Pragmatic Randomized Clinical Trial Research Articles

Evaluation of vascular photobiomodulation for orofacial pain and tension type headache following COVID 19 in a pragmatic randomized clinical trial

This pragmatic double-blind randomized clinical trial aims to assess the impact of vascular photobiomodulation on post-COVID-19 patients experiencing tension-type headache, orofacial pain, or both persisting for more than 3 months. Participants were divided into two groups: vascular photobiomodulation (VPBM) and simulated VPBM. Their conditions were evaluated using the Brief Pain Inventory (BPI), Visual Analogue Scale, and Headache Impact Test (HIT-6). Data analysis included both inter and intragroup assessments, employing per-protocol and intention-to-treat analyses. Significant differences were observed in pain levels pre- and post-treatment and between the two groups. These differences were evident in the average pain experienced in the previous week (p = 0.010) and various dimensions of the BPI questionnaire, such as the degree of pain interference with walking (p = 0.011), work (p = 0.009), sleep (p = 0.012), and enjoyment of life (p = 0.016). However, there was no statistically significant difference in headache impact on activities of daily living as measured by the HIT. Vascular photobiomodulation shows promise in reducing pain and enhancing the ability to engage in daily activities among post-COVID-19 patients experiencing persistent headaches and orofacial pain.

Effectiveness of the SYNCHRONIZE + Brief Intervention in Improving Mediterranean Diet Adherence, Nutritional Quality and Intake Pattern in Persons with Fibromyalgia and Chronic Fatigue Syndrome

Background: Multidisciplinary lifestyle interventions are being researched to treat fibromyalgia. However, the impact of nutrition as a key treatment component is little studied. This study aimed to evaluate the effectiveness of the SYNCHRONIZE + lifestyle multidisciplinary intervention in improving adherence to the Mediterranean diet, nutrition quality and dietary intake pattern in persons with fibromyalgia and chronic fatigue syndrome. Methods: A pragmatic randomized clinical trial was conducted in primary care. Data were collected using the 17-item energy-restricted Mediterranean Adherence Screener (er-MEDAS), the food frequency questionnaire (sFFQ) and the 24 h recall questionnaire (24 HR), in addition to chrono-nutritional, anthropometric, and body composition data, at baseline and 3-, 6-, and 12- month follow-up visits, and statistically analyzed. Results: A total of 158 participants were evaluated. Results showed the effectiveness of the intervention in improving adherence to the Mediterranean diet. The adherence depended on the group-time interaction being positive and significant at 3 and 6 months post-intervention in the INT group and on the participant age and educational level. Specifically, the intake of legumes, fruits, vegetables, nuts and blue fish was increased, while the intake of sweets and pastries, butter and cream and red and processed meat was reduced. Furthermore, the intake of chips and candies was also reduced, and the consumption of fermented food (yogurts, cheese, kefir) increased. Thus, general diet quality improved. Interestingly, the intake of key nutrients such as protein and iron increased. Furthermore, the number of night eaters was decreased significantly. Muscle mass index was also improved in the intervention group. These results were maintained in the medium to long term. Conclusion: SYNCHRONIZE + is a brief, low-cost, multidisciplinary intervention effective in improving adherence to the Mediterranean diet and improving nutritional and dietary intake patterns in persons with fibromyalgia and chronic fatigue syndrome. Further evaluation of the effect on quality of life and symptoms is needed.

Diagnostic Concordance Between Physiotherapist and Emergency Physicians for Patients With a Musculoskeletal Disorder in the Emergency Department.

Many patients present to the emergency department (ED) with a musculoskeletal disorder. In consequence, some hospitals have integrated autonomous management of musculoskeletal disorders by physiotherapists after triage. Although potential benefits were demonstrated, few studies have examined the agreement between physiotherapists' and emergency physicians' diagnosis. A better understanding of diagnostic concordance between physiotherapists and emergency physicians could inform the implementation of this care model. Secondary analysis of data obtained through a pilot pragmatic randomised clinical trial. Data from patients presenting a minor musculoskeletal disorder managed by a physiotherapist and an emergency physician were used. Diagnostic concordance was examined using raw agreement and Gwet's first-order agreement coefficient. Thirty-six participants were assessed by both professionals (36.8±18.2years; W: 55.6%). Overall raw agreement was 86.1% and the diagnostic concordance was almost perfect (Gwet's AC1: 0.84, 95% CI: 0.69-0.98). The most common disagreement was when physiotherapists suspected a bone fracture or contusion, whereas emergency physicians diagnosed a ligament or meniscus disorder. Our results show excellent diagnostic concordance between physiotherapists and emergency physicians, thus supporting the safety of physiotherapy care in the ED. More studies are needed to confirm these results with a larger variety of diagnoses and age strata.

