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A practical limitation of cluster randomized controlled trials (cRCTs) is that the number of available clusters may be small, resulting in an increased risk of baseline imbalance under simple randomization. Constrained randomization overcomes this issue by restricting the allocation to a subset of randomization schemes where sufficient overall covariate balance across comparison arms is achieved. However, for multi-arm cRCTs, several design and analysis issues pertaining to constrained randomization have not been fully investigated. Motivated by an ongoing multi-arm cRCT, we elaborate the method of constrained randomization and provide a comprehensive evaluation of the statistical properties of model-based and randomization-based tests under both simple and constrained randomization designs in multi-arm cRCTs, with varying combinations of design and analysis-based covariate adjustment strategies. In particular, as randomization-based tests have not been extensively studied in multi-arm cRCTs, we additionally develop most-powerful randomization tests under the linear mixed model framework for our comparisons. Our results indicate that under constrained randomization, both model-based and randomization-based analyses could gain power while preserving nominal type I error rate, given proper analysis-based adjustment for the baseline covariates. Randomization-based analyses, however, are more robust against violations of distributional assumptions. The choice of balance metrics and candidate set sizes and their implications on the testing of the pairwise and global hypotheses are also discussed. Finally, we caution against the design and analysis of multi-arm cRCTs with an extremely small number of clusters, due to insufficient degrees of freedom and the tendency to obtain an overly restricted randomization space.
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Projetos de Pesquisa , Análise por Conglomerados , Humanos , Distribuição Aleatória , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Cerebral malaria (CM) pathogenesis remains incompletely understood. Having shown low systemic levels of tetrahydrobiopterin (BH4), an enzymatic cofactor for neurotransmitter synthesis, we hypothesized that BH4 and BH4-dependent neurotransmitters would likewise be low in cerebrospinal fluid (CSF) in CM. METHODS: We prospectively enrolled Tanzanian children with CM and children with nonmalaria central nervous system conditions (NMCs). We measured CSF levels of BH4, neopterin, and BH4-dependent neurotransmitter metabolites, 3-O-methyldopa, homovanillic acid, and 5-hydroxyindoleacetate, and we derived age-adjusted z-scores using published reference ranges. RESULTS: Cerebrospinal fluid BH4 was elevated in CM (nâ =â 49) compared with NMC (nâ =â 51) (z-score 0.75 vs -0.08; Pâ <â .001). Neopterin was increased in CM (z-score 4.05 vs 0.09; Pâ <â .001), and a cutoff at the upper limit of normal (60 nmol/L) was 100% sensitive for CM. Neurotransmitter metabolite levels were overall preserved. A higher CSF BH4/BH2 ratio was associated with increased odds of survival (odds ratio, 2.94; 95% confidence interval, 1.03-8.33; Pâ =â .043). CONCLUSION: Despite low systemic BH4, CSF BH4 was elevated and associated with increased odds of survival in CM. Coma in malaria is not explained by deficiency of BH4-dependent neurotransmitters. Elevated CSF neopterin was 100% sensitive for CM diagnosis and warrants further assessment of its clinical utility for ruling out CM in malaria-endemic areas.
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Biopterinas/líquido cefalorraquidiano , Malária Cerebral/mortalidade , Neopterina/líquido cefalorraquidiano , Neurotransmissores/líquido cefalorraquidiano , Pterinas/líquido cefalorraquidiano , Biopterinas/análogos & derivados , Doenças do Sistema Nervoso Central/líquido cefalorraquidiano , Criança , Pré-Escolar , Feminino , Ácido Homovanílico/líquido cefalorraquidiano , Humanos , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Lactente , Malária Cerebral/líquido cefalorraquidiano , Masculino , Estudos Prospectivos , Valores de Referência , Tanzânia/epidemiologia , Tirosina/análogos & derivadosRESUMO
During April and May 2020, we studied 20 patients hospitalized with coronavirus disease 2019 (COVID-19), their hospital rooms (fomites and aerosols), and their close contacts for molecular and culture evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Among >400 samples, we found molecular evidence of virus in most sample types, especially the nasopharyngeal (NP), saliva, and fecal samples, but the prevalence of molecular positivity among fomites and aerosols was low. The agreement between NP swab and saliva positivity was high (89.5%; κ = 0.79). Two NP swabs collected from patients on days 1 and 7 post-symptom onset had evidence of infectious virus (2 passages over 14 days in Vero E6 cells). In summary, the low molecular prevalence and lack of viable SARS-CoV-2 virus in fomites and air samples implied low nosocomial risk of SARS-CoV-2 transmission through inanimate objects or aerosols.
