in humans have been limited by small sample sizes. Therefore, a meta-analysis was conducted to determine if adding an alpha-2 antagonist to a D2 antagonist improves schizophrenia treatment by reducing negative symptoms. METHODS Randomized, placebo-controlled trials of the addition of an alpha-2 antagonist to a D2 antagonist were identified through a PubMed search. Treatment effects were measured using schizophrenia rating scales and meta-analyzed as standardized mean differences using random effects models. RESULTS Eight unique studies were identified, each including 18 to 41 patients and lasting four to eight weeks. The overall effect size of add-on alpha-2 therapy across the eight trials was an improvement of 0.16 (95% C.I., -.30 to 0.62) for positive symptoms, 0.84 (95% C.I., .17 to 1.51) for negative symptoms, 0.28 (95% C.I., -.08 to 0.64) for general symptoms, and .80 (95% C.I., .15 to 1.46) for symptoms overall. Negative symptom improvements were independent of improvements in depressive symptoms, measured using the Hamilton depression rating scale, for 3 of the 5 studies. CONCLUSIONS Add-on agents with alpha-2 antagonist activity appear to improve the efficacy of D2 antagonists for the treatment of schizophrenia by reducing negative symptoms. These results support conducting a more definitive confirmatory clinical trial.

Are meat and heme iron intake associated with pancreatic cancer? Results from the NIH-AARP diet and health cohort

Several studies on pancreatic cancer have reported significant positive associations for intake of red meat but null associations for heme iron. We assessed total, red, white and processed meat intake, meat cooking methods and doneness and heme iron and mutagen intake in relation to pancreatic cancer in the NIH‐AARP Diet and Health Study cohort. A total of 322,846 participants (187,265 men and 135,581 women) successfully completed and returned the food frequency questionnaire between 1995 and 1996. After a mean follow‐up of 9.2 years (up to 10.17 years), 1,417 individuals (895 men and 522 women) developed exocrine pancreatic cancer. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), and trends were calculated using the median value of each quantile. Models incorporated age as the time metric and were adjusted for smoking history, body mass index, self‐reported diabetes and energy‐adjusted saturated fat. Pancreatic cancer risk significantly increased with intake of total meat (Q5 vs. Q1: HR = 1.20, 95% CI 1.02–1.42, p‐trend = 0.03), red meat (HR = 1.22, 95% CI 1.01–1.48, p‐trend = 0.02), high‐temperature cooked meat (HR = 1.21, 95% CI 1.00–1.45, p‐trend = 0.02), grilled/barbequed meat (HR = 1.24, 95% CI 1.03–1.50, p‐trend = 0.007), well/very well done meat (HR = 1.32, 95% CI 1.10–1.58, p‐trend = 0.005) and heme iron from red meat (Q4 vs. Q1: HR = 1.21, 95% CI 1.01–1.45, p‐trend = 0.04). When stratified by sex, these associations remained significant in men but not women except for white meat intake in women (HR = 1.33, 95% CI 1.02–1.74, p‐trend = 0.04). Additional studies should confirm our findings that consuming heme iron from red meat increases pancreatic cancer risk.

Hypothesis Cadmium Explains, in Part, Why Smoking Increases the Risk of Cardiovascular Disease

INTRODUCTION Cigarette smoking is a major risk factor for cardiovascular disease via acute and chronic mechanisms, some of which remain unclear. One plausible but untested hypothesis concerns cadmium (Cd), a component of cigarette smoke, which is injurious to vascular endothelial cells and is independently associated with cardiovascular disease. To contribute to the formulation of this hypothesis, we performed a meta-analysis of the available data that consisted of cross-sectional studies useful to formulate but not test hypotheses. METHODS PubMed and Google Scholar were searched by combining the terms smoking, Cd, correlation, blood, human, and tobacco. Following abstract review, 10 cross-sectional studies were identified. We compared serum Cd levels between smokers and nonsmokers using standardized mean differences (SMDs) as well as correlation coefficients between smoking and Cd. RESULTS The estimated overall random effects SMD in Cd between smokers and nonsmokers was 1.13 (95% confidence interval [CI], .70-1.56) with significant heterogeneity (Q = 8.6, P < .001). The estimated overall random effects correlation coefficient between smoking and Cd was .54 (95% CI, .30-.72) with significant heterogeneity (Q = 71.3, P < .01). CONCLUSIONS Despite major inherent limitations of meta-analyses of cross-sectional studies, we believe that the data contribute to the formulation of the hypothesis that Cd explains, in part, why smokers have an increased risk of cardiovascular disease. Further research, including analytic studies designed a priori are necessary to test the hypothesis.

