Michael O. Harhay

Prevalence and Trends of Metabolic Syndrome in the Adult U.S. Population, 1999-2010

OBJECTIVES This study sought to characterize the prevalence of metabolic syndrome (MetS), its 5 components, and their pharmacological treatment in U.S. adults by sex and race/ethnicity over time. BACKGROUND MetS is a constellation of clinical risk factors for cardiovascular disease, stroke, kidney disease, and type 2 diabetes mellitus. METHODS Prevalence estimates were estimated in adults (≥ 20 years of age) from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010 (in 2-year survey waves). The biological thresholds, defined by the 2009 Joint Scientific Statement, were: 1) waist circumference ≥ 102 cm (males adults) and ≥ 88 cm (female adults); 2) fasting plasma glucose ≥ 100 mg/dl; 3) blood pressure of ≥ 130/85 mm Hg; 4) triglycerides ≥ 150 mg/dl; and 5) high-density lipoprotein-cholesterol (HDL-C) <40 mg/dl (male adults) and <50 mg/dl (female adults). Prescription drug use was estimated for lipid-modifying agents, anti-hypertensives, and anti-hyperglycemic medications. RESULTS From 1999 and 2000 to 2009 and 2010, the age-adjusted prevalence of MetS (based on biologic thresholds) decreased from 25.5% (95% confidence interval [CI]: 22.5% to 28.6%) to 22.9% (95% CI: 20.3% to 25.5%). During this period, hypertriglyceridemia prevalence decreased (33.5% to 24.3%), as did elevated blood pressure (32.3% to 24.0%). The prevalence of hyperglycemia increased (12.9% to 19.9%), as did elevated waist circumference (45.4% to 56.1%). These trends varied considerably by sex and race/ethnicity. Decreases in elevated blood pressure, suboptimal triglycerides, and high-density lipoprotein-cholesterol prevalence have corresponded with increases in anti-hypertensive and lipid-modifying drugs, respectively. CONCLUSIONS The increasing prevalence of abdominal obesity, particularly among female adults, highlights the urgency of addressing abdominal obesity as a healthcare priority. The use of therapies for MetS components aligns with favorable trends in their prevalence.

Epidemiology and control of human gastrointestinal parasites in children.

Parasites found in the human gastrointestinal tract can be largely categorized into two groups, protozoa and helminths. The soil-transmitted helminths (Ascaris lumbricoides, hookworm and Trichuris trichiura) are the most prevalent, infecting an estimated one-sixth of the global population. Infection rates are highest in children living in sub-Saharan Africa, followed by Asia and then Latin America and the Caribbean. The current momentum towards global drug delivery for their control is at a historical high through the efforts of numerous initiatives increasingly acting in coordination with donors, governments and local communities. Together, they have delivered enormous quantities of drugs, especially anthelmintics to children through nationwide annual or biannual mass drug administration largely coordinated through schools. However, a much larger and rapidly growing childhood population in these regions remains untreated and suffering from more than one parasite. Mass drug administration has profound potential for control but is not without considerable challenges and concerns. A principal barrier is funding. Stimulating a research and development pipeline, supporting the necessary clinical trials to refine treatment, in addition to procuring and deploying drugs (and sustaining these supply chains), requires substantial funding and resources that do not presently exist. Limited options for chemotherapy raise concerns about drug resistance developing through overuse, however, satisfactory pharmacoepidemiology and monitoring for drug resistance requires more developed health infrastructures than are generally available. Further, the limited pharmacopeia does not include any effective second-line options if resistance emerges, and the research and development pipeline is severely depressed. Herein, we discuss the major gastrointestinal protozoa and helminths reviewing their impact on child health, changing epidemiology and how this relates to their control.

New, Improved Treatments for Chagas Disease: From the R&D Pipeline to the Patients

Endemic throughout Latin America with a prevalence rate of approximately 1.4%, Chagas disease (CD) is estimated to kill 14,000 people every year, which is more people in the region each year than any other parasite-born disease, including malaria [1],[2]. Brazilian physician Carlos Chagas first described CD exactly a century ago [3], and its socioeconomic impact makes it the most important parasitic disease in the Americas [4]. Estimated to infect somewhere between 8 to 14 million people, CD both afflicts the poor and, like other neglected tropical diseases, “promotes poverty” [2],[5]. Through its impact on worker productivity, and by causing premature disability and death, CD annually costs an estimated 667,000 disability-adjusted life years lost [1],[6]. In the case of Brazil alone, losses of over US

