Prediction of Obliteration After the Gamma Knife Radiosurgery of Arteriovenous Malformations Using Hand-Crafted Radiomics and Deep-Learning Methods.

INTRODUCTION: Brain arteriovenous malformations (bAVMs) are vascular abnormalities that can be treated with embolization or radiotherapy to prevent the risk of future rupture. In this study, we use hand-crafted radiomics and deep learning techniques to predict favorable vs. unfavorable outcomes following Gamma Knife radiosurgery (GKRS) of bAVMs and compare their prediction performances. METHODS: One hundred twenty-six patients seen at one academic medical center for GKRS obliteration of bAVMs over 15 years were retrospectively reviewed. Forty-two patients met the inclusion criteria. Favorable outcomes were defined as complete nidus obliteration demonstrated on cerebral angiogram and asymptomatic recovery. Unfavorable outcomes were defined as incomplete obliteration or complications relating to the AVM that developed after GKRS. Outcome predictions were made using a random forest model with hand-crafted radiomic features and a fine-tuned ResNet-34 convolutional neural network (CNN) model. The performance was evaluated by using a ten-fold cross-validation technique. RESULTS: The average accuracy and area-under-curve (AUC) values of the Random Forest Classifier (RFC) with radiomics features were 68.5 ±9.80% and 0.705 ±0.086, whereas those of the ResNet-34 model were 60.0 ±11.9% and 0.694 ±0.124. Four radiomics features used with RFC discriminated unfavorable response cases from favorable response cases with statistical significance. When cropped images were used with ResNet-34, the accuracy and AUC decreased to 59.3 ± 14.2% and 55.4 ±10.4%, respectively. CONCLUSIONS: A hand-crafted radiomics model and a pre-trained CNN model can be fine-tuned on pre-treatment MRI scans to predict clinical outcomes of AVM patients undergoing GKRS with equivalent prediction performance. The outcome predictions are promising but require further external validation on more patients.

Determining Herd Immunity Thresholds for Hepatitis A Virus Transmission to Inform Vaccination Strategies Among People Who Inject Drugs in 16†US States.

BACKGROUND: Widespread outbreaks of person-to-person transmitted hepatitis A virus (HAV), particularly among people who inject drugs (PWID), continue across the United States and globally. However, the herd immunity threshold and vaccination coverage required to prevent outbreaks are unknown. We used surveillance data and dynamic modeling to estimate herd immunity thresholds among PWID in 16 US states. METHODS: We used a previously published dynamic model of HAV transmission calibrated to surveillance data from outbreaks involving PWID in 16 states. Using state-level calibrated models, we estimated the basic reproduction number (R0) and herd immunity threshold for PWID in each state. We performed a meta-analysis of herd immunity thresholds to determine the critical vaccination coverage required to prevent most HAV outbreaks among PWID. RESULTS: Estimates of R0 for HAV infection ranged from 2.2 (95% confidence interval [CI], 1.9-2.5) for North Carolina to 5.0 (95% CI, 4.5-5.6) for West Virginia. Corresponding herd immunity thresholds ranged from 55% (95% CI, 47%-61%) for North Carolina to 80% (95% CI, 78%-82%) for West Virginia. Based on the meta-analysis, we estimated a pooled herd immunity threshold of 64% (95% CI, 61%-68%; 90% prediction interval, 52%-76%) among PWID. Using the prediction interval upper bound (76%) and assuming 95% vaccine efficacy, we estimated that vaccination coverage of 80% could prevent most HAV outbreaks. CONCLUSIONS: Hepatitis A vaccination programs in the United States may need to achieve vaccination coverage of at least 80% among PWID in order to prevent most HAV outbreaks among this population.

Pharmacologic and Nonpharmacologic Treatment Modalities for Bone Loss in SCI - Proposal for Combined Approach.

