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BMJ Open Sep 2023spp is responsible for 8%-15% of total bacteraemias with an associated global mortality around 23%-30%. Regarding the clinical management of enterococcal bacteraemia,...
Randomised, open-label, non-inferiority clinical trial on the efficacy and safety of a 7-day vs 14-day course of antibiotic treatment for uncomplicated enterococcal bacteraemia: the INTENSE trial protocol.
INTRODUCTION
spp is responsible for 8%-15% of total bacteraemias with an associated global mortality around 23%-30%. Regarding the clinical management of enterococcal bacteraemia, the evidence on the duration of antibiotic treatment is scarce and the studies do not discriminate between complicated and uncomplicated bacteraemia.
METHODS
The INTENSE study is a multicentre, open-label, randomised, pragmatic, phase-IV clinical trial to demonstrate the non-inferiority of a 7-day vs 14-day course for the treatment of uncomplicated enterococcal bacteraemia and incorporating the early switching to oral antibiotics when feasible. The primary efficacy endpoint is the clinical cure at day 30±2 after the end of the treatment. Secondary endpoints will include the rate of relapse or infective endocarditis, length of stay, duration of intravenous therapy, infection and the evaluation of the safety of both treatment arms through the recording and analysis of adverse events. For a 6% non-inferiority margin and considering a 5% withdrawal rate, 284 patients will be included.
ANALYSIS
The difference in proportions with one-sided 95% CIs will be calculated for the clinical cure rate using the control group as reference. For secondary categorical endpoints, a similar analysis will be performed and Mann-Whitney U-test will be used to compare median values of quantitative variables. A superiority analysis applying the response adjusted for days of antibiotic risk will be performed if there were incidents in recruitment; will allow obtaining results with 194 patients recruited.
ETHICS AND DISSEMINATION
The study has obtained the authorisation from the Spanish Regulatory Authority, the approval of the ethics committee and the agreement of the directors of each centre. Data will be published in peer-reviewed journals.
TRIAL REGISTRATION NUMBER
NCT05394298.
Topics: Humans; Bacterial Infections; Bacteremia; Anti-Bacterial Agents; Endocarditis; Control Groups; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Clinical Trials, Phase IV as Topic
PubMed: 37673453
DOI: 10.1136/bmjopen-2023-075699 -
Journal of General Internal Medicine May 2024In contrast to traditional randomized controlled trials, embedded pragmatic clinical trials (ePCTs) are conducted within healthcare settings with real-world patient... (Review)
Review
In contrast to traditional randomized controlled trials, embedded pragmatic clinical trials (ePCTs) are conducted within healthcare settings with real-world patient populations. ePCTs are intentionally designed to align with health system priorities leveraging existing healthcare system infrastructure and resources to ease intervention implementation and increase the likelihood that effective interventions translate into routine practice following the trial. The NIH Pragmatic Trials Collaboratory, funded by the National Institutes of Health (NIH), supports the conduct of large-scale ePCT Demonstration Projects that address major public health issues within healthcare systems. The Collaboratory has a unique opportunity to draw on the Demonstration Project experiences to generate lessons learned related to ePCTs and the dissemination and implementation of interventions tested in ePCTs. In this article, we use case studies from six completed Demonstration Projects to summarize the Collaboratory's experience with post-trial interpretation of results, and implications for sustainment (or de-implementation) of tested interventions. We highlight three key lessons learned. First, ineffective interventions (i.e., ePCT is null for the primary outcome) may be sustained if they have other measured benefits (e.g., secondary outcome or subgroup) or even perceived benefits (e.g., staff like the intervention). Second, effective interventions-even those solicited by the health system and/or designed with significant health system partner buy-in-may not be sustained if they require significant resources. Third, alignment with policy incentives is essential for achieving sustainment and scale-up of effective interventions. Our experiences point to several recommendations to aid in considering post-trial sustainment or de-implementation of interventions tested in ePCTs: (1) include secondary outcome measures that are salient to health system partners; (2) collect all appropriate data to allow for post hoc analysis of subgroups; (3) collect experience data from clinicians and staff; (4) engage policy-makers before starting the trial.