Urban parasitology: visceral leishmaniasis in Brazil

1.3 billion in wages and industrial productivity were due to the disabilities of workers with CD [7]. CD is an important public health issue, both in Latin America and increasingly around the world: the infection rate in endemic areas is estimated to be 1.4% [8], with geographic variation from 0.1% to 45.2% [9]. Vectorial transmission has been significantly reduced due to control efforts like the Southern Cone Initiative [10],[11] and others [11],[12]. However, there are areas producing new cases such as regions untouched by vector control efforts [13], special areas with non-domiciliated triatomine [14], and the Amazon region with recent cases reported via oral transmission and by wild triatomine [15]. And still to this day, millions of patients remain without adequate treatment for this silently debilitating and potentially fatal disease. Although no official global figures exist, it is estimated that no more than 1% of those infected are believed to receive any treatment at all. An increasing number of CD patients are also seen in non-endemic, developed countries because of globalization and the movement of unknowingly infected people from Latin America to other parts of the world [16],[17],[18]. The appearance of Trypanosoma cruzi in blood banks in the United States has led the Food and Drug Administration (FDA) to recently issue a draft guidance on CD screening [19].

Impact of primary health care on mortality from heart and cerebrovascular diseases in Brazil: a nationwide analysis of longitudinal data

Since the early 1980s, visceral leishmaniasis (VL) which is, in general, a rural zoonotic disease, has spread to the urban centers of the north, and now the south and west of Brazil. The principal drivers differ between cities, though human migration, large urban canid populations (animal reservoir), and a decidedly peripatetic and adaptable sand fly vector are the primary forces. The exact number of urban cases remains unclear as a result of challenges with surveillance. However, the number of urban cases registered continues to increase annually. Most control initiatives (e.g. culling infected dogs and household spraying to kill the sand fly) could be effective, but have proven hard to maintain at large scales due to logistical, financial and other reasons. In this article, the urbanization of VL in Brazil is reviewed, touching on these and other topics related to controlling VL within and outside Brazil.

Evaluation of disease-specific health-related quality of life in patients with pulmonary arterial hypertension

Objectives To evaluate the impact of Brazil’s recently implemented Family Health Program (FHP), the largest primary health care programme in the world, on heart and cerebrovascular disease mortality across Brazil from 2000 to 2009. Design Ecological longitudinal design, evaluating the impact of FHP using negative binomial regression models for panel data with fixed effects specifications. Setting Nationwide analysis of data from Brazilian municipalities covering the period from 2000 to 2009. Data sources 1622 Brazilian municipalities with vital statistics of adequate quality. Main outcome measures The annual FHP coverage and the average FHP coverage in previous years were used as main independent variables and classified as none (0%), incipient (<30%), intermediate (30-69%), or consolidated (≥70%). Age standardised mortality rates from causes in the group of cerebrovascular (ICD-10 codes I60-69), ischaemic (ICD-10 I20-25), and other forms of heart diseases (ICD-10 I30-52), which were included in the national list of ambulatory care-sensitive conditions, were calculated for each municipality for each year. They accounted for 40% of all deaths from these groups during the study period. Results FHP coverage was negatively associated with mortality rates from cerebrovascular and heart diseases (ambulatory care-sensitive conditions) in both unadjusted and adjusted models for demographic, social, and economic confounders. The FHP had no effect on the mortality rate for accidents, used as a control. The rate ratio for the effect of consolidated annual FHP coverage on cerebrovascular disease mortality and on heart disease mortality was 0.82 (95% confidence interval 0.79 to 0.86) and 0.79 (0.75 to 0.80) respectively, reaching the value of 0.69 (0.66 to 0.73) and 0.64 (0.59 to 0.68) when the coverage was consolidated during all the previous eight years. Moreover, FHP coverage increased the number of health education activities, domiciliary visits, and medical consultations and reduced hospitalisation rates for cerebrovascular and heart disease. Several complementary analyses showed quantitatively similar results. Conclusions Comprehensive and community based primary health care programmes, such as the FHP in Brazil, acting through cardiovascular disease prevention, care, and follow-up can contribute to decreased cardiovascular disease morbidity and mortality in a developing country such as Brazil.

