Intervention Clusters Research Articles

The effect of providing women sustained access to HIV self-tests on male partner testing, couples testing, and HIV incidence in Kenya: a cluster-randomised trial.

HIV self-testing can overcome barriers to HIV testing, but its potential as an HIV prevention strategy for women in sub-Saharan Africa has not been assessed. We examined whether sustained provision of self-tests to women promotes testing among sexual partners and reduces HIV incidence. We conducted a pair-matched cluster-randomised trial in 66 community clusters in Siaya County, Kenya. Clusters were communities with a high prevalence of transactional sex, including beach communities along Lake Victoria and inland communities with hotspots for transactional sex such as bars and hotels. Within clusters, we recruited HIV-negative women aged 18 years or older with two or more sexual partners within the past 4 weeks. In each of the 33 cluster pairs, we randomly assigned clusters to an intervention and comparison group. In intervention clusters, we provided participants with multiple self-tests at regular intervals and encouraged secondary distribution of self-tests to sexual partners. In comparison clusters, we provided participants referral cards for facility-based testing. Follow-up visits and HIV testing occurred at 6-month intervals for up to 24 months. The primary outcome of HIV incidence among all participants who contributed at least one HIV test was analysed using discrete-time mixed effects models. This study is registered with ClinicalTrials.gov, NCT03135067. Between June 4, 2017, and Aug 31, 2018, we enrolled 2090 participants (1033 in the 33 intervention clusters and 1057 in the 33 comparison clusters). Participants' median age was 25 years (IQR 22-31) and 1390 (66·6%) of 2086 participants reported sex work as an income source. 1840 participants completed the 18-month follow-up and 570 participants completed the 24-month follow up, which ended on March 25, 2020, with a median follow-up duration of 17·6 months. HIV incidence was not significantly different between the intervention and comparison groups (1·2 vs 1·0 per 100 person-years; hazard ratio 1·2, 95% CI 0·6-2·3, p=0·64). Social harms related to study participation occurred in three participants (two in the intervention group and one in the comparison group). Sustained provision of multiple self-tests to women at high risk of HIV infection in Kenya enabled secondary distribution of self-tests to sexual partners but did not affect HIV incidence. National Institute of Mental Health; Center for Health Incentives and Behavioral Economics; National Institute of Allergies and Infectious Diseases; University of Pennsylvania Center for AIDS Research.

Triaging and referring in adjacent general and emergency departments (the TRIAGE trial): A cluster randomised controlled trial.

To determine whether a new triage system safely diverts a proportion of emergency department (ED) patients to a general practitioner cooperative (GPC). Unblinded randomised controlled trial with weekends serving as clusters (three intervention clusters for each control). The intervention was triage by a nurse using a new extension to the Manchester Triage System assigning low-risk patients to the GPC. During intervention weekends, patients were encouraged to follow this assignment; it was not communicated during control weekends (all patients remained at the ED). The primary outcome was the proportion of patients assigned to and handled by the GPC during intervention weekends. The trial was randomised for the secondary outcome: the proportion of patients assigned to the GPC. Additional outcomes were association of these outcomes with possible confounders (study tool parameters, nurse, and patient characteristics), proportion of patients referred back to the ED by the GPC, hospitalisations, and performance of the study tool to detect primary care patients (the opinion of the treating physician was the gold standard). In the intervention group, 838/6294 patients (13.3%, 95% CI 12.5 to 14.2) were assigned to the GPC, in the control group this was 431/1744 (24.7%, 95% CI 22.7 to 26.8). In total, 599/6294 patients (9.5%, 95% CI 8.8 to 10.3) experienced the primary outcome which was influenced by the reason for encounter, age, and the nurse. 24/599 patients (4.0%, 95% CI 2.7 to 5.9) were referred back to the ED, three were hospitalised. Positive and negative predictive values of the studied tool during intervention weekends were 0.96 (95%CI 0.94 to 0.97) and 0.60 (95% CI 0.58 to 0.62). Out of the patients assigned to the GPC, 2.4% (95% CI 1.7 to 3.4) were hospitalised. ED nurses using a new tool safely diverted 9.5% of the included patients to primary care. ClinicalTrials.gov Identifier: NCT03793972.

Changing hygiene behaviours: a cluster-randomized trial, Ethiopia.

ObjectiveTo determine whether a water, sanitation and hygiene intervention could change hygiene behaviours thought to be important for trachoma control.MethodsWe conducted a cluster-randomized trial in rural Ethiopia from 9 November 2015 to 5 March 2019. We randomized 20 clusters to an intervention consisting of water and sanitation infrastructure and hygiene promotion and 20 clusters to no intervention. All intervention clusters received a primary-school hygiene curriculum, community water point, household wash station, household soap and home visits from hygiene promotion workers. We assessed intervention fidelity through annual household surveys.FindingsOver the 3 years, more wash stations, soap and latrines were seen at households in the intervention clusters than the control clusters: risk difference 47 percentage points (95% confidence interval, CI: 41–53) for wash stations, 18 percentage points (95% CI: 12–24) for soap and 12 percentage points (95% CI: 5–19) for latrines. A greater proportion of people in intervention clusters reported washing their faces with soap (e.g. risk difference 21 percentage points; 95% CI: 15–27 for 0–5 year-old children) and using a latrine (e.g. risk difference 9 percentage points; 95% CI: 2–15 for 6–9 year-old children). Differences between the intervention and control arms were not statistically significant for many indicators until the programme had been implemented for at least a year; they did not decline during later study visits.ConclusionThe community- and school-based intervention was associated with improved hygiene access and behaviours, although changes in behaviour were slow and required several years of the intervention.