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COVID-19/transmissão , COVID-19/virologia , Fômites/virologia , SARS-CoV-2/fisiologia , Adulto , Aerossóis , Idoso , Idoso de 80 Anos ou mais , Animais , COVID-19/epidemiologia , Chlorocebus aethiops , Microbiologia Ambiental , Fezes/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Saliva/virologia , Células Vero , Carga ViralRESUMO
BACKGROUND: China is thought to be a hotspot for zoonotic influenza virus emergence, yet there have been few prospective studies examining the occupational risks of such infections. METHODS: We present the first 2 years of data collected from a 5-year, prospective, cohort study of swine-exposed and -unexposed participants at 6 swine farms in China. We conducted serological and virological surveillance to examine evidence for swine influenza A virus infection in humans. RESULTS: Of the 658 participants (521 swine-exposed and 137 swine-unexposed), 207 (31.5%) seroconverted against at least 1 swine influenza virus subtype (swine H1N1 or H3N2). Swine-exposed participants' microneutralization titers, especially those enrolled at confined animal feeding operations (CAFOs), were higher against the swine H1N1 virus than were other participants at 12 and 24 months. Despite elevated titers, among the 187 study subjects for whom we had complete follow-up, participants working at swine CAFOs had significantly greater odds of seroconverting against both the swine H1N1 (odds ratio [OR] 19.16, 95% confidence interval [CI] 3.55-358.65) and swine H3N2 (OR 2.97, 95% CI 1.16-8.01) viruses, compared to unexposed and non-CAFO swine workers with less intense swine exposure. CONCLUSIONS: While some of the observed increased risk against swine viruses may have been explained by exposure to human influenza strains, study data suggest that even with elevated preexisting antibodies, swine-exposed workers were at high risk of infection with enzootic swine influenza A viruses.
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Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Infecções por Orthomyxoviridae , Doenças dos Suínos , Animais , Anticorpos Antivirais , China/epidemiologia , Estudos de Coortes , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/epidemiologia , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/veterinária , Estudos Prospectivos , Estudos Soroepidemiológicos , Suínos , Doenças dos Suínos/epidemiologia , Zoonoses/epidemiologiaRESUMO
BACKGROUND: Little is known about community knowledge of myocardial infarction symptoms and perceptions of self-risk in sub-Saharan Africa. METHODS: A community survey was conducted in northern Tanzania, where the prevalence of cardiovascular risk factors is high. Households were selected randomly in a population-weighted fashion and surveys were administered to self-identified household healthcare decision-makers. Respondents were asked to list all symptoms of a heart attack and asked whether they thought they had a chance of suffering a heart attack. Associations between participant sociodemographic features and responses to these questions were assessed with Pearson's chi-squared and the Student t test. RESULTS: There were 718 survey participants, with median (IQR) age 48 (32, 62) years. Of these, 115 (16.0%) were able to identify any conventional symptom of a heart attack, including 24 (3.3%) respondents who cited chest pain as a possible symptom. There was no association between ability to identify a conventional symptom and gender, level of education, socioeconomic status, urban residence, or age. Of respondents, 198 (27.6%) thought they had a chance of suffering a heart attack. Older respondents were more likely to perceive themselves to be at risk (P < .001), but there was no association between perception of self-risk and gender, level of education, socioeconomic status, or urban residence. CONCLUSIONS: In northern Tanzania, knowledge of myocardial infarction symptoms is poor among all segments of the population and only a minority of residents perceive themselves to be at risk of this disease. Educational interventions regarding ischemic heart disease are urgently needed.