Topics: Humans; Pragmatic Clinical Trials as Topic; United States
PubMed: 38216853
DOI: 10.1007/s11606-023-08593-7 -
BMC Anesthesiology Oct 2023ICU survivors often suffer from prolonged physical and mental impairments resulting in the so called "Post-Intensive Care Syndrome" (PICS). The aftercare of former ICU... (Randomized Controlled Trial)
Randomized Controlled Trial
Piloting an ICU follow-up clinic to improve health-related quality of life in ICU survivors after a prolonged intensive care stay (PINA): feasibility of a pragmatic randomised controlled trial.
BACKGROUND
ICU survivors often suffer from prolonged physical and mental impairments resulting in the so called "Post-Intensive Care Syndrome" (PICS). The aftercare of former ICU patients affected by PICS in particular has not been addressed sufficiently in Germany so far. The aim of this study was to evaluate the feasibility of a pragmatic randomised trial (RCT) comparing an intensive care unit (ICU) follow-up clinic intervention to usual care.
METHODS
This pilot study in a German university hospital evaluated the feasibility of a pragmatic RCT. Patients were assigned in a 1:1 ratio to an ICU follow-up clinic intervention or to usual care. The concept of this follow-up clinic was previously developed in a participatory process with patients, next of kin, health care professionals and researchers. We performed a process evaluation and determined acceptability, fidelity, completeness of measurement instruments and practicality as feasibility outcomes. The RCT's primary outcome (health-related quality of life) was assessed six months after ICU discharge by means of the physical component scale of the Short-Form-12 self-report questionnaire.
RESULTS
The pilot study was conducted from June 2020 to May 2021 with 21 and 20 participants in the intervention and control group. Principal findings related to feasibility were 85% consent rate (N = 48), 62% fidelity rate, 34% attrition rate (N = 41) and 77% completeness of outcome measurements. The primary effectiveness outcome (health-related quality of life) could be measured in 93% of participants who completed the study (N = 27). The majority of participants (85%) needed assistance with follow-up questionnaires (practicality). Median length of ICU stay was 13 days and 85% (N = 41) received mechanical ventilation, median Sequential Organ Failure Assessment Score was nine. Six-month follow-up assessment was planned for all study participants and performed for 66% (N = 41) of the participants after 197 days (median).
CONCLUSION
The participatory developed intervention of an ICU follow-up clinic and the pragmatic pilot RCT both seem to be feasible. We recommend to start a pragmatic RCT on the effectiveness of the ICU follow-up clinic.
TRIAL REGISTRATION
ClinicalTrials.gov US NLM, NCT04186468, Submission: 02/12/2019, Registration: 04/12/2019, https://clinicaltrials.gov/ct2/show/NCT04186468.
Topics: Humans; Quality of Life; Follow-Up Studies; Feasibility Studies; Pilot Projects; Intensive Care Units; Critical Care; Survivors
PubMed: 37838669
DOI: 10.1186/s12871-023-02255-1 -
Frontiers in Endocrinology 2023Approximately 10%-15% of subjects with hypothyroidism on L-thyroxine (LT4) alone have persistent symptoms affecting their quality of life (QoL). Although the cause is... (Review)
Review
Designing a combined liothyronine (LT3), L- thyroxine (LT4) trial in symptomatic hypothyroid subjects on LT4 - the importance of patient selection, choice of LT3 and trial design.
