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BMJ Surgery, Interventions, & Health... 2024Clinical trials of innovative neural implants are rapidly increasing and diversifying, but little is known about participants' post-trial access to the device and...
OBJECTIVES
Clinical trials of innovative neural implants are rapidly increasing and diversifying, but little is known about participants' post-trial access to the device and ongoing clinical care. This exploratory study examines common practices in the planning and coordination of post-trial access to neurosurgical devices. We also explore the perspectives of trial investigators on the barriers to post-trial access and ongoing care, as well as ethical questions related to the responsibilities of key stakeholder groups.
DESIGN SETTING AND PARTICIPANTS
Trial investigators (n=66) completed a survey on post-trial access in the most recent investigational trial of a surgically implanted neural device they had conducted. Survey respondents predominantly specialized in neurosurgery, neurology and psychiatry, with a mean of 14.8 years of experience working with implantable neural devices.
MAIN OUTCOME MEASURES
Outcomes of interest included rates of device explantation during or at the conclusion of the trial (pre-follow-up) and whether plans for post-trial access were described in the study protocol. Outcomes also included investigators' greatest 'barrier' and 'facilitator' to providing research participants with post-trial access to functional implants and perspectives on current arrangements for the sharing of post-trial responsibilities among key stakeholders.
RESULTS
Trial investigators reported either 'all' (64%) or 'most' (33%) trial participants had remained implanted after the end of the trial, with 'infection' and 'non-response' the most common reasons for explantation. When asked to describe the main barriers to facilitating post-trial access, investigators described limited funding, scarcity of expertise and specialist clinical infrastructure and difficulties maintaining stakeholder relationships. Notwithstanding these barriers, investigators overwhelmingly (95%) agreed there is an ethical obligation to provide post-trial access when participants individually benefit during the trial.
CONCLUSIONS
On occasions when devices were explanted during or at the end of the trial, this was done out of concern for the safety and well-being of participants. Further research into common practices in the post-trial phase is needed and essential to ethical and pragmatic discussions regarding stakeholder responsibilities.
PubMed: 38646454
DOI: 10.1136/bmjsit-2024-000262 -
Frontiers in Aging Neuroscience 2023Postoperative delirium (POD) is an acute, transient brain disorder associated with decreased postoperative quality of life, dementia, neurocognitive changes, and...
Evaluating the effects of S-ketamine on postoperative delirium in elderly patients following total hip or knee arthroplasty under intraspinal anesthesia: a single-center randomized, double-blind, placebo-controlled, pragmatic study protocol.
INTRODUCTION
Postoperative delirium (POD) is an acute, transient brain disorder associated with decreased postoperative quality of life, dementia, neurocognitive changes, and mortality. A small number of trials have explored the role of S-ketamine in the treatment of POD due to its neuroprotective effects. Surprisingly, these trials have failed to yield supportive results. However, heterogeneity in delirium assessment methodologies, sample sizes, and outcome settings as well as deficiencies in S-ketamine use methods make the evidence provided by these studies less persuasive. Given the severe impact of POD on the health of elderly patients and the potential for S-ketamine to prevent it, we believe that designing a large sample size, and rigorous randomized controlled trial for further evaluation is necessary.
METHODS
This is a single-center, randomized, double-blind, placebo-controlled, pragmatic study. Subjects undergoing total hip or knee arthroplasty will be randomized in a 1:1 ratio to intervention ( = 186) and placebo ( = 186) groups. This trial aims to explore the potential role of S-ketamine in the prevention of POD. Its primary outcome is the incidence of POD within 3 postoperative days. Secondary outcomes include the number of POD episodes, the onset and duration of POD, the severity and subtype of POD, pain scores and opioid consumption, sleep quality, clinical outcomes, and safety outcomes.
