Burden of Disease and Treatment Patterns Amongst Patients With Vitiligo: Findings From a National, Longitudinal Retrospective Study in the United Kingdom.

This retrospective study, using UK Clinical Practice Research Datalink and Hospital Episode Statistics databases, analysed 17,239 incident patients with vitiligo. Mean incidence of vitiligo was 0.16 (2010-2021) per 1000 person-years (range: 0.10 [2010-COVID] to 0.19 [2013/2018]); prevalence increased from 0.21% (2010) to 0.38% (2021). The most common comorbidities recorded after vitiligo diagnosis were diabetes (19.4%), eczema (8.9%), thyroid disease (7.5%), and rheumatoid arthritis (6.9%). Mental health diagnoses recorded at any time were most commonly depression and/or anxiety (24.6%), depression (18.5%), anxiety (16.0%), and sleep disturbance (12.7%); recorded after vitiligo diagnosis in 6.4%, 4.4%, 5.5%, and 3.9%, respectively. Mental health comorbidities were more common among White patients (eg, depression and/or anxiety, 29.0%) than Black (18.8%), Asian (16.1%), and other ethnicities (21.4%). In adolescents, depression and/or anxiety was most commonly diagnosed after vitiligo diagnosis (7.4% vs before, 1.8%). Healthcare resources were used most frequently in the first year after vitiligo diagnosis (incident cohort), typically dermatology-related outpatient appointments (101.9/100 person-years) and general practitioner consultations (97.9/100 person-years). In the year after diagnosis, 60.8% of incident patients did not receive vitiligo-related treatments (ie, topical corticosteroids, topical calcineurin inhibitors, oral corticosteroids, phototherapy), increasing to 82.0% the next year; median (95% CI) time from diagnosis to first treatment was 34.0 (31.6-36.4) months. Antidepressants and/or anxiolytics were recorded for 16.7% of incident patients in the year after diagnosis. In 2019, 85.0% of prevalent patients did not receive vitiligo-related treatments; 16.6% had a record of antidepressant and/or anxiolytic treatments. Most patients were not on vitiligo-related treatments within a year of diagnosis, with time to first treatment >2 years, suggesting that vitiligo may be dismissed as unimportant and not treated early, in part due to limited effectiveness of available treatments. New effective treatments, early initiation, and psychological intervention and support are needed to reduce vitiligo burden on patients.

The Treatment Patterns with Brolucizumab in Germany (REALIZE) Study: A Retrospective Cohort Study Based on Longitudinal Prescription Data.

INTRODUCTION: This study describes real-world treatment patterns in Germany for brolucizumab, an anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD). METHODS: This single-arm retrospective cohort study used German patient-level prescription data. Patients aged ≥ 50 years, who received ≥ 1 brolucizumab prescription in one eye only (unilateral) and had a minimum of 12 months follow-up were included. Three cohorts were defined from the overall population: anti-VEGF treatment-naive patients ("treatment-naive"); anti-VEGF treatment-experienced patients ("treatment-experienced"); and of the treatment-experienced cohort, patients persistent on brolucizumab for 12 months ("treatment-experienced persistent"), i.e. who received ≥ 2 brolucizumab injections and did not discontinue or use other anti-VEGF agents in that period. Descriptive statistics were used to analyse patient characteristics and injection intervals. RESULTS: A total of 2089 patients with at least 12 months follow-up and one brolucizumab injection were analysed. Most were female (58.1%), aged 80+ years (54.7%). A total of 539 (25.8%) were treatment-naive, 1550 (74.2%) treatment-experienced and, of those, 787 (50.8%) were persistent. Overall, the median (interquartile range, IQR) number of brolucizumab injections during the 12 months follow-up was 5.0 (3.0-8.0). In the treatment-naive and treatment-experienced sub-cohorts it was 5.0 (3.0-8.0) and 5.0 (3.0-9.0) injections, respectively. In the treatment-experienced persistent cohort the median (IQR) number of injections was 8.0 (5.0-10.0). In this same cohort, the median (IQR) treatment interval between anti-VEGF injections before switch to brolucizumab was 5.1 (4.0-8.0) weeks, whilst the brolucizumab interval at 12 months after switch was 8.0 (6.0-11.9) weeks. Of treatment-experienced patients, 67% extended their treatment interval and those with pre-switch intervals less than 6 weeks (< q6w), in particular, had meaningful treatment interval extensions. CONCLUSION: Patients who switched to brolucizumab had a median treatment interval extension of about 3 weeks at 12 months. These results show that treatment with brolucizumab has the potential to reduce treatment burden in patients with nAMD in routine clinical practice.

