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Abstract Background Methylmercury (MeHg) is a neurotoxin primarily found in seafood; exposures in reproductive-age women are of concern due to vulnerability of the developing fetus. MeHg is mainly eliminated via an enterohepatic cycle involving the liver and gallbladder. Dysfunction in these organs has been associated with slower MeHg elimination in laboratory animals. We hypothesized that women testing positive for chronic hepatitis B (HBV) or C (HCV), both associated with risk of longer-term liver and gallbladder impairment, would have higher total blood mercury (TBHg) concentrations than those negative for the viruses, reflecting slower MeHg elimination. Methods Geometric mean (GM) TBHg levels from a representative sample of over 5,000 seafood-consuming, reproductive-age women from eight years (2001–2008) of the US NHANES survey were compared by viral hepatitis status (as determined by serological assay) using multiple linear regression. Adjustment was made for estimated MeHg intake from seafood consumption, social and demographic variables and other predictors. Results Women with chronic HBV had 1.52 (95% CI 1.13, 2.05, p Conclusions While study design prevents inferences on causality, the finding that MeHg biomarkers differ by hepatitis status in this population suggests viral hepatitis may alter the pace of MeHg elimination. Offspring of HBV-infected seafood-consuming women may be at higher risk of MeHg-induced developmental delays than offspring of those uninfected. Possible reasons for the unanticipated negative association with HCV are explored.

Abstract Background Distance learning may be useful for building health research capacity. However, evidence that it can improve knowledge and skills in health research, particularly in resource-poor settings, is limited. We compared the impact and acceptability of teaching two distinct content areas, Biostatistics and Research Ethics, through either on-line distance learning format or traditional on-site training, in a randomized study in India. Our objective was to determine whether on-line courses in Biostatistics and Research Ethics could achieve similar improvements in knowledge, as traditional on-site, classroom-based courses. Methods Subjects: Volunteer Indian scientists were randomly assigned to one of two arms. Intervention: Students in Arm 1 attended a 3.5-day on-site course in Biostatistics and completed a 3.5-week on-line course in Research Ethics. Students in Arm 2 attended a 3.5-week on-line course in Biostatistics and 3.5-day on-site course in Research Ethics. For the two course formats, learning objectives, course contents and knowledge tests were identical. Main Outcome Measures: Improvement in knowledge immediately and 3-months after course completion, compared to baseline. Results Baseline characteristics were similar in both arms (n = 29 each). Median knowledge score for Biostatistics increased from a baseline of 49% to 64% (p < 0.001) 3 months after the on-site course, and from 48% to 63% (p = 0.009) after the on-line course. For the on-site Research Ethics course, median score increased from 69% to 83% (p = 0.005), and for the on-line Research Ethics course from 62% to 80% (p < 0.001). Three months after the course, median gains in knowledge scores remained similar for the on-site and on-line platforms for both Biostatistics (16% vs. 12%; p = 0.59) and Research Ethics (17% vs. 13%; p = 0.14). Conclusion On-line and on-site training formats led to marked and similar improvements of knowledge in Biostatistics and Research Ethics. This, combined with logistical and cost advantages of on-line training, may make on-line courses particularly useful for expanding health research capacity in resource-limited settings.

Background: Prediabetes is a highly prevalent condition that heralds an increased risk of progression to type 2 diabetes, along with associated microvascular and macrovascular complications. The Diabetes Prevention Program (DPP) is an established effective intervention for diabetes prevention. However, participation in this 12-month lifestyle change program has historically been low. Digital DPPs have emerged as a scalable alternative, accessible asynchronously and recognized by the Centers for Disease Control and Prevention (CDC). Yet, most digital programs still incorporate human coaching, potentially limiting scalability. Furthermore, existing effectiveness results of digital DPPs are primarily derived from per protocol, longitudinal non-randomized studies, or comparisons to control groups that do not represent the standard of care DPP. The potential of an AI-powered DPP as an alternative to the DPP is yet to be investigated. We propose a randomized controlled trial (RCT) to directly compare these two approaches., Methods: This open-label, multicenter, non-inferiority RCT will compare the effectiveness of a fully automated AI-powered digital DPP (ai-DPP) with a standard of care human coach-based DPP (h-DPP). A total of 368 participants with elevated body mass index (BMI) and prediabetes will be randomized equally to the ai-DPP (smartphone app and Bluetooth-enabled body weight scale) or h-DPP (referral to a CDC recognized DPP). The primary endpoint, assessed at 12 months, is the achievement of the CDC's benchmark for type 2 diabetes risk reduction, defined as any of the following: at least 5% weight loss, at least 4% weight loss and at least 150 min per week on average of physical activity, or at least a 0.2-point reduction in hemoglobin A1C. Physical activity will be objectively measured using serial actigraphy at baseline and at 1-month intervals throughout the trial. Secondary endpoints, evaluated at 6 and 12 months, will include changes in A1C, weight, physical activity measures, program engagement, and cost-effectiveness. Participants include adults aged 18-75 years with laboratory confirmed prediabetes, a BMI of ≥ 25 kg/m 2 (≥ 23 kg/m 2 for Asians), English proficiency, and smartphone users. This U.S. study is conducted at Johns Hopkins Medicine in Baltimore, MD, and Reading Hospital (Tower Health) in Reading, PA., Discussion: Prediabetes is a significant public health issue, necessitating scalable interventions for the millions affected. Our pragmatic clinical trial is unique in directly comparing a fully automated AI-powered approach without direct human coach interaction. If proven effective, it could be a scalable, cost-effective strategy. This trial will offer vital insights into both AI and human coach-based behavioral change strategies in real-world clinical settings., Trial Registration: ClinicalTrials.gov NCT05056376. Registered on September 24, 2021, https://clinicaltrials.gov/study/NCT05056376., (© 2024. The Author(s).)

Background: Urbanization influences food systems and food security, but research on these associations in low- and middle-income countries remain limited, partly because of the binary and unstandardized "urban compared with rural" classifications., Objectives: To develop a community urbanicity scale, to assess its associations with household food security, and to explore whether agricultural occupation modifies this relationship across the 3 agroecological zones (mountain, hill, Tarai ) of Nepal., Methods: Data came from a nationally and agroecologically representative, multistaged 2013 agri-food system survey of 4285 households with children <5 y in 63 communities (wards) in Nepal. A novel community-level urbanicity scale was constructed using factor analysis that included 8 domains. Multilevel mixed effects logistic regression was used to assess associations between urbanicity and household food security (measured using the validated Household Food Insecurity Access Scale), and to investigate modifying effects of agricultural occupation., Results: Urbanicity scores ranged between 13 and 69, of a possible 80 points. Most agricultural households in the mountains (67%) and hills (54%) were categorized food insecure. Increases in urbanicity were negatively associated with food insecurity, controlling for other factors (odds ratio [OR] per 10-unit urbanicity difference OR: 0.82; confidence interval [CI]: 0.71, 0.94; P ≤ 0.05). Agricultural occupation may have positively influenced this association though was not a statistically significant effect measure modifier ( P = 0.07)., Conclusions: The novel scale shows more nuance within Nepal's agroecological zones, which had similar urbanicity-to-food security relationships as well as overlapping urbanicity score distributions. Research and policy efforts should consider using scales providing more precise urbanicity measurement, and thus informative assessments on its role in predicting food insecurity, especially in agriculturally reliant populations., (© 2024 The Authors.)