Approximately 10%-15% of subjects with hypothyroidism on L-thyroxine (LT4) alone have persistent symptoms affecting their quality of life (QoL). Although the cause is unclear, there is evidence that "tissue T3 lack" may be responsible. If so, combining liothyronine (LT3) with LT4 would be helpful. However, randomized controlled trials (RCT), have not established greater efficacy for the LT3 + LT4 combination in these subjects than for LT4 alone. While the trial design may have been responsible, the use of unphysiological, short-acting LT3 preparations and non-thyroid-specific patient-reported outcome measures (PROMs) may have contributed. We recommend attention to the following aspects of trial design for future RCTs of LT3 + LT4 compared to LT4 alone: (a) Subject selection-(i) measurable symptoms (disadvantages should be recognized); (ii) using a validated thyroid specific PROM such as ThyPRO39 or the Composite scale derived from it; (iii) those taking over 1.2 μg/day or 100 μg/day (for pragmatic reasons) of LT4 defining a population likely without intrinsic thyroid activity who depend on exogenous LT4; (iv) recruiting a preponderance of subjects with autoimmune thyroiditis increasing generalisability; and (v) those with a high symptom load with a greater response to combination therapy e.g. those with the deiodinase 2 polymorphism. (b) The use of physiological LT3 preparations producing pharmacokinetic similarities to T3 profiles in unaffected subjects: two long-acting LT3 preparations are currently available and must be tested in phase 2b/3 RCTs. (c) The superiority of a crossover design in limiting numbers and costs while maintaining statistical power and ensuring that all subjects experienced the investigative medication.
Topics: Humans; Thyroxine; Triiodothyronine; Patient Selection; Hypothyroidism; Thyroid Hormones
PubMed: 38034018
DOI: 10.3389/fendo.2023.1282608 -
Research Square Dec 2023For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and...
Alliance for Clinical Trials in Oncology (Alliance) trial A022101/NRG-GI009: A pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: evaluating radiation, ablation, and surgery (ERASur).
BACKGROUND
For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed.
METHODS
The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16-26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility.
DISCUSSION
The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC.
PubMed: 38196590
DOI: 10.21203/rs.3.rs-3773522/v1 -
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 -
BMJ Open Aug 2023Many hospital presentations for acute coronary syndrome (ACS) occur in people previously hospitalised with coronary heart disease (CHD), leading to increased costs and...
Effect of an avatar-based discharge education application on knowledge and behaviour in people after acute coronary syndrome: protocol for a pragmatic prospective randomised controlled trial.
INTRODUCTION
Many hospital presentations for acute coronary syndrome (ACS) occur in people previously hospitalised with coronary heart disease (CHD), leading to increased costs and health burden. Secondary prevention education including a prehospital discharge plan is recommended for all individuals to reduce the risk of recurrence. However, many clinicians lack the time or support to provide education, and patients' uptake of secondary prevention programmes is limited. An avatar-based education app is a novel and engaging way to provide self-delivered, evidence-based secondary prevention information during the hospital admission and remains accessible after discharge. This protocol aims to evaluate the effect of an avatar-based education app on individuals with ACS.
METHODS AND ANALYSIS
This protocol describes a prospective, randomised controlled trial with 3-month follow-up and blinded assessment of 72 participants. Intervention group participants will download the app onto their own device during the hospital admission and independently complete six interactive education modules based on the National Heart Foundation's six steps to cardiac recovery. All participants will receive a text message reminder of the study after 3 weeks. Both groups will receive usual care consisting of bedside education and a pamphlet about cardiac rehabilitation. The primary outcome is knowledge of CHD, assessed using the Coronary Artery Disease Education Questionnaire II. Secondary outcomes include quality of life, response to heart attack symptoms, cardiac-related readmissions and mortality and modifiable cardiac risk factors. Engagement with the app will be evaluated objectively. Intention-to-treat analysis will be conducted, with between-group comparisons and 95% CIs of the primary outcome analysed using analysis of covariance, adjusting for baseline values.
ETHICS AND DISSEMINATION
This study protocol has been approved by the Western Sydney Local Health District Human Research Ethics Committee. The results of this study will be disseminated via a peer-reviewed journal and research thesis.
TRIAL REGISTRATION NUMBER
Australian New Zealand Clinical Trials Registry (ACTRN12622001436763).