Interventions to Reduce Pesticide Exposure from the Agricultural Sector in Africa: A Workshop Report.

Despite the fact that several cases of unsafe pesticide use among farmers in different parts of Africa have been documented, there is limited evidence regarding which specific interventions are effective in reducing pesticide exposure and associated risks to human health and ecology. The overall goal of the African Pesticide Intervention Project (APsent) study is to better understand ongoing research and public health activities related to interventions in Africa through the implementation of suitable target-specific situations or use contexts. A systematic review of the scientific literature on pesticide intervention studies with a focus on Africa was conducted. This was followed by a qualitative survey among stakeholders involved in pesticide research or management in the African region to learn about barriers to and promoters of successful interventions. The project was concluded with an international workshop in November 2021, where a broad range of topics relevant to occupational and environmental health risks were discussed such as acute poisoning, street pesticides, switching to alternatives, or disposal of empty pesticide containers. Key areas of improvement identified were training on pesticide usage techniques, research on the effectiveness of interventions targeted at exposure reduction and/or behavioral changes, awareness raising, implementation of adequate policies, and enforcement of regulations and processes.

Maternal drinking behaviour and co-exposure from smoking during and after pregnancy in relation to the neurocognitive function of school-children in the rural Western Cape.

BACKGROUND: Maternal substance use and its long-term effect on the neurocognitive functions of children is a global public health issue. Despite an increase in substance use in rural areas of low to middle-income countries, research is limited in these populations. OBJECTIVE: We have therefore explored the effect of maternal drinking and smoking behaviors on the neurocognitive functioning of rural school children. METHOD: A cross-sectional analysis on the determinants of current, past and gestational maternal alcohol use and gestational smoking on child neurocognitive functions was conducted on school-children (N = 482), embedded within the child health agricultural cohort (CapSA) study across seven schools in rural Western Cape, South Africa. Standardised neurocognitive assessment tools included the Cambridge Automated Neuropsychological Battery (CANTAB) and the KIDSCREEN-10 to measure health-related quality of life via a child questionnaire. Maternal smoking and drinking behaviour were captured using a parent/guardian questionnaire. RESULTS: Of the 482 parents/guardians who completed the survey, 29 % reported current drinking 27 % reported past drinking and 10 % reported maternal gestational drinking, while 31 % reported gestational smoking. Significant associations were observed between past and current maternal drinking and child's reduced rapid visual processing accuracy in attention [ß:-0.03; 95 % confidence interval (CI): -0.05;-0.004] and between maternal drinking during pregnancy and reduced child's spatial working memory (ß: -0.59; CI: -1.02; -0.15). Heavy (>5 cigarettes per day) gestational smoking was associated with lowered child's learning in memory (ß:-1.69; 95 % CI: -3.05; -0.33) and lower health-related quality of life (ß: -3.41; CI: -6.64; -0.17). The odds of a child repeating a grade were 1.69 (CI: 2.81-1.02) for those exposed to maternal gestational smoking and 1.68 (CI: 3.31-0.85) for those exposed to maternal gestational drinking compared to those who were not exposed. CONCLUSION: The consistent negative associations across all four maternal substance use proxies, six neurocognitive health outcomes and one health symptom is suggestive of adverse health effects, warranting longitudinal follow-up. Health policies to eliminate gestational substance use are recommended.