DISCUSSION
To our knowledge, this is the first pragmatic study that proposes to use S-ketamine to prevent POD. We reviewed a large body of literature to identify potential preoperative confounding variables that may bias associations between the intervention and primary outcome. We will use advanced statistical methods to correct potential confounding variables, improving the test's power and external validity of test results. Of note, the patient population included in this trial will undergo intraspinal anesthesia. Although large, multicenter, randomized controlled studies have found no considerable difference in the effects of regional and general anesthesia on POD, patients receiving intraspinal anesthesia have less exposure to at-risk drugs, such as sevoflurane, propofol, and benzodiazepines, than patients receiving general anesthesia. At-risk drugs have been shown to negatively interfere with the neuroprotective effects of S-ketamine, which may be the reason for the failure of a large number of previous studies. There is currently a lack of randomized controlled studies evaluating S-ketamine for POD prevention, and our trial helps to fill a gap in this area.Trial registration: http://www.chictr.org.cn, identifier ChiCTR2300075796.
PubMed: 38099265
DOI: 10.3389/fnagi.2023.1298661 -
Research Square Jul 2023Intensive lifestyle interventions (ILI) improve weight loss and cardiovascular risk factors, but health systems face challenges implementing them. We engaged...
Primary care delivery of behavioral weight loss services for adults with cardiovascular risk factors: development of pragmatic practice components and results of a randomized feasibility trial.
BACKGROUND
Intensive lifestyle interventions (ILI) improve weight loss and cardiovascular risk factors, but health systems face challenges implementing them. We engaged stakeholders to cocreate and evaluate feasibility of primary care implementation strategies and of a pragmatic randomization procedure to be used for a future effectiveness trial.
METHODS
The study setting was a single, urban primary care office. Patients with BMI ≥ 27 and ≥ 1 cardiovascular risk factor were sent a single electronic health record (EHR) message between December 2019 and January 2020 offering services to support an initial weight loss goal of about 10 pounds in 10 weeks. All patients who affirmed weight loss interest were pragmatically enrolled in the trial and offered "Basic Lifestyle Services" (BLS), including a scale that transmits weight data to the EHR using cellular networks, a coupon to enroll in lifestyle coaching resources through a partnering fitness organization, and periodic EHR messages encouraging use of these resources. About half (n = 42) of participants were randomized by an automated EHR algorithm to also receive "Customized Lifestyle Services" (CLS), including weekly email messages adapted to individual weight loss progress and telephonic coaching by a nurse for those facing challenges. Interventions and assessments spanned January to July 2020, with interference by the coronavirus pandemic. Weight measures were collected from administrative sources. Qualitative analysis of stakeholder recommendations and patient interviews assessed acceptability, appropriateness, and sustainability of intervention components.
RESULTS
Over 6 weeks, 426 patients were sent the EHR invitation message and 80 (18.8%) affirmed interest in the weight loss goal and were included for analysis. EHR data were available to ascertain a 6-month weight value for 77 (96%) patients. Overall, 62% of participants lost weight; 15.0% exhibited weight loss ≥ 5%, with no statistically significant difference between CLS or BLS arms (p = 0.85). CLS assignment increased participation in daily self-weighing (43% versus 21% of patients through 12 weeks) and enrollment in referral-based lifestyle support resources (52% versus 37%).
CONCLUSIONS
This preliminary study demonstrates feasibility of implementation strategies for primary care offices to offer and coordinate ILI core components, as well as a pragmatic randomization procedure for use in a future randomized comparative trial.
PubMed: 37547026
DOI: 10.21203/rs.3.rs-3074046/v1 -
Journal of the International AIDS... Oct 2023Urban refugee youth remain underserved by current HIV prevention strategies, including HIV self-testing (HIVST). Examining HIVST feasibility with refugees can inform...
Findings from the Tushirikiane mobile health (mHealth) HIV self-testing pragmatic trial with refugee adolescents and youth living in informal settlements in Kampala, Uganda.
INTRODUCTION
Urban refugee youth remain underserved by current HIV prevention strategies, including HIV self-testing (HIVST). Examining HIVST feasibility with refugees can inform tailored HIV testing strategies. We examined if HIVST and mobile health (mHealth) delivery approaches could increase HIV testing uptake and HIV status knowledge among refugee youth in Kampala, Uganda.
