Effect of Village Health Team Home Visits and Mobile Phone Consultations on Maternal and Newborn Care Practices in Masindi and Kiryandongo,Uganda: A Community-Intervention Trial

IntroductionThe World Health Organisation recommends home visits conducted by Community Health Workers (in Uganda known as Village Health Teams—VHTs) in order to improve maternal and newborn health. This study measured the effect of home visits combined with mobile phone consultations on maternal and newborn care practices.MethodIn a community intervention trial design 16 health centres in Masindi and Kiryandongo districts, Uganda were randomly and equally allocated to one of two arms: control and intervention arms. Eight control health centres received the usual maternal and newborn educational messages offered by professional health workers and eight intervention health centres that received an intervention package for maternal care and essential newborn care practices. In the intervention arm VHTs made two prenatal and one postnatal home visit to households. VHTs were provided with mobile phones to enable them make regular telephone consultations with health workers at the health centre serving the catchment area. The primary outcome was health facility delivery. Other outcomes included antenatal attendances, birth preparedness, cord and thermal care and breastfeeding practices. Analysis was by intention-to-treat.ResultsA total of 1385 pregnant women were analysed: 758 and 627 in the control and intervention arms respectively. Significant post-intervention differences were: delivery place [adjusted Odds Ratio aOR: 17.94(95%CI: 6.26–51.37); p<0.001], cord care [aOR: 3.05(95%CI: 1.81–5.12); p<0.001] thermal care [aOR: 7.58(95%CI: 2.52–22.82); p<0.001], and timely care-seeking for newborn illness [aOR: 4.93(95%CI: 1.59–15.31); p = 0.006].ConclusionVHTs can have an effect in promoting proper cord and thermal care for the newborn and improve timely care-seeking for health facility delivery and newborn illness, because they could answer questions and refer patients correctly. However, VHTs should be supported by professional health workers through the use of mobile phones.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02084680","term_id":"NCT02084680"}}NCT02084680     

Safety of Eplerenone for Kidney-Transplant Recipients with Impaired Renal Function and Receiving Cyclosporine A

BackgroundAnimal studies have highlighted the role of vascular mineralocorticoid receptor during Cyclosporine A-induced nephrotoxicity. Mineralocorticoid receptor antagonists could improve kidney survival but are not commonly used during renal impairment and in association with several immunosuppressive drugs due to a supposed higher risk of adverse events. We tested the tolerance of eplerenone according to its expected adverse events: hyperkalemia, metabolic acidosis, hypotension, acute kidney failure, or any other adverse event.MethodsWe conducted a single-center, prospective, open-label study in 31 kidney-transplant recipients with impaired renal function (30 and 50 mL/min/1.73m²) and receiving cyclosporine A. All patients received eplerenone 25 mg/d for 8 weeks. Serum potassium, renal function and expected adverse events were closely monitored.ResultsEight patients experienced mild hyperkalemia (>5 mmol/L), one moderate hyperkalemia (>5.5 mmol/L) and had to receive potassium-exchange resin. No severe hyperkalemia (>6 mmol/L) occurred. One acute kidney failure was observed, secondary to diarrhea. Basal serum potassium and bicarbonate were independently associated with a higher risk of developing mild hyperkalemia (>5 mmol/L) under treatment (OR 6.5, p = 0.003 and 0.7, p = 0.007, respectively). A cut-off value of 4.35 mmol/L for basal serum potassium was the best factor to predict the risk of developing mild hyperkalemia (>5 mmol/L).ConclusionsUntil eGFR falls to 30 mL/min/1.73m², eplerenone could be safely given to kidney-transplant recipients receiving cyclosporine A, if kalemia is closely monitored. When renal function is impaired and if basal kalemia is >4.35 mmol/L, then clinicians should properly balance risk and benefit of eplerenone use and offer dietary advice. An adequately powered prospective randomized study is now needed to test its efficiency (and safety) in this population.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01834768","term_id":"NCT01834768"}}NCT01834768     

Effects of a WHO-guided digital health intervention for depression in Syrian refugees in Lebanon: A randomized controlled trial

BackgroundMost displaced people with mental disorders in low- and middle-income countries do not receive effective care, and their access to care has deteriorated during the Coronavirus Disease 2019 (COVID-19) pandemic. Digital mental health interventions are scalable when digital access is adequate, and they can be safely delivered during the COVID-19 pandemic. We examined whether a new WHO-guided digital mental health intervention, Step-by-Step, in which participants were supported by a nonspecialist helper, was effective in reducing depression among displaced people in Lebanon.Methods and findingsWe conducted a single-blind, 2-arm pragmatic randomized clinical trial, comparing guided Step-by-Step with enhanced care as usual (ECAU) among displaced Syrians suffering from depression and impaired functioning in Lebanon. Primary outcomes were depression (Patient Health Questionnaire, PHQ-9) and impaired functioning (WHO Disability Assessment Schedule-12, WHODAS) at posttreatment. Secondary outcomes included subjective well-being, anxiety, post-traumatic stress, and self-described problems. A total of 569 displaced people from Syria with depression (PHQ-9 ≥ 10) and impaired functioning (WHODAS > 16) were randomized to Step-by-Step (N = 283; lost to follow-up: N = 167) or ECAU (N = 286; lost to follow-up: 133). Participants were considered to be lost to follow-up when they did not fill in the outcome measures at posttest or follow-up. Recruitment started on December 9, 2019 and was completed on July 9, 2020. The last follow-up assessments were collected in December 2020. The study team had access to the online platform, where they could see treatment arm assignment for each participant. All questionnaires were completed by participants online. Intention-to-treat (ITT) analyses showed intervention effects on depression (standardized mean differences [SMDs]: 0.48; 95% CI: 0.26; 0.70; p < 0.001), impaired functioning (SMD: 0.35; 95% CI: 0.14; 0.56; p < 0.001), post-traumatic stress (SMD: 0.36; 95% CI: 0.16; 0.56; p < 0.001), anxiety (SMD: 0.46; 95% CI: 0.24; 0.68; p < 0.001), subjective well-being (SMD: 0.47; 95% CI: 0.26; 0.68; p < 0.001), and self-identified personal problems (SMD: 0.49; 95% CI 0.28; 0.70; p < 0.001). Significant effects on all outcomes were maintained at 3 months follow-up. During the trial, one serious adverse event occurred, unrelated to the intervention. The main limitation of the current trial is the high dropout rate.ConclusionsIn this study, we found that a guided, digital intervention was effective in reducing depression in displaced people in Lebanon. The guided WHO Step-by-Step intervention we examined should be made available to communities of displaced people that have digital access.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03720769","term_id":"NCT03720769"}}NCT03720769.

