Environmental Factors Associated with Disease Progression after the First Demyelinating Event: Results from the Multi-Center SET Study

Objectives

To investigate the associations of environmental MS risk factors with clinical and MRI measures of progression in high-risk clinically isolated syndromes (CIS) after the first demyelinating event.

Methods

We analyzed 211 CIS patients (age: 28.9±7.8 years) enrolled in the SET study, a multi-center study of high-risk CIS patients. Pre-treatment samples were analyzed for IgG antibodies against cytomegalovirus (anti-CMV), Epstein Barr virus (EBV) early nuclear antigen-1 (EBNA-1), viral capsid antigen (VCA), early antigen-diffuse (EA-D), 25 hydroxy-vitamin D3 and cotinine levels and HLA DRB1*1501 status. The inclusion criteria required evaluation within 4 months of the initial demyelinating event, 2 or more brain MRI lesions and the presence of two or more oligoclonal bands in cerebrospinal fluid. All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24 months.

Results

The time to first relapse decreased and the number of relapses increased with anti-CMV IgG positivity. Smoking was associated with increased number and volume of contrast-enhancing lesions (CEL) during the 2-year period. The cumulative number of CEL and T2 lesions during the 2-year period was greater for individuals in the highest quartile of anti-EBV VCA IgG antibodies. The percent loss of brain volume was increased for those in the highest quartile of with anti-EBV VCA IgG antibodies.

Conclusions

Relapses in CIS patients were associated with CMV positivity whereas anti-EBV VCA positivity was associated with progression on MRI measures, including accumulation of CEL and T2 lesions and development of brain atrophy.     

Medication Persistence Rates and Factors Associated with Persistence in Patients Following Stroke: A Cohort Study

Background  

Medication nonadherence can be as high as 50% and results in suboptimal patient outcomes. Stroke patients in particular can benefit from pharmacotherapy for thrombosis, hypertension, and dyslipidemia but are at high risk for medication nonpersistence.     

Influence of Low-Level Prenatal Exposure to PCDD/Fs and PCBs on Empathizing,Systemizing and Autistic Traits: Results from the Duisburg Birth Cohort Study

Background

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are assumed to act as endocrine disruptor chemicals. Prenatal exposure to these pollutants might influence fetal steroid hormone levels, which are thought to be related to sex-typical development and autistic traits.

Objectives

We examined associations of prenatal levels of PCDD/Fs and PCBs with autism traits and sex-typical behaviour in childhood.

Methods

We measured levels of PCDD/Fs and PCBs in maternal blood samples during pregnancy using gas chromatography/high-resolution mass spectrometry. Sex-typical behaviour was assessed at 9 years of age (n = 96) and autistic traits at 10 years of age using the Social Responsiveness Scale (SRS; n = 100). Multiple regression analyses were conducted to estimate the associations between prenatal exposure and outcome variables.

Results

Blood concentrations (WHO₂₀₀₅-TEq) of ƩPCDD/Fs ranged from 2.93–46.45 pg/g _{lipid base} (median = 12.91 pg/g _{lipid base}) and concentrations of ƩPCBs were in the range of 1.24–25.47 pg/g _{lipid base} (median = 6.85 pg/g _{lipid base}) which is within the range of German background exposure. We found significant negative associations between PCDD/F levels in maternal blood and SRS scores in the whole group (β = -6.66, p < .05), in girls (β = -10.98, p < .05) and, in one SRS subscale, in boys (β = -6.86, p < .05). For PCB levels, associations with one SRS subscale were significant for the whole study group as were associations with two subscales in girls. We did not find significant associations between PCDD/F or PCB levels and sex-typical behaviour for either sex.

Conclusions

In an earlier part of this study, prenatal exposure to PCDD/Fs and PCBs was found to be associated with lower testosterone levels, therefore, our findings are consistent with the idea that autism spectrum conditions are related to fetal androgen levels. Several possible mechanisms, through which PCDD/Fs and PCBs might influence autistic behaviour, are discussed.     