METHODS
We conducted a three-arm pragmatic controlled trial across five informal settlements grouped into three sites in Kampala from 2020 to 2021 with peer-recruited refugee youth aged 16-24 years. The intervention was HIVST and HIVST + mHealth (HIVST with bidirectional SMS), compared with standard of care (SOC). Primary outcomes were self-reported HIV testing uptake and correct status knowledge verified by point-of-care testing. Some secondary outcomes included: depression, HIV-related stigma, and adolescent sexual and reproductive health (SRH) stigma at three time points (baseline [T0], 8 months [T1] and 12 months [T2]). We used generalized estimating equation regression models to estimate crude and adjusted odds ratios comparing arms over time, adjusting for age, gender and baseline imbalances. We assessed study pragmatism across PRECIS-2 dimensions.
RESULTS
We enrolled 450 participants (50.7% cisgender men, 48.7% cisgender women, 0.7% transgender women; mean age: 20.0, standard deviation: 2.4) across three sites. Self-reported HIV testing uptake increased significantly from T0 to T1 in intervention arms: HIVST arm: (27.6% [n = 43] at T0 vs. 91.2% [n = 135] at T1; HIVST + mHealth: 30.9% [n = 47] at T0 vs. 94.2% [n = 113] at T1]) compared with SOC (35.5% [n = 50] at T0 vs. 24.8% [ = 27] at T1) and remained significantly higher than SOC at T2 (p<0.001). HIV status knowledge in intervention arms (HIVST arm: 100% [n = 121], HIVST + mHealth arm: 97.9% [n = 95]) was significantly higher than SOC (61.5% [n = 59]) at T2. There were modest changes in secondary outcomes in intervention arms, including decreased depression alongside increased HIV-related stigma and adolescent SRH stigma. The trial employed both pragmatic (eligibility criteria, setting, organization, outcome, analysis) and explanatory approaches (recruitment path, flexibility of delivery flexibility, adherence flexibility, follow-up).
CONCLUSIONS
Offering HIVST is a promising approach to increase HIV testing uptake among urban refugee youth in Kampala. We share lessons learned to inform future youth-focused HIVST trials in urban humanitarian settings.
Topics: Adolescent; Female; Humans; Male; Young Adult; HIV; HIV Infections; HIV Testing; Refugees; Self-Testing; Uganda
PubMed: 37850816
DOI: 10.1002/jia2.26185 -
Clinical Trials (London, England) Oct 2023Embedded pragmatic clinical trials are increasingly recommended for non-pharmacological pain care research due to their focus on examining intervention effectiveness...
BACKGROUND/AIMS
Embedded pragmatic clinical trials are increasingly recommended for non-pharmacological pain care research due to their focus on examining intervention effectiveness within real-world settings. Engagement with patients, health care providers, and other partners is essential, yet there is limited guidance for how to use engagement to meaningfully inform the design of interventions to be tested in pain-related pragmatic clinical trials. This manuscript aims to describe the process and impacts of partner input on the design of two interventions (care pathways) for low back pain currently being tested in an embedded pragmatic trial in the Veterans Affairs health care system.
METHODS
Sequential cohort design for intervention development was followed. Engagement activities were conducted with 25 participants between November 2017 and June 2018. Participants included representatives from multiple groups: clinicians, administrative leadership, patients, and caregivers.
RESULTS
Partner feedback led to several changes in each of the care pathways to improve patient experience and usability. Major changes to the sequenced care pathway included transitioning from telephone-based delivery to a flexible telehealth model, increased specificity about pain modulation activities, and reduction of physical therapy visits. Major changes to the pain navigator pathway included transitioning from a traditional stepped care model to one that offers care in a feedback loop, increased flexibility regarding pain navigator provider type, and increased specificity for patient discharge criteria. Centering patient experience emerged as a key consideration from all partner groups.
CONCLUSION
Diverse input is important to consider before implementing new interventions in embedded pragmatic trials. Partner engagement can increase acceptability of new care pathways to patients and providers and enhance uptake of effective interventions by health systems.
TRIAL REGISTRATION
NCT#04411420. Registered on 2 June 2020.
Topics: Humans; Critical Pathways; Pain
PubMed: 37269070
DOI: 10.1177/17407745231178789 -
BMJ Open May 2024Lymphoedema is a chronic condition caused by lymphatic insufficiency. It leads to swelling of the limb/midline region and an increased risk of infection. Lymphoedema is...
