Overall effect of a campaign with measles vaccine on the composite outcome mortality or hospital admission: A cluster-randomized trial among children aged 9-59 months in rural Guinea-Bissau.

OBJECTIVES: Campaigns with measles vaccine (C-MV) are conducted to eradicate measles, but prior studies indicate that MV reduces non-measles mortality and hospital admissions too. We hypothesized that C-MV reduces death/hospital admission by 30%. METHODS: Between 2016-2019, we conducted a non-blinded cluster-randomized trial randomizing village clusters in rural Guinea-Bissau to a C-MV targeting children aged 9-59 months. In Cox proportional hazards models, we assessed the effect of C-MV, obtaining hazard ratios (HR) for the composite outcome (death/hospital admission). We also examined potential effect modifiers. RESULTS: Among 18,411 children (9636 in 111 intervention clusters/8775 in 110 control clusters), 379 events occurred (208 intervention/171 control) during a median follow-up period of 22 months. C-MV did not reduce the composite outcome (HR 1.12, 95% confidence interval 0.88-1.41). Mortality among enrolled children (5.3 intervention and 4.6 control, per 1000 person-years) was approximately half the pre-trial mortality rate (11.1 intervention and 8.9 control, per 1000 person-years). Neither planned nor explorative analyses of potential effect modifiers explained the contrasting results to prior studies. CONCLUSION: C-MV did not reduce overall mortality or hospital admission. This might be explained by changes in disease patterns, baseline differences in health status, and/or modifying effects of other campaigns during follow-up.

Reduction in Short-term Outpatient Consultations After a Campaign With Measles Vaccine in Children Aged 9-59 Months: Substudy Within a Cluster-Randomized Trial.

BACKGROUND: We assessed a measles vaccination campaign's potential short-term adverse events. METHODS: In a cluster-randomized trial assessing a measles vaccination campaign's effect on all-cause mortality and hospital admission among children aged 9-59 months in Guinea-Bissau, children received a measles vaccination (intervention) or a health check-up (control). One month to 2 months later, we visited a subgroup of children to ask mothers/guardians about outpatient consultations since enrollment. In log-binomial models, we estimated the relative risk (RR) of nonaccidental outpatient consultations. RESULTS: Among 8319 children (4437 intervention/3882 control), 652 nonaccidental outpatient consultations occurred (322 intervention/330 control). The measles vaccination campaign tended to reduce nonaccidental outpatient consultations by 16% (RR, 0.84 [95% confidence interval {CI}, .65-1.11]), especially if caused by respiratory symptoms (RR, 0.68 [95% CI, .42-1.11]). The reduction tended to be larger in children who prior to trial enrollment had a pentavalent vaccination (diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae type b) as the most recent vaccination (RR, 0.61 [95% CI, .42-.89]) than in children who prior to trial enrollment had a routine measles vaccination as the most recent vaccination (RR, 0.93 [95% CI, .68-1.26]) (P = .04 for interaction). CONCLUSIONS: In the short term, a measles vaccination campaign seems not to increase nonaccidental outpatient consultations but may reduce them. CLINICAL TRIALS REGISTRATION: NCT03460002.

The use of self-reported symptoms as a proxy for acute organophosphate poisoning after exposure to chlorpyrifos 50% plus cypermethrin 5% among Nepali farmers: a randomized, double-blind, placebo-controlled, crossover study.

BACKGROUND: Previous studies stating a high prevalence of occupational acute pesticide poisoning in developing countries have mainly relied on measurements of the rather non-specific self-reported acute pesticide poisoning symptoms. Only a few studies have measured the biomarker plasma cholinesterase (PchE) activity, in addition to the symptoms, when assessing occupational acute pesticide poisoning. This study evaluated self-reported symptoms as a proxy for acute organophosphate poisoning among Nepali farmers by examining self-reported acute organophosphate poisoning symptoms and PchE activity in response to occupational acute organophosphate exposure. METHODS: We performed a randomized, double-blind, placebo-controlled, crossover trial among 42 Nepali commercial vegetable farmers. The farmers were randomly assigned (ratio 1:1) to a 2-h organophosphate (chlorpyrifos 50% plus cypermethrin 5%: moderately hazardous) spray session or a 2-h placebo spray session, and after 7 days' washout, the farmers were assigned to the other spray session. Before and after each spray session farmers were interviewed about acute organophosphate poisoning symptoms and PchE activity was measured. Analyses were conducted with a Two Sample T-test and Mann Whitney U-test. RESULTS: We found no difference in the symptom sum or PchE activity from baseline to follow up among farmers spraying with organophosphate (symptom sum difference -1, p = 0.737; PchE mean difference 0.02 U/mL, p = 0.220), placebo (symptom sum difference 9, p = 0.394; PchE mean difference 0.02 U/mL, p = 0.133), or when comparing organophosphate to placebo (symptom p = 0.378; PchE p = 0.775). However, a high percentage of the farmers reported having one or more symptoms both at baseline and at follow up in the organophosphate spray session (baseline 47.6%, follow up 45.2%) and placebo spray session (baseline 35.7%, follow up 50.0%), and 14.3% of the farmers reported three or more symptoms after the organophosphate spray session as well as after the placebo spray session. CONCLUSION: We found a general presence of acute organophosphate symptoms among the farmers regardless of organophosphate exposure or poisoning. Thus, self-reported acute organophosphate symptoms seem to be a poor proxy for acute organophosphate poisoning as the occurrence of these symptoms is not necessarily associated with acute organophosphate poisoning. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02838303 . Registered 19 July 2016. Retrospectively registered.