The Effects of Workplace-Based HIV Self-testing on Uptake of Testing and Linkage to HIV Care or Prevention by Men in Uganda (WISe-Men): Protocol for a Cluster Randomized Trial.

BackgroundHIV testing uptake remains low among men in sub-Saharan Africa. HIV self-testing (HIVST) at the workplace is a novel approach to increase the availability of, and access to, testing among men. However, both access and linkage to posttest services remain a challenge.ObjectiveThe aim of this protocol is to describe a cluster randomized trial (CRT)—Workplace-Based HIV Self-testing Among Men (WISe-Men)—to evaluate the effect of HIVST in workplace settings on the uptake of HIV testing services (HTS) and linkage to treatment and prevention services among men employed in private security services in Uganda.MethodsThis is a two-arm CRT involving men employed in private security services in two Ugandan districts. The participants in the intervention clusters will undergo workplace-based HIVST using OraQuick test kits. Those in the control clusters will receive routine HTS at their work premises. In addition to HTS, participants in both the intervention and control arms will undergo other tests and assessments, which include blood pressure assessment, blood glucose and BMI measurement, and rapid diagnostic testing for syphilis. The primary outcome is the uptake of HIV testing. The secondary outcomes include HIV status reporting, linkage into HIV care and confirmatory testing following HIVST, initiation of antiretroviral therapy following a confirmatory HIV test, the uptake of voluntary medical male circumcision, consistent condom use, and the uptake of pre-exposure prophylaxis by the most at-risk populations.ResultsParticipant enrollment commenced in February 2020, and the trial is still recruiting study participants. Follow-up for currently enrolled participants is ongoing. Data collection and analysis is expected to be completed in December 2021.ConclusionsThe WISe-Men trial will provide information regarding whether self-testing at worksites increases the uptake of HIV testing as well as the linkage to care and prevention services at male-dominated workplaces in Uganda. Additionally, the findings will help us propose strategies for improving men’s engagement in HTS and ways to improve linkage to further care following a reactive or nonreactive HIVST result.Trial RegistrationClinicalTrials.gov NCT04164433; https://clinicaltrials.gov/ct2/show/NCT04164433International Registered Report Identifier (IRRID)DERR1-10.2196/25099

Initial Contraceptive Choices of Women Enrolled in a Cluster-Randomized Trial in Southwest Trifinio, Guatemala.

The aim of this analysis is to present initial contraceptive choices of women offered postpartum contraception in rural Guatemala. We trained community nurses participating in the delivery of a home-based antepartum and postpartum care program in rural Guatemala in contraceptive implant placement and had them offer condoms, pills, an injection, or an implant at women's home-based 40-day postpartum visit in intervention clusters of a non-blinded, cluster-randomized trial. Women who had already started postpartum contraception or were over the age of 35 were excluded from participation. The primary outcome of the trial was contraceptive use at 3months postpartum, so this initial analysis describes immediate preferences in the population. Of 208 women enrolled in the study, 108 were in intervention clusters and 100 lived in control clusters. In the intervention group, 32 women declined contraception, 36 women received the injectable, 30 women had an implant placed, 5 women started pills, 2 women chose condoms, and data on 3 women were missing. In the control clusters, 43 women were planning on the injectable, 11 planned on the implant, 10 did not want to start a method, 5 planned on sterilization, 2 aimed for natural family planning, 2 wanted a copper IUD, 1 woman wanted condoms, 18 did not know, and data on 8 women were missing. The contraceptive implant, which was not previously available in this community, had high uptake at 27.8% in the intervention group. Clinicaltrials.gov, NCT04005391; Retrospectively Registered 7/2/2019, https://clinicaltrials.gov/ct2/show/NCT04005391 Protocol: https://doi.org/10.1186/s13063-019-3735-3.

Protective effect of house screening against indoor Aedes aegypti in Mérida, Mexico: A cluster randomised controlled trial.