SurLym trial: study protocol for a multicentre pragmatic randomised controlled trial on the added value of reconstructive lymphatic surgery to decongestive lymphatic therapy for the treatment of lymphoedema.
INTRODUCTION
Lymphoedema is a chronic condition caused by lymphatic insufficiency. It leads to swelling of the limb/midline region and an increased risk of infection. Lymphoedema is often associated with mental and physical problems limiting quality of life. The first choice of treatment is a conservative treatment, consisting of exercises, skin care, lymph drainage and compression. Reconstructive lymphatic surgery is also often performed, that is, lymphovenous anastomoses, lymph node transfer or a combination. However, robust evidence on the effectiveness of reconstructive lymphatic surgery is missing. Therefore, the objective of this trial is to investigate the added value of reconstructive lymphatic surgery to the conservative treatment in patients with lymphoedema.
METHODS AND ANALYSIS
A multicentre randomised controlled and pragmatic trial was started in March 2022 in three Belgian university hospitals. 90 patients with arm lymphoedema and 90 patients with leg lymphoedema will be included. All patients are randomised between conservative treatment alone (control group) or conservative treatment with reconstructive lymphatic surgery (intervention group). Assessments are performed at baseline and at 1, 3, 6, 12, 18, 24 and 36 months. The primary outcome is lymphoedema-specific quality of life at 18 months. Key secondary outcomes are limb volume and duration of wearing the compression garment at 18 months. The approach of reconstructive lymphatic surgery is based on presurgical investigations including clinical examination, lymphofluoroscopy, lymphoscintigraphy, lymph MRI or CT angiography (if needed). All patients receive conservative treatment during 36 months, which is applied by the patient's own physical therapist and by the patient self. From months 7 to 12, the hours a day of wearing the compression garment are gradually decreased.
ETHICS AND DISSEMINATION
The study has been approved by the ethical committees of University Hospitals Leuven, Ghent University Hospital and CHU UCL Namur. Results will be disseminated via peer-reviewed journals and presentations.
TRIAL REGISTRATION NUMBER
NCT05064176.
Topics: Humans; Lymphedema; Quality of Life; Plastic Surgery Procedures; Pragmatic Clinical Trials as Topic; Belgium; Multicenter Studies as Topic; Leg
PubMed: 38729754
DOI: 10.1136/bmjopen-2023-078114 -
PloS One 2023Child maltreatment is a global public health crisis with negative consequences for physical and mental health. Children in low- and middle-income countries...
BACKGROUND
Child maltreatment is a global public health crisis with negative consequences for physical and mental health. Children in low- and middle-income countries (LMIC)-particularly those affected by poverty, armed conflict, and forced migration-may be at increased risk of maltreatment due to heightened parental distress and disruptions to social support networks. Parenting interventions have been shown to reduce the risk of child maltreatment as well as improve a range of caregiver and child outcomes, yet large-scale implementation remains limited in low-resource displacement settings. This study will examine the impact of an entertainment-education narrative film intervention on reducing physical and emotional abuse and increasing positive parenting among migrant and displaced families from Myanmar living in Thailand.
METHOD
The study is a pragmatic, superiority cluster randomized controlled trial with approximately 40 communities randomized to the intervention or treatment as usual arms in a 1:1 ratio. Participating families in the intervention arm will be invited to attend a community screening of the film intervention and a post-screening discussion, as well as receive a poster depicting key messages from the film. Primary outcomes are changes in physical abuse, emotional abuse, and positive parenting behaviour. Secondary outcomes include caregiver knowledge of positive parenting, caregiver attitudes towards harsh punishment, caregiver psychological distress, and family functioning. Outcomes will be assessed at 3 time points: baseline, 4 weeks post-intervention, and 4-month follow up. A mixed methods process evaluation will be embedded within the trial to assess intervention delivery, acceptability, perceived impacts, and potential mechanisms of change.
DISCUSSION
To our knowledge, this study will be the first randomized controlled trial evaluation of a film-based intervention to reduce child maltreatment among migrant and displaced families in a LMIC. An integrated knowledge translation approach will inform uptake of study findings and application to potential scale up pending evaluation results.