Increased risk of bone fracture due to bone mineral density (BMD) loss is a serious consequence of spinal cord injury (SCI). Traditionally, pharmaceutical approaches, such as bisphosphonates, have been prescribed to prevent bone loss. However, there is controversy in the literature regarding efficacy of these medications to mitigate the drastic bone loss following SCI. Individuals with SCI are particularly at risk of osteoporosis because of the lack of ambulation and weight bearing activities. In the past two decades, functional electric stimulation (FES) has allowed for another approach to treat bone loss. FES approaches are expanding into various modalities such as cycling and rowing exercises and show promising outcomes with minimal consequences. In addition, these non-pharmacological treatments can elevate overall physical and mental health. This article provides an overview of efficacy of different treatment options for BMD loss for SCI and advocates for a combined approach be pursued in standard of care.

Effect of imbalanced sampling and missing data on associations between gender norms and risk of adolescent HIV.

Background: Despite strides towards gender equality, inequalities persist or remain unstudied, due potentially to data gaps. Although mapped, the effects of key data gaps remain unknown. This study provides a framework to measure effects of gender- and age-imbalanced and missing covariate data on gender-health research. The framework is demonstrated using a previously studied pathway for effects of pre-marital sex norms among adults on adolescent HIV risk. Methods: After identifying gender-age-imbalanced Demographic and Health Survey (DHS) datasets, we resampled responses and restricted covariate data from a relatively complete, balanced dataset derived from the 2007 Zambian DHS to replicate imbalanced gender-age sampling and covariate missingness. Differences in model outcomes due to sampling were measured using tests for interaction. Missing covariate effects were measured by comparing fully-adjusted and reduced model fitness. Findings: We simulated data from 25 DHS surveys across 20 countries from 2005-2014 on four sex-stratified models for pathways of adult attitude-behaviour discordance regarding pre-marital sex and adolescent risk of HIV. On average, across gender-age-imbalanced surveys, males comprised 29.6% of responses compared to 45.3% in the gender-balanced dataset. Gender-age-imbalanced sampling significantly affected regression coefficients in 40% of model-scenarios (N = 40 of 100) and biased relative-risk estimates away from gender-age-balanced sampling outcomes in 46% (N = 46) of model-scenarios. Model fitness was robust to covariate removal with minor effects on male HIV models. No consistent trends were observed between sampling distribution and risk of biased outcomes. Interpretation: Gender-health model outcomes may be affected by sampling gender-age-imbalanced data and less-so by missing covariates. Although occasionally attenuated, the effect magnitude of gender-age-imbalanced sampling is variable and may mask true associations, thus misinforming policy dialogue. We recommend future surveys improve balanced gender-age sampling to promote research reliability. Funding: Bill & Melinda Gates Foundation grant OPP1140262 to Stanford University.

Gender-related data missingness, imbalance and bias in global health surveys.

Global surveys have built-in gender-related biases associated with data missingness across the gender dimensions of people's lives, imbalanced or incomplete representation of population groups, and biased ways in which gender information is elicited and used. While increasing focus is being placed on the integration of sex-disaggregated statistics into national programmes and on understanding effects of gender-based disparities on the health of all people, the data necessary for elucidating underlying causes of gender disparities and designing effective intervention programmes continue to be lacking. Approaches exist, however, that can reasonably address some shortcomings, such as separating questions of gender identification from biological sex. Qualitative research can elucidate ways to rephrase questions and translate gendered terms to avoid perpetuating historical gender biases and prompting biased responses. Non-health disciplines may offer lessons in collecting gender-related data. Ultimately, multidisciplinary global collaborations are needed to advance this evolving field and to set standards for how we measure gender in all its forms.

COVID-19 antibody seroprevalence in Santa Clara County, California.