ObjectiveTo evaluate the protective effect of house screening (HS) on indoor Aedes aegypti infestation, abundance and arboviral infection in Merida, Mexico.MethodsIn 2019, we performed a cluster randomised controlled trial (6 control and 6 intervention areas: 100 households/area). Intervention clusters received permanently fixed fiberglass HS on all windows and doors. The study included two cross‐sectional entomologic surveys, one baseline (dry season in May 2019) and one post‐intervention (PI, rainy season between September and October 2019). The presence and number of indoor Aedes females and blood‐fed females (indoor mosquito infestation) as well as arboviral infections with dengue (DENV) and Zika (ZIKV) viruses were evaluated in a subsample of 30 houses within each cluster.ResultsHS houses had significantly lower risk for having Aedes aegypti female mosquitoes (odds ratio [OR] = 0.56, 95% CI 0.33–0.97, p = 0.04) and blood‐fed females (OR = 0.53, 95% CI 0.28–0.97, p = 0.04) than unscreened households from the control arm. Compared to control houses, HS houses had significantly lower indoor Ae. aegypti abundance (rate ratio [RR] = 0.50, 95% CI 0.30–0.83, p = 0.01), blood‐fed Ae. aegypti females (RR = 0.48, 95% CI 0.27–0.85, p = 0.01) and female Ae. aegypti positive for arboviruses (OR = 0.29, 95% CI 0.10–0.86, p = 0.02). The estimated intervention efficacy in reducing Ae. aegypti arbovirus infection was 71%.ConclusionsThese results provide evidence supporting the use of HS as an effective pesticide‐free method to control house infestations with Aedes aegypti and reduce the transmission of Aedes‐transmitted viruses such as DENV, chikungunya (CHIKV) and ZIKV.

Some design considerations for cluster randomized trials with binary responses

This article discusses optimal allocation of experimental units in a control versus intervention cluster randomized trial for binary responses. Optimal allocations are based on a well known optimality criterion. To address the issue of parameter dependency on design criterion, locally, Bayesian, and min–max optimal designs are proposed. An efficiency analysis is carried out to assess the performance of proposed optimal designs. All theoretically obtained optimal designs are complemented by numerical experiments including a real data example which demonstrate that designs proposed are associated with a substantial increment in efficiency compared to the commonly used balanced design.

Effect of sunflower seed oil emollient therapy on newborn infant survival in Uttar Pradesh, India: A community-based, cluster randomized, open-label controlled trial.

Hospitalized preterm infants with compromised skin barrier function treated topically with sunflower seed oil (SSO) have shown reductions in sepsis and neonatal mortality rate (NMR). Mustard oil and products commonly used in high-mortality settings may possibly harm skin barrier integrity and enhance risk of infection and mortality in newborn infants. We hypothesized that SSO therapy may reduce NMR in such settings. This was a population-based, cluster randomized, controlled trial in 276 clusters in rural Uttar Pradesh, India. All newborn infants identified through population-based surveillance in the study clusters within 7 days of delivery were enrolled from November 2014 to October 2016. Exclusive, 3 times daily, gentle applications of 10 ml of SSO to newborn infants by families throughout the neonatal period were recommended in intervention clusters (n = 138 clusters); infants in comparison clusters (n = 138 clusters) received usual care, such as massage practice typically with mustard oil. Primary analysis was by intention-to-treat with NMR and post-24-hour NMR as the primary outcomes. Secondary analysis included per-protocol analysis and subgroup analyses for NMR. Regression analysis was adjusted for caste, first-visit weight, delivery attendant, gravidity, maternal age, maternal education, sex of the infant, and multiple births. We enrolled 13,478 (52.2% male, mean weight: 2,575.0 grams ± standard deviation [SD] 521.0) and 13,109 (52.0% male, mean weight: 2,607.0 grams ± SD 509.0) newborn infants in the intervention and comparison clusters, respectively. We found no overall difference in NMR in the intervention versus the comparison clusters [adjusted odds ratio (aOR) 0.96, 95% confidence interval (CI) 0.84 to 1.11, p = 0.61]. Acceptance of SSO in the intervention arm was high at 89.3%, but adherence to exclusive applications of SSO was 30.4%. Per-protocol analysis showed a significant 58% (95% CI 42% to 69%, p < 0.01) reduction in mortality among infants in the intervention group who were treated exclusively with SSO as intended versus infants in the comparison group who received exclusive applications of mustard oil. A significant 52% (95% CI 12% to 74%, p = 0.02) reduction in NMR was observed in the subgroup of infants weighing ≤1,500 g (n = 589); there were no statistically significant differences in other prespecified subgroup comparisons by low birth weight (LBW), birthplace, and wealth. No severe adverse events (SAEs) were attributable to the intervention. The study was limited by inability to mask allocation to study workers or participants and by measurement of emollient use based on caregiver responses and not actual observation. In this trial, we observed that promotion of SSO therapy universally for all newborn infants was not effective in reducing NMR. However, this result may not necessarily establish equivalence between SSO and mustard oil massage in light of our secondary findings. Mortality reduction in the subgroup of infants ≤1,500 g was consistent with previous hospital-based efficacy studies, potentially extending the applicability of emollient therapy in very low-birth-weight (VLBW) infants along the facility-community continuum. Further research is recommended to develop and evaluate therapeutic regimens and continuum of care delivery strategies for emollient therapy for newborn infants at highest risk of compromised skin barrier function. ISRCTN Registry ISRCTN38965585 and Clinical Trials Registry-India (CTRI/2014/12/005282) with WHO UTN # U1111-1158-4665.