Effectiveness of mailed outreach and patient navigation to promote HCC screening process completion: a multicentre pragmatic randomised clinical trial

BackgroundHepatocellular carcinoma (HCC) is plagued by failures across the cancer care continuum, leading to frequent late-stage diagnoses and high mortality. We evaluated the effectiveness of mailed outreach invitations plus patient...

Fatigue and Sleep-related Impairment as Predictors of the Effect of Nonpharmacological Therapies for Active duty Service Members With Chronic Pain: A Secondary Analysis of a Pragmatic Randomized Clinical Trial.

First-line treatments for chronic pain include selected complementary and integrative health therapies, including spinal manipulation, acupuncture, yoga, and massage; and standard rehabilitative care, including physical and occupational therapies. This study aimed to uncover critical factors that contribute to pain impact and the effectiveness of complementary and integrative health therapies and standard rehabilitative care among people with chronic pain, with a focus on the role of sleep-related impairment. We conducted a secondary analysis of data from a pragmatic randomized clinical trial of 280 U.S. active duty service members with chronic pain. Our study's multiple mediation analysis examined the indirect effect of complementary and integrative health therapies on pain impact through fatigue (β = - 0.43; 95% CI, -0.99 to -0.07). When stratified by sleep-related impairment, participants with T scores above the median of 62 demonstrated a significant negative indirect effect of complementary and integrative health therapies through fatigue (β = - 0.80; 95% CI, -2.31 to -0.14). This negative indirect effect was not significant for participants with sleep-related impairment T scores below the median (β = - 0.64; 95% CI, -1.48 to 0.07). These findings suggest that complementary and integrative health therapies are particularly effective in reducing pain impact for individuals with higher levels of sleep-related impairment, and that the effect of complementary and integrative health therapies is supported primarily by reducing fatigue.

Centralized Colorectal Cancer Screening Outreach in Federally Qualified Health Centers

Colorectal cancer (CRC) screening is effective but remains underused in federally qualified health centers (FQHCs). To assess the effectiveness of a centralized CRC screening outreach intervention involving mailed fecal immunochemical testing (FIT) outreach and patient navigation to colonoscopy after abnormal results of FIT. A pragmatic randomized clinical trial was conducted, using intention-to-treat analysis. Participants were enrolled from July 6, 2020, to September 17, 2021, and analyses were performed from July 6, 2023, to January 31, 2024. The study was conducted at independent FQHCs comprising 12 clinical delivery sites in North Carolina. The outreach intervention was centralized at an academic cancer center. Active individuals aged 50 to 75 years at average risk for CRC and not current with screening per US Preventive Services Task Force recommendations were included. In addition to usual care, intervention participants received mailed screening outreach materials including an introductory letter, FIT kit packet with instructions and return postage, and 2 reminder letters if needed. Intervention participants with positive results of mailed FIT were offered navigation to facilitate follow-up colonoscopy completion. Control participants received usual care alone. The primary outcome was completion of a US Preventive Services Task Force-recommended CRC screening test within 6 months determined by electronic health record review. Secondary outcomes were colonoscopy completion within 6 months after positive FIT results and detection of advanced colorectal neoplasia, defined as advanced adenoma or CRC. A total of 4002 participants were included (mean [SD] age, 59.6 [6.8] years; 2256 [56.4%] female; 364 (9.1%) Hispanic; 1082 [27.0%] non-Hispanic Black; 2288 [57.2%] non-Hispanic White; 1198 [29.9%] commercially insured; 617 [15.4%] Medicaid; 1227 [30.7%] Medicare; and 960 [24.0%] uninsured), with 2001 randomized to each group. Compared with controls, intervention participants were more likely to complete screening within 6 months of randomization (30.0% vs 9.7%; difference, 20.29 percentage points; 95% CI, 17.85-22.73 percentage points). The intervention was effective in all insurance types. In the intervention arm, 33 of 48 participants with positive FIT results (68.8%) completed follow-up colonoscopy within 6 months compared with 8 of 18 participants (44.4%) in the control arm (difference, 24.3 percentage points; 95% CI, -2.13 to 50.74 percentage points). Advanced colorectal neoplasia was detected in 29 intervention participants (1.4%) and 15 control participants (0.7%) (difference, 0.68 percentage points; 95% CI, 0.05-1.35 percentage points). In this randomized clinical trial of centralized screening outreach intervention in diverse patients served by independent FQHCs, CRC screening completion and advanced colorectal neoplasia detection were substantially increased. Future studies should examine the cost and scalability of this intervention in this context. ClinicalTrials.gov Identifier: NCT04406714.

