Find research datasets worth reusing

opencc-zeroDec 2020View details →

Data from: Initiating Antiretroviral Therapy for HIV at a Patient's First Clinic Visit: The RapIT Randomized Controlled Trial

Background: High rates of patient attrition from care between HIV testing and antiretroviral therapy (ART) initiation have been documented in sub-Saharan Africa, contributing to persistently low CD4 cell counts at treatment initiation. One reason for this is that starting ART in many countries is a lengthy and burdensome process, imposing long waits and multiple clinic visits on patients. We estimated the effect on uptake of ART and viral suppression of an accelerated initiation algorithm that allowed treatment-eligible patients to be dispensed their first supply of antiretroviral medications on the day of their first HIV-related clinic visit. Methods and Findings: RapIT was an unblinded randomized controlled trial of single-visit ART initiation in two public sector clinics in South Africa (a primary health clinic (PHC) and a hospital-based HIV clinic). Adult (≥18), non-pregnant patients receiving a positive HIV test or first treatment-eligible CD4 count were randomized to standard or rapid initiation. Rapid arm patients received a point-of-care (POC) CD4 count if needed; those ART-eligible received a POC TB test if symptomatic, POC blood tests, physical exam, education, counseling, and ARV dispensing. Standard arm patients followed standard clinic procedures (3-5 additional clinic visits over 2-4 weeks prior to ARV dispensing). Follow up was by record review only. The primary outcome was viral suppression, defined as initiated, retained in care, and suppressed (<=400 copies/ml) ≤ 10 months of study enrollment. Secondary outcomes included initiation of ART ≤ 90 days of study enrollment; retention in care; time to ART initiation; patient-level predictors of primary outcomes; prevalence of TB symptoms; and the feasibility and acceptability of the intervention. A survival analysis was conducted comparing attrition from care after ART initiation between the groups among those who initiated within 90 days. 377 patients were enrolled in the study between May 8, 2013 and August 29, 2014 (median CD4 count 210 cells/mm3). In the rapid arm, 119/187 patients (64%) initiated and were suppressed at 10 months, compared to 96/190 (51%) in the standard arm (RR 1.26 [1.05-1.50]. In the rapid arm 182/187 (97%) initiated ART ≤ 90 days, compared to 136/190 (72%) in the standard arm (relative risk [95% CI] 1.36 [1.24-1.49]. Among 318 patients who did initiate ART within 90 days, the hazard of attrition within the first 10 months did not differ between the treatment arms (HR 1.06; 95% CI 0.61-1.84). The study was limited by the small number of sites and small sample size and the generalizability of the results to other settings and to non-research conditions is uncertain. Conclusions: Offering single-visit ART initiation to adult patients in South Africa increased uptake of ART by 36% and viral suppression by 26%. It should be considered for adoption in the public sector in Africa.

Data from: The impact of hotspot-targeted interventions on malaria transmission in Rachuonyo south district in the western Kenyan highlands: a cluster-randomized controlled trial

Background: Malaria transmission is highly heterogeneous, generating malaria hotspots that can fuel malaria transmission across a wider area. Targeting hotspots may represent an efficacious strategy for reducing malaria transmission. We determined the impact of interventions targeted to serologically defined malaria hotspots on malaria transmission both inside hotspots and in surrounding communities. Methods and Findings: Twenty-seven serologically defined malaria hotspots were detected in a survey conducted from 24 June to 31 July 2011 that included 17,503 individuals from 3,213 compounds in a 100-km2 area in Rachuonyo South District, Kenya. In a cluster-randomized trial from 22 March to 15 April 2012, we randomly allocated five clusters to hotspot-targeted interventions with larviciding, distribution of long-lasting insecticide-treated nets, indoor residual spraying, and focal mass drug administration (2,082 individuals in 432 compounds); five control clusters received malaria control following Kenyan national policy (2,468 individuals in 512 compounds). Our primary outcome measure was parasite prevalence in evaluation zones up to 500 m outside hotspots, determined by nested PCR (nPCR) at baseline and 8 wk (16 June–6 July 2012) and 16 wk (21 August–10 September 2012) post-intervention by technicians blinded to the intervention arm. Secondary outcome measures were parasite prevalence inside hotpots, parasite prevalence in the evaluation zone as a function of distance from the hotspot boundary, Anopheles mosquito density, mosquito breeding site productivity, malaria incidence by passive case detection, and the safety and acceptability of the interventions. Intervention coverage exceeded 87% for all interventions. Hotspot-targeted interventions did not result in a change in nPCR parasite prevalence outside hotspot boundaries (p ≥ 0.187). We observed an average reduction in nPCR parasite prevalence of 10.2% (95% CI −1.3 to 21.7%) inside hotspots 8 wk post-intervention that was statistically significant after adjustment for covariates (p = 0.024), but not 16 wk post-intervention (p = 0.265). We observed no statistically significant trend in the effect of the intervention on nPCR parasite prevalence in the evaluation zone in relation to distance from the hotspot boundary 8 wk (p = 0.27) or 16 wk post-intervention (p = 0.75). Thirty-six patients with clinical malaria confirmed by rapid diagnostic test could be located to intervention or control clusters, with no apparent difference between the study arms. In intervention clusters we caught an average of 1.14 female anophelines inside hotspots and 0.47 in evaluation zones; in control clusters we caught an average of 0.90 female anophelines inside hotspots and 0.50 in evaluation zones, with no apparent difference between study arms. Our trial was not powered to detect subtle effects of hotspot-targeted interventions nor designed to detect effects of interventions over multiple transmission seasons. Conclusions: Despite high coverage, the impact of interventions targeting malaria vectors and human infections on nPCR parasite prevalence was modest, transient, and restricted to the targeted hotspot areas. Our findings suggest that transmission may not primarily occur from hotspots to the surrounding areas and that areas with highly heterogeneous but widespread malaria transmission may currently benefit most from an untargeted community-wide approach. Hotspot-targeted approaches may have more validity in settings where human settlement is more nuclear. Trial registration: ClinicalTrials.gov NCT01575613.