In a randomized controlled trial, Pim Cuijpers and colleagues evaluate the effects of the Step-by-Step guided digital mental health intervention on depression, impaired functioning, and other mental health outcomes among displaced Syrians living in Lebanon.     

Low numbers of blood and salivary natural killer cells are associated with a better response to belimumab in primary Sj?gren’s syndrome: results of the BELISS study

IntroductionIn this study, we sought to address changes in blood lymphocyte subpopulations and labial salivary gland (LSG) inflammation after belimumab treatment in patients with primary Sjögren’s syndrome (pSS) and to identify predictors of response to treatment.MethodsSequential blood lymphocyte subsets and LSG biopsies were analysed between week 0 (W0) and W28 in 15 patients with pSS treated with belimumab. Systemic response to treatment was defined as a decrease in the European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index score of ≥3 points at W28.ResultsAfter belimumab, we observed a decrease in blood B lymphocytes primarily involving CD27-negative/immunoglobulin D–positive naïve B cells (p=0.008). Lymphocytic sialadenitis (focus score >1) that was present in 12 patients (80.0 %) before belimumab treatment became negative in 5 of them after treatment (p=0.03). The median (interquartile range) LSG B-cell/T-cell ratio decreased from 0.58 (0.5–0.67) to 0.50 (0.5–0.5) (p=0.06). B-cell activating factor (BAFF) staining was detected in 11 (78.6 %) of 14 patients before belimumab treatment compared with 7 (50.0 %) of 14 after belimumab therapy (p=0.10). The median percentage of BAFF-positive cells in foci significantly decreased from 27.5 % (10–40) to 5 % (0–20) (p=0.03). A systemic response was achieved in six patients (40 %). The only predictor of response was the presence of a low number of natural killer (NK) cells, both in blood (8.5 % [7–10] vs 11 % [9–21]; p=0.04) and in LSG (20.6/mm³ [20.0–21.4] vs 30.0/mm³ [25.0–100.0], p=0.003). Serum BAFF levels did not influence response to treatment.ConclusionsLow blood and salivary NK cell numbers are associated with a better response to belimumab. This suggests that two distinct subsets of pSS may exist: one with a predominant type I interferon (IFN)–BAFF–B-cell axis, representing good responders to belimumab; and one with a predominant type II IFN–NK cell axis, representing non-responders.

Trial registration

ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT01160666","term_id":"NCT01160666"}}NCT01160666. Registered 9 July 2010.     

Comparison of two different folic acid doses with methotrexate – a randomized controlled trial (FOLVARI Study)

IntroductionThere is reasonable evidence that folic acid 5–10 mg per week leads to reduction in methotrexate (MTX) toxicity in rheumatoid arthritis (RA). However, this is based on studies conducted with lower MTX dosage than used currently. It is unclear whether higher doses of folic acid may be better in reducing toxicity.MethodsThis was a double-blind randomized controlled trial of 24 weeks duration. To be eligible, patients should have rheumatoid arthritis (1987 American College of Rheumatology criteria), be 18–75 years of age, not be on MTX and have active disease as defined by ‘Modified Disease Activity Score using three variables’ (DAS28(3)) > 3.2. MTX was started at 10 mg/week and escalated to 25 mg/week by 12 weeks. Folic acid was given at a dose of 10 mg (FA10) or 30 mg per week (FA30). Co-primary endpoints were incidence of toxicity (undesirable symptoms and laboratory abnormalities) and change in disease activity by 24 weeks. Intention-to-treat and per-protocol analyses were performed.ResultsAmong 100 patients enrolled, 51 and 49 were randomized to FA10 and FA30 respectively. By 24 weeks, there were 6 patient withdrawals in either group and mean(±SD) dose of MTX was 22.8 ± 4.4 and 21.4 ± 4.6 mg per week (p = 0.1). Frequency of patients with undesirable symptoms was non-significantly lower by 7.4 % (95 % confidence interval −27.4 to 12.7 %) in FA10 compared to FA30. There was also no difference in frequency of transaminitis (>Upper limit of normal (ULN)) (42.6, 45.7 %, p = 0.7) or transminitis as per primary endpoint (>2xULN) (10.6, 8.7 %, p = 1.0) or cytopenias (4.3, 4.3 %, p = 0.9). There was no difference in the primary end-point of occurrence of any adverse effect (symptom or laboratory) in FA10 and FA30 (46.8, 54.3 %, p = 0.5). At 24 weeks, DAS28(3) declined in both groups by a similar extent (−1.1 ± 1.0, −1.3 ± 1.0, p = 0.2) and ‘European League Against Rheumatism’ good or moderate response occurred in 56.9 and 67.4 % (p = 0.3).ConclusionsEven with the high doses of MTX used in current practice, there was no additional benefit (or harm) of a higher dose of folic acid (30 mg/week) over a usual dose (10 mg/week).