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Conhecimentos, Atitudes e Prática em Saúde , Infarto do Miocárdio/diagnóstico , Avaliação de Sintomas/estatística & dados numéricos , Adulto , Fatores Etários , Dor no Peito/etiologia , Distribuição de Qui-Quadrado , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Risco , Fatores Sexuais , Fatores Socioeconômicos , TanzâniaRESUMO
HealthMpowerment.org (HMP), is a mobile optimized, online intervention to reduce sexual risk behaviors among HIV-positive and HIV-negative young Black men who have sex with men (BMSM) by providing information and resources, fostering social support, and including game-based elements. A randomized controlled trial with 474 young BMSM compared HMP to an information-only control website. The rate of self-reported condomless anal intercourse (CAI) at 3-months was 32% lower in the intervention group compared to the control group (IRR 0.68, 95% CI 0.43, 0.93), however this effect was not sustained at 12 months. Among HIV-positive participants, the rate of CAI at 3-month follow-up was 82% lower among participants with detectable viral loads in the intervention group compared to the control group (IRR 0.18, 95% CI 0.04, 0.32). In a secondary analysis, when we limited to those who used HMP for over 60 min during the 3-month intervention period (n = 50, 25.8%), we estimated 4.85 (95% CI 2.15, 7.53) fewer CAI events than we would have expected in control participants, had they used the intervention at the same rate as the intervention group. Findings suggest that exposure to an online intervention can reduce the rate of CAI among young BMSM, at least in the short term. Given the stronger effect seen among those participants who complied with HMP, additional intervention engagement strategies are warranted.
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Negro ou Afro-Americano , Infecções por HIV/prevenção & controle , Promoção da Saúde , Homossexualidade Masculina , Internet , Comportamento de Redução do Risco , Sexo sem Proteção/prevenção & controle , Adulto , Negro ou Afro-Americano/psicologia , Negro ou Afro-Americano/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Measurements of anti-malarial antibodies are increasingly used as a proxy of transmission intensity. Most serological surveys are based on the use of cross-sectional data that, when age-stratified, approximates historical patterns of transmission within a population. Comparatively few studies leverage longitudinal data to explicitly relate individual infection events with subsequent antibody responses. METHODS: The occurrence of seroconversion and seroreversion events for two Plasmodium falciparum asexual stage antigens (MSP-1 and AMA-1) was examined using three annual measurements of 691 individuals from a cohort of individuals in a malaria-endemic area of rural east-central Tanzania. Mixed-effect logistic regression models were employed to determine factors associated with changes in serostatus over time. RESULTS: While the expected population-level relationship between seroprevalence and disease incidence was observed, on an individual level the relationship between individual infections and the antibody response was complex. MSP-1 antibody responses were more dynamic in response to the occurrence and resolution of infection events than AMA-1, while the latter was more correlated with consecutive infections. The MSP-1 antibody response to an observed infection seemed to decay faster over time than the corresponding AMA-1 response. Surprisingly, there was no evidence of an age effect on the occurrence of a conversion or reversion event. CONCLUSIONS: While the population-level results concur with previously published sero-epidemiological surveys, the individual-level results highlight the more complex relationship between detected infections and antibody dynamics than can be analysed using cross-sectional data. The longitudinal analysis of serological data may provide a powerful tool for teasing apart the complex relationship between infection events and the corresponding immune response, thereby improving the ability to rapidly assess the success or failure of malaria control programmes.
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Antígenos de Protozoários/imunologia , Malária Falciparum/epidemiologia , Proteínas de Membrana/imunologia , Proteína 1 de Superfície de Merozoito/imunologia , Proteínas de Protozoários/imunologia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Malária Falciparum/parasitologia , Masculino , Pessoa de Meia-Idade , Prevalência , População Rural , Estudos Soroepidemiológicos , Tanzânia/epidemiologia , Adulto JovemRESUMO
In the ventral visual pathway, early visual areas encode light patterns on the retina in terms of image properties, for example, edges and color, whereas higher areas encode visual information in terms of objects and categories. At what point does semantic knowledge, as instantiated in human language, emerge? We examined this question by studying whether semantic similarity in language relates to the brain's organization of object representations in inferior temporal cortex (ITC), an area of the brain at the crux of several proposals describing how the brain might represent conceptual knowledge. Semantic relationships among words can be viewed as a geometrical structure with some pairs of words close in their meaning (e.g., man and boy) and other pairs more distant (e.g., man and tomato). ITC's representation of objects similarly can be viewed as a complex structure with some pairs of stimuli evoking similar patterns of activation (e.g., man and boy) and other pairs evoking very different patterns (e.g., man and tomato). In this study, we examined whether the geometry of visual object representations in ITC bears a correspondence to the geometry of semantic relationships between word labels used to describe the objects. We compared ITC's representation to semantic structure, evaluated by explicit ratings of semantic similarity and by five computational measures of semantic similarity. We show that the representational geometry of ITC-but not of earlier visual areas (V1)-is reflected both in explicit behavioral ratings of semantic similarity and also in measures of semantic similarity derived from word usage patterns in natural language. Our findings show that patterns of brain activity in ITC not only reflect the organization of visual information into objects but also represent objects in a format compatible with conceptual thought and language.