Relation between organophosphate pesticide metabolite concentrations with pesticide exposures, socio-economic factors and lifestyles: A cross-sectional study among school boys in the rural Western Cape, South Africa.

Evidence on the relationship between lifestyle, socio-economic factors and pesticide exposure and urinary concentrations of organophosphate (OP) pesticide metabolites among children is generally incomplete. This study investigated the relationship between socio-economic factors and reported pesticide exposures and the sum of three urinary concentrations of dialkyl phosphate metabolites (DAP) among boys living in the rural areas of the Western Cape, South Africa. Data was collected during a cross-sectional study of 183 boys from three agricultural intense areas. Measurements included a questionnaire on socio-economic and pesticide exposures and urinary DAP concentrations. Most boys (70%) lived on farms with a median age of 12 years (range: 5.0-19.5 years). Children aged >14 years had lower DAP urine concentrations (median = 39.9 ng/ml; ß = -68.1 ng/ml; 95% CI: -136.8, 0.6) than children aged 9 years and younger (median = 107.0 ng/ml). DAP concentrations also varied significantly with area, with concentrations in the grape farming area, Hex River Valley (median = 61.8 ng/ml; ß = -52.1; 95% CI: -97.9, -6.3 ng/ml) and the wheat farming area, Piketberg (median = 72.4 ng/ml; ß = -54.2; 95% CI: 98.8, -9.7 ng/ml) lower than those in the pome farming area, Grabouw (median = 79.9 ng/ml). Other weaker and non-significant associations with increased DAP levels were found with increased household income, member of household working with pesticides, living on a farm, drinking water from an open water source and eating crops from the vineyard and or garden. The study found younger age and living in and around apple and grape farms to be associated with increased urinary DAP concentrations. Additionally, there were other pesticide exposures and socio-economic and lifestyle factors that were weakly associated with elevated urinary DAP levels requiring further study. The study provided more evidence on factors associated to urinary DAP concentrations especially in developing country settings.

Pesticide Research on Environmental and Human Exposure and Risks in Sub-Saharan Africa: A Systematic Literature Review.

On the African continent, ongoing agriculture intensification is accompanied by the increasing use of pesticides, associated with environmental and public health concerns. Using a systematic literature review, we aimed to map current geographical research hotspots and gaps around environmental and public health risks research of agriculture pesticides in Sub-Saharan Africa (SSA). Studies were included that collected primary data on past and current-used agricultural pesticides and assessed their environmental occurrence, related knowledge, attitude and practice, human exposure, and environmental or public health risks between 2006 and 2021. We identified 391 articles covering 469 study sites in 37 countries in SSA. Five geographical research hotspots were identified: two in South Africa, two in East Africa, and one in West Africa. Despite its ban for agricultural use, organochlorine was the most studied pesticide group (60%; 86% of studies included DDT). Current-used pesticides in agriculture were studied in 54% of the study sites (including insecticides (92%), herbicides (44%), and fungicides (35%)). Environmental samples were collected in 67% of the studies (e.g., water, aquatic species, sediment, agricultural produce, and air). In 38% of the studies, human subjects were investigated. Only few studies had a longitudinal design or assessed pesticide's environmental risks; human biomarkers; dose-response in human subjects, including children and women; and interventions to reduce pesticide exposure. We established a research database that can help stakeholders to address research gaps, foster research collaboration between environmental and health dimensions, and work towards sustainable and safe agriculture systems in SSA.

Association of activities related to pesticide exposure on headache severity and neurodevelopment of school-children in the rural agricultural farmlands of the Western Cape of South Africa.