Objective: As thyroid hormone metabolism slows with advancing age, treatment dosing requirements change. Guidelines recommend titration from a low starting dose for older adults with hypothyroidism while providing weight-based estimates for younger populations. However, rapid replacement may be appropriate with acute onset of overt hypothyroidism. Therefore, a weight-based recommendation specific to older adults is needed., Methods: We determined mean levothyroxine dose using actual and ideal body weight (IBW) ratios for the outcome of euthyroid on therapy relative to assay-specific and proposed age-specific ranges for independently living participants aged ≥65 years in the Baltimore Longitudinal Study of Aging. We examined risk factors to identify those at highest risk of overtreatment using regression analyses adjusted for potential covariables and clustering to account for multiple visits per individual., Results: One hundred eighty-five participants aged ≥65 years were on levothyroxine at 645 eligible visits. At euthyroid visits, participants were on an average dose of 1.09 μg/kg (1.35 μg/kg IBW), with 84% of euthyroid individuals on a dose of <1.6 μg/kg. Average euthyroid dose did not differ by sex using either actual body weight (ABW) or IBW. For obese individuals, mean euthyroid dose was lower if calculated using ABW (0.9 μg/kg vs 1.14 μg/kg; P < .01) but similar if calculated using IBW (1.42 vs 1.32 μg/kg IBW; P = .41) compared with those with a body mass index of <30., Conclusion: Thyroid hormone dose per body weight estimates for replacement in older adults (1.09 μg/kg ABW or 1.35 μg/kg IBW) are one-third lower than current weight-based dose recommendations for younger populations., Competing Interests: Disclosure The authors have no multiplicity of interest to disclose., (Copyright © 2023 AACE. All rights reserved.)

Context-specific research is needed on the relationship between household animal production and nutrition outcomes to inform programmes intervening in small-scale animal production. We examined associations between household animal/fishpond ownership and animal source food (ASF) consumption among 6- to 12-month-old infants enroled in the control arm of a cluster-randomised controlled trial in rural Bangladesh. We measured ASF consumption using a 7-day food frequency questionnaire at 6, 9 and 12 months and assessed household animal/fishpond ownership at 12 months. We developed negative binomial regression models with random intercepts for infant and cluster, controlling for infant age and sex, maternal age, socioeconomic status and season. Models were stratified by a dichotomised maternal decision-making score. Compared with infants in households without each animal type, those with 4-10 and ≥11 poultry consumed eggs 1.3 (95% confidence interval [CI]: 1.1, 1.6) and 1.6 (95% CI: 1.3, 2.0) times more, respectively; 2-3 and ≥4 dairy-producing animals consumed dairy 1.9 (95% CI: 1.3, 2.7) and 2.0 (95% CI: 1.3, 3.1) times more, respectively; and ≥12 meat-producing animals consumed meat 1.4 (95% CI: 1.0, 1.8) times more. It was unclear whether there was an association between fishpond ownership and fish consumption. Our results did not suggest that maternal decision-making power was a modifier in the relationship between animal/fishpond ownership and ASF consumption. In this South Asian context, strategies intervening in household animal production may increase infant consumption of eggs, dairy and meat, but not necessarily fish. Research is needed on the role of market access and other dimensions of women's empowerment., (© 2023 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Background: Eggs are nutrient-rich. Strengthening evidence of the impact of egg consumption on dietary quality can inform complementary feeding guidance., Objectives: We aimed to assess the effect of an egg intervention on dietary intakes among infants aged 6-12 mo in rural Bangladesh., Methods: We conducted a cluster-randomized controlled trial allocating clusters (n = 566) to enteric pathogen control or placebo treatment, with daily provision of a protein-rich meal, isocaloric meal, egg, or control. Nutrition education was provided to all arms. Our focus here is on the egg and control arms. Infants were enrolled at 3 mo. From 6 mo, we visited households weekly to distribute eggs and measure compliance. A semistructured feeding questionnaire assessed 24-h intake at 6, 9, and 12 mo. Assessments were repeated in ∼10% of subjects 2-29 d later. Using NCI SAS macros, we estimated usual intake distributions for energy, protein, fat, and 18 micronutrients and the proportion meeting intake recommendations. We compared the outcomes between the arms using clustered bootstrapping., Results: Data were available from 757 infants (137 clusters) and 943 infants (141 clusters) in the egg and control arms, respectively. In the egg arm compared with the control arm, the mean usual intakes were higher for energy (610 compared with 602 kcal/d, 9 mo; 669 compared with 658 kcal/d, 12 mo), crude protein (2.2 compared with 1.7 g/(kg·d), 9 mo; 2.4 compared with 1.9 g/(kg·d), 12 mo), available protein (2.0 compared with 1.6 g/(kg·d), 9 mo; 2.1 compared with 1.8 g/(kg·d), 12 mo), and for 13 and 14 micronutrients at 9 and 12 mo, respectively. The proportion meeting intake recommendations for most micronutrients was higher in the egg arm but remained <50% for 15 and 13 micronutrients at 9 and 12 mo, respectively., Conclusions: Daily egg consumption improved dietary intakes among Bangladeshi infants, but was insufficient to meet multiple micronutrient intake recommendations, demonstrating the need to be coupled with other strategies., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Continuous glucose monitors have shown great promise in improving outpatient blood glucose (BG) control; however, continuous glucose monitors are not routinely used in hospitals, and glucose management is driven by point-of-care (finger stick) and serum glucose measurements in most patients., Objective: This study aimed to evaluate times series approaches for prediction of inpatient BG using only point-of-care and serum glucose observations., Methods: Our data set included electronic health record data from 184,320 admissions, from patients who received at least one unit of subcutaneous insulin, had at least 4 BG measurements, and were discharged between January 1, 2015, and May 31, 2019, from 5 Johns Hopkins Health System hospitals. A total of 2,436,228 BG observations were included after excluding measurements obtained in quick succession, from patients who received intravenous insulin, or from critically ill patients. After exclusion criteria, 2.85% (3253/113,976), 32.5% (37,045/113,976), and 1.06% (1207/113,976) of admissions had a coded diagnosis of type 1, type 2, and other diabetes, respectively. The outcome of interest was the predicted value of the next BG measurement (mg/dL). Multiple time series predictors were created and analyzed by comparing those predictors and the index BG measurement (sample-and-hold technique) with next BG measurement. The population was classified by glycemic variability based on the coefficient of variation. To compare the performance of different time series predictors among one another, R 2 , root mean squared error, and Clarke Error Grid were calculated and compared with the next BG measurement. All these time series predictors were then used together in Cubist, linear, random forest, partial least squares, and k-nearest neighbor methods., Results: The median number of BG measurements from 113,976 admissions was 12 (IQR 5-24). The R 2 values for the sample-and-hold, 2-hour, 4-hour, 16-hour, and 24-hour moving average were 0.529, 0.504, 0.481, 0.467, and 0.459, respectively. The R 2 values for 4-hour moving average based on glycemic variability were 0.680, 0.480, 0.290, and 0.205 for low, medium, high, and very high glucose variability, respectively. The proportion of BG predictions in zone A of the Clarke Error Grid analysis was 61%, 59%, 27%, and 53% for 4-hour moving average, 24-hour moving average, 3 observation rolling regression, and recursive regression predictors, respectively. In a fully adjusted Cubist, linear, random forest, partial least squares, and k-nearest neighbor model, the R 2 values were 0.563, 0.526, 0.538, and 0.472, respectively., Conclusions: When analyzing time series predictors independently, increasing variability in a patient's BG decreased predictive accuracy. Similarly, inclusion of older BG measurements decreased predictive accuracy. These relationships become weaker as glucose variability increases. Machine learning techniques marginally augmented the performance of time series predictors for predicting a patient's next BG measurement. Further studies should determine the potential of using time series analyses for prediction of inpatient dysglycemia., (©Andrew D Zale, Mohammed S Abusamaan, John McGready, Nestoras Mathioudakis. Originally published in JMIR Formative Research (https://formative.jmir.org), 31.01.2023.)