Effect of Community-Based Kangaroo Mother Care Package on Neonatal Mortality Among Preterm and Low Birthweight Infants in Rural Pakistan: Protocol for a Cluster Randomized Controlled Trial.

BackgroundNeonatal mortality due to preterm birth and low birthweight remains a significant challenge in Pakistan. Kangaroo mother care (KMC) is a unique, low-cost intervention proven to reduce neonatal mortality and morbidity and increase exclusive breastfeeding rates. However, KMC has not been attempted in community settings in Pakistan. We aim to implement and evaluate the effectiveness of a community-based KMC package to reduce neonatal morbidity and mortality among preterm and low birthweight (LBW) infants, which will provide evidence for policy development and the large-scale implementation of KMC across the country.ObjectiveThe primary objective of this trial is to reduce neonatal mortality among preterm and LBW infants. The secondary objectives are growth (measured as weight gain), reduced incidence of possible serious bacterial infection, and increased exclusive breastfeeding and continued breastfeeding practices.MethodsWe designed a community-based cluster randomized controlled trial in one rural district of Pakistan. Stable, LBW babies (weighing 1200 grams to 2500 grams) are included in the study. The community KMC package, consisting of the KMC kit, information and counseling material, and community mobilization through KMC champions (village volunteers), was designed after preliminary research in the same geographical location and implemented in intervention clusters. The standard essential newborn care is offered in the control clusters. Infants are recruited and followed up by independent teams of data collectors. Data are collected on the duration of skin-to-skin contact, growth, breastfeeding practices, morbidities, neonatal mortality, and neurodevelopment status. Data analysis will be conducted based on the intention to treat principle. The Cox regression model will be used to assess the primary outcome of neonatal mortality. The secondary outcomes will be evaluated using linear or logistic regression.ResultsThe Ethics Review Committee of Aga Khan University, Pakistan, approved the study protocol in February 2017. Data collection began in August 2019 and will be completed in December 2021. Data analyses are yet to be completed.ConclusionsThis intervention may be effective in preventing sepsis and subsequently improve survival in LBW newborns in Pakistan and other low-income and middle-income countries worldwide.Trial Registrationclinicaltrials.gov NCT03545204; https://clinicaltrials.gov/ct2/show/NCT03545204International Registered Report Identifier (IRRID)DERR1-10.2196/28156

Community-based amoxicillin treatment for fast breathing pneumonia in young infants 7–59 days old: a cluster randomised trial in rural Bangladesh, Ethiopia, India and Malawi

IntroductionYoung infants 7–59 days old with fast breathing pneumonia presented to a primary level health facility receive a 7-day course of amoxicillin as per the WHO guideline. However, community-level health...

Causes and circumstances of maternal death: a secondary analysis of the Community-Level Interventions for Pre-eclampsia (CLIP) trials cohort

SummaryBackgroundIncomplete vital registration systems mean that causes of death during pregnancy and childbirth are poorly understood in low-income and middle-income countries. To inform global efforts to reduce maternal mortality, we compared physician review and computerised analysis of verbal autopsies (interpreting verbal autopsies [InterVA] software), to understand their agreement on maternal cause of death and circumstances of mortality categories (COMCATs) in the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials.MethodsThe CLIP trials took place in India, Pakistan, and Mozambique, enrolling pregnant women aged 12–49 years between Nov 1, 2014, and Feb 28, 2017. 69 330 pregnant women were enrolled in 44 clusters (36 008 in the 22 intervention clusters and 33 322 in the 22 control clusters). In this secondary analysis of maternal deaths in CLIP, we included women who died in any of the 22 intervention clusters or 22 control clusters. Trained staff administered the WHO 2012 verbal autopsy after maternal deaths. Two physicians (and a third for consensus, if needed) reviewed trial surveillance data and verbal autopsies, and, in intervention clusters, community health worker-led visit data. They determined cause of death according to the WHO International Classification of Diseases-Maternal Mortality (ICD-MM). Verbal autopsies were also analysed by InterVA computer models (versions 4 and 5) to generate cause of death. COMCAT analysis was provided by InterVA-5 and, in India, by physician review of Maternal Newborn Health Registry data. Causes of death and COMCATs assigned by physician review, Inter-VA-4, and InterVA-5 were compared, with agreement assessed with Cohen's κ coefficient.FindingsOf 61 988 pregnancies with successful follow-up in the CLIP trials, 143 maternal deaths were reported (16 deaths in India, 105 in Pakistan, and 22 in Mozambique). The maternal death rate was 231 (95% CI 193–268) per 100 000 identified pregnancies. Most deaths were attributed to direct maternal causes (rather than indirect or undetermined causes as per ICD-MM classification), with fair to good agreement between physician review and InterVA-4 (κ=0·56 [95% CI 0·43–0·66]) or InterVA-5 (κ=0·44 [0·30–0·57]), and InterVA-4 and InterVA-5 (κ=0·72 [0·60–0·84]). The top three causes of death were the same by physician review, InterVA-4, and InterVA-5 (ICD-MM categories obstetric haemorrhage, non-obstetric complications, and hypertensive disorders); however, attribution of individual patient deaths to obstetric haemorrhage varied more between methods (physician review, 38 [27%] deaths; InterVA-4, 69 [48%] deaths; and InterVA-5, 82 [57%] deaths), than did attribution to non-obstetric causes (physician review, 39 [27%] deaths; InterVA-4, 37 [26%] deaths; and InterVA-5, 28 [20%] deaths) or hypertensive disorders (physician review, 23 [16%] deaths; InterVA-4, 25 [17%] deaths; and InterVA-5, 24 [17%] deaths). Agreement for all nine ICD-MM categories was fair for physician review versus InterVA-4 (κ=0·48 [0·38–0·58]), poor for physician review versus InterVA-5 (κ=0·36 [0·27–0·46]), and good for InterVA-4 versus InterVA-5 (κ=0·69 [0·59–0·79]). The most commonly assigned COMCATs by InterVA-5 were emergencies (68 [48%] of 143 deaths) and health systems (62 [43%] deaths), and by physician review (India only) were health systems (seven [44%] of 16 deaths) and inevitability (five [31%] deaths); agreement between InterVA-5 and physician review (India data only) was poor (κ=0·04 [0·00–0·15]).InterpretationOur findings indicate that InterVA-5 is less accurate than InterVA-4 at ascertaining causes and circumstances of maternal death, when compared with physician review. Our results suggest a need to improve the next iteration of InterVA, and for researchers and clinicians to preferentially use InterVA-4 when recording maternal deaths.FundingUniversity of British Columbia (grantee of the Bill & Melinda Gates Foundation).