opencc-zeroDec 2016View details →

Data from: Adjunctive clindamycin for cellulitis: clinical trial comparing flucloxacillin with or without clindamycin for the treatment of limb cellulitis

Objective: To compare flucloxacillin with clindamycin to flucloxacillin alone for the treatment of limb cellulitis. Design: Parallel, double-blinded, randomised controlled trial. Setting: Emergency department attendances and general practice referrals within 20 hospitals in England. Interventions: Flucloxacillin, at a minimum of 500 mg 4 times per day for 5 days, with clindamycin 300 mg 4 times per day for 2 days given orally versus flucloxacillin given alone. Main outcome measures: The primary outcome was improvement at day 5. This was defined as being afebrile with either a reduction in affected skin surface temperature or a reduction in the circumference of the affected area. Secondary outcomes included resolution of systemic features, resolution of inflammatory markers, recovery of renal function, reduction in the affected area, decrease in pain, return to work or normal activities and the absence of increased side effects. Results: 410 patients were included in the trial. No significant difference was seen in improvement at day 5 for flucloxacillin with clindamycin (136/156, 87%) versus flucloxacillin alone (140/172, 81%)—OR 1.55 (95% CI 0.81 to 3.01), p=0.174. There was a significant difference in the number of patients with diarrhoea at day 5 in the flucloxacillin with clindamycin allocation (34/160, 22%) versus flucloxacillin alone (16/176, 9%)—OR 2.7 (95% CI 1.41 to 5.07), p=0.002. There was no clinically significant difference in any secondary outcome measures. There was no significant difference in the number of patients stating that they had returned to normal activities at the day 30 interview in the flucloxacillin with clindamycin allocation (99/121, 82%) versus flucloxacillin alone (104/129, 81%)—adjusted OR 0.90 (95% CI 0.44 to 1.84). Conclusions: The addition of a short course of clindamycin to flucloxacillin early on in limb cellulitis does not improve outcome. The addition of clindamycin doubles the likelihood of diarrhoea within the first few days.

opencc-zeroDec 2014View details →

Data from: A critical appraisal of clinical trials conducted and subsequent drug approvals in India and South Africa

Objectives: To assess the relation between the number of clinical trials conducted and respective new drug approvals in India and South Africa. Design: Construction and analysis of a comprehensive database of completed randomised controlled clinical trials based on clinicaltrials.gov from 1 January 2005 to 31 December 2010 and drug approval data from 2006 until 2013 for India and South Africa. Setting: USA, the EU, India and South Africa. Main outcome measures: Percentage of completed randomised clinical trials for an Investigational Medicinal Product (IMP) leading to new drug approval in India and South Africa. Results: A total of 622 eligible randomised controlled trials were identified as per search criteria for India and South Africa. Clustering them for the same sponsor and the same Investigational New Drug (IND) resulted in 453 eligible trials, that is, 224 for India and 229 for South Africa. The distribution of the market application approvals between the EU/USA as well as India and South Africa revealed that out of clinical trials with the participation of test centres in India and/or South Africa, 39.6% (India) clinical trials and 60.1% (South Africa) clinical trials led to market authorisation in the EU/USA without a New Drug Application (NDA) approval in India or South Africa. Conclusions: Despite an increase in clinical trial activities, there is a clear gap between the number of trials conducted and market availability of these new drugs in India and South Africa. Drug regulatory authorities, investigators, institutional review boards and patient groups should direct their efforts to ensuring availability of new drugs in the market that have been tested and researched on their population.