Background: Although a finding of isolated elevated thyrotropin (TSH) often leads to treatment with thyroid hormone, it is not specific to a diagnosis of subclinical hypothyroidism, particularly in older adults. We have previously used longitudinal assessment of TSH and free thyroxine (FT4) to distinguish primary and secondary changes in the hypothalamic-pituitary-thyroid (HPT) axis, an approach which is impractical for clinical diagnosis., Objective: Identify contemporaneous clinical tests and criteria that predict the longitudinally-derived HPT axis phenotype in those with isolated elevated TSH., Methods: Using data from Baltimore Longitudinal Study of Aging, participants with over three years of follow up not on thyroid hormone replacement, with a TSH above the reference range and an in-range FT4 at the current visit, and at least 1% per year increase in TSH (mean 6.9% annual increase; n=72), we examined correlations between various clinical factors and the change in FT4 across the phenotypic range from emerging hypothyroidism, with falling FT4, to adaptive stress-response, with rising FT4., Results: Current FT4 level, but not TSH, Free T3, anti-TPO antibody status, age or sex, was significantly associated with phenotype, determined by the annual rate of change in FT4 in those with elevated and rising TSH, both as a continuous variable (β=0.07 per ng/dL increase in FT4; p<0.001) and in quartiles (p<0.001). We estimated a threshold for FT4 of less than 0.89 ng/dL (11.45 pmol/L; the 24 th percentile of the reference range), as predictive of a phenotype in the first quartile, consistent with subclinical hypothyroidism, while a FT3:FT4 ratio below 2.77 predicted a phenotype in the fourth quartile, more consistent with adaptive stress-response., Conclusions: In those with isolated elevated TSH, a FT4 in the lowest quartile of the reference range differentiates those with developing hypothyroidism from other HPT-axis aging changes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abbey, McGready, Sokoll, Simonsick and Mammen.)

Background: Inpatient glucose management can be challenging due to evolving factors that influence a patient's blood glucose (BG) throughout hospital admission. The purpose of our study was to predict the category of a patient's next BG measurement based on electronic medical record (EMR) data., Methods: EMR data from 184,361 admissions containing 4,538,418 BG measurements from five hospitals in the Johns Hopkins Health System were collected from patients who were discharged between January 1, 2015 and May 31, 2019. Index BGs used for prediction included the 5th to penultimate BG measurements ( N  = 2,740,539). The outcome was category of next BG measurement: hypoglycemic (BG  ≤  70 mg/dl), controlled (BG 71-180 mg/dl), or hyperglycemic (BG > 180 mg/dl). A random forest algorithm that included a broad range of clinical covariates predicted the outcome and was validated internally and externally., Findings: In our internal validation test set, 72·8%, 25·7%, and 1·5% of BG measurements occurring after the index BG were controlled, hyperglycemic, and hypoglycemic respectively. The sensitivity/specificity for prediction of controlled, hyperglycemic, and hypoglycemic were 0·77/0·81, 0·77/0·89, and 0·73/0·91, respectively. On external validation in four hospitals, the ranges of sensitivity/specificity for prediction of controlled, hyperglycemic, and hypoglycemic were 0·64-0·70/0·80-0·87, 0·75-0·80/0·82-0·84, and 0·76-0·78/0·87-0·90, respectively., Interpretation: A machine learning algorithm using EMR data can accurately predict the category of a hospitalized patient's next BG measurement. Further studies should determine the effectiveness of integration of this model into the EMR in reducing rates of hypoglycemia and hyperglycemia., Competing Interests: The authors declared that there is no potential conflict of interest., (© 2022 The Author(s).)

Background: Achondroplasia is the most common genetic skeletal disorder causing disproportionate short stature/dwarfism. Common additional features include spinal stenosis, midface retrusion, macrocephaly and a generalized spondylometaphyseal dysplasia which manifest as spinal cord compression, sleep disordered breathing, delayed motor skill acquisition and genu varus with musculoskeletal pain. To better understand the interactions and health outcomes of these potential complications, we embarked on a multi-center, natural history study entitled CLARITY (achondroplasia natural history study). One of the CLARITY objectives was to develop growth curves (length/height, weight, head circumference, weight-for-height) and corresponding reference tables of mean and standard deviations at 1 month increments from birth through 18 years for clinical use and research for achondroplasia patients., Methods: All available retrospective anthropometry data including length/height, weight and head circumference from achondroplasia patients were collected at 4 US skeletal dysplasia centers (Johns Hopkins University, AI DuPont Hospital for Children, McGovern Medical School University of Texas Health, University of Wisconsin School of Medicine and Public Health). Weight-for-age values beyond 3 SD above the mean were excluded from the weight-for-height and weight-for-age curves to create a stricter tool for weight assessment in this population., Results: Over 37,000 length/height, weight and head circumference measures from 1374 patients with achondroplasia from birth through 75 years of age were compiled in a REDCap database. Stature and weight data from birth through 18 years of age and head circumference from birth through 5 years of age were utilized to construct new length/height-for-age, weight-for-age, head circumference-for-age and weight-for-height curves., Conclusion: Achondroplasia-specific growth curves are essential for clinical care of growing infants and children with this condition. In an effort to provide prescriptive, rather than purely descriptive, references for weight in this population, extreme weight values were omitted from the weight-for-age and weight-for-height curves. This well-phenotyped cohort may be studied with other global achondroplasia populations (e.g. Europe, Argentina, Australia, Japan) to gain further insight into environmental or ethnic influences on growth., (© 2021. The Author(s).)

Introduction: Tracing patients lost to follow-up (LTFU) from HIV care is widely practiced, yet we have little knowledge of its causal effect on care engagement. In a prospective, Zambian cohort, we examined the effect of tracing on return to care within 2 years of LTFU., Methods: We traced a stratified, random sample of LTFU patients who had received HIV care between August 2013 and July 2015. LTFU was defined as a gap of >90 days from last scheduled appointment in the routine electronic medical record. Extracting 2 years of follow-up visit data through 2017, we identified patients who returned. Using random selection for tracing as an instrumental variable (IV), we used conditional two-stage least squares regression to estimate the local average treatment effect of tracer contact on return. We examined the observational association between tracer contact and return among patient sub-groups self-confirmed as disengaged from care., Results: Of the 24,164 LTFU patients enumerated, 4380 were randomly selected for tracing and 1158 were contacted by a tracer within a median of 14.8 months post-loss. IV analysis found that patients contacted by a tracer because they were randomized to tracing were no more likely to return than those not contacted (adjusted risk difference [aRD]: 3%, 95% CI: -2%, 8%, p = 0.23). Observational data showed that among contacted, disengaged patients, the rate of return was higher in the week following tracer contact (IR 5.74, 95% CI: 3.78-8.71) than in the 2 weeks to 1-month post-contact (IR 2.28, 95% CI: 1.40-3.72). There was a greater effect of tracing among patients lost for >6 months compared to those contacted within 3 months of loss., Conclusions: Overall, tracer contact did not causally increase LTFU patient return to HIV care, demonstrating the limited impact of tracing in this program, where contact occurred months after patients were LTFU. However, observational data suggest that tracing may speed return among some LTFU patients genuinely out-of-care. Further studies may improve tracing effectiveness by examining the mechanisms underlying the impact of tracing on return to care, the effect of tracing at different times-since-loss and using more accurate identification of patients who are truly disengaged to target tracing., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: There are no prospective studies comparing hospitalization and post-hospitalization outcomes between teaching internal medicine services and non-teaching hospitalists, and no prospective studies comparing these outcomes between locum and employed hospitalists., Objective: To compare the length of stay, hospital costs readmission rate, and mortality rate in patients treated by teaching internal medicine services vs. hospitalists and among patients treated by locum vs. employed hospitalists., Design: Prospective cohort study. Propensity score was used to obtain weighted estimates., Setting: Referral center., Patients: All patients 18 years and older admitted to internal medicine services., Intervention: Treatment by teaching internal medicine services vs. hospitalists. Treatment by locum hospitalists vs. employed hospitalists., Main Measures: Primary outcome was adjusted length of stay and secondary outcomes included hospital cost, inpatient mortality, 30-day all-cause readmission, and 30-day mortality., Key Results: A total of 1273 patients were admitted in the study period. The mean patient age was 61 ± 19 years, and the sample was 52% females. Teaching internal medicine physicians admitted 526 patients and non-teaching hospitalists admitted 747 patients. Being seen exclusively by teaching internal medicine physicians comports with a shorter adjusted hospital stay by 0.6 days (95% CI - 1.07 to - 0.22, P = .003) compared to non-teaching hospitalists. Adjusted length of stay was 1 day shorter in patients seen exclusively by locums compared to patients seen exclusively by employed services (95% CI - 1.6 to - 0.43, P < .001) with an adjusted average hospital cost saving of 1339 dollars (95% CI - 2037 to - 642, P < .001). There was no statistically significant difference in other outcomes., Conclusions: Teaching internal medicine services care was associated with a shorter stay but not with increased costs, readmission, or mortality compared to non-teaching services. In contrary to the "expected," patients treated by locums had shorter stays and decreased hospital costs but no increase in readmissions or mortality., (© 2021. Society of General Internal Medicine.)