Optimizing Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older Adults (OPERAM): cluster randomised controlled trial

ObjectiveTo examine the effect of optimising drug treatment on drug related hospital admissions in older adults with multimorbidity and polypharmacy admitted to hospital.DesignCluster randomised controlled trial.Setting110 clusters of inpatient wards...

Process evaluation of the Bridging the Age Gap in Breast Cancer decision support intervention cluster randomised trial

BackgroundThe Bridging the Age Gap in Breast Cancer research programme sought to improve treatment decision-making for older women with breast cancer by developing and testing, in a cluster randomised trial (n = 1339 patients), two decision support interventions (DESIs). Both DESIs were used in the intervention arm and each comprised an online risk prediction model, brief decision aid and information booklet. One DESI supported the decision to have either primary endocrine therapy (PET) or surgery with adjuvant therapies and the second supported the decision to have adjuvant chemotherapy after surgery or not.MethodsSixteen sites were randomly selected to take part in the process evaluation. Multiple methods of data collection were used. Medical Research Council (MRC) guidelines for the evaluation of complex interventions were used.ResultsEighty-two patients, mean age 75.5 (range 70–93), provided data for the process evaluation. Seventy-three interviews were completed with patients. Ten clinicians from six intervention sites took part in telephone interviews. Dose: Ninety-one members of staff in the intervention arm received intervention training. Reach: The online tool was accessed on 324 occasions by 27 clinicians. Reasons for non-use of the online tool were commonly that the patient had already made a decision or that there was no online access in the clinic. Of the 32 women for whom there were data available, fifteen from the intervention arm and six from the usual care arm were offered a choice of treatment. Fidelity: Clinicians used the online tool in different ways, with some using it during the consultation and others checking the online survival estimates before the consultation. Adaptation: There was evidence of adaptation when using the DESIs. A lack of infrastructure, e.g. internet access, was a barrier to the use of the online tool. The brief decision aid was rarely used. Mediators: Shared decision-making: Most patients felt able to contribute to decision-making and expressed high levels of satisfaction with the process. Participants’ responses to intervention: Six patients reported the DESIs to be very useful, one somewhat useful and two moderately useful.ConclusionsClinicians who participated were mainly supportive of the interventions and had attempted some adaptations to make the interventions applicable, but there were practical and engagement barriers that led to sub-optimal adoption in routine practice.Trial registrationISRCTN46099296. Registered on 11 August 2016—retrospectively registered

Blood pressure thresholds in pregnancy for identifying maternal and infant risk: a secondary analysis of Community-Level Interventions for Pre-eclampsia (CLIP) trial data