OBJECTIVE: Children and adolescents living in agricultural areas are likely to be exposed to mixtures of pesticides during their daily activities, which may impair their neurodevelopment. We investigated various such activities in relation to headache severity and neurodevelopment of school-children living in rural agricultural areas in the Western Cape of South Africa. METHOD: We used baseline date from 1001 school-children of the Child Health Agricultural Pesticide Cohort Study in South Africa (CapSA) aged 9-16 from seven schools and three agriculture areas in the Western Cape. Questionnaires were administrated to assess activities related to pesticide exposure and health symptoms addressing four types of activities: 1) child farm activities related to pesticide handling, 2) eating crops directly from the field, 3) contact with surface water around the field, and 4) seen and smelt pesticide spraying activities. Neurocognitive performance across three domains of attention, memory and processing speed were assessed by means of an iPad-based cognitive assessment tool, Cambridge Automated NeuroPsychological Battery (CANTAB). Headache severity was enquired using a standard Headache Impact Test (HIT-6) tool. Cross-sectional regression analysis was performed. RESULTS: About 50% of the cohort report to have ever been engaged in activities related to pesticide exposure including farm activities, eating crops directly from the field and leisure activities. Headache severity score was consistently increased in relation to pesticide-related farm activities (score increase of 1.99; 95% CI: 0.86, 3.12), eating crops (1.52; 0.41, 2.67) and leisure activities of playing, swimming or bathing in nearby water (1.25; 0.18, 2.33). For neurocognitive outcomes, an overall negative trend with pesticide exposure-related activities was observed. Among others, involvement in pesticide-related farm activities was associated with a lower multi-tasking accuracy score (-2.74; -5.19, -0.29), while lower strategy in spatial working memory (-0.29; -0.56; -0.03) and lower paired associated learning (-0.88; -1.60, -0.17) was observed for those who pick crops off the field compared to those who do not pick crops off the field. Eating fruits directly from the vineyard or orchard was associated with a lower motor screening speed (-0.06; -0.11, -0.01) and lower rapid visual processing accuracy score (-0.02; -0.03, 0.00). CONCLUSIONS: Children who indicate activities related to pesticide exposure may be at higher risk for developing headaches and lower cognitive performance in the domains of attention, memory and processing speed. However, self-reported data and cross-sectional design are a limitation. Future research in CapSA will consider pesticide exposure estimations via urinary biomarkers and longitudinal assessment of cognitive functions.

Different aspects of electronic media use, symptoms and neurocognitive outcomes of children and adolescents in the rural Western Cape region of South Africa.

BACKGROUND: Electronic media use is increasing in low- and middle-income countries, thus we aim to investigate the prevalence of different aspects of e-media use and its association to symptoms and neurocognitive outcomes in rural South Africa. METHODS: In the cohort study, "Child health Agricultural Pesticide study in South Africa (CapSA)", of 1001 children and adolescents, aged 9-16 years, we enquired at baseline about the following aspects of e-media use: (1) call duration (2) total screen time (3) night-time awakenings from mobile phone use, and (4) Mobile Phone Problematic Use. Four health outcomes were included: sleep disturbance, health related quality of life (HRQoL), headaches and cognitive performance, assessed through six tests on domains of attention, memory and processing speed, using the iPad-based software, CAmbridge Neuropsychological Test Automated Battery (CANTAB). Linear regression analysis adjusted for relevant confounders was conducted with categorized exposure variables low, medium and high use. RESULTS: One third of the cohort (31.8%) are mobile phone users reporting average duration of calls per day up to 75 min (mean = 2.5 mins; SD = 8.9 mins). Amongst 46% of the cohort who report e-media device use, total screen time ranged from 1 min to 441 min (mean = 28.3; SD = 53.0). Findings Amongst those reporting regular night-time awakenings (≥1 times per week) from mobile phones, HRQol declined by 2.9 (95% CI: -6.1, 0.3), the sleep disturbance score increased by 2.0 (1.1, 2.9) units and headache impact score significantly increased by 5.4 (2.6; 8.2) units compared to non-exposed. Cognitive performance scores tended to be slightly improved mostly in moderate e-media users. The reaction response speed was consistently improved amongst all four exposure groups compared to non-users. CONCLUSION: These results are among the first from Africa on benefits and risks associated with e-media use. Our findings imply that with regard to the education of adolescents, a vigilant balance is needed to profit from the beneficial effects of moderate e-media use on cognition, while preventing the negative side effects for HRQoL, sleep disturbance and headache severity.