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01583959","term_id":"NCT01583959"}}NCT01583959 Registered 15 March 2012     

Genetic Variants of LDLR and PCSK9 Associated with Variations in Response to Antihypercholesterolemic Effects of Armolipid Plus with Berberine

Background

Armolipid Plus (AP) is a nutraceutical that contains policosanol, fermented rice with red yeast, berberine, coenzyme Q10, folic acid, and astaxanthin. It has been shown to be effective in reducing plasma LDL cholesterol (LDLc) levels. In the multicenter randomized trial {"type":"clinical-trial","attrs":{"text":"NCT01562080","term_id":"NCT01562080"}}NCT01562080, there was large interindividual variability in the plasma LDLc response to AP supplementation. We hypothesized that the variability in LDLc response to AP supplementation may be linked to LDLR and PCSK9 polymorphisms.

Material and Methods

We sequenced the LDLR 3′ and 5′ untranslated regions (UTR) and the PCSK9 5′ UTR of 102 participants with moderate hypercholesterolemia in trial {"type":"clinical-trial","attrs":{"text":"NCT01562080","term_id":"NCT01562080"}}NCT01562080. In this trial, 50 individuals were treated with AP supplementation and the rest with placebo.

Results

Multiple linear regression analysis, using the response of LDLc levels to AP as the dependent variable, revealed that polymorphisms rs2149041 (c.-3383C>G) in the PCSK9 5′ UTR and rs14158 (c.*52G>A) in the LDLR 3′ UTR explained 14.1% and 6.4%, respectively, of the variability after adjusting for gender, age, and BMI of individuals. Combining polymorphisms rs2149041 and rs14158 explained 20.5% of this variability (p < 0.004).

Conclusions

Three polymorphisms in the 3′ UTR region of LDLR, c.*52G>A, c.*504G>A, and c.*773A>G, and two at the 5′ UTR region of PCSK9, c.−3383C>G and c.−2063A>G, were associated with response to AP. These results could explain the variability observed in the response to berberine among people with moderate hypercholesterolemia, and they may be useful in identifying patients who could potentially benefit from supplementation with AP.     

Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial

BackgroundSTAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL).Methods and findingsPatients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire.Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively.ConclusionsProstate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00268476","term_id":"NCT00268476"}}NCT00268476, ISRCTN.com ISRCTN78818544.

Chris C Parker and colleagues report long-term findings on overall survival and local complications in men with metastatic prostate cancer treated with radiotherapy.     

Immune and endothelial activation markers and risk stratification of childhood pneumonia in Uganda: A secondary analysis of a prospective cohort study

BackgroundDespite the global burden of pneumonia, reliable triage tools to identify children in low-resource settings at risk of severe and fatal respiratory tract infection are lacking. This study assessed the ability of circulating host markers of immune and endothelial activation quantified at presentation, relative to currently used clinical measures of disease severity, to identify children with pneumonia who are at risk of death.Methods and findingsWe conducted a secondary analysis of a prospective cohort study of children aged 2 to 59 months presenting to the Jinja Regional Hospital in Jinja, Uganda between February 2012 and August 2013, who met the Integrated Management of Childhood Illness (IMCI) diagnostic criteria for pneumonia. Circulating plasma markers of immune (IL-6, IL-8, CXCL-10/IP-10, CHI3L1, sTNFR1, and sTREM-1) and endothelial (sVCAM-1, sICAM-1, Angpt-1, Angpt-2, and sFlt-1) activation measured at hospital presentation were compared to lactate, respiratory rate, oxygen saturation, procalcitonin (PCT), and C-reactive protein (CRP) with a primary outcome of predicting 48-hour mortality. Of 805 children with IMCI pneumonia, 616 had severe pneumonia. Compared to 10 other immune and endothelial activation markers, sTREM-1 levels at presentation had the best predictive accuracy in identifying 48-hour mortality for children with pneumonia (AUROC 0.885, 95% CI 0.841 to 0.928; p = 0.03 to p < 0.001) and severe pneumonia (AUROC 0.870, 95% CI 0.824 to 0.916; p = 0.04 to p < 0.001). sTREM-1 was more strongly associated with 48-hour mortality than lactate (AUROC 0.745, 95% CI 0.664 to 0.826; p < 0.001), respiratory rate (AUROC 0.615, 95% CI 0.528 to 0.702; p < 0.001), oxygen saturation (AUROC 0.685, 95% CI 0.594 to 0.776; p = 0.002), PCT (AUROC 0.650, 95% CI 0.566 to 0.734; p < 0.001), and CRP (AUROC 0.562, 95% CI 0.472 to 0.653; p < 0.001) in cases of pneumonia and severe pneumonia. The main limitation of this study was the unavailability of radiographic imaging.ConclusionsIn this cohort of Ugandan children, sTREM-1 measured at hospital presentation was a significantly better indicator of 48-hour mortality risk than other common approaches to risk stratify children with pneumonia. Measuring sTREM-1 at clinical presentation may improve the early triage, management, and outcome of children with pneumonia at risk of death.Trial registrationThe trial was registered at clinicaltrial.gov ({"type":"clinical-trial","attrs":{"text":"NCT 04726826","term_id":"NCT04726826"}}NCT 04726826).

Chloe R. McDonald and colleagues assess the ability of immune and endothelial activation markers to identify risk of death from pneumonia among children in Uganda.     