Purpose: Achondroplasia is the most common short stature skeletal dysplasia (1:20,000-30,000), but the risk of adverse health outcomes from cardiovascular diseases, pain, poor function, excess weight, and sleep apnea is unclear. A multicenter retrospective natural history study was conducted to understand medical and surgical practices in achondroplasia., Methods: Data from patients with achondroplasia evaluated by clinical geneticists at Johns Hopkins University, A.I. duPont Hospital for Children, McGovern Medical School UTHealth, and University of Wisconsin were populated into a REDCap database. All available retrospective medical records of anthropometry (length/height, weight, occipitofrontal circumference), surgery, polysomnography (PSG), and imaging (e.g., X-ray, magnetic resonance imaging) were included., Results: Data from 1,374 patients (48.8% female; mean age 15.4 ± 13.9 years) constitute the primary achondroplasia cohort (PAC) with 496 subjects remaining clinically active and eligible for prospective studies. Within the PAC, 76.0% had a de novo FGFR3 pathologic variant and 1,094 (79.6%) had one or more achondroplasia-related surgeries. There are ≥37,000 anthropometry values, 1,631 PSGs and 10,727 imaging studies., Conclusion: This is the largest multicenter achondroplasia natural history study, providing a vast array of medical information for use in caring for these patients. This well-phenotyped cohort is a reference population against which future medical and surgical interventions can be compared., (© 2021. The Author(s).)

Background: Although elevated thyrotropin (TSH) is common in older adults, controversy exists over what degree of elevation should be treated with thyroid hormone supplements. Isolated, elevated TSH in this population can be consistent with aging-related adaptations rather than indicative of primary thyroid disease, raising the possibility that thyroid hormone replacement may be harmful., Objectives: Determine the association between all-cause mortality and levothyroxine use among older adults., Design: Longitudinal observational study., Setting: Baltimore Longitudinal Study of Aging., Participants: One thousand two hundred and fifty eight community dwelling adult participants aged 65+ with an average of 9 years of follow up., Measurements: Thyroid and pituitary hormone levels and thyroid hormone supplementation were determined at each visit. Incident rate ratios (IRR) for all-cause mortality were calculated using time-dependent Poisson regression models to accommodate the varying start times. To isolate the effects of hormone replacement from its effects on TSH, the association between treatment and all-cause mortality was analyzed in participants with stable thyroid function status throughout follow-up (N = 638)., Results: Thyroid hormone supplementation was not associated with a significant increase all-cause mortality in the subsequent year in the fully adjusted model (IRR = 1.40, 95% confidence interval (CI) = 0.93-2.12). In a stratified analysis of euthyroid participants, thyroid hormone use was associated with significantly greater mortality, with an adjusted IRR = 1.81 (95% CI = 1.10-2.98)., Conclusion: The increased mortality associated with thyroid hormone use among the subclass of euthyroid community dwelling older adults is consistent with a model in which TSH elevation can result from a variety of underlying pathophysiologic processes, not all of which should be treated with thyroid hormone supplementation. Clinicians should consider overall clinical status when interpreting an isolated elevated TSH in older adults., (© 2021 The American Geriatrics Society.)

We examined the relationship between past-year violence victimization and viral load (VL) failure among consecutively-sampled male and female adolescents and young adults, aged 15-24, in four HIV clinics in Ndola, Zambia. Measures of past-year physical violence, psychological abuse, and forced sex were adapted from the ICAST-C and WHO Multi-Country Study. Using logistic regression, we derived associations between VL failure (≥ 1000 copies/mL) and: any victimization; cumulative victimization; and types and perpetrators of violence. Among 272 youth (59.2% female, 72.8% perinatally infected), 73.5% (n = 200) experienced past-year violence and 36.8% (n = 100) had VL failure. Higher odds of VL failure were observed for participants who reported high frequency of any violence versus no violence victimization (adjusted OR, aOR: 3.58; 95% CI 1.14-11.27), high frequency of psychological abuse versus no psychological abuse (aOR: 3.32; 95% CI 1.26-8.70), any versus no violence from a family member other than a parent/caregiver for physical violence (aOR: 2.18, 95% CI 1.05-4.54) and psychological abuse (aOR: 2.50; 95% CI 1.37-4.54), and any versus no physical violence from a friend/peer (aOR: 2.14, 95% CI 1.05-4.36). Past-year violence victimization was associated with VL failure when considering the frequency, type, and perpetrator of violence. Programs addressing violence among youth living with HIV may be critical to improving viral suppression and preventing onward transmission.

Background: Dynamic movement of patients in and out of HIV care is prevalent, but there is limited information on patterns of patient re-engagement or predictors of return to guide HIV programs to better support patient engagement., Methods: From a probability-based sample of lost to follow-up, adult patients traced by peer educators from 31 Zambian health facilities, we prospectively followed disengaged HIV patients for return clinic visits. We estimated the cumulative incidence of return and the time to return using Kaplan-Meier methods. We used univariate and multivariable Cox proportional hazards regression to conduct a risk factor analysis identifying predictors of incident return across a social ecological framework., Results: Of the 556 disengaged patients, 73.0% [95% confidence interval (CI): 61.0 to 83.8] returned to HIV care. The median follow-up time from disengagement was 32.3 months (interquartile range: 23.6-38.9). The rate of return decreased with time postdisengagement. Independent predictors of incident return included a previous gap in care [adjusted Hazard Ratio (aHR): 1.95, 95% CI: 1.23 to 3.09] and confronting a stigmatizer once in the past year (aHR: 2.14, 95% CI: 1.25 to 3.65). Compared with a rural facility, patients were less likely to return if they sought care from an urban facility (aHR: 0.68, 95% CI: 0.48 to 0.96) or hospital (aHR: 0.52, 95% CI: 0.33 to 0.82)., Conclusions: Interventions are needed to hasten re-engagement in HIV care. Early and differential interventions by time since disengagement may improve intervention effectiveness. Patients in urban and tertiary care settings may need additional support. Improving patient resilience, outreach after a care gap, and community stigma reduction may facilitate return. Future re-engagement research should include causal evaluation of identified factors., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: Accurate clinical decision support tools are needed to identify patients at risk for iatrogenic hypoglycemia, a potentially serious adverse event, throughout hospitalization., Objective: To predict the risk of iatrogenic hypoglycemia within 24 hours after each blood glucose (BG) measurement during hospitalization using a machine learning model., Design, Setting, and Participants: This retrospective cohort study, conducted at 5 hospitals within the Johns Hopkins Health System, included 54 978 admissions of 35 147 inpatients who had at least 4 BG measurements and received at least 1 U of insulin during hospitalization between December 1, 2014, and July 31, 2018. Data from the largest hospital were split into a 70% training set and 30% test set. A stochastic gradient boosting machine learning model was developed using the training set and validated on internal and external validation., Exposures: A total of 43 clinical predictors of iatrogenic hypoglycemia were extracted from the electronic medical record, including demographic characteristics, diagnoses, procedures, laboratory data, medications, orders, anthropomorphometric data, and vital signs., Main Outcomes and Measures: Iatrogenic hypoglycemia was defined as a BG measurement less than or equal to 70 mg/dL occurring within the pharmacologic duration of action of administered insulin, sulfonylurea, or meglitinide., Results: This cohort study included 54 978 admissions (35 147 inpatients; median [interquartile range] age, 66.0 [56.0-75.0] years; 27 781 [50.5%] male; 30 429 [55.3%] White) from 5 hospitals. Of 1 612 425 index BG measurements, 50 354 (3.1%) were followed by iatrogenic hypoglycemia in the subsequent 24 hours. On internal validation, the model achieved a C statistic of 0.90 (95% CI, 0.89-0.90), a positive predictive value of 0.09 (95% CI, 0.08-0.09), a positive likelihood ratio of 4.67 (95% CI, 4.59-4.74), a negative predictive value of 1.00 (95% CI, 1.00-1.00), and a negative likelihood ratio of 0.22 (95% CI, 0.21-0.23). On external validation, the model achieved C statistics ranging from 0.86 to 0.88, positive predictive values ranging from 0.12 to 0.13, negative predictive values of 0.99, positive likelihood ratios ranging from 3.09 to 3.89, and negative likelihood ratios ranging from 0.23 to 0.25. Basal insulin dose, coefficient of variation of BG, and previous hypoglycemic episodes were the strongest predictors., Conclusions and Relevance: These findings suggest that iatrogenic hypoglycemia can be predicted in a short-term prediction horizon after each BG measurement during hospitalization. Further studies are needed to translate this model into a real-time informatics alert and evaluate its effectiveness in reducing the incidence of inpatient iatrogenic hypoglycemia.