Factors Associated with HIV Prevalence and HIV Testing in Sierra Leone: Findings from the 2008 Demographic Health Survey

BackgroundThe Sierra Leone Demographic Health Survey 2008 found an HIV prevalence of 1.5%. This study investigates associations with HIV infection and HIV testing.MethodsHouseholds were selected using stratified multi-stage sampling. In all selected households women aged 15–49 were eligible. In every second household men aged 15–59 were also eligible. Participants were asked to consent for anonymous HIV testing. All participants interviewed and tested were analysed. Multiple logistic regression identified associations with HIV infection, undiagnosed infection and with ever having a voluntary HIV test among sexually active participants.ResultsOf 7495 invited 86% (6,475) agreed to an interview and HIV test. Among 96 HIV positive participants, 78% had never taken a voluntary HIV test so were unaware of their serostatus, and 86% were sexually active in the last 12 months among whom 96% did not use a condom at last intercourse. 11% of all participants had previously voluntarily tested. Among women who had tested, 60% did so in antenatal care. We found that those living in an urban area, and those previously married, were more likely to be HIV infected. Voluntary HIV testing was more common in those aged 25–44, living in an urban area, females, having secondary or higher education, having first sexual intercourse at age 17 years or older, and using condoms at last sex. Although 82% of men and 69% of women had heard of HIV, only 35% and 29% respectively had heard of antiretroviral therapy.ConclusionsThe HIV prevalence in Sierra Leone has been stable. HIV testing, however, is uncommon and most infected individuals are unaware of their serostatus. This could allow the epidemic to escalate as individuals with undiagnosed infection are unlikely to change their behaviour or access treatment. Improving knowledge and increasing testing need to remain central to HIV prevention interventions in Sierra Leone.     

Evaluation of Clinical and Immunological Markers for Predicting Virological Failure in a HIV/AIDS Treatment Cohort in Busia,Kenya

Background

In resource-limited settings where viral load (VL) monitoring is scarce or unavailable, clinicians must use immunological and clinical criteria to define HIV virological treatment failure. This study examined the performance of World Health Organization (WHO) clinical and immunological failure criteria in predicting virological failure in HIV patients receiving antiretroviral therapy (ART).

Methods

In a HIV/AIDS program in Busia District Hospital, Kenya, a retrospective, cross-sectional cohort analysis was performed in April 2008 for all adult patients (>18 years old) on ART for ≥12 months, treatment-naive at ART start, attending the clinic at least once in last 6 months, and who had given informed consent. Treatment failure was assessed per WHO clinical (disease stage 3 or 4) and immunological (CD4 cell count) criteria, and compared with virological failure (VL >5,000 copies/mL).

Results

Of 926 patients, 123 (13.3%) had clinically defined treatment failure, 53 (5.7%) immunologically defined failure, and 55 (6.0%) virological failure. Sensitivity, specificity, positive predictive value, and negative predictive value of both clinical and immunological criteria (combined) in predicting virological failure were 36.4%, 83.5%, 12.3%, and 95.4%, respectively.

Conclusions

In this analysis, clinical and immunological criteria were found to perform relatively poorly in predicting virological failure of ART. VL monitoring and new algorithms for assessing clinical or immunological treatment failure, as well as improved adherence strategies, are required in ART programs in resource-limited settings.     

Mortality,Causes of Death and Associated Factors Relate to a Large HIV Population-Based Cohort

Introduction

Antiretroviral therapy has led to a decrease in HIV-related mortality and to the emergence of non-AIDS defining diseases as competing causes of death. This study estimates the HIV mortality rate and their risk factors with regard to different causes in a large city from January 2001 to June 2013.

Materials and Methods

We followed-up 3137 newly diagnosed HIV non-AIDS cases. Causes of death were classified as HIV-related, non-HIV-related and external. We examined the effect of risk factors on survival using mortality rates, Kaplan-Meier plots and Cox models. Finally, we estimated survival for each main cause of death groups through Fine and Gray models.

Mortality Results

182 deaths were found [14.0/1000 person-years of follow-up (py); 95% confidence interval (CI):12.0–16.1/1000 py], 81.3% of them had a known cause of death. Mortality rate by HIV-related causes and non-HIV-related causes was the same (4.9/1000 py; CI:3.7–6.1/1000 py), external was lower [1.7/1000 py; (1.0–2.4/1000 py)].