Aclidinium bromide and formoterol fumarate as a fixed-dose combination in COPD: pooled analysis of symptoms and exacerbations from two six-month,multicentre, randomised studies (ACLIFORM and AUGMENT)

Background

The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta₂-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment. The effect of this combination on symptoms of COPD and exacerbations is less well established. We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).

Methods

Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV₁]/forced vital capacity <70 % and FEV₁ ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®. Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.

Results

The pooled intent-to-treat population included 3394 patients. Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05). Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05). The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05). Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies. Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).

Conclusions

Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD. Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.

Trial registration

{"type":"clinical-trial","attrs":{"text":"NCT01462942","term_id":"NCT01462942"}}NCT01462942 and {"type":"clinical-trial","attrs":{"text":"NCT01437397","term_id":"NCT01437397"}}NCT01437397 (ClinicalTrials.gov)

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0250-2) contains supplementary material, which is available to authorized users.     

Evaluation of multiple micronutrient supplementation and medium-quantity lipid-based nutrient supplementation in pregnancy on child development in rural Niger: A secondary analysis of a cluster randomized controlled trial

BackgroundIt is estimated that over 250 million children under 5 years of age in low- and middle-income countries (LMICs) do not reach their full developmental potential. Poor maternal diet, anemia, and micronutrient deficiencies during pregnancy are associated with suboptimal neurodevelopmental outcomes in children. However, the effect of prenatal macronutrient and micronutrient supplementation on child development in LMIC settings remains unclear due to limited evidence from randomized trials.Methods and findingsWe conducted a 3-arm cluster-randomized trial (n = 53 clusters) that evaluated the efficacy of (1) prenatal multiple micronutrient supplementation (MMS; n = 18 clusters) and (2) lipid-based nutrient supplementation (LNS; n = 18 clusters) as compared to (3) routine iron–folic acid (IFA) supplementation (n = 17 clusters) among pregnant women in the rural district of Madarounfa, Niger, from March 2015 to August 2019 (ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT02145000","term_id":"NCT02145000"}}NCT02145000). Children were followed until 2 years of age, and the Bayley Scales of Infant and Toddler Development III (BSID-III) were administered to children every 3 months from 6 to 24 months of age. Maternal report of WHO gross motor milestone achievement was assessed monthly from 3 to 24 months of age. An intention-to-treat analysis was followed. Child BSID-III data were available for 559, 492, and 581 singleton children in the MMS, LNS, and IFA groups, respectively. Child WHO motor milestone data were available for 691, 781, and 753 singleton children in the MMS, LNS, and IFA groups, respectively. Prenatal MMS had no effect on child BSID-III cognitive (standardized mean difference [SMD]: 0.21; 95% CI: −0.20, 0.62; p = 0.32), language (SMD: 0.16; 95% CI: −0.30, 0.61; p = 0.50) or motor scores (SMD: 0.18; 95% CI: −0.39, 0.74; p = 0.54) or on time to achievement of the WHO gross motor milestones as compared to IFA. Prenatal LNS had no effect on child BSID-III cognitive (SMD: 0.17; 95% CI: −0.15, 0.49; p = 0.29), language (SMD: 0.11; 95% CI: −0.22, 0.44; p = 0.53) or motor scores (SMD: −0.04; 95% CI: −0.46, 0.37; p = 0.85) at the 24-month endline visit as compared to IFA. However, the trajectory of BSID-III cognitive scores during the first 2 years of life differed between the groups with children in the LNS group having higher cognitive scores at 18 and 21 months (approximately 0.35 SD) as compared to the IFA group (p-value for difference in trajectory <0.001). Children whose mothers received LNS also had earlier achievement of sitting alone (hazard ratio [HR]: 1.57; 95% CI: 1.10 to 2.24; p = 0.01) and walking alone (1.52; 95% CI: 1.14 to 2.03; p = 0.004) as compared to IFA, but there was no effect on time to achievement of other motor milestones. A limitation of our study is that we assessed child development up to 2 years of age, and, therefore, we may have not captured effects that are easier to detect or emerge at older ages.ConclusionsThere was no benefit of prenatal MMS on child development outcomes up to 2 years of age as compared to IFA. There was evidence of an apparent positive effect of prenatal LNS on cognitive development trajectory and time to achievement of selected gross motor milestones.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02145000","term_id":"NCT02145000"}}NCT02145000.

Christopher R. Sudfeld and colleagues evaluate the benefit of multiple micronutrient supplementation and medium‐quantity lipid‐based nutrient supplementation in pregnancy on child development in rural Niger.     

Resistance exercise improves muscle strength,health status and pain intensity in fibromyalgia—a randomized controlled trial

IntroductionFibromyalgia (FM) is characterized by persistent widespread pain, increased pain sensitivity and tenderness. Muscle strength in women with FM is reduced compared to healthy women. The aim of this study was to examine the effects of a progressive resistance exercise program on muscle strength, health status, and current pain intensity in women with FM.MethodsA total of 130 women with FM (age 22–64 years, symptom duration 0–35 years) were included in this assessor-blinded randomized controlled multi-center trial examining the effects of progressive resistance group exercise compared with an active control group. A person-centred model of exercise was used to support the participants’ self-confidence for management of exercise because of known risks of activity-induced pain in FM. The intervention was performed twice a week for 15 weeks and was supervised by experienced physiotherapists. Primary outcome measure was isometric knee-extension force (Steve Strong®), secondary outcome measures were health status (FIQ total score), current pain intensity (VAS), 6MWT, isometric elbow-flexion force, hand-grip force, health related quality of life, pain disability, pain acceptance, fear avoidance beliefs, and patient global impression of change (PGIC). Outcomes were assessed at baseline and immediately after the intervention. Long-term follow up comprised the self-reported questionnaires only and was conducted after 13–18 months. Between-group and within-group differences were calculated using non-parametric statistics.ResultsSignificant improvements were found for isometric knee-extension force (p = 0.010), health status (p = 0.038), current pain intensity (p = 0.033), 6MWT (p = 0.003), isometric elbow flexion force (p = 0.02), pain disability (p = 0.005), and pain acceptance (p = 0.043) in the resistance exercise group (n = 56) when compared to the control group (n = 49). PGIC differed significantly (p = 0.001) in favor of the resistance exercise group at post-treatment examinations. No significant differences between the resistance exercise group and the active control group were found regarding change in self-reported questionnaires from baseline to 13–18 months.ConclusionsPerson-centered progressive resistance exercise was found to be a feasible mode of exercise for women with FM, improving muscle strength, health status, and current pain intensity when assessed immediately after the intervention.