Data from: Effect of ecological momentary assessment, goal-setting and personalized phone-calls on adherence to interval walking training using the InterWalk application among patients with type 2 diabetes – a pilot randomized controlled trial

Objectives: The objective was to investigate the feasibility and usability of structured text-messages, goal-setting and phone-calls on adherence to a 12-week self-conducted interval walking training (IWT) program, delivered by the InterWalk smartphone among patients with type 2 diabetes (T2D). Methods: In a two-arm pilot randomized controlled trial (Denmark, March 2014 to February 2015), patients with T2D (18-80 years with a Body Mass Index of 18 and 40 kg/m2) were randomly allocated to 12 weeks of IWT with (intervention) or without additional support (control). The primary outcome was the difference between groups in accumulated time of interval walking training across 12 weeks. All patients were encouraged to use the InterWalk application to perform IWT for ≥90 minute/week. Patients in the intervention group made individual goals regarding lifestyle change, received automated text-messages once a week, inquiring about exercise adherence. In case of consistent non-adherence, the patients would receive a phone-call inquiring about the reason for non-adherence. The control group did not receive additional support. Information about training adherence was assessed objectively. Usability of structured text-messages was assessed based on response rates and self-reported satisfaction after 12-weeks. Results: Thirty-seven patients with T2D (66 years, 65% female, hemoglobin 1Ac 50.3 mmol/mol) where included (n=18 and n=19 in intervention and control group, respectively). The retention rate was 83%. The intervention group accumulated [95%CI] 345 -7, 698 minutes of IWT more than the control group. The response rate for the text-messages was 83% (68% for males and 90% for females). Forty-one percent of the intervention and 25% of the control group were very satisfied with their participation. Conclusion: The combination of structured text-messages, goal-setting with the possibility of follow-up phone calls are considered feasible interventions to attain training adherence when using the InterWalk app during a 12-week period in patients with T2D. Some uncertainty about the effect size of adherence remains.

Data from: Improving rational use of ACTs through diagnosis-dependent subsidies: evidence from a cluster-randomized controlled trial in western Kenya

Background: More than half of artemisinin combination therapies (ACTs) consumed globally are dispensed in the retail sector where diagnostic testing is uncommon, leading to overconsumption and poor targeting. In many malaria-endemic countries, ACTs sold over-the-counter are available at heavily subsidized prices, further contributing to their misuse. Inappropriate use of ACTs can have serious implications for the spread of drug resistance and leads to poor outcomes for non-malaria patients treated with incorrect drugs. We evaluated the public health impact of an innovative strategy that targets ACT subsidies to confirmed malaria cases by coupling free diagnostic testing with a diagnosis-dependent ACT subsidy. Methods and Findings: We conducted a cluster-randomized controlled trial in 32 community clusters in western Kenya (population ~160,000). Eligible clusters had retail outlets selling ACTs and existing community health worker (CHW) programs and were randomly assigned 1:1 to control and intervention arms. In intervention areas, CHWs were available in their villages to perform malaria rapid diagnostic tests on demand for any individual >1 year of age experiencing a malaria-like illness. Malaria RDT positive individuals received a voucher for a discount on a quality-assured ACT, redeemable at a participating retail medicine outlet. In control areas, CHWs offered a standard package of health education, prevention and referral services. We conducted four population-based surveys, at baseline, 6 months, 12 months and 18 months, of a random sample of households with fever in the last 4 weeks to evaluate predefined, individual-level outcomes. The primary outcome was uptake of malaria diagnostic testing at 12 months. The main secondary outcome was rational ACT use, defined as the proportion of ACTs used by test-positive individuals. Analyses followed the intention-to-treat principle using generalized estimating equations to account for clustering with pre-specified adjustment for gender, age, education and wealth. All descriptive statistics and regressions were weighted to account for sampling design. Between July 2015 and May 2017, 32,404 participants were tested for malaria and 10,870 vouchers were issued. 7416 randomly-selected participants with recent fever from all 32 clusters were surveyed. The majority of recent fevers were in children under 18 years (62.9%, n=4653). The gender of enrolled participants was balanced in children (50.0%, n=2318 v 50.2%, n=2335), but more adult women were enrolled than men (78.0%, n=2139 v 22.0%, n=604). At baseline, 67.6% (n=1362) of participants took an ACT for their illness and 40.3% (n=810) of all participants took an ACT purchased from a retail outlet. At 12 months, 50.5% (n=454) in the intervention arm and 43.4% (n=389) in the control arm had a malaria diagnostic test for their recent fever (Adjusted Risk Difference=9 percentage points [pp], 95%CI: 2-15pp, p=0.015; Adjusted Risk Ratio=1.20, 95%CI:1.05-1.38, p=0.015). By 18-months, the ARR had increased to 1.25 (95%CI:1.09-1.44, p=0.005). Rational use of ACTs in the intervention area increased from 41.7% (n=279) at baseline to 59.6% (n=403) and was 40% higher in the intervention arm at 18 months (Adj RR 1.40, 95%CI: 1.19-1.64). While intervention effects increased between 12 and 18 months, we were not able to estimate longer-term impact of the intervention and could not independently evaluate the effects of the free testing and the voucher on uptake of testing. Conclusions: Diagnosis-dependent ACT subsidies and community-based interventions that include the private sector can have an important impact on diagnostic testing and population-wide rational use of ACTs. Targeting of the ACT subsidy itself to those with a positive malaria diagnostic test may also improve sustainability and reduce the cost of retail sector ACT subsidies.

opencc-zeroJul 2019View details →

Data from: A single session of hyperbaric oxygen therapy demonstrates acute and long-lasting neuroplasticity effects in humans: a replicated, randomized controlled clinical trial