Survival Results

Kaplan-Meier estimate showed worse survival in intravenous drug user (IDU) and heterosexuals than in men having sex with men (MSM). Factors associated with HIV-related causes of death include: IDU male (subHazard Ratio (sHR):3.2; CI:1.5–7.0) and <200 CD4 at diagnosis (sHR:2.7; CI:1.3–5.7) versus ≥500 CD4. Factors associated with non-HIV-related causes of death include: ageing (sHR:1.5; CI:1.4–1.7) and heterosexual female (sHR:2.8; CI:1.1–7.3) versus MSM. Factors associated with external causes of death were IDU male (sHR:28.7; CI:6.7–123.2) and heterosexual male (sHR:11.8; CI:2.5–56.4) versus MSM.

Conclusion and Recommendation

There are important differences in survival among transmission groups. Improved treatment is especially necessary in IDUs and heterosexual males.     

Validation of Six Short and Ultra-short Screening Instruments for Depression for People Living with HIV in Ontario: Results from the Ontario HIV Treatment Network Cohort Study

Objective

Major depression affects up to half of people living with HIV. However, among HIV-positive patients, depression goes unrecognized 60–70% of the time in non-psychiatric settings. We sought to evaluate three screening instruments and their short forms to facilitate the recognition of current depression in HIV-positive patients attending HIV specialty care clinics in Ontario.

Methods

A multi-centre validation study was conducted in Ontario to examine the validity and accuracy of three instruments (the Center for Epidemiologic Depression Scale [CESD₂₀], the Kessler Psychological Distress Scale [K₁₀], and the Patient Health Questionnaire depression scale [PHQ₉]) and their short forms (CESD₁₀, K₆, and PHQ₂) in diagnosing current major depression among 190 HIV-positive patients in Ontario. Results from the three instruments and their short forms were compared to results from the gold standard measured by Mini International Neuropsychiatric Interview (the “M.I.N.I.”).

Results

Overall, the three instruments identified depression with excellent accuracy and validity (area under the curve [AUC]>0.9) and good reliability (Kappa statistics: 0.71–0.79; Cronbach’s alpha: 0.87–0.93). We did not find that the AUCs differed in instrument pairs (p-value>0.09), or between the instruments and their short forms (p-value>0.3). Except for the PHQ_2, the instruments showed good-to-excellent sensitivity (0.86–1.0) and specificity (0.81–0.87), excellent negative predictive value (>0.90), and moderate positive predictive value (0.49–0.58) at their optimal cut-points.

Conclusion

Among people in HIV care in Ontario, Canada, the three instruments and their short forms performed equally well and accurately. When further in-depth assessments become available, shorter instruments might find greater clinical acceptance. This could lead to clinical benefits in fast-paced speciality HIV care settings and better management of depression in HIV-positive patients.     

Factors Associated with Unplanned Dialysis Starts in Patients followed by Nephrologists: A Retropective Cohort Study

The number of patients starting dialysis is increasing world wide. Unplanned dialysis starts (patients urgently starting dialysis in hospital) is associated with increased costs and high morbidity and mortality. Risk factors for starting dialysis urgently in hospital have not been well studied. The primary objective of this study was to identify risk factors for unplanned dialysis starts in patients followed in a multidisciplinary chronic kidney disease (CKD) clinic. We performed a retrospective cohort study of 649 advanced CKD patients followed in a multidisciplinary CKD clinic at a tertiary care hospital from January 01, 2010 to April 30, 2013. Patients were classified as unplanned start (in hospital) or elective start. Multivariable logistic regression was used to identify variables associated with unplanned dialysis initiation. 184 patients (28.4%) initiated dialysis, of which 76 patients (41.3%) initiated dialysis in an unplanned fashion and 108 (58.7%) starting electively. Unplanned start patients were more likely to have diabetes (68.4% versus 51.9%; p = 0.04), CAD (42.1% versus 24.1%; p = 0.02), congestive heart failure (36.8% versus 17.6%; p = 0.01), and were less likely to receive modality education (64.5% vs 89.8%; p < 0.01) or be assessed by a surgeon for access creation (40.8% vesrus78.7% p < 0.01). On multivariable analysis, higher body mass index (OR 1.07, 95% CI 1.02, 1.13), and a history of congestive heart failure (OR 2.41, 95% CI 1.09, 5.41) were independently associated with an unplanned start. Unplanned dialysis initiation is common among advanced CKD patients, even if they are followed in a multidisciplinary chronic kidney disease clinic. Timely education and access creation in patients at risk may lead to lower costs and less morbidity and mortality.     