Trial registration

ClinicalTrials.gov identification number: {"type":"clinical-trial","attrs":{"text":"NCT01226784","term_id":"NCT01226784"}}NCT01226784, Oct 21, 2010.     

Gene expression changes reflect clinical response in a placebo-controlled randomized trial of abatacept in patients with diffuse cutaneous systemic sclerosis

IntroductionSystemic sclerosis is an autoimmune disease characterized by inflammation and fibrosis of the skin and internal organs. We sought to assess the clinical and molecular effects associated with response to intravenous abatacept in patients with diffuse cutaneous systemic.MethodsAdult diffuse cutaneous systemic sclerosis patients were randomized in a 2:1 double-blinded fashion to receive abatacept or placebo over 24 weeks. Primary outcomes were safety and the change in modified Rodnan Skin Score (mRSS) at week 24 compared with baseline. Improvers were defined as patients with a decrease in mRSS of ≥30 % post-treatment compared to baseline. Skin biopsies were obtained for differential gene expression and pathway enrichment analyses and intrinsic gene expression subset assignment.ResultsTen subjects were randomized to abatacept (n = 7) or placebo (n = 3). Disease duration from first non-Raynaud’s symptom was significantly longer (8.8 ± 3.8 years vs. 2.4 ± 1.6 years, p = 0.004) and median mRSS was higher (30 vs. 22, p = 0.05) in the placebo compared to abatacept group. Adverse events were similar in the two groups. Five out of seven patients (71 %) randomized to abatacept and one out of three patients (33 %) randomized to placebo experienced ≥30 % improvement in skin score. Subjects receiving abatacept showed a trend toward improvement in mRSS at week 24 (−8.6 ± 7.5, p = 0.0625) while those in the placebo group did not (−2.3 ± 15, p = 0.75). After adjusting for disease duration, mRSS significantly improved in the abatacept compared with the placebo group (abatacept vs. placebo mRSS decrease estimate −9.8, 95 % confidence interval −16.7 to −3.0, p = 0.0114). In the abatacept group, the patients in the inflammatory intrinsic subset showed a trend toward greater improvement in skin score at 24 weeks compared with the patients in the normal-like intrinsic subset (−13.5 ± 3.1 vs. −4.5 ± 6.4, p = 0.067). Abatacept resulted in decreased CD28 co-stimulatory gene expression in improvers consistent with its mechanism of action. Improvers mapped to the inflammatory intrinsic subset and showed decreased gene expression in inflammatory pathways, while non-improver and placebos showed stable or reverse gene expression over 24 weeks.ConclusionsClinical improvement following abatacept therapy was associated with modulation of inflammatory pathways in skin.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00442611","term_id":"NCT00442611"}}NCT00442611. Registered 1 March 2007.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0669-3) contains supplementary material, which is available to authorized users.     

Renal Outcomes of Pioglitazone Compared with Acarbose in Diabetic Patients: A Randomized Controlled Study

ObjectiveTo assess the effect of pioglitazone on renal outcome, including urinary albumin excretion and estimated glomerular filtration rate (eGFR), in diabetic patients.DesignA prospective, randomized, open-labeled, controlled study.SettingTaipei Veterans General Hospital.PatientsSixty type 2 diabetic patients treated with sulfonylureas and metformin, whose glycated hemoglobin (HbA1c) levels were between 7% and 10% and eGFR was between 45 and 125 mL/min/1.73 m².InterventionThe patients were randomized to receive acarbose or pioglitazone and followed up for 6 months. Thirty patients were randomly assigned to receive acarbose, and 30 patients were assigned to receive pioglitazone.MeasurementsThe primary study endpoint was the changes in the urinary albumin-to-creatinine ratio (UACR). The secondary endpoint was the changes in eGFR and other parameters.ResultsAfter 6 months of treatment, the mean changes in UACR were −18 ± 104 and 12 ± 85 (p = 0.25, between groups) for the acarbose and pioglitazone groups, respectively. The mean changes in eGFR were 0 ± 14 and −7 ± 16 mL/min/1.73 m² (p = 0.09, between groups) for the acarbose and pioglitazone groups, respectively. The reductions in HbA1c were similar in both groups. Fasting blood glucose was lower in the pioglitazone group than in the acarbose group. Significant body weight gain was observed in the pioglitazone group as compared with the acarbose group (1.3 ± 2.8 vs. −0.6 ± 1.5 kg, p = 0.002).ConclusionIn type 2 diabetic patients who were treated with sulfonylureas and metformin and possessed HbA1c levels between 7% and 10%, additional acarbose or pioglitazone for 6 months provided similar glycemic control and eGFR and UACR changes. In the pioglitazone group, the patients exhibited significant body weight gain.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01175486","term_id":"NCT01175486"}}NCT01175486     