BACKGROUND: Measuring the seroprevalence of antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is central to understanding infection risk and fatality rates. We studied Coronavirus Disease 2019 (COVID-19)-antibody seroprevalence in a community sample drawn from Santa Clara County. METHODS: On 3 and 4 April 2020, we tested 3328 county residents for immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to SARS-CoV-2 using a rapid lateral-flow assay (Premier Biotech). Participants were recruited using advertisements that were targeted to reach county residents that matched the county population by gender, race/ethnicity and zip code of residence. We estimate weights to match our sample to the county by zip, age, sex and race/ethnicity. We report the weighted and unweighted prevalence of antibodies to SARS-CoV-2. We adjust for test-performance characteristics by combining data from 18 independent test-kit assessments: 14 for specificity and 4 for sensitivity. RESULTS: The raw prevalence of antibodies in our sample was 1.5% [exact binomial 95% confidence interval (CI) 1.1-2.0%]. Test-performance specificity in our data was 99.5% (95% CI 99.2-99.7%) and sensitivity was 82.8% (95% CI 76.0-88.4%). The unweighted prevalence adjusted for test-performance characteristics was 1.2% (95% CI 0.7-1.8%). After weighting for population demographics, the prevalence was 2.8% (95% CI 1.3-4.2%), using bootstrap to estimate confidence bounds. These prevalence point estimates imply that 53 000 [95% CI 26 000 to 82 000 using weighted prevalence; 23 000 (95% CI 14 000-35 000) using unweighted prevalence] people were infected in Santa Clara County by late March-many more than the ∼1200 confirmed cases at the time. CONCLUSION: The estimated prevalence of SARS-CoV-2 antibodies in Santa Clara County implies that COVID-19 was likely more widespread than indicated by the number of cases in late March, 2020. At the time, low-burden contexts such as Santa Clara County were far from herd-immunity thresholds.

Comparison of World Health Organization and Demographic and Health Surveys data to estimate sub-national deworming coverage in pre-school aged children.

BACKGROUND: The key metric for monitoring the progress of deworming programs in controlling soil-transmitted helminthiasis (STH) is national drug coverage reported to the World Health Organization (WHO). There is increased interest in utilizing geographically-disaggregated data to estimate sub-national deworming coverage and equity, as well as gender parity. The Demographic and Health Surveys (DHS) offer a potential source of sub-national data. This study aimed to compare deworming coverage routinely reported to WHO and estimated by DHS in pre-school aged children to inform global STH measurement and evaluation. METHODOLOGY: We compared sub-national deworming coverage in pre-school aged children reported to WHO and estimated by DHS aligned geospatially and temporally. We included data from Burundi (2016-2017), Myanmar (2015-2016), and the Philippines (2017) based on data availability. WHO provided data on the date and sub-national coverage per mass drug administration reported by Ministries of Health. DHS included maternally-reported deworming status within the past 6 months for each child surveyed. We estimated differences in sub-national deworming coverage using WHO and DHS data, and performed sensitivity analyses. PRINCIPAL FINDINGS: We compared data on pre-school aged children from 13 of 18 districts in Burundi (N = 6,835 in DHS), 11 of 15 districts in Myanmar (N = 1,462 in DHS) and 16 of 17 districts in the Philippines (N = 7,594 in DHS) following data exclusion. The national deworming coverages estimated by DHS in Burundi, Myanmar, and the Philippines were 75.5% (95% CI: 73.7%-77.7%), 47.0% (95% CI: 42.7%-51.3%), and 48.0% (95% CI: 46.0%-50.0%), respectively. The national deworming coverages reported by WHO in Burundi, Myanmar, and the Philippines were 80.1%, 93.6% and 75.7%, respectively. The mean absolute differences in district-level coverage reported to WHO and estimated by DHS in Burundi, Myanmar, and the Philippines were 9.5%, 41.5%, and 24.6%, respectively. Across countries, coverage reported to WHO was frequently higher than DHS estimates (32 of 40 districts). National deworming coverage from DHS estimates were similar by gender within countries. CONCLUSIONS AND SIGNIFICANCE: Agreement of deworming coverage reported to WHO and estimated by DHS data was heterogeneous across countries, varying from broadly compatible in Burundi to largely discrepant in Myanmar. DHS data could complement deworming data reported to WHO to improve data monitoring practices and serve as an independent sub-national source of coverage data.