A cross-sectional survey of cadmium biomarkers and cigarette smoking

Abstract Cadmium contamination of tobacco may contribute to the health hazards of cigarette smoking. The 2005–2012 United States National Health and Nutrition Examination Survey data provided a unique opportunity to conduct a cross-sectional survey of cadmium biomarkers and cigarette smoking. Among a sample of 6761 participants, we evaluated mean differences and correlations between cadmium biomarkers in the blood and urine and characteristics of never, former and current smokers. We found statistically significant differences in mean cadmium biomarker levels between never and former smokers as well as between never and current smokers. In current smokers, duration in years had a higher correlation coefficient with urinary than blood cadmium levels. In contrast, number of cigarettes smoked per day had a higher correlation coefficient with blood than urinary cadmium levels. These data suggest that blood and urine cadmium biomarker levels differ by duration and dose. These findings should be considered in evaluating any association between cadmium and smoking related diseases, especially cardiovascular disease.

Benefit of additional screening for progressive multifocal leukoencephalopathy in patients with multiple sclerosis taking natalizumab: a decision analysis.

ObjectivePatients with multiple sclerosis (MS) taking natalizumab are at risk for progressive multifocal leukoencephalopathy (PML). We sought to describe the outcomes of discontinuing natalizumab on the basis of PML risk and those of obtaining additional screening across a range of scenarios using decision tree models. MethodsHealth state probabilities and values, measured as the proportion of quality–adjusted life years (PQALY) relative to baseline health, were based on literature review. Probabilities of worsening MS while continuing and discontinuing natalizumab were set to 0.23 and 0.44. For discontinuing therapy, PML risk, worsening MS value, and PML value were varied. For additional screening, the probability of discontinuing natalizumab without screening, PML risk, worsening MS value, and PML value were set to 33%, 1.1%, 0.88, and 0.09, respectively, with test sensitivity and specificity varying from 0.50 to 1. ResultsDiscontinuing natalizumab provided no benefit until PML risk reached 2.9%, assuming an MS relapse value of 0.88 and a PML value of 0.09. Additional screening changed the PQALY by −0.3% to 1.5%, largely influenced by specificity. Assuming a sensitivity of 80% and a specificity of 99%, screening increases the PQALY by 1.2%. ConclusionsThe highest PML risk identified by stratification is below 2.9%, suggesting that continuing natalizumab outweighs PML risk for most patients on the basis of theoretical calculations. However, decisions based on additional screening with high-specificity tests, including polymerase chain reaction cerebrospinal fluid tests for John Cunningham virus, may provide benefit and should be clinically tested. Increased precision of probabilities and quality-of-life values are also needed to improve decision making.

Commentary on "Race, socioeconomic status, health-related quality of life, and self-care of type 2 diabetes mellitus among adults in North Carolina".

The Centers for Disease Control and Prevention initiated the Behavioral Risk Factors Surveillance System (BRFSS) in 1984 to supplement their annual series of surveillance surveys to monitor the prevalence of infectious and chronic diseases, as well as risk factors for future disease in the US population. The BRFSS is a telephone survey conducted at the state level to assess the health behaviors of Americans from smoking to the use of preventive services. These surveys provide a basis for understanding population health and targets for control and prevention in the United States. These efforts have tracked the increasing prevalence of chronic diseases, which now account for 7 of the top 10 causes of death in the United States. Of these, diabetes mellitus may pose the greatest cumulative threat to morbidity, resource expenditures, and mortality, given the broad range of its complications and the management of those complications. In this issue of the Southern Medical Journal, Piper and colleagues analyzed BRFSS data from self-reported diabetics in North Carolina to determine predictors of self-care. Respondents were classified as having good self-care if they took a diabetes mellitus management class/course and checked their blood glucose daily; however, diabetes mellitus type and insulin use were not recorded in the BRFSS. The authors found that diabetics without insurance, with less education, and with lower income levels were less likely to report good self-care. These predictors are consistent with known predictors of diabetes mellitus and health in North Carolina. Together, these results describe a potentially viscous pathway of disparity in which those who are poor and with decreased access to health care are more likely to develop disease, are less likely to care for their disease, and then are more likely to suffer from complications of their disease. Understanding predictors of self-care is an important step in identifying targets to reduce this disparity. A strength of this study is that the sample is representative of individuals with diabetes mellitus in North Carolina and is not focused solely on a subsample such as those with access to health care or more advanced disease. The findings of this study are limited by potential misclassification error because some respondents with type 2 diabetes mellitus managed without insulin may have been falsely defined as practicing poor self-care for less frequent glucose monitoring, which is unnecessary in this group. If these individuals also were more likely to have better health, then this would have biased the results. The authors also found that individuals with diabetes mellitus who perceived their health as being poor were more likely to practice good self-care even after adjusting for potential demographic confounders. This is consistent with prior work showing that diabetics with worse disease are more likely to be involved in their care. Johnston and colleagues found that veterans with diabetes were more likely to practice good foot self-care if they had a prior foot ulcer, while Nahin and colleagues found that those with worse disease were more likely to pursue alternative medical strategies. Unfortunately, these findings reflect the opposite of prevention. Understanding what motivates diabetics to care for their disease is the first step to targeting interventions to limit complications. Nearly 1 in 4 individuals with diabetes mellitus in United States has uncontrolled disease with a hemoglobin A1c of 98%, with racial minorities and patients with decreased levels of education predominantly affected. Despite this, the attention of most healthcare providers regarding advances in the management of diabetes mellitus during the last 2 decades was diverted by mega-randomized trials such as the National Institutes of HealthYfunded Action to Control Cardiovascular Risk in Diabetes study and industry-supported Action in Invited Commentary