SummaryBackgroundBlood pressure measurement is a marker of antenatal care quality. In well resourced settings, lower blood pressure cutoffs for hypertension are associated with adverse pregnancy outcomes. We aimed to study the associations between blood pressure thresholds and adverse outcomes and the diagnostic test properties of these blood pressure cutoffs in low-resource settings.MethodsWe did a secondary analysis of data from 22 intervention clusters in the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials (NCT01911494) in India (n=6), Mozambique (n=6), and Pakistan (n=10). We included pregnant women aged 15–49 years (12–49 years in Mozambique), identified in their community by trained community health workers, who had data on blood pressure measurements and outcomes. The trial was unmasked. Maximum blood pressure was categorised as: normal blood pressure (systolic blood pressure [sBP] <120 mm Hg and diastolic blood pressure [dBP] <80 mm Hg), elevated blood pressure (sBP 120–129 mm Hg and dBP <80 mm Hg), stage 1 hypertension (sBP 130–139 mm Hg or dBP 80–89 mm Hg, or both), non-severe stage 2 hypertension (sBP 140–159 mm Hg or dBP 90–109 mm Hg, or both), or severe stage 2 hypertension (sBP ≥160 mm Hg or dBP ≥110 mm Hg, or both). We classified women according to the maximum blood pressure category reached across all visits for the primary analyses. The primary outcome was a maternal, fetal, or neonatal mortality or morbidity composite. We estimated dose-response relationships between blood pressure category and adverse outcomes, as well as diagnostic test properties.FindingsBetween Nov 1, 2014, and Feb 28, 2017, 21 069 women (6067 in India, 4163 in Mozambique, and 10 839 in Pakistan) contributed 103 679 blood pressure measurements across the three CLIP trials. Only women with non-severe or severe stage 2 hypertension, as discrete diagnostic categories, experienced more adverse outcomes than women with normal blood pressure (risk ratios 1·29–5·88). Using blood pressure categories as diagnostic thresholds (women with blood pressure within the category or any higher category vs those with blood pressure in any lower category), dose-response relationships were observed between increasing thresholds and adverse outcomes, but likelihood ratios were informative only for severe stage 2 hypertension and maternal CNS events (likelihood ratio 6·36 [95% CI 3·65–11·07]) and perinatal death (5·07 [3·64–7·07]), particularly stillbirth (8·53 [5·63–12·92]).InterpretationIn low-resource settings, neither elevated blood pressure nor stage 1 hypertension were associated with maternal, fetal, or neonatal mortality or morbidity adverse composite outcomes. Only the threshold for severe stage 2 hypertension met diagnostic test performance standards. Current diagnostic thresholds for hypertension in pregnancy should be retained.FundingUniversity of British Columbia, the Bill & Melinda Gates Foundation.

Predictive Monitoring-Impact in Acute Care Cardiology Trial (PM-IMPACCT): Protocol for a Randomized Controlled Trial.

BackgroundPatients in acute care wards who deteriorate and are emergently transferred to intensive care units (ICUs) have poor outcomes. Early identification of patients who are decompensating might allow for earlier clinical intervention and reduced morbidity and mortality. Advances in bedside continuous predictive analytics monitoring (ie, artificial intelligence [AI]–based risk prediction) have made complex data easily available to health care providers and have provided early warning of potentially catastrophic clinical events. We present a dynamic, visual, predictive analytics monitoring tool that integrates real-time bedside telemetric physiologic data into robust clinical models to estimate and communicate risk of imminent events. This tool, Continuous Monitoring of Event Trajectories (CoMET), has been shown in retrospective observational studies to predict clinical decompensation on the acute care ward. There is a need to more definitively study this advanced predictive analytics or AI monitoring system in a prospective, randomized controlled, clinical trial.ObjectiveThe goal of this trial is to determine the impact of an AI-based visual risk analytic, CoMET, on improving patient outcomes related to clinical deterioration, response time to proactive clinical action, and costs to the health care system.MethodsWe propose a cluster randomized controlled trial to test the impact of using the CoMET display in an acute care cardiology and cardiothoracic surgery hospital floor. The number of admissions to a room undergoing cluster randomization was estimated to be 10,424 over the 20-month study period. Cluster randomization based on bed number will occur every 2 months. The intervention cluster will have the CoMET score displayed (along with standard of care), while the usual care group will receive standard of care only.ResultsThe primary outcome will be hours free from events of clinical deterioration. Hours of acute clinical events are defined as time when one or more of the following occur: emergent ICU transfer, emergent surgery prior to ICU transfer, cardiac arrest prior to ICU transfer, emergent intubation, or death. The clinical trial began randomization in January 2021.ConclusionsVery few AI-based health analytics have been translated from algorithm to real-world use. This study will use robust, prospective, randomized controlled, clinical trial methodology to assess the effectiveness of an advanced AI predictive analytics monitoring system in incorporating real-time telemetric data for identifying clinical deterioration on acute care wards. This analysis will strengthen the ability of health care organizations to evolve as learning health systems, in which bioinformatics data are applied to improve patient outcomes by incorporating AI into knowledge tools that are successfully integrated into clinical practice by health care providers.Trial RegistrationClinicalTrials.gov NCT04359641; https://clinicaltrials.gov/ct2/show/NCT04359641International Registered Report Identifier (IRRID)DERR1-10.2196/29631

Does community-based distribution of HIV self-tests increase uptake of HIV testing? Results of pair-matched cluster randomised trial in Zambia

ObjectivesEnding HIV by 2030 is a global priority. Achieving this requires alternative HIV testing strategies, such as HIV self-testing (HIVST) to reach all individuals with HIV testing services (HTS). We...