TRIAL REGISTRATION
The study was prospectively registered with the Thai Clinical Trials Registry on 22 February 2023 (TCTR20230222005).
Topics: Child; Humans; Child Abuse; Myanmar; Parenting; Parents; Randomized Controlled Trials as Topic; Transients and Migrants; Pragmatic Clinical Trials as Topic
PubMed: 37903143
DOI: 10.1371/journal.pone.0293623 -
British Journal of Anaesthesia Jan 2024Child anxiety before general anaesthesia and surgery is common. Midazolam is a commonly used premedication to address this. Melatonin is an alternative anxiolytic,... (Randomized Controlled Trial)
Randomized Controlled Trial
The MAGIC trial: a pragmatic, multicentre, parallel, noninferiority, randomised trial of melatonin versus midazolam in the premedication of anxious children attending for elective surgery under general anaesthesia.
BACKGROUND
Child anxiety before general anaesthesia and surgery is common. Midazolam is a commonly used premedication to address this. Melatonin is an alternative anxiolytic, however trials evaluating its efficacy in children have delivered conflicting results.
METHODS
This multicentre, double-blind randomised trial was performed in 20 UK NHS Trusts. A sample size of 624 was required to declare noninferiority of melatonin. Anxious children, awaiting day case elective surgery under general anaesthesia, were randomly assigned 1:1 to midazolam or melatonin premedication (0.5 mg kg, maximum 20 mg) 30 min before transfer to the operating room. The primary outcome was the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF). Secondary outcomes included safety. Results are presented as n (%) and adjusted mean differences with 95% confidence intervals.
RESULTS
The trial was stopped prematurely (n=110; 55 per group) because of recruitment futility. Participants had a median age of 7 (6-10) yr, and 57 (52%) were female. Intention-to-treat and per-protocol modified Yale Preoperative Anxiety Scale-Short Form analyses showed adjusted mean differences of 13.1 (3.7-22.4) and 12.9 (3.1-22.6), respectively, in favour of midazolam. The upper 95% confidence interval limits exceeded the predefined margin of 4.3 in both cases, whereas the lower 95% confidence interval excluded zero, indicating that melatonin was inferior to midazolam, with a difference considered to be clinically relevant. No serious adverse events were seen in either arm.
CONCLUSION
Melatonin was less effective than midazolam at reducing preoperative anxiety in children, although the early termination of the trial increases the likelihood of bias.
CLINICAL TRIAL REGISTRATION
ISRCTN registry: ISRCTN18296119.
Topics: Child; Humans; Female; Male; Midazolam; Melatonin; Premedication; Anxiety; Anesthesia, General; Double-Blind Method
PubMed: 37953202
DOI: 10.1016/j.bja.2023.10.011 -
Trials Apr 2024Immediately after birth, the oxygen saturation is between 30 and 50%, which then increases to 85-95% within the first 10 min. Over the last 10 years, recommendations...
BACKGROUND
Immediately after birth, the oxygen saturation is between 30 and 50%, which then increases to 85-95% within the first 10 min. Over the last 10 years, recommendations regarding the ideal level of the initial fraction of inspired oxygen (FiO) for resuscitation in preterm infants have changed from 1.0, to room air to low levels of oxygen (< 0.3), up to moderate concentrations (0.3-0.65). This leaves clinicians in a challenging position, and a large multi-center international trial of sufficient sample size that is powered to look at safety outcomes such as mortality and adverse neurodevelopmental outcomes is required to provide the necessary evidence to guide clinical practice with confidence.
METHODS
An international cluster, cross-over randomized trial of initial FiO of 0.3 or 0.6 during neonatal resuscitation in preterm infants at birth to increase survival free of major neurodevelopmental outcomes at 18 and 24 months corrected age will be conducted. Preterm infants born between 23 and 28 weeks' gestation will be eligible. Each participating hospital will be randomized to either an initial FiO concentration of either 0.3 or 0.6 to recruit for up to 12 months' and then crossed over to the other concentration for up to 12 months. The intervention will be initial FiO of 0.6, and the comparator will be initial FiO of 0.3 during respiratory support in the delivery room. The sample size will be 1200 preterm infants. This will yield 80% power, assuming a type 1 error of 5% to detect a 25% reduction in relative risk of the primary outcome from 35 to 26.5%. The primary outcome will be a composite of all-cause mortality or the presence of a major neurodevelopmental outcome between 18 and 24 months corrected age. Secondary outcomes will include the components of the primary outcome (death, cerebral palsy, major developmental delay involving cognition, speech, visual, or hearing impairment) in addition to neonatal morbidities (severe brain injury, bronchopulmonary dysplasia; and severe retinopathy of prematurity).