Purpose: Multiparametric magnetic resonance imaging (mpMRI)-ultrasound (US) fusion prostate biopsy (FBx) has demonstrated increased accuracy for prostate cancer detection at designated centers of excellence. There is a concern if their results can be reproduced in smaller centers. Here, we evaluate the outcomes of FBx from a smaller academic center., Methods: A retrospective review of patients without a prior diagnosis of prostate cancer undergoing FBx from January 2014 to November 2019 was performed. Histopathological results were grouped into low-risk disease (Grade Group 1), intermediate-risk disease (Grade Group 2 and 3), and high-risk disease (Grade Group 4 or 5). Clinically significant (CS) prostate cancer was defined as Grade Group ≥ 2., Results: Five hundred and six men were included. Median age (IQR) and PSA (IQR) were 65.2 (60.3-70.2) years and 6.9 (5.2-9.7) ng/ml, respectively. There was no difference in overall cancer detection between FBx and SBx (53.6% vs 56.4% p  = .1507). CS cancer detection was significantly higher with FBx (39.6% vs 35.3, p  = .0275). FBx also outperformed SBx in diagnosing CS disease in patients with prior history of negative prostate biopsy (36.9% vs 27.9%, p  < .001)., Conclusion: FBx detects a higher proportion of clinically significant disease and a lower proportion of clinically insignificant disease compared to SBx, in line with outcomes demonstrated by centers of excellence.

Reproductive coercion (RC), or partner interference in reproductive decisions, limits women's autonomy. Little is known about RC behaviors and measurement in low- and middle-income countries (LMICs). In this mixed-methods study, we examined the transferability of the US-developed RC Scale to the Kenyan context. Through community-based sampling, recent intimate partner violence (IPV) survivors were recruited from Nairobi's informal settlements. We conducted quantitative analyses (n = 327) to assess the transferability of RC measures via exploratory factor analysis and used descriptive statistics to examine prevalence and continuous metrics. We conducted in-depth interviews (IDIs; n = 30) to contextualize results. Psychometric analyses indicated a two-factor solution comprising pregnancy coercion and condom manipulation (alpha = 0.86). Eighty-two percent of IPV survivors reported experiencing RC (pregnancy coercion = 76.6 percent; condom manipulation = 59.5 percent). IDIs highlighted women's multiple, severe RC experiences; experiences described in IDIs were largely consistent with quantitative findings. We found the RC Scale was transferable to this LMIC context, where IPV survivors face prevalent, severe RC and would benefit from linkage to woman-centered support services., (© 2020 The Population Council, Inc.)

Background: Little is known about violence against HIV-positive adolescents and young adults (AYA) in sub-Saharan Africa. This analysis examines experiences of violence victimization, and the perpetrators of this violence, among AYA living with HIV, aged 15-24 years, in Zambia., Methods: We analyzed baseline data from 272 AYA (60.1% female, 71.0% perinatally infected) enrolled in Project YES! (Youth Engaging for Success), a randomized controlled trial conducted in four HIV clinics in Ndola, Zambia. Violence measures were adapted from the ICAST-C and the WHO Multi-Country Study on Women's Health and Domestic Violence. Youth could report up to 12 perpetrator types for past-year experiences of violence. We estimated lifetime and past-year prevalence of physical violence, psychological abuse, and forced sex, disaggregated by sex and age group. Estimates were weighted using sex and age data from the 2013-14 Zambian Demographic and Health Survey to be representative of HIV-positive AYA in Zambia., Results: Estimated lifetime prevalence of any violence victimization was 78.2%. Past-year prevalence was 72.0% among males and 74.5% among females. Almost half of AYA (46.1%) had ever experienced polyvictimization (2+ types of violence). Psychological abuse was most common (70.4% lifetime, 65.3% past-year), followed by physical violence (50.8% lifetime, 44.7% past-year) and forced sex (10.4% lifetime, 4.7% past-year). Among past-year victims, males experienced more violence than females from a friend/peer (74.3% vs. 45.1%, p<0.001); females experienced more violence than males from a romantic partner (33.3% vs. 5.0%, p<0.001), parent/caregiver (32.4% vs. 17.6%, p = 0.02), and stranger (19.7% vs. 5.2%, p<0.001)., Conclusion: The widespread and overlapping prevalence of multiple types of violence highlights the critical need for prevention and response efforts that are tailored to youths' sex and the perpetrator type. Future research should explore violence victimization and HIV outcomes, and the measurement of psychological abuse and sexual violence, among HIV-positive AYA in the region., Competing Interests: The authors have declared that no competing interests exist.

Women in sub-Saharan Africa are disproportionately at risk for the dual epidemics of intimate partner violence (IPV) and HIV. Little is known about how specific violence profiles affect women's HIV risk, limiting effective intervention. We analysed couples' data from the Zambia Demographic and Health Survey 2013-2014 to evaluate relationships among IPV, male partner HIV status and women's HIV status. We considered the individual and combined effects of physical, sexual, emotional, and high controlling behaviour violence and accumulated violence exposure, respectively. Among partnered women, 48.9% ( n  = 2,812) experienced IPV victimisation, of whom 52.1% ( n  = 1,465) reported polyvictimisation (experiencing two or more violence types). Female HIV prevalence was 13.2%. Adjusted for demographics, HIV was significantly higher for women who experienced three (17.3%, aPR 1.33, 95%CI: 1.04-1.69, p  = 0.02) or four (22.1%, aPR 1.66, 95%CI: 1.23-2.26, p  ≤ 0.01) types versus no IPV. Violence including emotional and/or high controlling victimisation was associated with female HIV infection (aPR: 1.31, 95%CI: 1.09-1.57, p  = 0.01). Physical and/or sexual violence victimisation in the absence of other victimisation was not associated with HIV (aPR: 0.92, 95%CI:0.73-1.15, p  = 0.46). IPV and HIV interventions are incomplete without addressing emotional and controlling IPV and the role of coercive relationship dynamics in transmission risk.