The 5-HT1A receptor agonist buspirone improves esophageal motor function and symptoms in systemic sclerosis: a 4-week,open-label trial

BackgroundAcute administration of the oral 5-HT₁A receptor agonist buspirone, which is commonly used as an anxiolytic drug, may improve compromised lower esophageal sphincter function. In an open-label trial we assessed the effects of buspirone on esophageal motor function and symptoms in patients with esophageal involvement associated with systemic sclerosis (SSc).MethodsThirty consecutive patients with SSc and symptomatic esophageal involvement, despite treatment with proton pump inhibitors, underwent high resolution manometry and chest computed tomography for assessment of motor function and esophageal dilatation, respectively. Regurgitation, heartburn, dysphagia, and chest pain severity was subjectively scored by visual analog scales. Manometric parameters (primary endpoint) and symptom severity (secondary endpoint) were re-examined after 4-week daily administration of 20 mg buspirone. Other medications remained unchanged.ResultsEight patients did not complete the trial because of buspirone-associated dizziness (n = 2), or nausea (n = 2), or reluctancy to undergo final manometry. In the remaining 22 patients lower esophageal sphincter (LES) resting pressure increased from 7.7 ± 3.9 to 12.2 ± 4.6 mmHg (p = 0.00002) after buspirone administration; other manometric parameters did not change. Statistical analysis revealed negative correlation between individual increases in resting LES pressure and supra-aortic esophageal diameter (r = -0.589, p = 0.017), suggesting a more beneficial effect in patients with less severely affected esophageal function. Heartburn and regurgitation scores decreased at 4 weeks compared to baseline (p = 0.001, and p = 0.022, respectively).ConclusionOur findings warrant more conclusive evaluation with a double-blind controlled study; however, buspirone could potentially be given under observation for objective improvement in all patients with SSc who report reflux symptoms despite undergoing standard treatment.

Trial registration

ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02363478","term_id":"NCT02363478"}}NCT02363478 Registered: 21-02-2014.     

G6PD Deficiency and Antimalarial Efficacy for Uncomplicated Malaria in Bangladesh: A Prospective Observational Study

BackgroundThe Bangladeshi national treatment guidelines for uncomplicated malaria follow WHO recommendations but without G6PD testing prior to primaquine administration. A prospective observational study was conducted to assess the efficacy of the current antimalarial policy.MethodsPatients with uncomplicated malaria, confirmed by microscopy, attending a health care facility in the Chittagong Hill Tracts, Bangladesh, were treated with artemether-lumefantrine (days 0–2) plus single dose primaquine (0.75mg/kg on day2) for P. falciparum infections, or with chloroquine (days 0–2) plus 14 days primaquine (3.5mg/kg total over 14 days) for P. vivax infections. Hb was measured on days 0, 2 and 9 in all patients and also on days 16 and 30 in patients with P. vivax infection. Participants were followed for 30 days. The study was registered with the clinical trials website ({"type":"clinical-trial","attrs":{"text":"NCT02389374","term_id":"NCT02389374"}}NCT02389374).ResultsBetween September 2014 and February 2015 a total of 181 patients were enrolled (64% P. falciparum, 30% P. vivax and 6% mixed infections). Median parasite clearance times were 22.0 (Interquartile Range, IQR: 15.2–27.3) hours for P. falciparum, 20.0 (IQR: 9.5–22.7) hours for P. vivax and 16.6 (IQR: 10.0–46.0) hours for mixed infections. All participants were afebrile within 48 hours, two patients with P. falciparum infection remained parasitemic at 48 hours. No patient had recurrent parasitaemia within 30 days. Adjusted male median G6PD activity was 7.82U/gHb. One male participant (1/174) had severe G6PD deficiency (<10% activity), five participants (5/174) had mild G6PD deficiency (10–60% activity). The Hb nadir occurred on day 2 prior to primaquine treatment in P. falciparum and P. vivax infected patients; mean fractional fall in Hb was -8.8% (95%CI -6.7% to -11.0%) and -7.4% (95%CI: -4.5 to -10.4%) respectively.ConclusionThe current antimalarial policy remains effective. The prevalence of G6PD deficiency was low. Main contribution to haemolysis in G6PD normal individuals was attributable to acute malaria rather than primaquine administration.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02389374","term_id":"NCT02389374"}}NCT02389374     

Passive surveillance of human African trypanosomiasis in Côte d’Ivoire: Understanding prevalence,clinical symptoms and signs,and diagnostic test characteristics

BackgroundLittle is known about the diagnostic performance of rapid diagnostic tests (RDTs) for passive screening of human African trypanosomiasis (HAT) in Côte d’Ivoire. We determined HAT prevalence among clinical suspects, identified clinical symptoms and signs associated with HAT RDT positivity, and assessed the diagnostic tests’ specificity, positive predictive value and agreement.MethodsClinical suspects were screened with SD Bioline HAT, HAT Sero-K-Set and rHAT Sero-Strip. Seropositives were parasitologically examined, and their dried blood spots tested in trypanolysis, ELISA/Tbg, m18S-qPCR and LAMP. The HAT prevalence in the study population was calculated based on RDT positivity followed by parasitological confirmation. The association between clinical symptoms and signs and RDT positivity was determined using multivariable logistic regression. The tests’ Positive Predictive Value (PPV), specificity and agreement were determined.ResultsOver 29 months, 3433 clinical suspects were tested. The RDT positivity rate was 2.83%, HAT prevalence 0.06%. Individuals with sleep disturbances (p<0.001), motor disorders (p = 0.002), convulsions (p = 0.02), severe weight loss (p = 0.02) or psychiatric problems (p = 0.04) had an increased odds (odds ratios 1.7–4.6) of being HAT RDT seropositive. Specificities ranged between 97.8%-99.6% for individual RDTs, and 93.3–98.9% for subsequent tests on dried blood spots. The PPV of the individual RDTs was below 14.3% (CI 2–43), increased to 33.3% (CI 4–78) for serial RDT combinations, and reached 67% for LAMP and ELISA/Tbg on RDT positives. Agreement between diagnostic tests was poor to moderate (Kappa ≤ 0.60), except for LAMP and ELISA/Tbg (Kappa = 0.66).ConclusionIdentification of five key clinical symptoms and signs may simplify referral for HAT RDT screening. The results confirm the appropriateness of the diagnostic algorithm presently applied, with screening by SD Bioline HAT or HAT Sero-K-Set, supplemented with trypanolysis. ELISA/Tbg could replace trypanolysis and is simpler to perform.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03356665","term_id":"NCT03356665"}}NCT03356665.     