Health and Economic Outcomes of Posterior Spinal Fusion for Children With Neuromuscular Scoliosis.

OBJECTIVES: Neuromuscular scoliosis (NMS) can result in severe disability. Nonoperative management minimally slows scoliosis progression, but operative management with posterior spinal fusion (PSF) carries high risks of morbidity and mortality. In this study, we compare health and economic outcomes of PSF to nonoperative management for children with NMS to identify opportunities to improve care. METHODS: We performed a cost-effectiveness analysis. Our decision analytic model included patients aged 5 to 20 years with NMS and a Cobb angle ≥50°, with a base case of 15-year-old patients. We estimated costs, life expectancy, quality-adjusted life-years (QALYs), and incremental cost-effectiveness from published literature and conducted sensitivity analyses on all model inputs. RESULTS: We estimated that PSF resulted in modestly decreased discounted life expectancy (10.8 years) but longer quality-adjusted life expectancy (4.84 QALYs) than nonoperative management (11.2 years; 3.21 QALYs). PSF costs $75 400 per patient. Under base-case assumptions, PSF costs $50 100 per QALY gained. Our findings were sensitive to quality of life (QoL) and life expectancy, with PSF favored if it significantly increased QoL. CONCLUSIONS: In patients with NMS, whether PSF is cost-effective depends strongly on the degree to which QoL improved, with larger improvements when NMS is the primary cause of debility, but limited data on QoL and life expectancy preclude a definitive assessment. Improved patient-centered outcome assessments are essential to understanding the effectiveness of NMS treatment alternatives. Because the degree to which PSF influences QoL substantially impacts health outcomes and varies by patient, clinicians should consider shared decision-making during PSF-related consultations.

Gender norms and health: insights from global survey data.

Despite global commitments to achieving gender equality and improving health and wellbeing for all, quantitative data and methods to precisely estimate the effect of gender norms on health inequities are underdeveloped. Nonetheless, existing global, national, and subnational data provide some key opportunities for testing associations between gender norms and health. Using innovative approaches to analysing proxies for gender norms, we generated evidence that gender norms impact the health of women and men across life stages, health sectors, and world regions. Six case studies showed that: (1) gender norms are complex and can intersect with other social factors to impact health over the life course; (2) early gender-normative influences by parents and peers can have multiple and differing health consequences for girls and boys; (3) non-conformity with, and transgression of, gender norms can be harmful to health, particularly when they trigger negative sanctions; and (4) the impact of gender norms on health can be context-specific, demanding care when designing effective gender-transformative health policies and programmes. Limitations of survey-based data are described that resulted in missed opportunities for investigating certain populations and domains. Recommendations for optimising and advancing research on the health impacts of gender norms are made.

Comparison of Strategies and Incidence Thresholds for Vi Conjugate Vaccines Against Typhoid Fever: A Cost-effectiveness Modeling Study.

Background: Typhoid fever remains a major public health problem globally. While new Vi conjugate vaccines hold promise for averting disease, the optimal programmatic delivery remains unclear. We aimed to identify the strategies and associated epidemiologic conditions under which Vi conjugate vaccines would be cost-effective. Methods: We developed a dynamic, age-structured transmission and cost-effectiveness model that simulated multiple vaccination strategies with a typhoid Vi conjugate vaccine from a societal perspective. We simulated 10-year vaccination programs with (1) routine immunization of infants (aged <1 year) through the Expanded Program on Immunization (EPI) and (2) routine immunization of infants through the EPI plus a 1-time catch-up campaign in school-aged children (aged 5-14 years). In the base case analysis, we assumed a 0.5% case-fatality rate for all cases of clinically symptomatic typhoid fever and defined strategies as highly cost-effective by using the definition of a low-income country (defined as a country with a gross domestic product of $1045 per capita). We defined incidence as the true number of clinically symptomatic people in the population per year. Results: Vi conjugate typhoid vaccines were highly cost-effective when administered by routine immunization activities through the EPI in settings with an annual incidence of >50 cases/100000 (95% uncertainty interval, 40-75 cases) and when administered through the EPI plus a catch-up campaign in settings with an annual incidence of >130 cases/100000 (95% uncertainty interval, 50-395 cases). The incidence threshold was sensitive to the typhoid-related case-fatality rate, carrier contribution to transmission, vaccine characteristics, and country-specific economic threshold for cost-effectiveness. Conclusions: Typhoid Vi conjugate vaccines would be highly cost-effective in low-income countries in settings of moderate typhoid incidence (50 cases/100000 annually). These results were sensitive to case-fatality rates, underscoring the need to consider factors contributing to typhoid mortality (eg, healthcare access and antimicrobial resistance) in the global vaccination strategy.

