Childhood and adolescent factors shaping vulnerability to underage entry into sex work: A quantitative hierarchical analysis of female sex workers in Nairobi, Kenya

Objective To explore factors associated with early age at entry into sex work, among a cohort of female sex workers (FSWs) in Nairobi, Kenya. Background Younger age at sex work initiation increases the risk of HIV acquisition, condom non-use, violence victimisation and alcohol and/or substance use problems. This study aimed to understand factors in childhood and adolescence that shape the vulnerability to underage sex work initiation. Design Building on previous qualitative research with this cohort, analysis of behavioural-biological cross-sectional data using hierarchical logistic regression. Participants and measures FSWs aged 18-45 years were randomly selected from seven Sex Workers Outreach Programme clinics in Nairobi, and between June and December 2019, completed a baseline behavioural-biological survey. Measurement tools included WHO Adverse Childhood Experiences, Alcohol, Smoking and Substance Involvement Screening Test and questionnaires on sociodemographic information, sexual risk behaviours and gender-based violence. Descriptive statistics and logistic regression were conducted using hierarchical modelling. Results Of the 1003 FSWs who participated in the baseline survey (response rate 96%), 176 (17.5%) initiated sex work while underage (<18 years). In the multivariable analysis, factors associated with entering sex work while underage included incomplete secondary school education (aOR=2.82; 95% CI=1.69 to 4.73), experiencing homelessness as a child (aOR=2.20; 95% CI=1.39 to 3.48), experiencing childhood physical or sexual violence (aOR=1.85; 95% CI=1.09 to 3.15), young age of sexual debut (≤15 years) (aOR=5.03; 95% CI=1.83 to 13.79) and being childless at time of sex work initiation (aOR=9.80; 95% CI=3.60 to 26.66). Conclusions Lower education level and childhood homelessness, combined with sexual violence and sexual risk behaviours in childhood, create pathways to underage initiation into sex work. Interventions designed for girls and young women at these pivotal points in their lives could help prevent underage sex work initiation and their associated health, social and economic consequences

Syndemic of factors that shape the early lives of women who enter into sex work: A qualitative methods study from Nairobi, Kenya

Objective To explore the structural and social co-factors that shape the early lives of women who enter sex work in Nairobi, Kenya. Design Thematic analysis of qualitative data collected as part of the Maisha Fiti study among female sex workers (FSWs) in Nairobi. Participants and measures FSWs aged 18-45 years were randomly selected from seven Sex Workers Outreach Programme clinics in Nairobi and participated in baseline behavioural-biological surveys. Participants in this qualitative study were randomly selected from the Maisha Fiti study cohort and were interviewed between October 2019 and July 2020. Women described their lives from childhood, covering topics including sex work, violence and financial management. Results 48 out of 1003 Maisha Fiti participants participated in the in-depth qualitative interviews. FSWs described how physical and sexual violence, poverty and incomplete education in their childhood and adolescence intertwined with early pregnancy, marriage, intimate partner violence and relationship breakdown in their adolescence and early adulthood. The data analysis found clear syndemic relationships between these risk factors, particularly childhood violence, poverty and incomplete education and highlighted pathways leading to financial desperation and caring for dependents, and subsequent entry into sex work. Women perceived sex work as risky and most would prefer alternative work if possible, but it provided them with some financial independence and agency. Conclusions This is the first study in Kenya to qualitatively explore the early lives of sex workers from a syndemic perspective. This method identified the pivotal points of (1) leaving school early due to poverty or pregnancy, (2) breakdown of early intimate relationships and (3) women caring for dependents on their own. Complex, multi-component structural interventions before these points could help increase school retention, reduce teenage pregnancy, tackle violence, support young mothers and reduce entry into sex work and the risk that it entails by expanding livelihood options

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding: Bill & Melinda Gates Foundation

Identification of human errors of commission using Sneak Analysis

Sneak Analysis was adapted for use in identifying human errors of commission. Flow diagrams were developed to guide the analyst through a series of questions aimed at locating sneak paths, sneak indications, sneak labels, and sneak timing. An illustration of the application of this methodology in a nuclear environment is given and a computerized tool to support Sneak Analysis is described. A nuclear power plant loss of coolant accident is used as the example of sneak analysis of reactor safety. 8 figs

Safety, Pharmacokinetics, and Pharmacodynamics of the DR5 Antibody LBY135 Alone and in Combination with Capecitabine in Patients with Advanced Solid Tumors

Purpose: We evaluated the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, biologic activity, and antitumor efficacy of the DR5 antibody, LBY135 ± capecitabine. Experimental design: Escalating LBY135 was administered every 21 days, alone (Arm1) or with capecitabine (Arm2), to patients with advanced solid tumors. Results: In Arm1 (n=40), LBY135 (0.3–40 mg/kg) resulted in no dose-limiting toxicities; adverse events (AEs) included fatigue, hypotension, abdominal pain, dyspnea, and nausea. Stable disease (SD) was observed in 21/38 (55.3%) patients. In Arm2 (n=33), LBY135 (1–40 mg/kg) plus capecitabine resulted in 3 DLTs (each grade 3): dehydration and mucosal inflammation (1 mg/kg), colitis (20mg/kg), and diarrhea (40 mg/kg). AEs included fatigue, nausea, dyspnea, and vomiting. Partial response was observed in 2 patients (rectal and breast cancer) and SD in 12/27 (44.4%) patients. Mean elimination half-life of LBY135 ± capecitabine at saturation of clearance (≥10 mg/kg) ranged between 146–492 hours. Immunogenicity was detected in 16/73 (22%) patients, of which 6 patients experienced reduced LBY135 exposure with repeat dosing. M30/M65 levels were not predictive for LBY135 response. FDG-PET responses were not consistently associated with RECIST responses. Conclusions: LBY135 was well tolerated up to 40mg/kg, the maximal dose administered; no MTD for LBY135 ± capecitabine was defined. Clearance was saturated at doses ≥10 mg/kg