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A hospital admission offers smokers an opportunity to quit. Smoking cessation counseling provided in the hospital is effective, but only if it continues for more than one month after discharge. Providing smoking cessation medication at discharge may add benefit to counseling. A major barrier to translating this research into clinical practice is sustaining treatment during the transition to outpatient care. An evidence-based, practical, cost-effective model that facilitates the continuation of tobacco treatment after discharge is needed. This paper describes the design of a comparative effectiveness trial testing a hospital-initiated intervention against standard care. A two-arm randomized controlled trial compares the effectiveness of standard post-discharge care with a multi-component smoking cessation intervention provided for three months after discharge. Current smokers admitted to Massachusetts General Hospital who receive bedside smoking cessation counseling, intend to quit after discharge and are willing to consider smoking cessation medication are eligible. Study participants are recruited following the hospital counseling visit and randomly assigned to receive Standard Care or Extended Care after hospital discharge. Standard Care includes a recommendation for a smoking cessation medication and information about community resources. Extended Care includes up to three months of free FDA-approved smoking cessation medication and five proactive computerized telephone calls that use interactive voice response technology to provide tailored motivational messages, offer additional live telephone counseling calls from a smoking cessation counselor, and facilitate medication refills. Outcomes are assessed at one, three, and six months after hospital discharge. The primary outcomes are self-reported and validated seven-day point prevalence tobacco abstinence at six months. Other outcomes include short-term and sustained smoking cessation, post-discharge utilization of smoking cessation treatment, hospital readmissions and emergency room visits, and program cost per quit. This study tests a disseminable smoking intervention model for hospitalized smokers. If effective and widely adopted, it could help to reduce population smoking rates and thereby reduce tobacco-related mortality, morbidity, and health care costs. United States Clinical Trials Registry NCT01177176.

Heart failure is a prevalent health problem associated with costly hospital readmissions. Transitional care programs have been shown to reduce readmissions but are costly to implement. Evidence regarding the effectiveness of telemonitoring in managing the care of this chronic condition is mixed. The objective of this randomized controlled comparative effectiveness study is to evaluate the effectiveness of a care transition intervention that includes pre-discharge education about heart failure and post-discharge telephone nurse coaching combined with home telemonitoring of weight, blood pressure, heart rate, and symptoms in reducing all-cause 180-day hospital readmissions for older adults hospitalized with heart failure. A multi-center, randomized controlled trial is being conducted at six academic health systems in California. A total of 1,500 patients aged 50 years and older will be enrolled during a hospitalization for treatment of heart failure. Patients in the intervention group will receive intensive patient education using the ‘teach-back’ method and receive instruction in using the telemonitoring equipment. Following hospital discharge, they will receive a series of nine scheduled health coaching telephone calls over 6 months from nurses located in a centralized call center. The nurses also will call patients and patients’ physicians in response to alerts generated by the telemonitoring system, based on predetermined parameters. The primary outcome is readmission for any cause within 180 days. Secondary outcomes include 30-day readmission, mortality, hospital days, emergency department (ED) visits, hospital cost, and health-related quality of life. BEAT-HF is one of the largest randomized controlled trials of telemonitoring in patients with heart failure, and the first explicitly to adapt the care transition approach and combine it with remote telemonitoring. The study population also includes patients with a wide range of demographic and socioeconomic characteristics. Once completed, the study will be a rich resource of information on how best to use remote technology in the care management of patients with chronic heart failure. ClinicalTrials.gov # NCT01360203 .

The introduction of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus-1 (HIV-1) prevention in Africa presents new challenges for health systems that are already overburdened because PrEP delivery requires frequent clinic visits (generally every 3 months) for HIV-1 testing and PrEP refills. HIV-1 self-testing (HIVST) has the potential to improve the efficiency of PrEP delivery by decreasing the number of clinic visits. Here, we describe the rationale and design of a randomized, noninferiority trial designed to test the effectiveness and safety of using HIVST to support PrEP delivery in Kenya. The JiPime-JiPrEP (Kiswahili for ‘Test Yourself, PrEP Yourself’) study is a three-arm randomized trial taking place in Thika, Kenya. Participants (n = 495) are eligible for enrollment if they are at least 18 years old, HIV-1 seronegative, and have been taking PrEP for 1 month. Three distinct participant types will be enrolled: men (n = 165) and women (n = 165) who are in mutually disclosed HIV-1 serodiscordant relationships, and women (n = 165) who are at HIV-1 risk and not in a known serodiscordant relationship. Participants in each of these subpopulations will be 1:1:1 randomized to: 1) the standard of care, with quarterly clinic visits; 2) oral HIVST, with biannual clinic visits plus oral HIVSTs to use at the quarters between those visits; or 3) blood-based HIVST, with biannual clinic visits plus blood-based HIVSTs. All participants will complete quantitative surveys and provide blood samples for the objective measurement of PrEP adherence at baseline, 6 months, and 12 months. The primary outcomes are PrEP adherence, PrEP continuation, and HIV-1 testing, measured at 6 months and secondarily at 12 months. The findings from this trial can help to understand how HIVST—a new HIV-1 testing technology—can support health systems in sub-Saharan Africa. Additionally, the findings can inform policy aimed at improving the efficiency of PrEP implementation and scale-up in Kenya. ClinicalTrials.gov, NCT03593629 . Retrospectively registered on 20 July 2018.