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Imageamento por Ressonância Magnética/métodos , Estimulação Luminosa/métodos , Semântica , Lobo Temporal/fisiologia , Córtex Visual/fisiologia , Vias Visuais/fisiologia , Adolescente , Feminino , Humanos , MasculinoRESUMO
Objective: This study evaluated the Hearing Environments and Reflection on Quality of Life (HEAR-QL) questionnaire in rural Alaska, including an addendum crafted through community feedback to reflect the local context. The objectives were to assess whether HEAR-QL score was inversely correlated with hearing loss and middle ear disease in an Alaska Native population. Methods: The HEAR-QL questionnaires for children and adolescents were administered as part of a cluster randomized trial in rural Alaska from 2017 to 2019. Enrolled students completed an audiometric evaluation and HEAR-QL questionnaire on the same day. A cross-sectional evaluation of questionnaire data was utilized. Results: A total of 733 children (ages 7-12 years) and 440 adolescents (ages ≥13 years) completed the questionnaire. Median HEAR-QL scores were similar among children with and without hearing loss (Kruskal-Wallis, p = .39); however, adolescent HEAR-QL scores significantly decreased with increasing hearing loss (p < .001). Median HEAR-QL scores were significantly lower in both children (p = .02) and adolescents (p < .001) with middle ear disease compared with those without. In both children and adolescents, the addendum scores were strongly correlated with total HEAR-QL score (ρSpearman = 0.72 and 0.69, respectively). Conclusions: The expected negative association between hearing loss and HEAR-QL score was observed in adolescents. However, there was significant variability that could not be explained by hearing loss, and further investigation is warranted. The expected negative association was not observed in children. HEAR-QL scores were associated with middle ear disease in both children and adolescents, making it potentially valuable in populations where the prevalence of ear infections is high. Level of Evidence: Level 2 Clinicaltrials.gov registration numbers: NCT03309553.
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Growing evidence suggests considerable variation in endemic typhoid fever incidence at some locations over time, yet few settings have multi-year incidence estimates to inform typhoid control measures. We sought to describe a decade of typhoid fever incidence in the Kilimanjaro Region of Tanzania. Cases of blood culture confirmed typhoid were identified among febrile patients at two sentinel hospitals during three study periods: 2007-08, 2011-14, and 2016-18. To account for under-ascertainment at sentinel facilities, we derived adjustment multipliers from healthcare utilization surveys done in the hospital catchment area. Incidence estimates and credible intervals (CrI) were derived using a Bayesian hierarchical incidence model that incorporated uncertainty of our observed typhoid fever prevalence, of healthcare seeking adjustment multipliers, and of blood culture diagnostic sensitivity. Among 3,556 total participants, 50 typhoid fever cases were identified. Of typhoid cases, 26 (52%) were male and the median (range) age was 22 (<1-60) years; 4 (8%) were aged <5 years and 10 (20%) were aged 5 to 14 years. Annual typhoid fever incidence was estimated as 61.5 (95% CrI 14.9-181.9), 6.5 (95% CrI 1.4-20.4), and 4.0 (95% CrI 0.6-13.9) per 100,000 persons in 2007-08, 2011-14, and 2016-18, respectively. There were no deaths among typhoid cases. We estimated moderate typhoid incidence (≥10 per 100â000) in 2007-08 and low (<10 per 100â000) incidence during later surveillance periods, but with overlapping credible intervals across study periods. Although consistent with falling typhoid incidence, we interpret this as showing substantial variation over the study periods. Given potential variation, multi-year surveillance may be warranted in locations making decisions about typhoid conjugate vaccine introduction and other control measures.