Efficacy of IVRS-based mHealth intervention in reducing cardiovascular risk in metabolic syndrome: A cluster randomized trial

AimsEfficacy of mobile-phone based intervention for reducing cardiovascular risk in metabolic syndrome (MetSyn). MethodsWe screened adults 20–60 years in 10 villages in India for MetSyn using stratified cluster sampling. Lifestyle and biochemical risk factors were assessed. International Harmonized Criteria were used for diagnosis. Villages were randomized with 5 each in control and intervention groups. Interactive voice response system (IVRS) in Hindi was developed. In intervention clusters two messages for promotion of healthy lifestyle and medical treatment were broadcast daily over 12-months and risk factors reassessed. Results1012/1200(84%) persons were screened and MetSyn diagnosed in 286(28.3%). Villages were divided into 5 control(n = 136) and 5 intervention(n = 147) clusters. Baseline characteristics in both clusters were similar. Acceptability of intervention was >60% in 80% participants. At 12 months, significantly greater participants in intervention vs control clusters had healthier lifestyle (healthy diet 28.8vs14.7%, physical activity 25.9vs13.1%, tobacco 13.7vs32.5%), anthropometry (waist circumference 85.7 ± 6.3vs88.6 ± 14.0 cm, body mass index 21.9 ± 2.8vs23.1 ± 2.9 kg/m2), systolic BP 123.6 ± 7.7vs128.6 ± 14.1 mmHg, fasting glucose 95.6 ± 19.4vs109.4 ± 43.7 mg/dl, cholesterol 175.5 ± 36.5vs186.4 ± 43.3 mg/dl, and triglycerides 147.6 ± 48.3vs159.5 ± 60.7 mg/dl (p < 0.01). Prevalence of metabolic syndrome declined in intervention group by 22.3%vs3.9%, p < 0.001). ConclusionAn interactive voice response system based technology significantly reduced multiple cardiovascular risk factors and prevalence of metabolic syndrome.

Mass drug administration for the acceleration of malaria elimination in a region of Myanmar with artemisinin-resistant falciparum malaria: a cluster-randomised trial

To contain multidrug-resistant Plasmodium falciparum, malaria elimination in the Greater Mekong subregion needs to be accelerated while current antimalarials remain effective. We evaluated the safety, effectiveness, and potential resistance selection of dihydroartemisinin-piperaquine mass drug administration (MDA) in a region with artemisinin resistance in Myanmar. We did a cluster-randomised controlled trial in rural community clusters in Kayin (Karen) state in southeast Myanmar. Malaria prevalence was assessed using ultrasensitive quantitative PCR (uPCR) in villages that were operationally suitable for MDA (villages with community willingness, no other malaria control campaigns, and a population of 50-1200). Villages were eligible to participate if the prevalence of malaria (all species) in adults was greater than 30% or P falciparum prevalence was greater than 10% (or both). Contiguous villages were combined into clusters. Eligible clusters were paired based on P falciparum prevalence (estimates within 10%) and proximity. Community health workers provided routine malaria case management and distributed long-lasting insecticidal bed-nets (LLINs) in all clusters. Randomisation of clusters (1:1) to the MDA intervention group or control group was by public coin-flip. Group allocations were not concealed. Three MDA rounds (3 days of supervised dihydroartemisinin-piperaquine [target total dose 7 mg/kg dihydroartemisinin and 55 mg/kg piperaquine] and single low-dose primaquine [target dose 0·25 mg base per kg]) were delivered to intervention clusters. Parasitaemia prevalence was assessed at 3, 5, 10, 15, 21, 27, and 33 months. The primary outcomes were P falciparum prevalence at months 3 and 10. All clusters were included in the primary analysis. Adverse events were monitored from the first MDA dose until 1 month after the final dose, or until resolution of any adverse event occurring during follow-up. This trial is registered with ClinicalTrials.gov, NCT01872702. Baseline uPCR malaria surveys were done in January, 2015, in 43 villages that were operationally suitable for MDA (2671 individuals). 18 villages met the eligibility criteria. Three villages in close proximity were combined into one cluster because a border between them could not be defined. This gave a total of 16 clusters in eight pairs. In the intervention clusters, MDA was delivered from March 4 to March 17, from March 30 to April 10, and from April 27 to May 10, 2015. The weighted mean absolute difference in P falciparum prevalence in the MDA group relative to the control group was -10·6% (95% CI -15·1 to -6·1; p=0·0008) at month 3 and -4·5% (-10·9 to 1·9; p=0·14) at month 10. At month 3, the weighted P falciparum prevalence was 1·4% (0·6 to 3·6; 12 of 747) in the MDA group and 10·6% (7·0 to 15·6; 56 of 485) in the control group. Corresponding prevalences at month 10 were 3·2% (1·5 to 6·8; 34 of 1013) and 5·8% (2·5 to 12·9; 33 of 515). Adverse events were reported for 151 (3·6%) of 4173 treated individuals. The most common adverse events were dizziness (n=109) and rash or itching (n=20). No treatment-related deaths occurred. In this low-transmission setting, the substantial reduction in P falciparum prevalence resulting from support of community case management was accelerated by MDA. In addition to supporting community health worker case management and LLIN distribution, malaria elimination programmes should consider using MDA to reduce P falciparum prevalence rapidly in foci of higher transmission. The Global Fund to Fight AIDS, Tuberculosis and Malaria.