Malnutrition amongst under-fives remains common in resource-poor countries and is resistant to current interventions. New opportunities have emerged to target “environmental enteric dysfunction” (EED) that refers to the abnormal gut structure and function that results from colonisation of the gut with pathogenic microbes and compromises nutrition and growth in early life. Although the gut microbiome may provide a defence against ingested gut pathogens through colonisation resistance, its development is adversely affected by multiple environmental factors. Dietary supplements of pro- or synbiotics may build the resilience of the gut microbiome against these environmental factors and boost colonisation resistance. We aim to assess whether dietary supplementation of newborns in rural Kenya with pro/synbiotics prevents or ameliorates EED and improves growth. Six hundred newborns less than 4 days old will be recruited from Homa Bay County Teaching and Referral Hospital, western Kenya. Newborns will be randomly allocated, stratified by HIV exposure, in a 1:1:1:1 ratio to one of 4 study arms to receive either of two synbiotics, a probiotic or no supplement. Supplements will be given daily for 10 days and then weekly until 6 months of age. Participants will be followed until the age of 2 years. The primary outcome is systemic inflammation at 6 months assessed by plasma alpha-1-acid glycoprotein. Secondary outcomes include biomarkers of gut health and growth, anthropometric indices, morbidity and mortality. As dietary supplements with pro- or synbiotics may improve gut health and can be administered in early life, our findings may inform the package of interventions to prevent malnutrition and improve growth in Africa and similar low-resource settings. Pan African Clinical Trials Registry, Trial number: PACTR202003893276712. Date: 02/03/2020 https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9798

The prevalence of depression in patients with acute coronary syndrome, i.e. myocardial infarction and unstable angina, is higher than in the general population. The prevalence of anxiety is higher as well. Both depression and anxiety are associated with poor cardiac outcomes and higher mortality. Comorbid depression in patients with acute coronary syndrome often goes undiagnosed, and it is therefore a challenging task to prevent this risk factor. The study of DEpression in Coronary ARtery Disease (DECARD) is designed to examine if it is possible to prevent depression in patients with acute coronary syndrome. Two hundred forty non-depressed patients with acute coronary syndrome are randomized to treatment with either escitalopram or placebo for 1 year. Psychiatric and cardiac assessment of patients is performed to evaluate the possibility of preventing depression. Diagnosis of depression and Hamilton Depression Scale are the primary outcome measures. This is the first study of prevention of depression in patients after acute coronary syndrome with a selective serotonin reuptake inhibitor. http://www.ClinicalTrials.gov Identifier: NCT00140257

New treatments are needed for people with treatment-resistant depression (TRD), who do not benefit from anti-depressants and many of whom do not recover fully with psychological treatments. The Community Navigator programme was co-produced with service users and practitioners. It is a novel social intervention which aims to reduce loneliness and thus improve health outcomes for people with TRD. Participants receive up to 10 individual meetings with a Community Navigator, who helps them to map their social world and set and enact goals to enhance their social connections and reduce loneliness. Participants may also access group meet-ups with others in the programme every 2 months, and may be offered modest financial support to enable activities to support social connections. A researcher-blind, multi-site, 1:1 randomised controlled trial with N = 306 participants will test the effectiveness of the Community Navigator programme for people with TRD in secondary community mental health teams (CMHTs). Our primary hypothesis is that people who are offered the Community Navigator programme as an addition to usual CMHT care will be less depressed, assessed using the PHQ-9 self-report measure, at 8-month, end-of-treatment follow-up, compared to a control group receiving usual CMHT care and a booklet with information about local social groups and activities. We will follow participants up at end-of-treatment and at 14 months, 6 months after end-of-treatment follow-up. Secondary outcomes include the following: loneliness, anxiety, personal recovery, self-efficacy, social network, social identities. We will collect data about health-related quality of life and service use to investigate the cost-effectiveness of the Community Navigator programme. This trial will provide definitive evidence about the effectiveness and cost-effectiveness of the Community Navigator programme and whether it can be recommended for use in practice. The trial is due to finish in August 2025. Prospectively registered on 8th July 2022 at: ISRCTN13205972.