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Febre Tifoide , Vacinas Tíficas-Paratíficas , Teorema de Bayes , Feminino , Humanos , Incidência , Masculino , Inquéritos e Questionários , Tanzânia/epidemiologia , Febre Tifoide/epidemiologia , Febre Tifoide/prevenção & controleRESUMO
Each year, > 3 million children die in sub-Saharan Africa before their fifth birthday. Most deaths are preventable or avoidable through interventions delivered in the primary healthcare system. However, evidence regarding the impact of health system characteristics on child survival is sparse. We assembled a retrospective cohort of > 250,000 children in seven countries in sub-Saharan Africa. We described their health service context at the subnational level using standardized surveys and employed parametric survival models to estimate the effect of three major domains of health services-quality, access, and cost-on infant and child survival, after adjusting for child, maternal, and household characteristics. Between 1995 and 2015 we observed 13,629 deaths in infants and 5149 in children. In fully-adjusted models, the largest effect sizes were related to fees for services. Immunization fees were correlated with poor child survival (HR = 1.20, 95% CI 1.12-1.28) while delivery fees were correlated with poor infant survival (HR = 1.11, 95% CI 1.01-1.21). Accessibility of facilities and greater concentrations of private facilities were associated with improved infant and child survival. The proportion of facilities with a doctor was correlated with increased risk of death in children and infants. We quantify the impact of health service environment on survival up to five years of age. Reducing health care costs and improving the accessibility of health facilities should remain a priority for improving infant and child survival. In the absence of these fundamental investments, more specialized interventions may not achieve their desired impact.
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Mortalidade da Criança/tendências , Atenção à Saúde , Mortalidade Infantil/tendências , Atenção Primária à Saúde , África Subsaariana/epidemiologia , Fatores Etários , Criança , Pré-Escolar , Feminino , Custos de Cuidados de Saúde , Acessibilidade aos Serviços de Saúde , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Qualidade da Assistência à Saúde , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
Background: According to the World Health Organization (WHO), in 2018, an estimated 228 million malaria cases occurred worldwide with most cases occurring in sub-Saharan Africa. Scale-up of vector control tools coupled with increased access to diagnosis and effective treatment has resulted in a large decline in malaria prevalence in some areas, but other areas have seen little change. Although interventional studies demonstrate that preventing malaria during pregnancy can reduce the rate of low birth weight (i.e. child's birth weight <2500 g), it remains unknown whether natural changes in parasite transmission and malaria burden can improve birth outcomes. Methods: We conducted an observational study of the effect of changing malaria burden on low birth weight using data from 18,112 births in 19 countries in sub-Saharan African countries during the years 2000-2015. Specifically, we conducted a difference-in-differences study via a pair-of-pairs matching approach using the fact that some sub-Saharan areas experienced sharp drops in malaria prevalence and some experienced little change. Results: A malaria prevalence decline from a high rate (Plasmodium falciparum parasite rate in children aged 2-up-to-10 (i.e. PfPR2-10) > 0.4) to a low rate (PfPR2-10 < 0.2) is estimated to reduce the rate of low birth weight by 1.48 percentage points (95% confidence interval: 3.70 percentage points reduction, 0.74 percentage points increase), which is a 17% reduction in the low birth weight rate compared to the average (8.6%) in our study population with observed birth weight records (1.48/8.6 ≈ 17%). When focusing on first pregnancies, a decline in malaria prevalence from high to low is estimated to have a greater impact on the low birth weight rate than for all births: 3.73 percentage points (95% confidence interval: 9.11 percentage points reduction, 1.64 percentage points increase). Conclusions: Although the confidence intervals cannot rule out the possibility of no effect at the 95% confidence level, the concurrence between our primary analysis, secondary analyses, and sensitivity analyses, and the magnitude of the effect size, contribute to the weight of the evidence suggesting that declining malaria burden can potentially substantially reduce the low birth weight rate at the community level in sub-Saharan Africa, particularly among firstborns. The novel statistical methodology developed in this article-a pair-of-pairs approach to a difference-in-differences study-could be useful for many settings in which different units are observed at different times. Funding: Ryan A. Simmons is supported by National Center for Advancing Translational Sciences (UL1TR002553). The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Malaria infects around 230 million people each year, mostly in sub-Saharan Africa, and causes more than 400,000 deaths. Pregnant women are particularly susceptible to malaria. The parasite that causes malaria can sap the mother's iron stores and may starve the baby of nutrients. Babies born to infected mothers often have low birth weights, which can have lasting effects on their health and brain development. Previous studies suggest that preventing malaria in pregnant women using insecticide-treated bed nets or medications may improve birth outcomes. Successful efforts to prevent malaria have led to substantially fewer infections in sub-Saharan Africa. But success has been uneven with some communities continuing to have high rates of infection. These differences may allow scientists to better understand the community-level impact of falling rates of malaria on pregnancy outcomes in the real world. Heng et al. estimated that reducing malaria transmission minimises the number of infants born with low birth weights in communities in sub-Saharan Africa. In an observational study, they used data on more than 18,000 births in 19 countries in this region between 2000 and 2015 to assess the effects of declining malaria rates on birth weights. They found that a decrease of malaria prevalence is estimated to reduce the rate of low birth weight by 1.48%, which is a 17% reduction in the number of observed newborns with low birth weight in the study population. First-born infants appeared to benefit the most. This highlights that malaria interventions are beneficial for pregnant women and their newborns. Most analyses of the impact and cost-benefit of malaria control have ignored the potential advantages of malaria control on birth weight, and may thus undermine the benefits of malaria control. The approach used by Heng et al. may further be useful for other epidemiologists studying global health.