Impact of Adolescents' Screen Time and Nocturnal Mobile Phone-Related Awakenings on Sleep and General Health Symptoms: A Prospective Cohort Study.

Nocturnal media use has been linked to adolescents' sleeping problems in cross-sectional studies which do not address reverse causality. To prospectively assess the new occurrence of sleep problems or health symptoms in relation to electronic media use and nocturnal mobile phone use, we used data from the longitudinal Swiss HERMES (Health Effects Related to Mobile phone usE in adolescentS) cohort on 843 children from 7th to 9th grade. Logistic regression models were fitted and adjusted for relevant confounders. Adolescents reporting at baseline and follow-up at least one nocturnal awakenings from their own mobile phone per month were more likely to have developed restless sleep (Odds Ratio (OR): 5.66, 95% Confidence Interval: 2.24⁻14.26) and problems falling asleep (3.51, 1.05⁻11.74) within one year compared to adolescents without nocturnal awakenings. A similar pattern was observed for developing symptoms, although somewhat less pronounced in terms of the magnitude of the odds ratios. With respect to high screen time at baseline and follow-up, associations were observed for falling asleep (2.41, 1.41⁻4.13), exhaustibility (1.76, 1.02⁻3.03), lack of energy (1.76, 1.04⁻2.96) and lack of concentration (2.90, 1.55⁻5.42). Our results suggest a detrimental effect of screen time and mobile phone-related awakenings on sleep problems and related health symptoms. However, the results should be interpreted cautiously with respect to adolescents' natural changes in circadian rhythm, which may coincidence with an increase in mobile phone and media use.

A prospective cohort study of school-going children investigating reproductive and neurobehavioral health effects due to environmental pesticide exposure in the Western Cape, South Africa: study protocol.

BACKGROUND: Research on reproductive health effects on children from low-level, long-term exposure to pesticides currently used in the agricultural industry is limited and those on neurobehavioral effects have produced conflicting evidence. We aim at investigating the association between pesticide exposure on the reproductive health and neurobehavior of children in South Africa, by including potential relevant co-exposures from the use of electronic media and maternal alcohol consumption. METHODS: The design entails a prospective cohort study with a follow-up duration of 2 years starting in 2017, including 1000 school going children between the ages of 9 to 16 years old. Children are enrolled with equal distribution in sex and residence on farms and non-farms in three different agricultural areas (mainly apple, table grapes and wheat farming systems) in the Western Cape, South Africa. The neurobehavior primary health outcome of cognitive functioning was measured through the iPad-based CAmbridge Neuropsychological Test Automated Battery (CANTAB) including domains for attention, memory, and processing speed. The reproductive health outcomes include testicular size in boys and breast size in girls assessed in a physical examination, and blood samples to detect hormone levels and anthropometric measurements. Information on pesticide exposure, co-exposures and relevant confounders are obtained through structured questionnaire interviews with the children and their guardians. Environmental occurrence of pesticides will be determined while using a structured interview with farm owners and review of spraying records and collection of passive water and air samples in all three areas. Pesticide metabolites will be analysed in urine and hair samples collected from the study subjects every 4 months starting at baseline. DISCUSSION: The inclusion of three different agricultural areas will yield a wide range of pesticide exposure situations. The prospective longitudinal design is a further strength of this study to evaluate the reproductive and neurobehavioural effects of different pesticides on children. This research will inform relevant policies and regulatory bodies to improve the health, safety and learning environments for children and families in agricultural settings.