Antiretroviral therapy (ART) has led to dramatic improvements in survival for people living with HIV, but is unable to cure infection, or induce viral control off therapy. Designing intervention trials with novel agents with the potential to confer a period of HIV remission without ART remains a key scientific and community goal. We detail the rationale, design, and outcomes of a randomised, placebo-controlled trial of two HIV-specific long-acting broadly neutralising antibodies (bNAbs): 3BNC117-LS and 10-1074-LS, which target CD4 binding site and V3 loop respectively, on post-treatment viral control. RIO is a randomised, placebo-controlled, double-blinded prospective phase II study. Eligible individuals will have started ART within 3 months of primary HIV infection and have viral sequences that appear to be sensitive to both bNAbs. It will randomise 72 eligible participants 1:1 to the following arms via a two-stage design. In Stage 1, arm A participants are given dual long-acting (LS-variants) bNAbs infusions, followed by intensively monitored Analytical Treatment Interruption (ATI) (n = 36); in arm B, participants receive placebo infusions followed by ATI. The primary endpoint will be time to viral rebound within 36 weeks after ATI. Upon viral rebound, the participant and researcher are unblinded. Participants in arm A recommence ART and complete the study. Participants in arm B are invited to restart ART and enroll into Stage 2 where they will receive open-label LS bNAbs, followed by a second ATI 24 weeks after. Secondary and exploratory endpoints include adverse events, time to undetectable viraemia after restarting ART, immunological markers, HIV proviral DNA, serum bNAb concentrations in blood, bNAb resistance at viral rebound, and quality of life measures. The two-stage design was determined in collaboration with community involvement. This design allows all participants the option to receive bNAbs. It also tests the hypothesis that bNAbs may drive sustained HIV control beyond the duration of detectable bNAb concentrations. Community representatives were involved at all stages. This included the two-stage design, discussion on the criteria to restart ART, frequency of monitoring visits off ART, and reducing the risk of onward transmission to HIV-negative partners. It also included responding to the challenges of COVID-19. The protocol is registered on Clinical.trials.gov and EudraCT and has approval from UK Ethics and MHRA.

Lower extremity trauma during earthquakes accounts for the largest burden of disaster-related injuries. Insufficient pain management is common in resource-limited disaster settings, and regional anesthesia (RA) may reduce pain in injured patients beyond current standards of care. To date, no controlled trials have been conducted to evaluate the use of RA for pain management in a disaster setting. The Regional Anesthesia for Painful Injuries after Disasters (RAPID) study aims to evaluate whether regional anesthesia (RA), either with or without ultrasound (US) guidance, can reduce pain from earthquake-related lower limb injuries in a disaster setting. The proposed study is a blinded, randomized controlled equivalence trial among earthquake victims with serious lower extremity injuries in a resource-limited setting. After obtaining informed consent, study participants will be randomized in a 1:1:1 allocation to either: standard care (parenteral morphine at 0.1 mg/kg); standard care plus a landmark-guided fascia iliaca compartment block (FICB); or standard care plus an US-guided femoral nerve block. General practice humanitarian response providers who have undergone a focused training in RA will perform nerve blocks with 20 ml 0.5 % levobupivacaine. US sham activities will be used in the standard care and FICB arms and a normal saline injection will be given to the control group to blind both participants and nonresearch team providers. The primary outcome measure will be the summed pain intensity difference calculated using a standard 11-point Numerical Rating Scale reported by patients over 24 h of follow-up. Secondary outcome measures will include overall analgesic requirements, adverse events, and participant satisfaction. Given the high burden of lower extremity injuries in the aftermath of earthquakes and the currently limited treatment options, research into adjuvant interventions for pain management of these injuries is necessary. While anecdotal reports on the use of RA for patients injured during earthquakes exist, no controlled studies have been undertaken. If demonstrated to be effective in a disaster setting, RA has the potential to significantly assist in reducing both acute suffering and long-term complications for survivors of earthquake trauma. ClinicalTrials.gov ( NCT02698228 ), registered on 16 February 2016.

Transcranial direct current stimulation (tDCS) has the potential to modulate cortical excitability and enhance the effects of walking training in people with Parkinson’s disease. This study will examine the efficacy of the addition of tDCS to a task-specific walking training to improve walking and mobility and to reduce falls in people with Parkinson’s disease. This is a two-arm, prospectively registered, randomized trial with concealed allocation, blinded assessors, participants and therapists, and intention-to-treat analysis. Twenty-four individuals with Parkinson’s disease, categorized as slow or intermediate walkers (walking speeds ≤ 1.0 m/s), will be recruited. The experimental group will undertake a 30-min walking training associated with tDCS, for 4 weeks. The control group will undertake the same walking training, but with sham-tDCS. The primary outcome will be comfortable walking speed. Secondary outcomes will include walking step length, walking cadence, walking confidence, mobility, freezing of gait, fear of falling, and falls. Outcomes will be collected by a researcher blinded to group allocation at baseline (week 0), after intervention (week 4), and 1 month beyond intervention (week 8). tDCS associated with walking training may help improve walking of slow and intermediate walkers with Parkinson’s disease. If walking is enhanced, the benefits may be accompanied by better mobility and reduced fear of falling, and individuals may experience greater free-living physical activity at home and in the community. Brazilian Registry of Clinical Trials (ReBEC) RBR-6bvnx6 . Registered on September 23, 2019