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Recém-Nascido de Baixo Peso , Malária/complicações , Malária/epidemiologia , África Subsaariana/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Malária Falciparum/complicações , Malária Falciparum/epidemiologia , Masculino , Plasmodium falciparum , Gravidez , PrevalênciaRESUMO
Disease outbreaks can readily threaten swine production operations sometimes resulting in large economic losses. Pathogen surveillance in swine farms can be an effective approach for the early identification of new disease threats and the mitigation of transmission before broad dissemination among a herd occurs. Non-invasive environmental bioaerosol sampling could be an effective and affordable approach for conducting routine surveillance in farms, providing an additional tool for farmers to protect their animals and themselves from new disease threats. In this pilot study, we implemented a non-invasive, prospective bioaerosol sampling strategy in a swine farm located in the United States to detect economically important swine pathogens. Farm personnel collected air samples from two swine barns for 23 weeks between July and December 2017. Samples were then tested within 24 hr of collection by molecular techniques for a number of economically important swine pathogens. Of the 86 bioaerosol samples collected, 4 (4.7%) were positive for influenza A, 1 (1.2%) was positive for influenza D, 13 (15.1%) were positive for PCV2, and 13 (15.1%) were positive for PCV3. Overall, this pilot study showed that our bioaerosol surveillance strategy was feasible and able to generate data that could be quickly disseminated back to the farm stakeholders (within 24 hr). We were also able to identify PCV2, PCV3 and influenza A virus in air samples as clinical disease became apparent in the pigs, strongly suggesting that bioaerosol sampling can be used as an effective non-invasive surveillance approach for the detection of multiple pathogens in this and likely other animal production environments.
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Microbiologia do Ar , Circovirus/isolamento & purificação , Fazendas , Orthomyxoviridae/isolamento & purificação , Animais , Infecções por Circoviridae/epidemiologia , Infecções por Circoviridae/veterinária , Infecções por Circoviridae/virologia , Monitoramento Ambiental , Monitoramento Epidemiológico , Fazendeiros , Humanos , Vírus da Influenza A/isolamento & purificação , North Carolina , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/veterinária , Infecções por Orthomyxoviridae/virologia , Projetos Piloto , Estudos Prospectivos , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/virologia , Thogotovirus/isolamento & purificaçãoRESUMO
BACKGROUND: A large proportion of artemisinin-combination therapy (ACT) anti-malarial medicines is consumed by individuals that do not have malaria. The over-consumption of ACTs is largely driven by retail sales in high malaria-endemic countries to clients who have not received a confirmatory diagnosis. This study aims to target ACT sales to clients receiving a confirmatory diagnosis using malaria rapid diagnostic tests (mRDTs) at retail outlets in Kenya and Nigeria. METHODS: This study comprises two linked four-arm 2 × 2 factorial cluster randomized controlled trials focused on malaria diagnostic testing and conditional ACT subsidies with the goal to evaluate provider-directed and client-directed interventions. The linked trials will be conducted at two contrasting study sites: a rural region around Webuye in western Kenya and the urban center of Lagos, Nigeria. Clusters are 41 and 48 participating retail outlets in Kenya and Nigeria, respectively. Clients seeking care at participating outlets across all arms will be given the option of paying for a mRDT-at a study-recommended price-to be conducted at the outlet. In the provider-directed intervention arm, the outlet owner receives a small monetary incentive to perform the mRDT. In the client-directed intervention arm, the client receives a free ACT if they purchase an mRDT and receive a positive test result. Finally, the fourth study arm combines both the provider- and client-directed interventions. The diagnosis and treatment choices made during each transaction will be captured using a mobile phone app. Study outcomes will be collected through exit interviews with clients, who sought care for febrile illness, at each of the enrolled retail outlets. RESULTS: The primary outcome measure is the proportion of all ACTs that are sold to malaria test-positive clients in each study arm. For all secondary outcomes, we will evaluate the degree to which the interventions affect purchasing behavior among people seeking care for a febrile illness at the retail outlet. CONCLUSIONS: If our study demonstrates that malaria case management can be improved in the retail sector, it could reduce overconsumption of ACTs and enhance targeting of publicly funded treatment reimbursements, lowering the economic barrier to appropriate diagnosis and treatment for patients with malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT04428307 , registered June 9, 2020, and NCT04428385 , registered June 9, 2020.