Variations in label information and nicotine levels in electronic cigarette refill liquids in South Korea: regulation challenges.

BACKGROUND: In South Korea, the consumption of liquid nicotine used in electronic cigarettes has dramatically increased from 4310 L in 2012 to 7220 L in 2013. This study aimed to examine the level of heterogeneity of contents of the labels and discrepancy of the nicotine content between that indicated on the label and the actual values for electronic cigarette liquid refill products in South Korea. METHODS: We purchased 32 electronic cigarette liquid refill products (17 Korean domestic, 15 imported ones) and one pure nicotine product at six different electronic cigarette retail stores in Seoul between May and June 2014. The actual nicotine concentrations of each product were measured by a blinded analyst at Roswell Park Cancer Institute, Buffalo, NY, USA. RESULTS: Three out of 15 imported liquid refill products provided manufacturing dates, while expiration dates were available on eight products. The range of nicotine concentration was from "not detected" to 17.5 mg/mL. Labeling discrepancies of the concentrations ranged from -32.2% to 3.3% among electronic cigarette liquid refill products. The highest concentration (150.3 ± 7.9 mg/mL) was found in a sample labeled as "pure nicotine". CONCLUSIONS: There is no standardization of labelling among electronic cigarette liquids sampled from retail stores and the labels did not accurately reflect the content. One product labeled "pure nicotine" raises concerns, since it may be poisonous to consumers, especially to children. This study revealed the urgent need for the development of product regulations in South Korea.

Nicotine levels in electronic cigarette refill solutions: A comparative analysis of products from the U.S., Korea, and Poland.

BACKGROUND: Electronic cigarettes vaporize nicotine dissolved in glycerine and/or propylene glycol (e-liquid). Due to a lack of regulations, e-liquids may contain inaccurately labelled nicotine levels. Our aim was to test nicotine levels in samples of e-liquids from three countries. METHODS: We measured nicotine concentration in 32, 29 and 30 e-liquids purchased between 2013 and 2014 from locations in the United States (US), South Korea, and Poland, respectively. RESULTS: Nicotine concentration in the US products varied from 0 to 36.6 mg/mL. Traces of nicotine were found in three US products labelled as 'nicotine free'. Two-thirds of South Korean products did not contain detectable amounts of nicotine, whereas nicotine concentration in other products varied from 6.4±0.7 to 150.3±7.9 (labelled as 'pure nicotine') mg/mL. In products from Poland, nicotine concentration varied from 0 to 24.7±0.1 mg/mL. Overall, we found significant discrepancies (>20%) in the labelled nicotine concentrations in 19% of analysed e-liquids. CONCLUSION: Most of the analysed samples had no significant discrepancies in labelled nicotine concentrations and contained low nicotine levels. However some products labelled as 'nicotine-free' had detectable levels of the substance, suggesting insufficient manufacturing quality control. We identified a single product labelled as 'pure nicotine' which contained significantly higher concentration of the drug, increasing the risk of accidental poisoning. The study reveals the need for quality standards of these new nicotine containing products.