Purpose: Animal studies have demonstrated anti-inflammatory, and anti-nociceptive properties of hyperbaric oxygen therapy (HBOT). However, physiological data are scarce in humans. In a recent experimental study, the authors used the burn injury (BI) model observing a decrease in secondary hyperalgesia area (SHA) in the HBOT-group compared to a control-group.Surprisingly, a long-lasting neuroplasticity effect mitigating the BI-induced SHA-response was seen in the HBOT-preconditioned group. The objective of the present study, therefore, was to confirm our previous findings using an examiner-blinded, block-randomized, controlled, crossover study design. Patients and methods: Nineteen healthy subjects attended two BI-sessions with an inter-session interval of ≥28 days. The BIs were induced on the lower legs by a contact thermode (12.5 cm2, 47C°, 420 s). The subjects were block-randomized to receive HBOT (2.4 ATA, 100% O2, 90 min) or ambient conditions ([AC]; 1 ATA, 21% O2), dividing cohorts equally into two sequence allocations: HBOT-AC or AC-HBOT. All sensory assessments performed during baseline, BI, and post-intervention phases were at homologous time points irrespective of sequence allocation. The primary outcome was SHA, comparing interventions and sequence allocations. Data are mean (95% CI). Results: During HBOT-sessions a mitigating effect on SHAs was demonstrated compared to AC-sessions, ie, 18.8 (10.5–27.0) cm2 vs 32.0 (20.1–43.9) cm2 (P=0.021), respectively. In subjects allocated to the sequence AC-HBOT a significantly larger mean difference in SHA in the AC-session vs the HBOT-session was seen 25.0 (5.4–44.7) cm2 (P=0.019). In subjects allocated to the reverse sequence, HBOT-AC, no difference in SHA between sessions was observed (P=0.55), confirming a preconditioning, long-lasting (≥28 days) effect of HBOT. Conclusion: Our data demonstrate that a single HBOT-session compared to control is associated with both acute and long-lasting mitigating effects on BI-induced SHA, confirming central anti-inflammatory, neuroplasticity effects of hyperbaric oxygen therapy.

opencc-zeroJun 2019View details →

Data from: Auriculotherapy in the prevention of postoperative urinary retention in patients with thoracotomy and thoracic epidural analgesia: a randomized, double-blinded trial

Background: Thoracic epidural analgesia is associated with a high rate of postoperative urine retention (POUR). Auriculotherapy can reduce visceral dysfunction and can be helpful in anesthesiology and pain control. The aim of this study was to test the efficacy of preoperative auriculotherapy to decrease the occurrence of POUR. Methods: This single-center, double-blinded, two-arm randomized study was performed between January 2015 and May 2016 in a tertiary care university hospital. Male patients scheduled for an elective lung surgical procedure under combined general anesthesia and thoracic epidural analgesia were included. Auriculotherapy (A group) was performed once the patient was under general anesthesia with five semi-permanent needles inserted in both ears at the "Shen Men", "bladder", "pelvic parasympathetic", "anterior hypothalamus", and "frontal lobe" points). Five small round patches of adhesive pads were positioned bilaterally at the same points in the Control group (C group). The main outcome measure was the requirement for bladder catheterization during the day and the first night following surgery. Results: Fifty-three patients were randomized and 25 analyzed in each group. Requirement for bladder catheterization was different between groups: 24 C group patients (96%) and 18 A group patients (72%) (p=0.049, Fisher exact test; Odds Ratio=0.11 [0.01–0.95]. The number of patients needed to treat with auriculotherapy to avoid one case of bladder catheterization was four. No adverse effect was observed due to auriculotherapy. Conclusion: This study demonstrates that auriculotherapy is a safe and useful technique reducing POUR in thoracotomy patients benefiting from thoracic epidural analgesia.

opencc-zeroDec 2018View details →

Data from: Sharing of clinical trial data and results reporting practices among large pharmaceutical companies: cross sectional descriptive study and pilot of a tool to improve company practices

Objectives: To develop and pilot a tool to measure and improve pharmaceutical companies' clinical trial data sharing policies and practices. Design: Cross sectional descriptive analysis. Setting: Large pharmaceutical companies with novel drugs approved by the US Food and Drug Administration in 2015. Data sources: Data sharing measures were adapted from 10 prominent data sharing guidelines from expert bodies and refined through a multi-stakeholder deliberative process engaging patients, industry, academics, regulators, and others. Data sharing practices and policies were assessed using data from ClinicalTrials.gov, Drugs@FDA, corporate websites, data sharing platforms and registries (eg, the Yale Open Data Access (YODA) Project and Clinical Study Data Request (CSDR)), and personal communication with drug companies. Main outcome measures: Company level, multicomponent measure of accessibility of participant level clinical trial data (eg, analysis ready dataset and metadata); drug and trial level measures of registration, results reporting, and publication; company level overall transparency rankings; and feasibility of the measures and ranking tool to improve company data sharing policies and practices. Results: Only 25% of large pharmaceutical companies fully met the data sharing measure. The median company data sharing score was 63% (interquartile range 58-85%). Given feedback and a chance to improve their policies to meet this measure, three companies made amendments, raising the percentage of companies in full compliance to 33% and the median company data sharing score to 80% (73-100%). The most common reasons companies did not initially satisfy the data sharing measure were failure to share data by the specified deadline (75%) and failure to report the number and outcome of their data requests. Across new drug applications, a median of 100% (interquartile range 91-100%) of trials in patients were registered, 65% (36-96%) reported results, 45% (30-84%) were published, and 95% (69-100%) were publicly available in some form by six months after FDA drug approval. When examining results on the drug level, less than half (42%) of reviewed drugs had results for all their new drug applications trials in patients publicly available in some form by six months after FDA approval. Conclusions: It was feasible to develop a tool to measure data sharing policies and practices among large companies and have an impact in improving company practices. Among large companies, 25% made participant level trial data accessible to external investigators for new drug approvals in accordance with the current study's measures; this proportion improved to 33% after applying the ranking tool. Other measures of trial transparency were higher. Some companies, however, have substantial room for improvement on transparency and data sharing of clinical trials.