A randomized controlled trial of gamification to increase physical activity among black and Hispanic breast and prostate cancer survivors: Rationale and design of the ALLSTAR clinical trial

Survivors of breast and prostate cancer, especially those that are Black and/or Hispanic, are at high risk for cardiovascular events. Physical activity can reduce the risk of cardiovascular events in cancer survivors, but Black and Hispanic people are less likely to engage in routine physical activity. Concepts from behavioral economics have been used to design scalable, low-touch gamification interventions that increase physical activity in individuals at high risk for cardiovascular events, but the effectiveness of these strategies in Black and Hispanic survivors of breast and prostate cancer is uncertain. ALLSTAR (NCT05176756) is a pragmatic, virtual randomized controlled trial designed to evaluate the effectiveness of a gamification intervention informed by behavioral economic concepts to increase daily physical activity in Black and Hispanic breast and prostate cancer survivors who received cardiotoxic therapies and have additional risk factors for cardiovascular disease. Patients are either referred by their cancer care team or identified by electronic health record searches; contacted by letter, email, text message and/or phone; and complete enrollment and informed consent on the Penn Way to Health online platform. Patients are then provided with a wearable fitness tracker, establish a baseline daily step count, set a goal to increase daily step count by 1,500-3,000 steps from baseline, and are randomized 1:1 to control or gamification. Interventions continue for 6 months, with follow-up for an additional 3 months to evaluate the durability of behavior change. The trial has met its enrollment goal of 150 participants, with a primary endpoint of change from baseline in daily steps over the 6-month intervention period. Key secondary endpoints include change from baseline in daily steps over the 3-month post-intervention follow-up period, change in moderate to vigorous physical activity over the intervention and follow-up periods, and change in patient-reported measures of physical function, fatigue, and overall quality of life. ALLSTAR is a virtual, pragmatic randomized clinical trial powered to demonstrate whether gamification is superior to control in increasing physical activity in Black and Hispanic breast and prostate cancer survivors. Its results will have important implications for strategies to promote physical activity in survivors of breast and prostate cancer, specifically among minority populations. clinicaltrials.gov; https://clinicaltrials.gov/study/NCT05176756.

My virtual escape from patient life: a feasibility study on the experiences and benefits of individualized virtual reality for inpatients in palliative cancer care

BackgroundCancer patients benefit from Virtual Reality (VR) in burdensome situations, but evidence is scarce for palliative situations. Based on earlier work in palliative care, individualized VR interventions like seeing the patient’s home may address a patient’s wish to be at home and thus have a greater effect compared to standard VR content. Yet, some patients and relatives may be concerned about their privacy. Also, patient stakeholders raised concerns about triggering depressed mood or homesickness.AimTo test the feasibility and safety of individualized vs. standard 360°video VR interventions in palliative cancer inpatients.MethodsProspective observational study with patient-reported outcome measurement using validated instruments of well-being (MDBF), symptoms and psychosocial burden (IPOS), cybersickness (SSQ), presence experience (SPES), subjective benefit (2 items), content analysis of interviews, and field notes. Individualized VR content was recorded with action camcorder-technology to protect the patients’ privacy.ResultsSeventeen patients participated, median age 65 years (range 20–82), 9 women (53%), 8 single or widowed (47%), 4 childless (23.5%), 4 academics (23.5%), with a median length of stay of 9 days (1–75) in the hematology (10), palliative care (3), or radiotherapy (2) unit of a German university hospital. Eight patients (53.3%) chose their own home environments or family for individualized VR-content. All participants enjoyed the intervention. Compared to standard VR content the individualized VR tended to have a stronger effect on well-being and emotional touch. It was not inferior in terms of psychosocial burden and cybersickness. No subjective and relevant side effects occurred. The patients well tolerated the assessments. However, most patients demanded a lighter headset and a desire for more interactivity.ConclusionsIndividualization of VR content shows potential for enhancement of immersion, which improves the VR experience and does not harm in terms of depressed mood or worsening of symptoms. The patients’ and family desire for privacy is feasible with the support of family members who recorded the individualized videos, which is easily manageable today. We suggest a pragmatic randomized clinical trial to compare the effects of individualized vs. standard VR-content.Trial registrationRegistered at German Clinical Trials Register (Deutsches Register Klinischer Studien; DRKS); registration number: DRKS00032172; registration date: 11/07/2023.