Prevalence,Recurrence, and Incidence of Current Depressive Symptoms among People Living with HIV in Ontario,Canada: Results from the Ontario HIV Treatment Network Cohort Study

IntroductionCurrent studies of depression among people living with HIV focus on describing its point prevalence. Given the fluctuating nature of depression and its profound impacts on clinical and quality-of-life outcomes, this study aimed to examine the prevalence, recurrence and incidence of current depressive symptoms and its underlying catalysts longitudinally and systematically among these individuals.MethodsWe conducted a prospective cohort study between October 1, 2007 and December 31, 2012 using longitudinal linked data sources. Current depressive symptoms was identified using the Centre for Epidemiologic Studies Depression Scale or the Kessler Psychological Distress Scale, first at baseline and again during follow-up interviews. Multivariable regressions were used to characterize the three outcomes.ResultsOf the 3,816 HIV-positive participants, the point prevalence of depressive symptoms was estimated at 28%. Of the 957 participants who were identified with depressive symptoms at baseline and who had at least two years of follow-up, 43% had a recurrent episode. The cumulative incidence among 1,745 previously depressive symptoms free participants (at or prior to baseline) was 14%. During the five-year follow-up, our multivariable models showed that participants with greater risk of recurrent cases were more likely to feel worried about their housing situation. Participants at risk of developing incident cases were also likely to be younger, gay or bisexual, and unable to afford housing-related expenses.ConclusionsDepressive symptoms are prevalent and likely to recur among people living with HIV. Our results support the direction of Ontario’s HIV/AIDS Strategy to 2026, which addresses medical concerns associated with HIV (such as depression) and the social drivers of health in order to enhance the overall well-being of people living with or at risk of HIV. Our findings reinforce the importance of providing effective mental health care and demonstrate the need for long-term support and routine management of depression, particularly for individuals at high risk.     

Risk and Prognostic Factors of Inpatient Mortality Associated with Unintentional Insecticide and Herbicide Poisonings: A Retrospective Cohort Study

Introduction

Pesticide poisoning is an important public health problem worldwide. The study aimed to determine the risk of all-cause and cause-specific inpatient mortality and to identify prognostic factors for inpatient mortality associated with unintentional insecticide and herbicide pesticide poisonings.

Methods

We performed a retrospective cohort study of 3,986 inpatients recruited at hospitalization between 1999 and 2008 in Taiwan. We used the International Classification of Disease, 9th ed., Clinical Modification external causes of injury codes to classify poisoning agents into accidental poisoning by insecticides and herbicides. Comparisons in mortality rates were made between insecticide poisoning patients and herbicide poisoning patients by using the Cox proportional hazards models to estimate multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs).

Results

There were 168 deaths during 21,583 person-days of follow-up evaluation (7.8 per 1,000 person-days). The major causes of mortality for insecticide poisonings were the toxic effect of organophosphate and coma, and the major causes of mortality for herbicide poisonings were the toxic effect of other pesticides and the toxic effect of organophosphate. The mortality for herbicide exposure was fourfold higher than that for insecticide exposure. The factors associated with inpatient mortality were herbicide poisonings (HR = 4.58, 95% CI 3.29 to 6.37) and receiving mechanical ventilation treatment (HR = 3.85, 95% CI 2.73 to 5.42).

Conclusions

We demonstrated that herbicides stand out as the dominant agent for poisoning-related fatalities. The control of and limiting access to herbicide agents and developing appropriate therapeutic regimens, including emergency care, should be priorities.     