DISCUSSION
The use of supplementary oxygen may be crucial but also potentially detrimental to preterm infants at birth. The HiLo trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants. Should 60% initial oxygen concertation increase survival free of major neurodevelopmental outcomes at 18-24 months corrected age, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice.
TRIAL REGISTRATION
The trial was registered on January 31, 2019, at ClinicalTrials.gov with the Identifier: NCT03825835.
Topics: Humans; Infant; Infant, Newborn; Gestational Age; Infant, Extremely Premature; Infant, Very Low Birth Weight; Oxygen; Resuscitation; Randomized Controlled Trials as Topic
PubMed: 38576007
DOI: 10.1186/s13063-024-08080-2 -
Trials Sep 2023A substantial proportion of patients with bipolar disorder experience daily subsyndromal mood swings, and the term "mood instability" reflecting the variability in mood...
The effect of smartphone-based monitoring and treatment including clinical feedback versus smartphone-based monitoring without clinical feedback in bipolar disorder: the SmartBipolar trial-a study protocol for a randomized controlled parallel-group trial.
INTRODUCTION
A substantial proportion of patients with bipolar disorder experience daily subsyndromal mood swings, and the term "mood instability" reflecting the variability in mood seems associated with poor prognostic factors, including impaired functioning, and increased risk of hospitalization and relapse. During the last decade, we have developed and tested a smartphone-based system for monitoring bipolar disorder. The present SmartBipolar randomized controlled trial (RCT) aims to investigate whether (1) daily smartphone-based outpatient monitoring and treatment including clinical feedback versus (2) daily smartphone-based monitoring without clinical feedback or (3) daily smartphone-based mood monitoring only improves mood instability and other clinically relevant patient-related outcomes in patients with bipolar disorder.
METHODS AND ANALYSIS
The SmartBipolar trial is a pragmatic randomized controlled parallel-group trial. Patients with bipolar disorder are invited to participate as part of their specialized outpatient treatment for patients with bipolar disorder in Mental Health Services in the Capital Region of Denmark. The included patients will be randomized to (1) daily smartphone-based monitoring and treatment including a clinical feedback loop (intervention group) or (2) daily smartphone-based monitoring without a clinical feedback loop (control group) or (3) daily smartphone-based mood monitoring only (control group). All patients receive specialized outpatient treatment for bipolar disorder in the Mental Health Services in the Capital Region of Denmark. The trial started in March 2021 and has currently included 150 patients. The outcomes are (1) mood instability (primary), (2) quality of life, self-rated depressive symptoms, self-rated manic symptoms, perceived stress, satisfaction with care, cumulated number and duration of psychiatric hospitalizations, and medication (secondary), and (3) smartphone-based measures per month of stress, anxiety, irritability, activity, and sleep as well as the percentage of days with presence of mixed mood, days with adherence to medication and adherence to smartphone-based self-monitoring. A total of 201 patients with bipolar disorder will be included in the SmartBipolar trial.
ETHICS AND DISSEMINATION
The SmartBipolar trial is funded by the Capital Region of Denmark and the Independent Research Fund Denmark. Ethical approval has been obtained from the Regional Ethical Committee in The Capital Region of Denmark (H-19067248) as well as data permission (journal number: P-2019-809). The results will be published in peer-reviewed academic journals, presented at scientific meetings, and disseminated to patients' organizations and media outlets.
TRIAL REGISTRATION
Trial registration number: NCT04230421. Date March 1, 2021. Version 1.
Topics: Humans; Bipolar Disorder; Feedback; Smartphone; Ambulatory Care; Mood Disorders; Randomized Controlled Trials as Topic
PubMed: 37700334
DOI: 10.1186/s13063-023-07625-1