High-Risk Medications in Persons Living With Dementia

Individuals with Alzheimer disease (AD) and Alzheimer disease-related dementias (ADRD) may be at increased risk for adverse outcomes relating to inappropriate prescribing of certain high-risk medications, including antipsychotics, sedative-hypnotics, and strong anticholinergic agents. To evaluate the effect of a patient/caregiver and prescriber-mailed educational intervention on potentially inappropriate prescribing to patients with AD or ADRD. This prospective, open-label, pragmatic randomized clinical trial, embedded in 2 large national health plans, was conducted from April 2022 to June 2023. The trial included patients with AD or ADRD and use of any of 3 drug classes targeted for deprescribing (antipsychotics, sedative-hypnotics, or strong anticholinergics). Patients were randomized to 1 of 3 arms: (1) a mailing of educational materials specific to the medication targeted for deprescribing to both the patient and their prescribing clinician; (2) a mailing to the prescribing clinician only; or (3) a usual care arm. Analysis was performed using a modified intention-to-treat approach. The primary study outcome was the dispensing of the medication targeted for deprescribing during a 6-month study observation period. Secondary outcomes included changes in medication-specific mean daily dose and health service utilization. Among 12 787 patients included in the modified intention-to-treat analysis, 8742 (68.4%) were female, and the mean (SD) age was 77.3 (9.4) years. The cumulative incidence of being dispensed a medication targeted for deprescribing was 76.7% (95% CI, 75.4-78.0) in the patient and prescriber mailing group, 77.9% (95% CI, 76.5-79.1) in the prescriber mailing only group, and 77.5% (95% CI, 76.2-78.8) in the usual care group. Hazard ratios were 0.99 (95% CI, 0.94-1.04) for the patient and prescriber group and 1.00 (95% CI, 0.96-1.06) for the prescriber only group compared with the usual care group. There were no differences between the groups for secondary outcomes. These findings suggest medication-specific educational mailings targeting patients with AD or ADRD and their clinicians are not effective in reducing the use of high-risk medications. ClinicalTrials.gov Identifier: NCT05147428.

Design and rationale of a pragmatic randomized clinical trial of early dronedarone versus usual care to change and improve outcomes in persons with first-detected atrial fibrillation – the CHANGE AFIB study

BackgroundWhile there are several completed clinical trials that address treatment strategies in patients with symptomatic and recurrent atrial fibrillation (AF), there are no randomized clinical trials that address first-line rhythm control of new-onset AF. Recent data suggest that early initiation of rhythm control within 1 year can improve outcomes. MethodsIn this open-label pragmatic clinical trial nested within the Get With The Guidelines Atrial Fibrillation registry, approximately 3,000 patients with first-detected AF will be enrolled at approximately 200 sites. Participants will be randomized (1:1) to treatment with dronedarone in addition to usual care versus usual care alone. The primary endpoint will be time to first cardiovascular (CV) hospitalization or death from any cause through 12 months from randomization. Secondary endpoints will include a WIN ratio (all-cause death, ischemic stroke or systemic embolism, heart failure hospitalization, acute coronary hospitalization), CV hospitalization, and all-cause mortality. Patient reported outcomes will be analyzed based on change in Atrial Fibrillation Effect on Quality of Life (AFEQT) and change in Mayo AF-Specific Symptom Inventory (MAFSI) from baseline to 12 months. ConclusionCHANGE AFIB will determine if treatment with dronedarone in addition to usual care is superior to usual care alone for the prevention of CV hospitalization or death from any cause in patients with first-detected AF. The trial will also determine whether initiation of rhythm control at the time of first-detected AF affects CV events or improves patient reported outcomes. ClinicalTrials.gov #- NCT05130268