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Antimaláricos , Malária , Antimaláricos/uso terapêutico , Administração de Caso , Humanos , Quênia , Malária/diagnóstico , Malária/tratamento farmacológico , Motivação , Nigéria , Setor Privado , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Statistical efficiency can be gained in clinical trials by using composites of time-to-event outcomes when the individual component outcomes have low event rates. However, the utility of continuous composite outcome measures is not as clear. Efficiency can be either gained or lost by using a continuous composite outcome measure depending on several factors, including the strength of correlation between the component outcomes and the size of the treatment effect on each component. In this article we review these concepts from the standpoint of planning a new trial. Statistical properties of composites formed from normally distributed continuous outcomes are discussed. An example dataset is used to demonstrate concepts and complete mathematical details are provided. Finally, a conceptual model for clinical trial design with continuous composites is proposed that could be used as a guide to evaluate the utility of a continuous composite outcome in a future trial based on existing knowledge in the therapeutic area.
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INTRODUCTION: In many malaria-endemic countries, the private retail sector is a major source of antimalarial drugs. However, the rarity of malaria diagnostic testing in the retail sector leads to overuse of the first-line class of antimalarial drugs known as artemisinin-combination therapies (ACTs). The goal of this study was to identify the combination of malaria rapid diagnostic test (RDT) and ACT subsidies that maximises the proportion of clients seeking care in a retail outlet that choose to purchase an RDT (RDT uptake) and use ACTs appropriately. METHODS: 842 clients seeking care in 12 select retail outlets in western Kenya were recruited and randomised into 4 arms of different combinations of ACT and RDT subsidies, with ACT subsidies conditional on a positive RDT. The outcomes were RDT uptake (primary) and appropriate and targeted ACT use (secondary). Participants' familiarity with RDTs and their confidence in test results were also evaluated. RESULTS: RDT uptake was high (over 96%) across the study arms. Testing uptake was 1.025 times higher (98% CI 1.002 to 1.049) in the RDT subsidised arms than in the unsubsidised groups. Over 98% of clients were aware of malaria testing, but only 35% had a previous experience with RDTs. Nonetheless, confidence in the accuracy of RDTs was high. We found high levels of appropriate use and targeting of ACTs, with 86% of RDT positives taking an ACT, and 93.4% of RDT negatives not taking an ACT. The conditional ACT subsidy did not affect the RDT test purchasing behaviour (risk ratio: 0.994; 98% CI 0.979 to 1.009). CONCLUSION: Test dependent ACT subsidies may contribute to ACT targeting. However, in this context, high confidence in the accuracy of RDTs and reliable supplies of RDTs and ACTs likely played a greater role in testing uptake and adherence to test results.