Hypertension prevalence: an examination of urban and rural Haiti

Abstract Background With the burden of disease shifting from communicable to non-communicable diseases, hypertension is rising as a major health concern in developing nations. Absence of data for surveillance and effect of non-communicable diseases restrict the ability of stakeholders to respond effectively. We aim to estimate the prevalence of hypertension in Haiti and analyse differences in hypertensive status among urban and rural location, age, and sex. Methods We reviewed medical charts at two Haitian clinics: one in the urban city of Port-au-Prince and one in the rural village of Marmont in the Central Plateau, and recorded age, sex, weight, blood pressure, location of patient (urban vs rural), and present treatments and which specific medications. Participants included all non-pregnant outpatients older than 25 years who visited the clinics at least once between Jan 1, 2011. and June 15, 2013. 1019 patients were included in the study; 520 from Port-au-Prince and 490 from Marmont. Findings The overall prevalence of hypertension was 34·4% (n=351, 95% CI 31·8–37·8); with a prevalence of 31·6% (n=167, 95% CI 27·6–35·3) in Port-au-Prince and a prevalence of 37·6% (n=184, 95% CI 34·5–40·9) and Marmont. Younger participants had lower rates of hypertension than did older participants. Patients aged 25–34 years had a hypertension prevalence of 12·0% (n=41), aged 35–44 years of 23·8% (n=51), aged 45–54 years of 46·9% (n=91), aged 55–64 years of 58·6% (n=65), and aged older than 65 years of 65·6% (n=103). No observable differences were noted between locations within the same age group. When sex was compared, 34·7% (n=227) of women and 34·0% (n=124) of men were hypertensive. Women in the rural location had a significantly higher prevalence (39·0%, n=122) of hypertension than women in the urban location (30·8%, n=105, p=0·028). Of 351 total hypertensive participants, only 54·1% (n=190) showed any evidence of being prescribed antihypertensives in their chart. Interpretation This study suggests that hypertension is a major health problem in Haiti. Interventions are needed to address the proper management of hypertensive patients through medications and follow-ups, particularly in rural hypertensive women. Further research needs to be done to confirm the increased hypertension prevalence in rural locations in Haiti and to explore the causes of the differing hypertension prevalence in populations by location and sex. Funding Global Health Scholar Award from the Department of Public Health Sciences at University of Miami.

Association between positive and negative affect and musculoskeletal pain among US home health aides

ABSTRACT As the US population ages, there is an expected increase in demand for home health aides (HHAs); therefore, it is important to ensure their occupational well-being. Previous studies have demonstrated associations between negative emotions and musculoskeletal pain. Using survey data collected from 285 HHAs, we characterize the association between affect and musculoskeletal pain. Affect was measured using the Positive and Negative Affect Schedule, while musculoskeletal pain was measured using the Brief Pain Inventory. We found that as positive affect composite score increased, musculoskeletal pain decreased [β = –0.57, t(124) = –7.01, p < .001]. There was no significant association between the negative affect composite score and musculoskeletal pain. However, several individual moods were associated with decreased or increased pain. These data suggest that some moods may buffer against musculoskeletal pain, while others may predispose HHAs to musculoskeletal pain.

Are Fire Policies Fair When They Mandate the Use of Chemical Flame Retardants Without Mandating Their Safety Testing

FireandhealthpoliciesintheUnitedStatesappeartobe unbalanced. On the one hand, US regulations re-quiretheinclusionofchemicalflameretardants(CFRs)inmanyhouseholdandclothingitemswiththegoalofsavingfamiliesfromdeathandinjuryduetofires.Ontheother hand, there is no accompanying requirement toestablishthesafetyofthechemicalsusedtoachievethisgoal,despiteawealthofdatasuggestingtoxicity.

Mega-Randomized Clinical Trials for Blockbuster Drugs

Many commonly used medications lack information regarding their adverse effects, effectiveness relative to other treatment options, and mortality benefits. In his Viewpoint, Dr Ioannidis1 suggested requiring pharmaceutical companies to fund mega-randomized clinical trials (RCTs) for medications with more than