Electronic Nudges to Increase Influenza Vaccination in Patients With Chronic Diseases

Despite strong worldwide guideline recommendations, influenza vaccination rates remain suboptimal among young and middle-aged patients with chronic diseases. Effective scalable strategies to increase vaccination are needed. To investigate whether electronically delivered letter-based nudges informed by behavioral science could increase influenza vaccination uptake among patients aged 18 to 64 years with chronic diseases. Nationwide pragmatic registry-based randomized clinical implementation trial conducted between September 24, 2023, and May 31, 2024, enrolling all Danish citizens aged 18 to 64 years who met criteria for free-of-charge influenza vaccination in light of preexisting chronic disease. All trial data were sourced from nationwide administrative health registries. Randomized in 2.45:1:1:1:1:1:1 ratio to no letter (usual care) or 6 different behaviorally informed electronic letters. The primary end point was receipt of influenza vaccination on or before January 1, 2024, assessed in 7 prespecified coprimary comparisons (all intervention groups pooled vs usual care and each individual intervention group vs usual care). Absolute risk difference in proportions and a crude relative risk were calculated for each comparison. A total of 299 881 participants (53.2% [159 454] female, median age, 52.0 [IQR, 39.8-59.0] years) were randomized. Compared with usual care, influenza vaccination rates were higher among those receiving any intervention letter (any intervention letter, 39.6% vs usual care, 27.9%; difference, 11.7 percentage points; 99.29% CI, 11.2-12.2 percentage points; P < .001). Each individual letter type significantly increased influenza vaccination with the largest effect sizes observed with a repeated letter sent 10 days after the initial letter (repeated letter, 41.8% vs usual care, 27.9%; difference, 13.9 percentage points; 99.29% CI, 13.1-14.7 percentage points; P < .001) and a letter emphasizing potential cardiovascular benefits of vaccination (cardiovascular gain, 39.8% vs usual care, 27.9%; difference, 11.9 percentage points; 99.29% CI, 11.1-12.7 percentage points; P < .001). Vaccination rates were improved across major subgroups. In a nationwide randomized clinical implementation trial, electronically delivered letter-based nudges markedly increased influenza vaccination compared with usual care among young and middle-aged patients with chronic diseases. The results of this study suggest that simple, scalable, and cost-efficient electronic letter strategies may have substantial public health implications. ClinicalTrials.gov Identifier: NCT06030739.

Comparison of Apixaban Versus Enoxaparin for Venous Thromboembolism Prevention After Radical Cystectomy: The CARE Trial

CARE is a pragmatic randomized clinical trial designed to compare adherence, satisfaction, patient out-of-pocket costs, and venous thromboembolism (VTE) rates between apixaban and enoxaparin prescribed as VTE prophylaxis on discharge after radical cystectomy.

Screening for Helicobacter pylori to Prevent Gastric Cancer

Effects of screening for Helicobacter pylori on gastric cancer incidence and mortality are unknown. To evaluate the effects of an invitation to screen for H pylori on gastric cancer incidence and mortality. A pragmatic randomized clinical trial of residents aged 50 to 69 years in Changhua County, Taiwan, eligible for biennial fecal immunochemical tests (FIT) for colon cancer screening. Participants were randomized to either an invitation for H pylori stool antigen (HPSA) + FIT assessment or FIT alone. The study was conducted between January 1, 2014, and September 27, 2018. Final follow-up occurred December 31, 2020. Invitation for testing for H pylori stool antigen. The primary outcomes were gastric cancer incidence and gastric cancer mortality. All invited individuals were analyzed according to the groups to which they were randomized. Of 240 000 randomized adults (mean age, 58.1 years [SD, 5.6]; 46.8% female), 63 508 were invited for HPSA + FIT, and 88 995 were invited for FIT alone. Of the 240 000 randomized, 38 792 who were unreachable and 48 705 who did not receive an invitation were excluded. Of those invited, screening participation rates were 49.6% (31 497/63 508) for HPSA + FIT and 35.7% (31 777/88 995) for FIT alone. Among 12 142 participants (38.5%) with positive HPSA results, 8664 (71.4%) received antibiotic treatment, and eradication occurred in 91.9%. Gastric cancer incidence rates were 0.032% in the HPSA + FIT group and 0.037% in the FIT-alone group (mean difference, -0.005% [95% CI, -0.013% to 0.003%]; P = .23). Gastric cancer mortality rates were 0.015% in the HPSA + FIT group and 0.013% in the FIT-alone group (mean difference, 0.002% [95% CI, -0.004% to 0.007%]; P = .57). After adjusting for differences in screening participation, length of follow-up, and patient characteristics in post hoc analyses, an invitation for HPSA + FIT was associated with lower rates of gastric cancer (0.79 [95% CI, 0.63-0.98]) but not with gastric cancer mortality (1.02 [95% CI, 0.73-1.40]), compared with FIT alone. Among participants who received antibiotics, the most common adverse effects were abdominal pain or diarrhea (2.1%) and dyspepsia or poor appetite (0.8%). Among residents of Taiwan, an invitation to test for HPSA combined with FIT did not reduce rates of gastric cancer or gastric cancer mortality, compared with an invitation for FIT alone. However, when differences in screening participation and length of follow-up were accounted for, gastric cancer incidence, but not gastric cancer mortality, was lower in the HSPA + FIT group, compared with FIT alone. ClinicalTrials.gov Identifier: NCT01741363.