Information nudges for influenza vaccination: Evidence from a large-scale cluster-randomized controlled trial in Finland

BackgroundVaccination is the most effective means of preventing the spread of infectious diseases. Despite the proven benefits of vaccination, vaccine hesitancy keeps many people from getting vaccinated.Methods and findingsWe conducted a large-scale cluster randomized controlled trial in Finland to test the effectiveness of centralized written reminders (distributed via mail) on influenza vaccination coverage. The study included the entire older adult population (aged 65 years and above) in 2 culturally and geographically distinct regions with historically low (31.8%, n = 7,398, mean age 75.5 years) and high (57.7%, n = 40,727, mean age 74.0 years) influenza vaccination coverage. The study population was randomized into 3 treatments: (i) no reminder (only in the region with low vaccination coverage); (ii) an individual-benefits reminder, informing recipients about the individual benefits of vaccination; and (iii) an individual- and social-benefits reminder, informing recipients about the additional social benefits of vaccination in the form of herd immunity. There was no control treatment group in the region with high vaccination coverage as general reminders had been sent in previous years. The primary endpoint was a record of influenza vaccination in the Finnish National Vaccination Register during a 5-month follow-up period (from October 18, 2018 to March 18, 2019). Vaccination coverage after the intervention in the region with historically low coverage was 41.8% in the individual-benefits treatment, 38.9% in the individual- and social-benefits treatment and 34.0% in the control treatment group. Vaccination coverage after the intervention in the region with historically high coverage was 59.0% in the individual-benefits treatment and 59.2% in the individual- and social-benefits treatment. The effect of receiving any type of reminder letter in comparison to control treatment group (no reminder) was 6.4 percentage points (95% CI: 3.6 to 9.1, p < 0.001). The effect of reminders was particularly large among individuals with no prior influenza vaccination (8.8 pp, 95% CI: 6.5 to 11.1, p < 0.001). There was a substantial positive effect (5.3 pp, 95% CI: 2.8 to 7.8, p < 0.001) among the most consistently unvaccinated individuals who had not received any type of vaccine during the 9 years prior to the study. There was no difference in influenza vaccination coverage between the individual-benefit reminder and the individual- and social-benefit reminder (region with low vaccination coverage: 2.9 pp, 95% CI: −0.4 to 6.1, p = 0.087, region with high vaccination coverage: 0.2 pp, 95% CI: −1.0 to 1.3, p = 0.724). Study limitations included potential contamination between the treatments due to information spillovers and the lack of control treatment group in the region with high vaccination coverage.ConclusionsIn this study, we found that sending reminders was an effective and scalable intervention strategy to increase vaccination coverage in an older adult population with low vaccination coverage. Communicating the social benefits of vaccinations, in addition to individual benefits, did not enhance vaccination coverage. The effectiveness of letter reminders about the benefits of vaccination to improve influenza vaccination coverage may depend on the prior vaccination history of the population.Trial registrationAEA RCT registry AEARCTR-0003520 and ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03748160","term_id":"NCT03748160"}}NCT03748160

Lauri Sääksvuori and co-workers study the benefits of reminders in an influenza vaccination program in Finland.     

Antiplaque Effect of Essential Oils and 0.2% Chlorhexidine on an In Situ Model of Oral Biofilm Growth: A Randomised Clinical Trial

ObjectiveTo evaluate the in situ antiplaque effect after 4 days of using of 2 commercial antimicrobial agents in short term on undisturbed plaque-like biofilm.InterventionThe participants wore an appliance in 3 different rinsing periods doing mouthwashes twice a day (1/0/1) with essential oils, 0.2% chlorhexidine or sterile water (negative control). At the end of each 4-day mouthwash period, samples were removed from the appliance. Posteriorly, after bacterial vital staining, samples were analysed using a Confocal Laser Scanning Microscope.ResultsThe essential oils and the 0.2% chlorhexidine were significantly more effective than the sterile water at reducing bacterial vitality, thickness and covering grade by the biofilm. No significant differences were found between the 0.2% chlorhexidine and the essential oils at reducing the bacterial vitality (13.2% vs. 14.7%). However, the 0.2% chlorhexidine showed more reduction than the essential oils in thickness (6.5 μm vs. 10.0 μm; p<0.05) and covering grade by the biofilm (20.0% vs. 54.3%; p<0.001).ConclusionThe essential oils and 0.2% chlorhexidine showed a high antiplaque effect. Although the 0.2% chlorhexidine showed better results with regard to reducing the thickness and covering grade by the biofilm, both antiseptics showed a high and similar antibacterial activity.