Is prevention of acute pesticide poisoning effective and efficient, with Locally Adapted Personal Protective Equipment? A randomized crossover study among farmers in Chitwan, Nepal.

BACKGROUND: Farmers' risk of pesticide poisoning can be reduced with personal protective equipment but in low-income countries farmers' use of such equipment is limited. OBJECTIVE: To examine the effectiveness and efficiency of Locally Adapted Personal Protective Equipment to reduce organophosphate exposure among farmers. METHODS: In a crossover study, 45 male farmers from Chitwan, Nepal, were randomly allocated to work as usual applying organophosphate pesticides wearing Locally Adapted Personal Protective Equipment or Daily Practice Clothing. For seven days before each experiment, each farmer abstained from using pesticides. Before and after organophosphate application, an interview surveys and blood tests were carried out, and analyzed with paired t-test, frequencies and percentages. RESULTS: The difference between follow-up mean for acute organophosphate poisoning symptoms in the two groups was 0.13 [95% CI -0.22;0.49] and for plasma cholinesterase (U/ml) -0.03 [95% CI -0.11;0.06]. The difference between follow-up mean minus baseline mean for acute organophosphate poisoning symptoms in the two groups was 0.29 [95% CI -0.26;0.84] and for plasma cholinesterase (U/ml) -0.01 [95% CI --0.08;0.06]. Wearing the Locally Adapted Personal Protective Equipment versus Daily Practice Clothing gave the following results, respectively: comfort 75.6% versus 100%, sense of heat 64.4% versus 31.3%, other problems 44.4% versus 33.3%, likeability 95.6% versus 77.8%. CONCLUSION: We cannot support the expectation that our farmers in Chitwan, Nepal working with Locally Adapted Personal Protective Equipment would have fewer acute organophosphate poisoning symptoms, higher plasma cholinesterase (U/mL) and find it more efficient to work with the equipment than farmers working with their Daily Practice Clothing. Based on the farmers' working behavior, compounds used, intensity and exposure duration we conclude that Locally Adapted Personal Protective Equipment does not provide additional protection during usual work practices. However, our Locally Adapted Personal Protective Equipment might offer protection from (certain) accidental overexposure. Trial Registration NCT02137317.

With long hours of work, might depression then lurk? A nationwide prospective follow-up study among Danish senior medical consultants.

OBJECTIVE: The aim of this study was to examine depression as a potential negative health effect of long work hours, anticipating an exposure-response relationship. METHOD: A nationwide prospective cohort study of 2790 Danish senior medical consultants was conducted (61.7% response rate). With the consent of Danish Data Protection Agency, data from a questionnaire survey was linked with data from a Medical Products Agency Register. Long work hours were defined based on a self-reported average of weekly work hours >40, while redemption of anti-depressive (AD) drug prescriptions defined depression. Proportional hazards Cox regression analyses were conducted adjusting for gender, age, marital status, medical specialty, decision authority at work, work social support, quantitative work demands, and AD drugs prescribed before baseline. RESULTS: Long weekly work hours did not increase the risk of redeeming AD drug prescriptions at all times during follow-up compared to the reference of 37-40 work hours [41-44 hours: hazard ratio (HR) 0.95, 95% confidence interval (95% CI) 0.5-1.8; 45-49 hours: HR 0.88, 95% CI 0.4-1.8; 50-54 hours: HR 0.83, 95% CI 0.3-2.1; 55-59 hours: HR 0.67, 95% CI 0.2-2.9; ≥ 60 hours: HR 0.48, 95% CI 0.1-3.7]. The same result emerged when work hours was applied in a continuous form (from 25-36 hours to 37-40 hours to 41-44 hours and so on) (HR 0.93, 95% CI 0.76-1.13) and when robust analyses were conducted (data not shown). CONCLUSIONS: This study does not support the anticipation that long work hours increase the risk of depression. If anything, long work hours vaguely appear to decrease the risk of redeeming AD drug prescriptions.