Effectiveness of a killed whole-cell oral cholera vaccine in Bangladesh: further follow-up of a cluster-randomised trial

Killed whole-cell oral cholera vaccines (OCVs) are widely used for prevention of cholera in developing countries. However, few studies have evaluated the protection conferred by internationally recommended OCVs for durations beyond 2 years of follow-up. In this study, we followed up the participants of a cluster-randomised controlled trial for 2 years after the end of the original trial. Originally, we had randomised 90 geographical clusters in Dhaka slums in Bangladesh in equal numbers (1:1:1) to a two-dose regimen of OCV alone (targeted to people aged 1 year or older), a two-dose regimen of OCV plus a water-sanitation-hygiene (WASH) intervention, or no intervention. There was no masking of group assignment. The WASH intervention conferred little additional protection to OCV and was discontinued at 2 years of follow-up. Surveillance for severe cholera was continued for 4 years. Because of the short duration and effect of the WASH intervention, we combined the two OCV intervention groups. The primary outcomes were OCV overall protection (protection of all members of the intervention clusters) and total protection (protection of individuals who got vaccinated in the intervention clusters) against severe cholera, which we assessed by multivariable survival models appropriate for cluster-randomised trials. This trial is registered on ClinicalTrials.gov, NCT01339845. The study was done between April 17, 2011, and Nov 1, 2015. 268 896 participants were present at the time of the first dose, with 188 206 in the intervention group and 80 690 in the control group. OCV coverage of the two groups receiving OCV was 66% (123 659 of 187 214 participants). During 4 years of follow-up, 441 first episodes of severe cholera were detected (243 episodes in the vaccinated groups and as 198 episodes in the unvaccinated group). Overall OCV protection was 36% (95% CI 19 to 49%) and total OCV protection was 46% (95% CI 32 to 58). Cumulative total vaccine protection was notably lower for people vaccinated before the age of 5 years (24%; -30 to 56) than for people vaccinated at age 5 years or older (49%; 35 to 60), although the differences in protection for the two age groups were not significant (p=0·3308). Total vaccine protection dropped notably (p=0·0115) after 3 years in children vaccinated at 1-4 years of age. These findings provide further evidence of long-term effectiveness of killed whole-cell OCV, and therefore further support for the use of killed whole-cell OCVs to control endemic cholera, but indicate that protection is shorter-lived in children vaccinated before the age of 5 years than in people vaccinated at the age of 5 years or older. Bill & Melinda Gates Foundation. For the Bengali translation of the abstract see Supplementary Materials section.

Efficacy of Wolbachia-Infected Mosquito Deployments for the Control of Dengue

BackgroundAedes aegypti mosquitoes infected with the wMel strain of Wolbachia pipientis are less susceptible than wild-type A. aegypti to dengue virus infection.MethodsWe conducted a cluster-randomized trial involving releases of wMel-infected A. aegypti mosquitoes for the control of dengue in Yogyakarta, Indonesia. We randomly assigned 12 geographic clusters to receive deployments of wMel-infected A. aegypti (intervention clusters) and 12 clusters to receive no deployments (control clusters). All clusters practiced local mosquito-control measures as usual. A test-negative design was used to assess the efficacy of the intervention. Patients with acute undifferentiated fever who presented to local primary care clinics and were 3 to 45 years of age were recruited. Laboratory testing was used to identify participants who had virologically confirmed dengue (VCD) and those who were test-negative controls. The primary end point was symptomatic VCD of any severity caused by any dengue virus serotype.ResultsAfter successful introgression of wMel into the intervention clusters, 8144 participants were enrolled; 3721 lived in intervention clusters, and 4423 lived in control clusters. In the intention-to-treat analysis, VCD occurred in 67 of 2905 participants (2.3%) in the intervention clusters and in 318 of 3401 (9.4%) in the control clusters (aggregate odds ratio for VCD, 0.23; 95% confidence interval [CI], 0.15 to 0.35; P=0.004). The protective efficacy of the intervention was 77.1% (95% CI, 65.3 to 84.9) and was similar against the four dengue virus serotypes. The incidence of hospitalization for VCD was lower among participants who lived in intervention clusters (13 of 2905 participants [0.4%]) than among those who lived in control clusters (102 of 3401 [3.0%]) (protective efficacy, 86.2%; 95% CI, 66.2 to 94.3).ConclusionsIntrogression of wMel into A. aegypti populations was effective in reducing the incidence of symptomatic dengue and resulted in fewer hospitalizations for dengue among the participants. (Funded by the Tahija Foundation and others; AWED ClinicalTrials.gov number, NCT03055585; Indonesia Registry number, INA-A7OB6TW.)