Data from: Agreements between industry and academia on publication rights: a retrospective study of protocols and publications of randomized clinical trials

Background: Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship by industry employees. Methods and Findings: We used a retrospective cohort of randomized clinical trials (RCTs) based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5%) mentioned an agreement regarding publication of results. Of these 456, 393 (86.2%) documented an industry partner's right to disapprove or at least review proposed manuscripts; 39 (8.6%) agreements were without constraints of publication. The remaining 24 (5.3%) protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0%) trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]). Of 71 agreements reported in publications, 52 (73.2%) were concordant with those documented in the protocol. In 14 of 37 (37.8%) publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements. Conclusions: Publication agreements constraining academic authors' independence are common. Journal articles seldom report on publication agreements, and, if they do, statements can be discrepant with the trial protocol.

opencc-zeroDec 2014View details →

Data from: Cost-effectiveness of a specialist geriatric medical intervention for frail older people discharged from acute medical units: economic evaluation in a two-centre randomised controlled trial (AMIGOS)

Background: Poor outcomes and high resource-use are observed for frail older people discharged from acute medical units. A specialist geriatric medical intervention, to facilitate Comprehensive Geriatric Assessment, was developed to reduce the incidence of adverse outcomes and associated high resource-use in this group in the post-discharge period. Objective: To examine the costs and cost-effectiveness of a specialist geriatric medical intervention for frail older people in the 90 days following discharge from an acute medical unit, compared with standard care. Methods: Economic evaluation was conducted alongside a two-centre randomised controlled trial (AMIGOS). 433 patients (aged 70 or over) at risk of future health problems, discharged from acute medical units within 72 hours of attending hospital, were recruited in two general hospitals in Nottingham and Leicester, UK. Participants were randomised to the intervention, comprising geriatrician assessment in acute units and further specialist management, or to control where patients received no additional intervention over and above standard care. Primary outcome was incremental cost per quality adjusted life year (QALY) gained. Results: We undertook cost-effectiveness analysis for 417 patients (intervention: 205). The difference in mean adjusted QALYs gained between groups at 3 months was -0.001 (95% confidence interval [CI]: -0.009, 0.007). Total adjusted secondary and social care costs, including direct costs of the intervention, at 3 months were £4412 (€5624, $6878) and £4110 (€5239, $6408) for the intervention and standard care groups, the incremental cost was £302 (95% CI: 193, 410) [€385, $471]. The intervention was dominated by standard care with probability of 62%, and with 0% probability of cost-effectiveness (at £20,000/QALY threshold). Conclusions: The specialist geriatric medical intervention for frail older people discharged from acute medical unit was not cost-effective. Further research on designing effective and cost-effective specialist service for frail older people discharged from acute medical units is needed.

Data from: Economic evaluation of a general hospital unit for older people with delirium and dementia (TEAM randomised controlled trial)

Background: One in three hospital acute medical admissions is of an older person with cognitive impairment. Their outcomes are poor and the quality of their care in hospital has been criticised. A specialist unit to care for older people with delirium and dementia (the Medical and Mental Health Unit, MMHU) was developed and then tested in a randomised controlled trial where it delivered significantly higher quality of, and satisfaction with, care, but no significant benefits in terms of health status outcomes at three months. Objective: To examine the cost-effectiveness of the MMHU for older people with delirium and dementia in general hospitals, compared with standard care. Methods: Six hundred participants aged over 65 admitted for acute medical care, identified on admission as cognitively impaired, were randomised to the MMHU or to standard care on acute geriatric or general medical wards. Cost per quality adjusted life year (QALY) gained, at 3-month follow-up, was assessed in trial-based economic evaluation (599/600 participants, intervention: 309). Multiple imputation and complete-case sample analyses were employed to deal with missing QALY data (55%). Results: The total adjusted health and social care costs, including direct costs of the intervention, at 3 months was £7714 and £7862 for MMHU and standard care groups, respectively (difference -£149 (95% confidence interval [CI]: -298, 4)). The difference in QALYs gained was 0.001 (95% CI: -0.006, 0.008). The probability that the intervention was dominant was 58%, and the probability that it was cost-saving with QALY loss was 39%. At £20,000/QALY threshold, the probability of cost-effectiveness was 94%, falling to 59% when cost-saving QALY loss cases were excluded. Conclusions: The MMHU was strongly cost-effective using usual criteria, although considerably less so when the less acceptable situation with QALY loss and cost savings were excluded. Nevertheless, this model of care is worthy of further evaluation.