Hypertension, compounded by obesity, contributes to cardiovascular disease and mortality. Data describing hypertension prevalence in adults with short stature skeletal dysplasias are lacking, perhaps due to poor fit of typical adult blood pressure cuffs on rhizomelic or contracted upper extremities. Through health screening research, blood pressure was measured in short stature adults attending support group meetings and skeletal dysplasia clinics. Blood pressure was measured with a commercially available, narrower adult cuff on the upper and/or lower segment of the arm. Height, weight, age, gender, diagnosis, exercise, and medications were collected. Subjects were classified as normotensive, prehypertensive, or hypertensive for group analysis; no individual clinical diagnoses were made. In 403 short stature adults, 42% were hypertensive (systolic >140, diastolic >90 OR taking antihypertensive medications). For every BMI unit and 1 kg weight increase in males, there was a 9% and an 8% increase, respectively, in the odds of hypertension versus normotension. In females, the increase was 10% and 6%, respectively. In those with achondroplasia, the most common short stature dysplasia, males (n = 106) had 10% greater odds of hypertension versus normotension for every BMI unit and kilogram increase. In females with achondroplasia (n = 128), the odds of hypertension versus normotension was 8% greater for each BMI unit and 7% for each additional kilogram. These data suggest a high population prevalence of hypertension among short stature adults. Blood pressure must be monitored as part of routine medical care, and measuring at the forearm may be the only viable clinical option in rhizomelic short stature adults with elbow contractures., (© 2019 Wiley Periodicals, Inc.)

Background: Lung function is complex trait with both genetic and environmental factors contributing to variation. It is unknown how geographic factors such as climate affect population respiratory health., Objective: To determine whether ambient air temperature is associated with lung function (FEV1) in the general population., Design/setting: Associations between spirometry data from two National Health and Nutrition Examination Survey (NHANES) periods representative of the U.S. non-institutionalized population and mean annual ambient temperature were assessed using survey-weighted multivariate regression., Participants/measurements: The NHANES III (1988-94) cohort included 14,088 individuals (55.6% female) and the NHANES 2007-12 cohort included 14,036 individuals (52.3% female), with mean ages of 37.4±23.4 and 34.4±21.8 years old and FEV1 percent predicted values of 99.8±15.8% and 99.2±14.5%, respectively., Results: After adjustment for confounders, warmer ambient temperatures were associated with lower lung function in both cohorts (NHANES III p = 0.020; NHANES 2007-2012 p = 0.014). The effect was similar in both cohorts with a 0.71% and 0.59% predicted FEV1 decrease for every 10°F increase in mean temperature in the NHANES III and NHANES 2007-2012 cohorts, respectively. This corresponds to ~2 percent predicted difference in FEV1 between the warmest and coldest regions in the continental United States., Conclusions: In the general U.S. population, residing in regions with warmer ambient air temperatures was associated with lower lung function with an effect size similar to that of traffic pollution. Rising temperatures associated with climate change could have effects on pulmonary function in the general population.

Background: Average thyrotropin (TSH) levels are known to be higher in older adults when measured in cross-sectional populations. Possible etiologies include differential survival, neutral aging changes, or increased disease prevalence at older ages. This study aimed to elucidate the mechanisms underlying changing thyroid function during aging, and to determine the association of changes with survival, by analyzing the individual thyroid axis over time., Methods: Individual patterns of changing TSH and free thyroxine (fT4) were determined in 640 participants in the Baltimore Longitudinal Study of Aging who had at least three measures of serum TSH and fT4, not on medications, over an average of seven years of follow-up. Participants with changing phenotypes were identified based on quintiles for both slopes. Those with alterations in primary thyroid gland function demonstrated intact negative feedback (rising TSH with declining fT4 or declining TSH with rising fT4). Other participants had a parallel rise or fall of TSH and fT4 levels, consistent with pituitary dysfunction. Predictors of phenotype were analyzed by logistic regression. Differential survival between thyroid aging phenotypes was analyzed using multivariate Cox regression., Results: While the majority of participants at all ages had stable thyroid function, changes were more common among older adults, with 32.3% of those aged >80 years but only 9.5% of those aged <60 years demonstrating thyroid function changes in the highest and lowest quintiles. Regression to the mean accounts for some of the changes, for example increased baseline TSH was associated with a falling TSH pattern (odds ratio = 1.4 [confidence interval 1.1-1.7] per 1 mIU/L). Importantly, changing thyroid function in either the upper or lower quintiles of slope for TSH and fT4 was associated with increased risk of death compared to stable thyroid status (hazard ratio = 5.4 [confidence interval 3.1-9.5])., Conclusions: Changing thyroid hormone function is increasingly common at older ages and is associated with decreased survival. Nonetheless, the tendency for abnormal thyroid function tests to resolve, along with altered pituitary responsiveness underlying some TSH elevations, suggests that an elevated TSH level should be not assumed to represent subclinical hypothyroidism in older adults. Thus, caution is appropriate when determining the need for thyroid hormone supplements in older adults.

Background: The presence of a "weekend effect" (increased mortality rate during Saturday and/or Sunday admissions) for hospitalized inpatients is uncertain., Purpose: We performed a systematic review to examine the presence of a weekend effect on hospital inpatient mortality., Data Sources: PubMed, EMBASE, SCOPUS, and Cochrane databases (January 1966-April 2013) were utilized for our search., Study Selection: We examined the mortality rate for hospital inpatients admitted during the weekend compared with those admitted during the workweek. To be included, the study had to provide discrete mortality data around the weekends (including holidays) versus weekdays, include patients who were admitted as inpatients over the weekend, and be published in English., Data Extraction: The primary outcome was all-cause weekend versus weekday mortality with subgroup analysis by personnel staffing levels, rates and times to procedures rates and delays, or illness severity., Data Synthesis: A total of 97 studies (N = 51,114,109 patients) were examined. Patients admitted on the weekends had a significantly higher overall mortality (relative risk, 1.19; 95% confidence interval, 1.14-1.23). With regard to the subgroup analyses, patients admitted on the weekends consistently had higher mortality than those admitted during the week, regardless of the levels of weekend/weekday differences in staffing, procedure rates and delays, and illness severity., Conclusions: Hospital inpatients admitted during weekends may have a higher mortality rate compared with inpatients admitted during the weekdays., (© 2017 Society of Hospital Medicine)

The height-for-age (HA) reference currently used for children with achondroplasia is not adaptable for electronic records or calculation of HA Z-scores. We report new HA curves and tables of mean and standard deviation (SD) HA, for calculating Z-scores, from birth-16 years in achondroplasia. Mixed longitudinal data were abstracted from medical records of achondroplasia patients from a single clinical practice (CIS, 1967-2004). Gender-specific height percentiles (5, 25, 50, 75, 95th) were estimated across the age continuum, using a 2 month window per time point smoothed by a quadratic smoothing algorithm. HA curves were constructed for 0-36 months and 2-16 years to optimize resolution for younger children. Mean monthly height (SD) was tabulated. These novel HA curves were compared to reference data currently in use for children with achondroplasia. 293 subjects (162 male/131 female) contributed 1,005 and 932 height measures, with greater data paucity with age. Mean HA tracked with original achondroplasia norms, particularly through mid-childhood (2-9 years), but with no evidence of a pubertal growth spurt. Standard deviation of height at each month interval increased from birth through 16 years. Birth length was lower in achondroplasia than average stature and, as expected, height deficits increased with age. A new HA reference is available for longitudinal growth assessment in achondroplasia, taking advantage of statistical modeling techniques and allowing for Z-score calculations. This is an important contribution to clinical care and research endeavors for the achondroplasia population., (© 2017 Wiley Periodicals, Inc.)