Extracellular Vesicle Proteins Associated with Systemic Vascular Events Correlate with Heart Failure: An Observational Study in a Dyspnoea Cohort

Background

SerpinF2, SerpinG1, CystatinC and CD14 are involved in inflammatory processes and plasma extracellular vesicle (EV) -levels of these proteins have been reported to be associated with systemic vascular events. Evidence is accumulating that inflammatory processes may play a pivotal role both in systemic vascular events and in heart failure. Therefore, we studied the association between plasma extracellular vesicle SerpinF2-, SerpinG1-, CystatinC and CD14-levels and the occurrence of acute heart failure in patients.

Methods and Result

Extracellular vesicle protein levels of SerpinG1, SerpinF2, CystatinC and CD14 were measured in an observational study of 404 subjects presenting with dysponea at the emergency department (4B-cohort). Plasma extracellular vesicles were precipitated in a total extracellular vesicles (TEX)-fraction and in separate LDL- and HDL-subfractions. Extracellular vesicle protein levels were measured with a quantitative immune assay in all 3 precipitates. Out of 404 subjects, 141 (35%) were diagnosed with acutely decompensated heart failure. After correction for confounders (including comorbidities and medications), levels of CD14 in the HDL-fraction (OR 1.53, p = 0.01), SerpinF2 in the TEX-and LDL-fraction (ORs respectively 0.71 and 0.65, p<0.05) and SerpinG1 in the TEX-fraction (OR 1.55, p = 0.004) were statistically significantly related to heart failure. Furthermore, extracellular vesicle CD14- and SerpinF2-levels were significantly higher in heart failure patients with preserved ejection fraction than in those with reduced ejection fraction.

Conclusion

Extracellular vesicle levels of CD14, SerpinG1 and SerpinF2 are associated with the occurrence of heart failure in subjects suspected for acute heart failure, suggesting common underlying pathophysiological mechanisms for heart failure and vascular events.     

Change in Body Size and Mortality: Results from the Melbourne Collaborative Cohort Study

Background

The association between change in weight or body mass index, and mortality is widely reported, however, both measures fail to account for fat distribution. Change in waist circumference, a measure of central adiposity, in relation to mortality has not been studied extensively.

Methods

We investigated the association between mortality and changes in directly measured waist circumference, hips circumference and weight from baseline (1990–1994) to wave 2 (2003–2007) in a prospective cohort study of people aged 40–69 years at baseline. Cox regression, with age as the time metric and follow-up starting at wave 2, adjusted for confounding variables, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for change in body size in relation to mortality from all causes, cardiovascular disease and cancer.

Results

There were 1465 deaths (109 cancer, 242 cardiovascular disease) identified during an average 7.7 years of follow-up from 21 298 participants. Compared to minimal increase in body size, loss of waist circumference (HR: 1.26; 95% CI: 1.09–1.47), weight (1.80; 1.54–2.11), or hips circumference (1.35; 1.15–1.57) were associated with an increased risk of all-cause mortality, particularly for older adults. Weight loss was associated with cardiovascular disease mortality (2.40; 1.57–3.65) but change in body size was not associated with obesity-related cancer mortality.

Conclusion

This study confirms the association between weight loss and increased mortality from all-causes for older adults. Based on evidence from observational cohort studies, weight stability may be the recommended option for most adults, especially older adults.     

Risk Factors and Indices of Osteomyelitis of the Jaw in Osteoporosis Patients: Results from a Hospital-Based Cohort Study in Japan

Background

Several studies have reported osteomyelitis of the jaw (OMJ) as a side effect of bisphosphonates (BPs), and the risk of oral BPs has been recently clarified. However, other systemic risk factors of OMJ remain unclear. Importantly, the possibility of risk classification based on the clinical characteristics of patients has not been explored. Here, we clarified risk factors of OMJ and evaluate the predictive accuracy of risk indices in osteoporosis patients.