Data from: Single-dose oral ciprofloxacin prophylaxis as a response to a meningococcal meningitis epidemic in the African meningitis belt: a three-arm, open-label, cluster-randomized trial

Background: Antibiotic prophylaxis for contacts of meningitis cases is not recommended during outbreaks in the African meningitis belt. We assessed the effectiveness of single-dose oral ciprofloxacin administered to household contacts and in village-wide distributions on the overall attack rate (AR) in an outbreak of meningococcal meningitis. Methods and findings: In this 3-arm, open-label, cluster-randomized trial during a meningococcal meningitis outbreak in Madarounfa District, Niger, villages notifying a suspected case were randomly assigned (1:1:1) to standard care (the control arm), single-dose oral ciprofloxacin for household contacts within 24 hours of case notification, or village-wide distribution of ciprofloxacin within 72 hours of first case notification. The primary outcome was the overall AR of suspected meningitis after inclusion. A random sample of 20 participating villages was enrolled to document any changes in fecal carriage prevalence of ciprofloxacin-resistant and extended-spectrum beta-lactamase (ESBL)–producing Enterobacteriaceae before and after the intervention. Between April 22 and May 18, 2017, 49 villages were included: 17 to the control arm, 17 to household prophylaxis, and 15 to village-wide prophylaxis. A total of 248 cases were notified in the study after the index cases. The AR was 451 per 100,000 persons in the control arm, 386 per 100,000 persons in the household prophylaxis arm (t test versus control p = 0.68), and 190 per 100,000 persons in the village-wide prophylaxis arm (t test versus control p = 0.032). The adjusted AR ratio between the household prophylaxis arm and the control arm was 0.94 (95% CI 0.52–1.73, p = 0.85), and the adjusted AR ratio between the village-wide prophylaxis arm and the control arm was 0.40 (95% CI 0.19‒0.87, p = 0.022). No adverse events were notified. Baseline carriage prevalence of ciprofloxacin-resistant Enterobacteriaceae was 95% and of ESBL-producing Enterobacteriaceae was >90%, and did not change post-intervention. One limitation of the study was the small number of cerebrospinal fluid samples sent for confirmatory testing. Conclusions: Village-wide distribution of single-dose oral ciprofloxacin within 72 hours of case notification reduced overall meningitis AR. Distributions of ciprofloxacin could be an effective tool in future meningitis outbreak responses, but further studies investigating length of protection, effectiveness in urban settings, and potential impact on antimicrobial resistance patterns should be carried out.

opencc-zeroDec 2018View details →

Data from: Refining eligibility criteria for amyotrophic lateral sclerosis clinical trials

Objective: To assess the effect of eligibility criteria on exclusion rates, generalizability and outcome heterogeneity in ALS clinical trials, and to assess the value of a risk-based inclusion criterion. Methods: A literature search was performed to summarize eligibility criteria of clinical trials. The extracted criteria were applied to an incidence cohort of 2,904 consecutive ALS patients to quantify their effects on generalizability and outcome heterogeneity. We evaluated the effect of a risk-based selection approach on trial design using a personalized survival prediction model. Results: We identified 38 trials: enrolled patients reveal a large variability between trials of all patient characteristics (p < 0.001), except for the proportion of males (p = 0.21). Exclusion rates varied widely (from 14% to 95%; mean 59.8% (95% CI 52.6-66.7)). Stratification of the eligible populations into prognostic subgroups showed that eligibility criteria lead to exclusion of patients in all prognostic groups. Eligibility criteria neither reduce heterogeneity in survival time (from 22.0 to 20.5 months, p = 0.09) nor affect between-patient variability in functional decline (from 0.62 to 0.65, p = 0.25). In none of the 38 trials were the eligibility criteria found to be more efficient than the prediction model in optimizing sample size and eligibility rate. Conclusions: The majority of ALS patients are excluded from trial participation, which questions the generalizability of trial results. Importantly, eligibility criteria only minimally improve homogeneity in trial endpoints. An individualized risk-based criterion could be used to balance the gains in trial design and loss in generalizability.