Clinical Relevance

Daily essential oils or 0.2% chlorhexidine mouthwashes are effective when reducing dental plaque formation in the short term. Although 0.2% chlorhexidine continues to be the “gold standard” in terms of antiplaque effect, essential oils could be considered a reliable alternative.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02124655","term_id":"NCT02124655"}}NCT02124655     

Reanalysis of the Rituximab in ANCA-Associated Vasculitis trial identifies granulocyte subsets as a novel early marker of successful treatment

IntroductionIn the present study, we sought to identify markers in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) that distinguish those achieving remission at 6 months following rituximab or cyclophosphamide treatment from those for whom treatment failed in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial.MethodsClinical and flow cytometry data from the RAVE trial were downloaded from the Immunology Database and Analysis Portal and Immune Tolerance Network TrialShare public repositories. Flow cytometry data were analyzed using validated automated gating and joined with clinical data. Lymphocyte and granulocyte populations were measured in patients who achieved or failed to achieve remission.ResultsThere was no difference in lymphocyte subsets and treatment outcome with either treatment. We defined a Granularity Index (GI) that measures the difference between the percentage of hypergranular and hypogranular granulocytes. We found that rituximab-treated patients who achieved remission had a significantly higher GI at baseline than those who did not (p = 0.0085) and that this pattern was reversed in cyclophosphamide-treated patients (p = 0.037). We defined optimal cutoff values of the GI using the Youden index. Cyclophosphamide was superior to rituximab in inducing remission in patients with GI below −9.25 % (67 % vs. 30 %, respectively; p = 0.033), whereas rituximab was superior to cyclophosphamide for patients with GI greater than 47.6 % (83 % vs. 33 %, respectively; p = 0.0002).ConclusionsWe identified distinct subsets of granulocytes found at baseline in patients with AAV that predicted whether they were more likely to achieve remission with cyclophosphamide or rituximab. Profiling patients on the basis of the GI may lead to more successful trials and therapeutic courses in AAV.

Trial registration

ClinicalTrials.gov identifier (for original study from which data were obtained): {"type":"clinical-trial","attrs":{"text":"NCT00104299","term_id":"NCT00104299"}}NCT00104299. Date of registration: 24 February 2005.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0778-z) contains supplementary material, which is available to authorized users.     

Evaluation of an on-site sanitation intervention against childhood diarrhea and acute respiratory infection 1 to 3.5 years after implementation: Extended follow-up of a cluster-randomized controlled trial in rural Bangladesh

BackgroundDiarrhea and acute respiratory infection (ARI) are leading causes of death in children. The WASH Benefits Bangladesh trial implemented a multicomponent sanitation intervention that led to a 39% reduction in the prevalence of diarrhea among children and a 25% reduction for ARI, measured 1 to 2 years after intervention implementation. We measured longer-term intervention effects on these outcomes between 1 to 3.5 years after intervention implementation, including periods with differing intensity of behavioral promotion.Methods and findingsWASH Benefits Bangladesh was a cluster-randomized controlled trial of water, sanitation, hygiene, and nutrition interventions ({"type":"clinical-trial","attrs":{"text":"NCT01590095","term_id":"NCT01590095"}}NCT01590095). The sanitation intervention included provision of or upgrades to improved latrines, sani-scoops for feces removal, children’s potties, and in-person behavioral promotion. Promotion was intensive up to 2 years after intervention initiation, decreased in intensity between years 2 to 3, and stopped after 3 years. Access to and reported use of latrines was high in both arms, and latrine quality was significantly improved by the intervention, while use of child feces management tools was low. We enrolled a random subset of households from the sanitation and control arms into a longitudinal substudy, which measured child health with quarterly visits between 1 to 3.5 years after intervention implementation. The study period therefore included approximately 1 year of high-intensity promotion, 1 year of low-intensity promotion, and 6 months with no promotion. We assessed intervention effects on diarrhea and ARI prevalence among children <5 years through intention-to-treat analysis using generalized linear models with robust standard errors. Masking was not possible during data collection, but data analysis was masked. We enrolled 720 households (360 per arm) from the parent trial and made 9,800 child observations between June 2014 and December 2016. Over the entire study period, diarrheal prevalence was lower among children in the sanitation arm (11.9%) compared to the control arm (14.5%) (prevalence ratio [PR] = 0.81, 95% CI 0.66, 1.00, p = 0.05; prevalence difference [PD] = −0.027, 95% CI −0.053, 0, p = 0.05). ARI prevalence did not differ between sanitation (21.3%) and control (22.7%) arms (PR = 0.93, 95% CI 0.82, 1.05, p = 0.23; PD = −0.016, 95% CI −0.043, 0.010, p = 0.23). There were no significant differences in intervention effects between periods with high-intensity versus low-intensity/no promotion. Study limitations include use of caregiver-reported symptoms to define health outcomes and limited data collected after promotion ceased.ConclusionsThe observed effect of the WASH Benefits Bangladesh sanitation intervention on diarrhea in children appeared to be sustained for at least 3.5 years after implementation, including 1.5 years after heavy promotion ceased. Existing latrine access was high in the study setting, suggesting that improving on-site latrine quality can deliver health benefits when latrine use practices are in place. Further work is needed to understand how latrine adoption can be achieved and sustained in settings with low existing access and how sanitation programs can adopt transformative approaches of excreta management, including safe disposal of child and animal feces, to generate a hygienic home environment.Trial registrationClinicalTrials.gov; {"type":"clinical-trial","attrs":{"text":"NCT01590095","term_id":"NCT01590095"}}NCT01590095; https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT01590095","term_id":"NCT01590095"}}NCT01590095.

Jesse Contreras and co-workers evaluate potential extended benefits over time of a multi-component sanitation intervention in Bangladesh.