Methods

We performed sub-analysis using a database developed for a retrospective cohort study in patients taking medications for osteoporosis at Kyoto University Hospital. Risk indices for OMJ were constructed using logistic regression analysis, and odds ratios (OR) for OMJ cases and 95% confidence intervals (CI) were estimated. Potential risk factors included in the statistical analysis were age; sex; diabetes; use of oral BPs, corticosteroids, cancer chemotherapy, antirheumatic drugs, and biologic agents; and their interactions. Risk indices were calculated by the sum of potential risk factors of an individual patient multiplied by the regression coefficients. The discriminatory power of the risk indices was assessed by receiver operating characteristic (ROC) analysis.

Results

In analysis of all patients, oral BPs (OR: 4.98, 95% CIs: 1.94-12.75), age (OR: 1.28, 95% CI: 1.06-1.60) and sex-chemotherapy interaction (OR: 11.70, 95% CI: 1.46-93.64) were significant risk factors of OMJ. Areas under the ROC curves of these risk indices provided moderate sensitivity or specificity regardless of group (0.683 to 0.718).

Conclusions

Our data suggest that oral BP use, age, and sex-chemotherapy are predictors of OMJ in osteoporosis patients. The risk indices are moderately high, and allow the prediction of OMJ incidence.     

Rates and Factors Associated with Major Modifications to First-Line Combination Antiretroviral Therapy: Results from the Asia-Pacific Region

Background

In the Asia-Pacific region many countries have adopted the WHO’s public health approach to HIV care and treatment. We performed exploratory analyses of the factors associated with first major modification to first-line combination antiretroviral therapy (ART) in resource-rich and resource-limited countries in the region.

Methods

We selected treatment naive HIV-positive adults from the Australian HIV Observational Database (AHOD) and the TREAT Asia HIV Observational Database (TAHOD). We dichotomised each country’s per capita income into high/upper-middle (T-H) and lower-middle/low (T-L). Survival methods stratified by income were used to explore time to first major modification of first-line ART and associated factors. We defined a treatment modification as either initiation of a new class of antiretroviral (ARV) or a substitution of two or more ARV agents from within the same ARV class.

Results

A total of 4250 patients had 961 major modifications to first-line ART in the first five years of therapy. The cumulative incidence (95% CI) of treatment modification was 0.48 (0.44–0.52), 0.33 (0.30–0.36) and 0.21 (0.18–0.23) for AHOD, T-H and T-L respectively. We found no strong associations between typical patient characteristic factors and rates of treatment modification. In AHOD, relative to sites that monitor twice-yearly (both CD4 and HIV RNA-VL), quarterly monitoring corresponded with a doubling of the rate of treatment modifications. In T-H, relative to sites that monitor once-yearly (both CD4 and HIV RNA-VL), monitoring twice-yearly corresponded to a 1.8 factor increase in treatment modifications. In T-L, no sites on average monitored both CD4 & HIV RNA-VL concurrently once-yearly. We found no differences in rates of modifications for once- or twice-yearly CD4 count monitoring.

Conclusions

Low-income countries tended to have lower rates of major modifications made to first-line ART compared to higher-income countries. In higher-income countries, an increased rate of RNA-VL monitoring was associated with increased modifications to first-line ART.     

Risk Factors Associated with HIV Infection among Male Homosexuals and Bisexuals Followed in an Open Cohort Study: Project Horizonte,Brazil (1994-2010)

Background

There has recently been an increase in HIV infection rates among men who have sex with men (MSM). This study aimed at investigating risk factors associated with incident HIV infection in a MSM cohort–Project Horizonte, Belo Horizonte, Minas Gerais, Brazil.

Methodology

This is a nested case-control study in an ongoing open cohort of homosexual and bisexual men, carried out in 1994–2010, during which 1,085 volunteers were enrolled. Each HIV seroconverted volunteer (case) was compared with three randomly selected HIV negative controls, matched by admission date and age (±3 years). During follow-up, 93 volunteers seroconverted and were compared with 279 controls.