Data from: Adjunctive use of modified Yunu-Jian in the non-surgical treatment of male smokers with chronic periodontitis: a randomized double-blind, placebo-controlled clinical trial

Background: Yunu-Jian (YJ) is a Chinese medicine (CM) heat purging formula, which is used to reduce wei huo (stomach-heat, SH) and enrich shen yin (kidney-yin, KY). This formula is also commonly used to manage diabetes mellitus and gum/oral inflammation. The activity of YJ can be modified or refined by the addition of other CM herbs and/or minor changes to one of its five key ingredients. The aim of this study was to evaluate the adjunctive use of modified YJ (mYJ) or YJ containing additional osteoblast-stimulating and inflammation-modulating CM herbs in the non-surgical periodontal treatment of smokers with chronic periodontitis in a randomized, double-blind, prospective, placebo-controlled study. Methods: Healthy adult male smokers with untreated chronic periodontitis who showed CM syndrome of SH and KY deficiency (KYD) whilst attending a dental teaching hospital from October to December, 2005, were invited to participate in a randomized double-blind, placebo-controlled clinical trial. The trial itself involved the once-daily oral administration of a placebo or mYJ for 3 months as an adjunct to non-surgical periodontal therapy. Several periodontal parameters, including radiographic alveolar bone density, were measured by computer-assisted densitometric image analysis (CADIA) on selected sites, and CM signs of SH and KYD were followed from their baseline values to various time points up to 12 months or the end of study. Results: Twenty-five smokers (consumed 25.0 ± 15.3 smoking-pack years, ranged 7.5–80; aged 46.3 ± 6.8 years) with periodontitis and SH and KYD were recruited (Placebo, n = 14; mYJ, n = 11). All of the participants showed good tolerance towards the CM recipe. All of the periodontal parameters had improved after 12-month follow-up, and no statistically significant differences were detected between the control group and test group, except for the higher CADIA values observed compared with the baseline at 12 months for test sites (P = 0.025). 4/3/3 test vs 14/13/13 control participants had persisting SH and KYD at 6, 9 and 12 months (P < 0.001), respectively. Conclusions: The adjunctive use of mYJ preserved the post-treatment increases in the radiographic alveolar bone density at the study sites and led to an overall improvement in SH and KYD compared with the controls.

opencc-zeroAug 2019View details →

Data from: Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function

Objective: We carried out first-in-patient studies of vamorolone, a first-in-class dissociative steroidal anti-inflammatory drug, in Duchenne muscular dystrophy. Methods: An open-label, multiple-ascending dose study of vamorolone was conducted in 48 boys with Duchenne muscular dystrophy (4 to <7 years, steroid-naïve). Dose levels were 0.25, 0.75, 2.0 and 6.0 mg/kg/day using an oral suspension formulation (12 boys/dose level; 1/3rd to 10x glucocorticoid dose in DMD). Results: Over a 24-week treatment period, oral administration of vamorolone at all doses tested was safe and well-tolerated. The 2.0 mg/kg/day dose group met the primary efficacy outcome of improved muscle function (time to stand; 24 weeks vamorolone treatment versus natural history controls), without evidence of most adverse effects of glucocorticoids. Significant dose-responsive improvements in 10 meter run/walk, and six-minute walk test were observed for 2.0 and 6.0 mg/kg/day dose groups. The morbidity of most concern to many chronic glucocorticoid users, bone loss, was not seen with vamorolone at any dose, as evidenced by serum osteocalcin. Biomarker outcomes for adrenal suppression and insulin resistance were also less impacted in vamorolone-treated DMD patients, relative to published studies of glucocorticoid therapy. Conclusions: Vamorolone demonstrated both efficacy and a reduction in adverse effects in DMD patients compared to traditional glucocorticoids in a 24-week, open-label study. Vamorolone has potential to replace chronic glucocorticoids in many disorders where side effects detract from patient quality of life. Classification of Evidence: This study provides Class II evidence that certain dosages of vamorolone are well tolerated and effective in improving muscle function in DMD.

opencc-zeroDec 2018View details →

Data from: Detection and initial management of gestational diabetes through primary health care services in Morocco: an effectiveness-implementation trial

Background: Gestational Diabetes Mellitus (GDM) testing and management in Morocco is associated with delays resulting in late commencement of treatment. To reduce delays and to increase access of women to GDM care, a country-adapted intervention targeting primary health care providers was designed to test the hypothesis that detection and initial management of GDM at the primary level of care improves newborn outcomes in terms of lower birthweights and less cases of macrosomia and impacts on maternal weight gain, glucose balance and pregnancy outcomes. Materials and methods: We conducted a cluster randomized controlled trial in two districts of Morocco. In each district, 10 health centers were randomly selected to serve either as intervention or control sites. Pregnant women attending antenatal care in the study facilities were eligible to participate. At the intervention sites, women were offered GDM screening by capillary glucose testing following International Association of Diabetes in Pregnancy Study Groups/WHO criteria. Women diagnosed with GDM received counselling on nutrition and exercise and were followed up through their health center whereas at control facilities routine practice was applied. Primary outcome was birthweight and secondary outcomes maternal weight gain, glucose control and pregnancy complications. We further assessed GDM prevalence in the intervention arm. Statistical analysis was performed on 210 recruited women. Continuous variables were reported using means while categorical variables using frequencies with tests of independence applying chi-squared tests. Differences of outcome variables between the two groups were estimated by mixed-effects regression models and effect sizes adjusted for confounders. The trial is registered under NCT02979756 at ClinicalTrials.gov. Results: GDM prevalence reached 23.7% in Marrakech. Birthweight in the intervention group was 147grams lower than in the control group (p = 0.08) as was the proportion of macrosomes (3.5% versus 18.4%; p< 0.001). In the intervention arm, women did two times more follow-ups than at control sites (p = 0.001) and mean follow-up intervals were shorter (11.3 days versus 18.7 days; p < 0.001). Overall, 30% more fasting blood sugar values were balanced (p = 0.005) and mean weekly maternal weight gain 49 grams lower (p = 0.032) in the intervention group. More women from control facilities had a delivery complication whereas more newborn complications were observed in women from intervention facilities. No difference between the two groups existed regarding mode of delivery and mean gestational age at delivery. One of the main limitations of the study was the Hawthorn-effect at control sites that might have led to an underestimation of the effect size. Conclusion: A high GDM prevalence in Morocco calls for a context-adapted screening and management approach to enable early interventions. GDM detection and care through antenatal care at primary health facilities may have positively impacted on newborn birthweight but findings are inconclusive. Results of this study will contribute to the decision on a potential upscaling of the intervention in Morocco. Future research could examine long term metabolic changes including diabetes type 2 in the cohort of women and their children.