Rationale: Expanding the use of cystic fibrosis transmembrane conductance regulator (CFTR) potentiators and correctors for the treatment of cystic fibrosis (CF) requires precise and accurate biomarkers. Sweat chloride concentration provides an in vivo assessment of CFTR function, but it is unknown the degree to which CFTR mutations account for sweat chloride variation., Objectives: To estimate potential sources of variation for sweat chloride measurements, including demographic factors, testing variability, recording biases, and CFTR genotype itself., Methods: A total of 2,639 sweat chloride measurements were obtained in 1,761 twins/siblings from the CF Twin-Sibling Study, French CF Modifier Gene Study, and Canadian Consortium for Genetic Studies. Variance component estimation was performed by nested mixed modeling., Measurements and Main Results: Across the tested CF population as a whole, CFTR gene mutations were found to be the primary determinant of sweat chloride variability (56.1% of variation) with contributions from variation over time (e.g., factors related to testing on different days; 13.8%), environmental factors (e.g., climate, family diet; 13.5%), other residual factors (e.g., test variability; 9.9%), and unique individual factors (e.g., modifier genes, unique exposures; 6.8%) (likelihood ratio test, P < 0.001). Twin analysis suggested that modifier genes did not play a significant role because the heritability estimate was negligible (H 2  = 0; 95% confidence interval, 0.0-0.35). For an individual with CF, variation in sweat chloride was primarily caused by variation over time (58.1%) with the remainder attributable to residual/random factors (41.9%)., Conclusions: Variation in the CFTR gene is the predominant cause of sweat chloride variation; most of the non-CFTR variation is caused by testing variability and unique environmental factors. If test precision and accuracy can be improved, sweat chloride measurement could be a valuable biomarker for assessing response to therapies directed at mutant CFTR.

Recent biomedical workforce policy efforts have centered on enhancing career preparation for trainees, and increasing diversity in the research workforce. Postdoctoral scientists, or postdocs, are among those most directly impacted by such initiatives, yet their career development remains understudied. This study reports results from a 2012 national survey of 1002 American biomedical postdocs. On average, postdocs reported increased knowledge about career options but lower clarity about their career goals relative to PhD entry. The majority of postdocs were offered structured career development at their postdoctoral institutions, but less than one-third received this from their graduate departments. Postdocs from all social backgrounds reported significant declines in interest in faculty careers at research-intensive universities and increased interest in nonresearch careers; however, there were differences in the magnitude and period of training during which these changes occurred across gender and race/ethnicity. Group differences in interest in faculty careers were explained by career interest differences formed during graduate school but not by differences in research productivity, research self-efficacy, or advisor relationships. These findings point to the need for enhanced career development earlier in the training process, and interventions sensitive to distinctive patterns of interest development across social identity groups., (© 2015 K. D. Gibbs et al. CBE—Life Sciences Education © 2015 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)

Background: Allergen skin prick testing remains an essential tool for diagnosing atopic disease and guiding treatment. Sensitivity needs to be defined for newly introduced devices., Objective: Our aim was to compare the performance of 10 current allergy skin prick test devices., Methods: Single- and multiheaded skin test devices (n = 10) were applied by a single operator in a prospective randomized manner. Histamine (1 and 6 mg/mL) and control diluent were introduced at 6 randomized locations onto the upper and lower arms of healthy subjects. Wheal and flare reactions were measured independently by 2 masked technicians., Results: Twenty-four subjects provided consent, and 768 skin tests were placed. Mean wheal diameter among devices differed from 3.0 mm (ComforTen; Hollister-Stier, Spokane, Wash) to 6.8 mm (UniTest PC; Lincoln Diagnostics, Decatur, Ill) using 1 mg/mL histamine (P < .001) and 4.8 mm (GREER Pick; Greer, Lenoir, NC) to 8.4 mm (Duotip-Test II; Lincoln Diagnostics, Decatur, Ill; and Sharp-Test; Panatrex, Placentia, Calif) using 6 mg/mL histamine (P < .001). The false-negative rates ranged from 0% to 45% with 1 mg/mL histamine. The analytical specificity was 100% for all devices tested. All devices were well tolerated, with average pain score of less than 4 on a 10-point visual analog scale. Pain scores were higher among women, but this did not reach statistical significance. The Multi-Test PC and the UniTest PC had the lowest pain scores compared with the other devices., Conclusions: All 10 skin prick test devices displayed good analytical sensitivity and specificity; however, 3 mm cannot arbitrarily be used as a positive threshold. The use of histamine at 1 mg/mL is unacceptable for certain devices but may be preferable for the most sensitive devices. On average, there was no pain score difference between multiheaded and single-head devices., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Both endogenous and exogenous thyrotoxicosis has been associated with atrial fibrillation and low bone mineral density. Therefore, this study investigated the risk factors associated with prevalent and incident thyrotoxicosis and the initiation of thyroid hormone therapy in a healthy, aging cohort., Methods: A total of 1450 ambulatory community volunteer participants in the Baltimore Longitudinal Study of Aging examined at the NIA Clinical Research Unit in Baltimore, MD, have undergone longitudinal monitoring of serum thyrotropin (TSH) and thyroid hormone (free thyroxine and free triiodothryonine) levels as well as medication use every one to four years, depending on age, between 2003 and 2014., Results: The prevalence of low TSH was 9.6% for participants on thyroid hormone and 0.8% for nontreated individuals (p < 0.001). New cases occurred at a rate of 17.7/1000 person-years of exposure to thyroid hormone therapy [CI 9-32/1000] and 1.5/1000 person-years in the unexposed population [CI 0.7-2.9/1000]. Women were more likely to be treated and more often overtreated than men were. The adjusted hazard ratio (HR) for thyrotoxicosis between treated and untreated women was 27.5 ([CI 7.2-105.4]; p < 0.001) and 3.8 for men ([CI 1.2-6.3]; p < 0.01). White race/ethnicity and older age were risk factors for thyroid hormone therapy but not overtreatment. Body mass index was not associated with starting therapy (HR = 1.0). Thyroid hormone initiation was highest among women older than 80 years of age (3/100 person-years). For one-third of treated participants with follow-up data, overtreatment persisted at least two years., Conclusions: Iatrogenic thyrotoxicosis accounts for approximately half of both prevalent and incident low TSH events in this community-based cohort, with the highest rates among older women, who are vulnerable to atrial fibrillation and osteoporosis. Physicians should be particularly cautious in treating subclinical hypothyroidism in elderly women in light of recent studies demonstrating no increased risk of cardiovascular morbidity or death for individuals with elevated TSH levels <10 mIU/L.

Background: Impairments of sensation, strength, and walking are common in multiple sclerosis (MS). The relationship among these abnormalities and how they change over time remains unclear., Objective: To determine the extent that quantitative lower extremity sensory and motor measures detect abnormalities over time, relate to global disability, and to walking speed in individuals with MS., Methods: This prospective, longitudinal analysis evaluated 136 MS subjects. Measures included measures of leg strength, sensation, the Expanded Disability Status Scale(EDSS) and timed 25-foot walk test (T25FW). Mixed effects regression models were used., Results: Our cohort׳s mean age is 44.3±10.8 years (mean±SD), EDSS score range 0–7.5, 66% were females, and follow-up time was 2.1±1.2 years. Strength significantly changed over time; the RRMS group demonstrated the greatest changes in ADF (3.3 lbs/yr) while the PPMS group showed significant HF changes (−2.1 lbs/yr). Walking speed was affected most by HF, especially in the weakest individuals (HF<20 lbs); T25FW increased by 0.20 s for each 1 lb loss (p=0.001). Likewise T25FW changed by 0.19 s for each 1 lb change in ADF (p<0.01)., Conclusion: Quantitative measures detected changes in sensation and strength over time, despite a stable respective functional systems scores of the EDSS. Quantitative measurement tools may improve the sensitivity of disability measures in MS and further investigation of these tools as outcomes in future clinical trials of rehabilitative and neuroreparative interventions is warranted.