Principal Findings

The risk factors associated with HIV seroconversion were: contact with partner’s blood during sexual relations (OR 3.7; 95% CI 1.2–11.6), attendance at gay saunas in search for sexual partners (OR 2.6; 95% CI 1.3–5.4), occasional intake of alcohol when flirting and engaging in sexual activity (OR 2.5; 95% CI 1.3–5.1), inconsistent use of condoms in receptive anal sex (OR 2.4; 95% CI 1.1–5.4), little interest to look up information about AIDS (OR 2.6; 95% CI 1.0–6.7) particularly in newspapers (OR 3.4; 95% CI 1.4–8.1).

Conclusions

This study shows that MSM are still engaging in risk behavior, such as unprotected anal intercourse, despite taking part in a cohort study on various preventive measures. New preventive strategies in touch with the epidemic’s development and the specificities of this particular population are needed.     

Incidence and Factors Associated With Acne in Transgender Adolescents on Testosterone: A Retrospective Cohort Study

ObjectiveThis retrospective cohort study aimed to assess incidence and predictors of acne among transgender adolescents receiving testosterone.MethodsWe analyzed records of patients aged <18 years, assigned female at birth, seen at Children’s Healthcare of Atlanta Pediatric Endocrinology clinic for testosterone initiation between January 1, 2016, and January 1, 2019, with at least 1-year follow-up documented. Bivariable analyses to determine the association of clinical and demographic factors with new acne diagnosis were performed.ResultsOf 60 patients, 46 (77%) did not have baseline acne, but of those 46 patients, 25 (54%) developed acne within 1 year of testosterone initiation. Overall incidence proportion was 70% at 2 years; patients who used progestin prior to or during follow-up were more likely to develop acne than nonusers (92% vs 33%, P <.001).ConclusionTransgender adolescents starting testosterone, particularly those taking progestin, should be monitored for acne development and treated proactively by hormone providers and dermatologists.     

Factors Associated with Results and Conclusions of Trials of Thiazolidinediones

Background

When a sponsor funds a study of two competing drugs in a head-to-head comparison, the results and conclusions are likely to favor the sponsor’s drug. Thiazolidinediones, oral medications used for the treatment of type 2 diabetes, are one of the most costly choices of oral anti-diabetic medications, yet they do not demonstrate clinically relevant differences in achieving lower glycosylated hemoglobin levels compared to other oral antidiabetic drugs. Our aim is to examine associations between research funding source, study design characteristics aimed at reducing bias, and other factors with the results and conclusions of randomized controlled trials (RCTs) of thiazolidinediones compared to other oral hypoglycemic agents.

Methods and Findings

This is a cross-sectional study of 61 published RCTs comparing a thiazolidinedione (glitazone) to another anti-diabetic drug or placebo for treatment of type 2 diabetes. Data on study design characteristics, funding source, author’s financial ties, results for primary outcomes, and author conclusions were extracted. Univariate logistic regression identified associations between independent variables and results and conclusions that favored the glitazone. Of the RCTs, 59% (36/61) were funded by industry, 39% (24/61) did not disclose any funding. Common study design weaknesses included inadequate blinding and lack of concealment of allocation. Trials that reported favorable glycemic control results for the glitazone were more likely to have adequate blinding (OR (95% CI)  = 5.42 (1.46, 21.19), p = 0.008) and have a corresponding author with financial ties to the glitazone manufacturer (OR (95% CI)  = 4.12 (1.05, 19.53); p = 0.04). Trials with conclusions favoring the glitazone were less likely to be funded by a comparator drug company than a glitazone company (OR (95% CI)  = 0.026 (0, 0.40), p = 0.003) and less likely to be published in journals with higher impact factors (OR (95% CI)  = 0.79 (0.62, 0.97), p = 0.011). One limitation of our study is that we categorized studies as funded by industry based on each article’s disclosure which could underestimate the number of industry sponsored studies and personal ties of investigators. Additionally, our study did not include any head-to-head comparisons of one glitazone to another.

Conclusions

Published RCT comparisons of glitazones with other anti-diabetic drugs or placebo are predominantly industry supported and this support, as well as the financial ties of study authors, appears to be associated with favorable findings.     