Topics: Humans; Acute Coronary Syndrome; Patient Discharge; Prospective Studies; Quality of Life; Australia; Randomized Controlled Trials as Topic
PubMed: 37604633
DOI: 10.1136/bmjopen-2023-073621 -
PloS One 2023Consideration for patients with visual impairment, from low vision to blindness, is an important part of building a barrier-free society. Some authors have elaborated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Consideration for patients with visual impairment, from low vision to blindness, is an important part of building a barrier-free society. Some authors have elaborated that visual impairment can indeed lead to delayed development in theory of mind, thereby causing pragmatic knowledge deficiency. Verifying whether those with eye conditions have pragmatic impairment is an essential way for their clinical evaluation, intervention and rehabilitation.
OBJECTIVE
We primarily carry out a meta-analysis of visual impairment from low vision to blindness and pragmatic impairment in people with low vision or blindness to verify visual impairment may cause pragmatic impairment.
DATA SOURCES
Electronic databases Pubmed, Medline, MesH, Psychinfo, Ovid, EBSCO and CNKI and the reference sections of previous reviews.
STUDY ELIGIBILITY CRITERIA
Studies were included when they built on primary data from clinical questionnaire surveys or field trials anywhere in the world, and when they reported impacts of visual impairment on social cognition, communication, skills, behavior and intelligence. In total, 25 original studies were included, in which 25735 people were evaluated.
RESULTS
Statistically, visual impairments and pragmatic impairment exist correlation due to the significant p value(p = 0.0005 < 0.05) in group and the subgroup sorted in the light of 18 years old (p < 0.0001 and p = 0.003 < 0.05). Psychologically, because people with visual impairment can not normally get non-verbal information, they can not get a complete pragmatic knowledge system. Pragmatic knowledge deficiency leads to abnormal in executive functions and development delay from the perspective of theory of mind, inducing pragmatic impairment. Therefore, visual impairment has an impact on pragmatic impairment.
CONCLUSION
The meta-analysis reveals robust evidence on the relationship of vision impairment and pragmatic impairment in children or adults. Such evidence may help to gradually improve the clinical evaluation, intervention and rehabilitation of these people.
Topics: Child; Humans; Adolescent; Vision, Low; Intelligence; Blindness
PubMed: 38064440
DOI: 10.1371/journal.pone.0294326 -
Journal of Pain and Symptom Management Aug 2023Advance care planning (ACP) pragmatic trials are needed.
BACKGROUND/PROBLEM
Advance care planning (ACP) pragmatic trials are needed.
PROPOSED SOLUTION
We determined key system-level activities to implement ACP interventions for a cluster-randomized pragmatic trial. We identified patients with serious illness from 50 primary care clinics across three University of California health systems using a validated algorithm. If patients lacked documented ACP within the last 3 years, they were eligible for an intervention: (Arm 1) an advance directive (AD); (Arm 2) AD + PREPAREforYourCare.org; (Arm 3) AD + PREPARE + lay health navigator outreach. Triggered by an appointment, we mailed and sent interventions through automated electronic health record (EHR) messaging. We collaborated with patients/caregivers, clinicians, payors, and national/health system leader advisors. We are currently finalizing 24 months follow-up data.
OUTCOMES/METHODS
We used the Consolidated Framework for Implementation Research (CFIR) and Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) frameworks to track secular trends and implementation efforts.
KEY MESSAGE/RESULTS
Required multisite, system-level activities: 1) obtaining leadership, legal/privacy, and EHR approvals; 2) standardizing ACP documentation; 3) providing clinician education; 3) validating an automated serious illness identification algorithm; 4) standardizing ACP messaging with input from over 100 key advisors; 5) monitoring secular trends (e.g., COVID); and 6) standardizing ACP workflows (e.g., scanned ADs). Of 8707 patients with serious illness, 6883 were eligible for an intervention. Across all arms, 99% received the mailed intervention, 78.3% had an active patient portal (64.2% opened intervention), and 90.5% of arm three patients (n = 2243) received navigator outreach.