Increasing biomedical workforce diversity remains a persistent challenge. Recent reports have shown that biomedical sciences (BMS) graduate students become less interested in faculty careers as training progresses; however, it is unclear whether or how the career preferences of women and underrepresented minority (URM) scientists change in manners distinct from their better-represented peers. We report results from a survey of 1500 recent American BMS Ph.D. graduates (including 276 URMs) that examined career preferences over the course of their graduate training experiences. On average, scientists from all social backgrounds showed significantly decreased interest in faculty careers at research universities, and significantly increased interest in non-research careers at Ph.D. completion relative to entry. However, group differences emerged in overall levels of interest (at Ph.D. entry and completion), and the magnitude of change in interest in these careers. Multiple logistic regression showed that when controlling for career pathway interest at Ph.D. entry, first-author publication rate, faculty support, research self-efficacy, and graduate training experiences, differences in career pathway interest between social identity groups persisted. All groups were less likely than men from well-represented (WR) racial/ethnic backgrounds to report high interest in faculty careers at research-intensive universities (URM men: OR 0.60, 95% CI: 0.36-0.98, p = 0.04; WR women: OR: 0.64, 95% CI: 0.47-0.89, p = 0.008; URM women: OR: 0.46, 95% CI: 0.30-0.71, p<0.001), and URM women were more likely than all other groups to report high interest in non-research careers (OR: 1.93, 95% CI: 1.28-2.90, p = 0.002). The persistence of disparities in the career interests of Ph.D. recipients suggests that a supply-side (or "pipeline") framing of biomedical workforce diversity challenges may limit the effectiveness of efforts to attract and retain the best and most diverse workforce. We propose incorporation of an ecological perspective of career development when considering strategies to enhance the biomedical workforce and professoriate through diversity.

Objective: To examine biomarkers of methylmercury (MeHg) intake in women and infants from seafood-consuming populations globally and characterize the comparative risk of fetal developmental neurotoxicity., Methods: A search was conducted of the published literature reporting total mercury (Hg) in hair and blood in women and infants. These biomarkers are validated proxy measures of MeHg, a neurotoxin found primarily in seafood. Average and high-end biomarkers were extracted, stratified by seafood consumption context, and pooled by category. Medians for average and high-end pooled distributions were compared with the reference level established by a joint expert committee of the Food and Agriculture Organization (FAO) and the World Health Organization (WHO)., Findings: Selection criteria were met by 164 studies of women and infants from 43 countries. Pooled average biomarkers suggest an intake of MeHg several times over the FAO/WHO reference in fish-consuming riparians living near small-scale gold mining and well over the reference in consumers of marine mammals in Arctic regions. In coastal regions of south-eastern Asia, the western Pacific and the Mediterranean, average biomarkers approach the reference. Although the two former groups have a higher risk of neurotoxicity than the latter, coastal regions are home to the largest number at risk. High-end biomarkers across all categories indicate MeHg intake is in excess of the reference value., Conclusion: There is a need for policies to reduce Hg exposure among women and infants and for surveillance in high-risk populations, the majority of which live in low-and middle-income countries.

Objective: MQX-503 is a novel nitroglycerine preparation designed to absorb quickly and allow local vasodilatation in the skin. We examined the efficacy and tolerability of this medication in Raynaud phenomenon (RP) in a laboratory-based study., Methods: In this multi-centre, double-blind, randomised, placebo-controlled, cross-over study, subjects were treated with 0.5% or 1.25% nitroglycerine or placebo gel. Subjects received each dose twice in a randomised order. Each study session consisted of baseline laser Doppler measurements, study gel application and 5 min of cold chamber exposure (-20°C). Blood flow (BF) was measured at the end of exposure and for the next 120 min at set intervals. Other outcome measures included achievement of baseline BF; the time to achieve 50% and 70% baseline skin temperature (ST); and pain, tingling and numbness scores., Results: 37 subjects completed 214 treatment periods. Time to achieve baseline BF was significantly shorter in the two treated groups (HR=1.77 and 2.02 for 0.5% and 1.25% vs placebo, respectively). The proportion of subjects achieving baseline BF was 45.8% for placebo, 66.2% for 0.5% and 69% for 1.25% (p=0.01 and p=0.002 for 0.5% and 1.25% vs placebo, respectively). No meaningful differences were seen in ST or pain/numbness/tingling scores. Treatment was well tolerated with no serious adverse events., Conclusions: Treatment with MQX-503 caused a significant improvement in skin BF compared with placebo. Data from this proof of concept study suggest benefit of MQX-503 in subjects with RP.

Objective: To develop a quasi-experimental method for estimating Population Health Management (PHM) program savings that mitigates common sources of confounding, supports regular updates for continued program monitoring, and estimates model precision., Data Sources: Administrative, program, and claims records from January 2005 through June 2009., Data Collection/extraction Methods: Data are aggregated by member and month., Study Design: Study participants include chronically ill adult commercial health plan members. The intervention group consists of members currently enrolled in PHM, stratified by intensity level. Comparison groups include (1) members never enrolled, and (2) PHM participants not currently enrolled. Mixed model smoothing is employed to regress monthly medical costs on time (in months), a history of PHM enrollment, and monthly program enrollment by intensity level. Comparison group trends are used to estimate expected costs for intervention members. Savings are realized when PHM participants' costs are lower than expected., Principal Findings: This method mitigates many of the limitations faced using traditional pre-post models for estimating PHM savings in an observational setting, supports replication for ongoing monitoring, and performs basic statistical inference., Conclusion: This method provides payers with a confident basis for making investment decisions., (© Health Research and Educational Trust.)

Purpose: To determine the extent that auditory force feedback (AFF) substitution improves performance during a simulated ophthalmic peeling procedure., Methods: A 25-gauge force-sensing microforceps was linked to two AFF modes. The "alarm" AFF mode sounded when the force reached 9 mN. The "warning" AFF mode made beeps with a frequency proportional to the generated force. Participants with different surgical experience levels were asked to peel a series of bandage strips off a platform as quickly as possible without exceeding 9 mN of force. In study arm A, participants peeled with alarm and warning AFF modes, the order randomized within the experience level. In study arm B, participants first peeled without AFF, then alarm or warning AFF (order randomized within the experience level), and finally without AFF., Results: Of the 28 "surgeon" participants, AFF improved membrane peeling performance, reducing average force generated (P < 0.01), SD of forces (P < 0.05), and force × time above 9 mN (P < 0.01). Short training periods with AFF improved subsequent peeling performance when AFF was turned off, with reductions in average force, SD of force, maximum force, time spent above 9 mN, and force × time above 9 mN (all P < 0.001). Except for maximum force, peeling with AFF reduced all force parameters (P < 0.05) more than peeling without AFF after completing a training session., Conclusions: AFF enables the surgeon to reduce the forces generated with improved precision during phantom membrane peeling, regardless of surgical experience. New force-sensing surgical tools combined with AFF offer the potential to enhance surgical training and improve surgical performance.

Objective: To compare student outcomes between concurrent online and on-campus sections of an introductory biostatistics course offered at a United States school of public health in 2005., Methods: Enrolled students (95 online, 92 on-campus) were invited to participate in a confidential online survey. The course outcomes were compared between the two sections adjusting for differences in student characteristics., Results: Seventy-two online (76%) and 66 (72%) on-campus enrollees participated. Unadjusted final exam scores for the online and on-campus sections were respectively 85.1 and 86.3 (p=0.50) in term 1, and 87.8 and 86.8 (p=0.51) in term 2. After adjustment for student characteristics, the average difference in scores between the two sections was -1.5 (95% CI: -5.4, 2.5) in term 1, and 0.8 (95% CI: -2.7, 4.3) in term 2., Conclusions: The results demonstrate that online and on-campus course formats of an introductory biostatistics course in a graduate school of public health can achieve similar student outcomes., (Copyright © 2012 Elsevier Inc. All rights reserved.)