Sarcopenia and mortality among a population‐based sample of community‐dwelling older adults

BACKGROUND Pulmonary arterial hypertension (PAH) remains a debilitating and life-threatening disease despite improvements in hemodynamics, exercise capacity and survival with recent therapeutic advances. Health-related quality of life (HRQOL) has, therefore, been proposed as an important outcome for evaluating care. Relatively little, however, is known regarding HRQOL or its determinants in PAH. The Minnesota Living with Heart Failure questionnaire was recently adapted and validated for HRQOL measurement in PAH. We applied this pulmonary hypertension-specific version (MLHF-PH) to a larger population of PAH patients. METHODS Ninety-three consecutive outpatients with PAH completed the MLHF-PH. Scores were assessed for correlations with demographics, symptoms, hemodynamics and treatments. RESULTS Patients with PAH had significantly impaired HRQOL as assessed by the disease-specific MLHF-PH. Each physical and emotional component, as well as total scores on the MLHF-PH indicated severely depressed HRQOL. As compared to other diagnoses, PAH associated with scleroderma had the worst HRQOL. Patients with WHO functional Class II symptoms reported better HRQOL than Class III patients. Fatigue, weakness and abdominal discomfort were each associated with more severely depressed HRQOL, as was current epoprostenol use. With the sole exception of the right atrial pressure, hemodynamic measurements did not correlate with HRQOL scores. Simultaneous evaluation of HRQOL with a non-disease-specific questionnaire (SF-36) revealed a similarly impaired status, although identified fewer associations with patient-specific factors. CONCLUSION Severely impaired HRQOL is present in this population of patients with PAH evaluated with a disease-specific questionnaire. The availability of a pulmonary hypertension-specific HRQOL questionnaire may enable further targeted investigations of factors that might improve outcomes.

Variation in Decisions to Forgo Life-Sustaining Therapies in US ICUs

Sarcopenia is a risk‐factor for all‐cause mortality among older adults, but it is unknown if sarcopenia predisposes older adults to specific causes of death. Further, it is unknown if the prognostic role of sarcopenia differs between males and females, and obese and non‐obese individuals.

Outcomes and statistical power in adult critical care randomized trials.

BACKGROUND The magnitude and implication of variation in end-of-life decision-making among ICUs in the United States is unknown. METHODS We reviewed data on decisions to forgo life-sustaining therapy (DFLSTs) in 269,002 patients admitted to 153 ICUs in the United States between 2001 and 2009. We used fixed-effects logistic regression to create a multivariable model for DFLST and then calculated adjusted rates of DFLST for each ICU. RESULTS Patient factors associated with increased odds of DFLST included advanced age, female sex, white race, and poor baseline functional status (all P < .001). However, associations with several of these factors varied among ICUs (eg, black race had an OR for DFLST from 0.18 to 2.55 across ICUs). The ICU staffing model was also found to be associated with DFLST, with an open ICU staffing model associated with an increased odds of a DFLST (OR = 1.19). The predicted probability of DFLST varied approximately sixfold among ICUs after adjustment for the fixed patient and ICU effects and was directly correlated with the standardized mortality ratios of ICUs (r = 0.53, 0.41-0.68). CONCLUSION Although patient factors explain much of the variability in DFLST practices, significant effects of ICU culture and practice influence end-of-life decision-making. The observation that an ICUs risk-adjusted propensity to withdraw life support is directly associated with its standardized mortality ratio suggests problems with using the latter as a quality measure.

Differential impact of the economic recession on alcohol use among white British adults, 2004–2010

RATIONALE Intensive care unit (ICU)-based randomized clinical trials (RCTs) among adult critically ill patients commonly fail to detect treatment benefits. OBJECTIVES Appraise the rates of success, outcomes used, statistical power, and design characteristics of published trials. METHODS One hundred forty-six ICU-based RCTs of diagnostic, therapeutic, or process/systems interventions published from January 2007 to May 2013 in 16 high-impact general or critical care journals were studied. MEASUREMENT AND MAIN RESULTS Of 146 RCTs, 54 (37%) were positive (i.e., the a priori hypothesis was found to be statistically significant). The most common primary outcomes were mortality (n = 40 trials), infection-related outcomes (n = 33), and ventilation-related outcomes (n = 30), with positive results found in 10, 58, and 43%, respectively. Statistical power was discussed in 135 RCTs (92%); 92 cited a rationale for their power parameters. Twenty trials failed to achieve at least 95% of their reported target sample size, including 11 that were stopped early due to insufficient accrual/logistical issues. Of 34 superiority RCTs comparing mortality between treatment arms, 13 (38%) accrued a sample size large enough to find an absolute mortality reduction of 10% or less. In 22 of these trials the observed control-arm mortality rate differed from the predicted rate by at least 7.5%. CONCLUSIONS ICU-based RCTs are commonly negative and powered to identify what appear to be unrealistic treatment effects, particularly when using mortality as the primary outcome. Additional concerns include a lack of standardized methods for assessing common outcomes, unclear justifications for statistical power calculations, insufficient patient accrual, and incorrect predictions of baseline event rates.