Assuntos
Antimaláricos , Malária , Antimaláricos/uso terapêutico , Febre/tratamento farmacológico , Humanos , Quênia/epidemiologia , Malária/diagnóstico , Malária/tratamento farmacológico , Malária/epidemiologia , Setor PrivadoRESUMO
OBJECTIVE: To evaluate a lay provider-delivered, brief intervention to reduce problem drinking and related family consequences among men in Kenya. The 5-session intervention combines behavioral activation (BA) and motivational interviewing (MI). It integrates family-related material explicitly and addresses central cultural factors through gender transformative strategies. METHOD: A nonconcurrent multiple-baseline design was used. We initiated treatment with 9 men ages 30 to 48 who were fathers and screened positive for problem drinking; the median Alcohol Use Identification Test score was 17 (harmful range). Participants were randomized to staggered start dates. We measured the primary outcome of weekly alcohol consumption 4 weeks before treatment, during treatment, and 4 weeks posttreatment using the Timeline Followback measure. Secondary outcomes were assessed using a pre-post assessment (1-month) of men's depression symptoms, drinking- and family-related problem behavior, involvement with child, time with family, family functioning, relationship quality (child and partner), and harsh treatment of child and partner. Men, partners, and children (ages 8-17) reported on family outcomes. RESULTS: Eight men completed treatment. Mixed-effects hurdle model analysis showed that alcohol use, both number of days drinking and amount consumed, significantly decreased during and after treatment. Odds of not drinking were 5.1 times higher posttreatment (95% CI [3.3, 7.9]). When men did drink posttreatment, they drank 50% less (95% CI [0.39, 0.65]). Wilcoxon signed-ranks test demonstrated pre-post improvements in depression symptoms and family related outcomes. CONCLUSION: Results provide preliminary evidence that a BA-MI intervention developed for lay providers may reduce alcohol use and improve family outcomes among men in Kenya. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Assuntos
Consumo de Bebidas Alcoólicas/prevenção & controle , Alcoolismo/terapia , Terapia Comportamental , Relações Familiares , Pai , Entrevista Motivacional , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/etnologia , Alcoolismo/etnologia , Criança , Relações Familiares/etnologia , Feminino , Humanos , Quênia/etnologia , Masculino , Pessoa de Meia-Idade , Entrevista Motivacional/métodosRESUMO
BACKGROUND: Acute respiratory infections are a common reason for antibiotic overuse. We previously showed that providing Sri Lankan clinicians with positive rapid influenza test results was associated with a reduction in antibiotic prescriptions. The economic impact of influenza diagnostic strategies is unknown. METHODS: We estimated the incremental cost per antibiotic prescription avoided with three diagnostic strategies versus standard care when managing Sri Lankan outpatients with influenza-like illness (ILI): (1) influenza clinical prediction tool, (2) targeted rapid influenza testing and (3) universal rapid influenza testing. We compared findings with literature-based estimates of the cost of antimicrobial resistance attributable to each antibiotic prescription. RESULTS: Standard care was less expensive than other strategies across all parameter values in one-way sensitivity analyses. The incremental cost per antibiotic prescription avoided with clinical prediction versus standard care was US$3.0, which was lower than the base-case estimate of the cost of antimicrobial resistance per ILI antibiotic prescription (US$12.5). The incremental cost per antibiotic prescription avoided with targeted testing and universal testing versus standard care were both higher than the base-case cost of antimicrobial resistance per ILI antibiotic prescription: US$49.1 and US$138.3, respectively. To obtain a cost-effectiveness ratio lower than US$12.5 with targeted testing versus standard care, the test price must be
RESUMO
BACKGROUND: Self-treatment with antimicrobials is common in sub-Saharan Africa. Little is known about the prevalence of this practice where malaria transmission intensity is low, and little is known about the prevalence of self-treatment with other medications such as antihypertensives and antihyperglycemics. METHODS: A two-stage randomized population-based cluster survey with selection proportional to population size was performed in northern Tanzania. Self-identified healthcare decision-makers from randomly selected households were asked to report instances of self-medication without a prescription in the preceding year. Associations between self-treatment and sociodemographic characteristics were assessed with Pearson's chi-squared and the Student's t-test. RESULTS: A total of 718 participants completed the survey, and 344 (47.9%) reported any household member obtaining medication without a prescription. Of these, 85 (11.8%) obtained an antimicrobial and four (0.6%) obtained an antihypertensive or antihyperglycemic. Of respondents reporting self-treatment, 306 (89.0%) selected the medication themselves. Self-treatment with antimicrobials was associated with post-primary education (OR 1.95, 95% CI 1.22-3.16, p=0.005), younger age (43.1 vs 48.7 years, p=0.007) and higher socioeconomic status score (0.42 vs 0.34, p=0.023). CONCLUSIONS: Self-treatment with antimicrobials in an area of low malaria transmission intensity was uncommon and self-treatment with antihypertensives and antihyperglycemics was rare.