Risk Factors Associated with Default from Multi- and Extensively Drug-Resistant Tuberculosis Treatment,Uzbekistan: A Retrospective Cohort Analysis

Background

The Médecins Sans Frontières project of Uzbekistan has provided multidrug-resistant tuberculosis treatment in the Karakalpakstan region since 2003. Rates of default from treatment have been high, despite psychosocial support, increasing particularly since programme scale-up in 2007. We aimed to determine factors associated with default in multi- and extensively drug-resistant tuberculosis patients who started treatment between 2003 and 2008 and thus had finished approximately 2 years of treatment by the end of 2010.

Methods

A retrospective cohort analysis of multi- and extensively drug-resistant tuberculosis patients enrolled in treatment between 2003 and 2008 compared baseline demographic characteristics and possible risk factors for default. Default was defined as missing ≥60 consecutive days of treatment (all drugs). Data were routinely collected during treatment and entered in a database. Potential risk factors for default were assessed in univariate analysis using chi-square test and in multivariate analysis with logistic regression.

Results

20% (142/710) of patients defaulted after a median of 6 months treatment (IQR 2.6–9.9). Factors associated with default included severity of resistance patterns (pre-extensively drug-resistant/extensively drug-resistant tuberculosis adjusted odds ratio 0.52, 95%CI: 0.31–0.86), previous default (2.38, 1.09–5.24) and age >45 years (1.77, 1.10–2.87). The default rate was 14% (42/294) for patients enrolled 2003–2006 and 24% (100/416) for 2007–2008 enrolments (p = 0.001).

Conclusions

Default from treatment was high and increased with programme scale-up. It is essential to ensure scale-up of treatment is accompanied with scale-up of staff and patient support. A successful first course of tuberculosis treatment is important; patients who had previously defaulted were at increased risk of default and death. The protective effect of severe resistance profiles suggests that understanding disease severity or fear may motivate against default. Targeted health education and support for at-risk patients after 5 months of treatment when many begin to feel better may decrease default.     

Risk Factors Associated with Recurrent Diarrheal Illnesses among Children in Kabul,Afghanistan: A Prospective Cohort Study

IntroductionChildhood diarrheal illnesses are a major public health problem. In low-income settings data on disease burden and factors associated with diarrheal illnesses are poorly defined, precluding effective prevention programs. This study explores factors associated with recurrent diarrheal illnesses among children in Kabul, Afghanistan.MethodsA cohort of 1–11 month old infants was followed for 18 months from 2007–2009. Data on diarrheal episodes were gathered through active and passive surveillance. Information on child health, socioeconomics, water and sanitation, and hygiene behaviors was collected. Factors associated with recurrent diarrheal illnesses were analyzed using random effects recurrent events regression models.Results3,045 children were enrolled and 2,511 (82%) completed 18-month follow-up. There were 14,998 episodes of diarrheal disease over 4,200 child-years (3.51 episodes/child-year, 95%CI 3.40–3.62). Risk of diarrheal illness during the winter season was 63% lower than the summer season (HR = 0.37, 95%CI 0.35–0.39, P<0.001). Soap for hand washing was available in 72% of households and 11.9% had toilets with septic/canalization. Half of all mothers reported using soap for hand washing. In multivariate analysis diarrheal illness was lower among children born to mothers with post-primary education (aHR = 0.79, 95%CI 0.69–0.91, p = 0.001), from households where maternal hand washing with soap was reported (aHR = 0.83, 95%CI 0.74–0.92, p<0.001) and with improved sanitation facilities (aHR = 0.76, 95%CI 0.63–0.93, p = 0.006). Malnourished children from impoverished households had significantly increased risks for recurrent disease [(aHR = 1.15, 95%CI 1.03–1.29, p = 0.016) and (aHR = 1.20, 95%CI 1.05–1.37, p = 0.006) respectively].ConclusionsMaternal hand washing and improved sanitation facilities were protective, and represent important prevention points among public health endeavors. The discrepancy between soap availability and utilization suggests barriers to access and knowledge, and programs simultaneously addressing these aspects would likely be beneficial. Enhanced maternal education and economic status were protective in this population and these findings support multi-sector interventions to combat illness.

Trial Registration

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