LESSONS LEARNED
Implementing a multisite health system-wide ACP program and pragmatic trial, with automated EHR-based cohort identification and intervention delivery, requires a high level of multidisciplinary key advisor engagement, standardization, and monitoring. These activities provide guidance for the implementation of other large-scale, population-based ACP efforts.
Topics: Humans; COVID-19; Advance Care Planning; Advance Directives; Documentation
PubMed: 37098388
DOI: 10.1016/j.jpainsymman.2023.04.022 -
JAMA Oct 2023Realizing the benefits of cancer screening requires testing of eligible individuals and processes to ensure follow-up of abnormal results. (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Realizing the benefits of cancer screening requires testing of eligible individuals and processes to ensure follow-up of abnormal results.
OBJECTIVE
To test interventions to improve timely follow-up of overdue abnormal breast, cervical, colorectal, and lung cancer screening results.
DESIGN, SETTING, AND PARTICIPANTS
Pragmatic, cluster randomized clinical trial conducted at 44 primary care practices within 3 health networks in the US enrolling patients with at least 1 abnormal cancer screening test result not yet followed up between August 24, 2020, and December 13, 2021.
INTERVENTION
Automated algorithms developed using data from electronic health records (EHRs) recommended follow-up actions and times for abnormal screening results. Primary care practices were randomized in a 1:1:1:1 ratio to (1) usual care, (2) EHR reminders, (3) EHR reminders and outreach (a patient letter was sent at week 2 and a phone call at week 4), or (4) EHR reminders, outreach, and navigation (a patient letter was sent at week 2 and a navigator outreach phone call at week 4). Patients, physicians, and practices were unblinded to treatment assignment.
MAIN OUTCOMES AND MEASURES
The primary outcome was completion of recommended follow-up within 120 days of study enrollment. The secondary outcomes included completion of recommended follow-up within 240 days of enrollment and completion of recommended follow-up within 120 days and 240 days for specific cancer types and levels of risk.
RESULTS
Among 11 980 patients (median age, 60 years [IQR, 52-69 years]; 64.8% were women; 83.3% were White; and 15.4% were insured through Medicaid) with an abnormal cancer screening test result for colorectal cancer (8245 patients [69%]), cervical cancer (2596 patients [22%]), breast cancer (1005 patients [8%]), or lung cancer (134 patients [1%]) and abnormal test results categorized as low risk (6082 patients [51%]), medium risk (3712 patients [31%]), or high risk (2186 patients [18%]), the adjusted proportion who completed recommended follow-up within 120 days was 31.4% in the EHR reminders, outreach, and navigation group (n = 3455), 31.0% in the EHR reminders and outreach group (n = 2569), 22.7% in the EHR reminders group (n = 3254), and 22.9% in the usual care group (n = 2702) (adjusted absolute difference for comparison of EHR reminders, outreach, and navigation group vs usual care, 8.5% [95% CI, 4.8%-12.0%], P < .001). The secondary outcomes showed similar results for completion of recommended follow-up within 240 days and by subgroups for cancer type and level of risk for the abnormal screening result.
CONCLUSIONS AND RELEVANCE
A multilevel primary care intervention that included EHR reminders and patient outreach with or without patient navigation improved timely follow-up of overdue abnormal cancer screening test results for breast, cervical, colorectal, and lung cancer.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03979495.
Topics: Female; Humans; Male; Middle Aged; Colorectal Neoplasms; Early Detection of Cancer; Lung Neoplasms; Mass Screening; Primary Health Care; Aftercare; Time Factors; Delayed Diagnosis; Neoplasms; Pragmatic Clinical Trials as Topic; United States; Aged; Reminder Systems; Electronic Health Records; Patient Navigation; Health Communication
PubMed: 37815566
DOI: 10.1001/jama.2023.18755