opencc-zeroDec 2016View details →

Data from: Ambulatory versus inpatient management of severe nausea and vomiting of pregnancy: a randomized control trial with patient preference arm

ABSTRACT Objective To determine whether ambulatory (outpatient, OP) treatment of severe nausea and vomiting of pregnancy (NVP) is as effective as inpatient (IP) care. Design Non-blinded randomized control trial (RCT) with patient preference arm Setting Multi-center Participants Women less than 20 weeks pregnant with severe NVP and associated ketonuria Methods Women participating in the RCT were randomized via web-based application to either ambulatory or IP treatment. Women declining randomisation entered the patient preference trial (PPT) arm. Protocols, data collection and follow-up were the same for all participants. Main Outcome Measures Primary outcome was reduction in Pregnancy Unique Quantification of Emesis (PUQE) score at 48 hours. Secondary outcomes were duration of treatment; improvement in symptom scores and ketonuria at 48 hours; re-attendances within 7 days of discharge; and comparison of symptoms at 7 days post discharge Results 152/174 eligible women agreed to participate with 77/152 (51%) recruited to the RCT and 79/152 (49%) to the PPT. Patients were initially compared in 4 groups (randomized IP, randomized OP, non-randomized IP and non-randomized OP). Comprehensive cohort analysis of participants in the (RCT) and (PPT) did not demonstrate any differences in patient demographics or baseline clinical characteristics. Pooled analysis of IP versus OP groups showed no difference in reduction in PUQE score at 48 hours (p=0.86). There was no difference in change in eating score (p=0.69), drinking score (p=0.77), wellbeing rating (p=0.64) or reduction in ketonuria (p=0.47) at 48 hours, with no difference in duration of index treatment episode (p=0.83) or re-attendances within 7 days (p=0.52). Conclusions Ambulatory management is an effective alternative to inpatient management of severe NVP. The trial also demonstrated that many women requiring treatment for HG have a strong preferences regarding treatment setting, which needs to be considered by care providers, especially given the psychological impact of HG.

Data from: First-in-human randomized controlled trial of an oral, replicating Adenovirus 26 vector vaccine for HIV-1

Background: Live, attenuated viral vectors that express HIV-1 antigens are being investigated as an approach to generating durable immune responses against HIV-1 in humans. We recently developed a replication-competent, highly attenuated Ad26 vector that expresses mosaic HIV-1 Env (rcAd26.MOS1.HIV-Env, "rcAd26"). Here we present the results of a first-in-human, placebo-controlled clinical trial to test the safety, immunogenicity and mucosal shedding of rcAd26 given orally. Methods: Healthy adults were randomly assigned to receive a single oral dose of vaccine or placebo at 5:1 ratio in a dosage escalation of 10^8 to 10^11 rcAd26 VP (nominal doses) at University of Rochester Medical Center, Rochester, NY, USA. Participants were isolated and monitored for reactogenicity for 10 days post-vaccination, and adverse events were recorded up to day 112. Rectal and oropharyngeal secretions were evaluated for shedding of the vaccine. Humoral and cellular immune responses were measured. Household contacts were monitored for secondary vaccine transmission. Results: We enrolled 22 participants and 11 household contacts between February 7 and June 24, 2015. 18 participants received one dose of HIV-1 vaccine and 4 participants received placebo. The vaccine caused only mild to moderate adverse events. No vaccine-related SAEs were observed. No infectious rcAd26 viral particles were detected in rectal or oropharyngeal secretions from any participant. Env-specific ELISA and ELISPOT responses were undetectable. No household contacts developed vaccine-induced HIV-1 seropositivity or vaccine-associated illness. Conclusions: The highly attenuated rcAd26.MOS1.HIV-Env vaccine was well tolerated up to 10^11 VP in healthy, HIV-1-uninfected adults, though the single dose was poorly immunogenic suggesting the replicative capacity of the vector was too attenuated. There was no evidence of shedding of infectious virus or secondary vaccine transmission following the isolation period. These data suggest the use of less attenuated viral vectors in future studies of live, oral HIV-1 vaccines. Clinical Trials Registration: NCT02366013