The Precision Resuscitation With Crystalloids in Sepsis (PRECISE) Trial

Intravenous fluids are an essential part of treatment in sepsis, but there remains clinical equipoise on which type of crystalloid fluids to use in sepsis. A previously reported sepsis subphenotype (ie, group D) has demonstrated a substantial mortality benefit from balanced crystalloids compared with normal saline. To test the hypothesis that targeting balanced crystalloids to patients with group D sepsis through an electronic health record (EHR) alert will reduce 30-day inpatient mortality. The Precision Resuscitation With Crystalloids in Sepsis (PRECISE) trial is a parallel-group, multihospital, single-blind, pragmatic randomized clinical trial to be conducted at 6 hospitals in the Emory Healthcare system. Patients with suspicion of group D infection in whom a clinician initiates an order for normal saline in the emergency department (ED) or intensive care unit (ICU) will be randomized to usual care and intervention arms. An EHR alert that appears in the ED and ICUs to nudge clinicians to use balanced crystalloids instead of normal saline. The primary outcome is 30-day inpatient mortality. Secondary outcomes are ICU admission, in-hospital mortality, receipt of vasoactive drugs, receipt of new kidney replacement therapy, and receipt of mechanical ventilation (vasoactive drugs, kidney replacement therapy, and mechanical ventilation are counted if they occur after randomization and within the 30-day study period). Intention-to-treat analysis will be conducted. The PRECISE trial may be one of the first precision medicine trials of crystalloid fluids in sepsis. Using routine vital signs (temperature, heart rate, respiratory rate, and blood pressure), available even in low-resource settings, a validated machine learning algorithm will prospectively identify and enroll patients with group D sepsis who may have a substantial mortality reduction from used of balanced crystalloids compared with normal saline. On finalizing participant enrollment and analyzing the data, the study's findings will be shared with the public through publication in a peer-reviewed journal. With use of a validated machine learning algorithm, precision resuscitation in sepsis could fundamentally redefine international standards for intravenous fluid resuscitation. ClinicalTrials.gov Identifier: NCT06253585.

Benefits and Harms of Hepatocellular Carcinoma Screening Outreach in Patients with Cirrhosis: A Multi-Center Randomized Clinical Trial.

The value of hepatocellular carcinoma (HCC) screening is defined by the balance of benefits from early tumor detection vs harms due to false positive results. We evaluated the value of a mailed outreach strategy for HCC screening in patients with cirrhosis. We conducted a multi-center pragmatic randomized clinical trial comparing mailed outreach for HCC screening (n = 1436) and usual care with visit-based screening (n = 1436) among patients with cirrhosis at three health systems from March 2018 to September 2021. Outcomes of interest were early-stage HCC detection (ie, screening benefit) and diagnostic evaluation for false positive or indeterminate results (ie, screening harm). Screening harm was categorized as mild, moderate, and severe based on number and type of diagnostic exams. All patients were included in intention-to-screen analyses. Of 125 patients diagnosed with HCC (67 outreach and 58 usual care), 71.2% were found at an early stage per the Milan Criteria. Early tumor detection did not significantly differ between the outreach and usual care arms (64.2% vs 79.3%, p = .06). The proportion of patients with physical harms also did not differ between the outreach and usual care arms (10.8% vs 10.7%, p = .95) with 5.9% in both arms having mild harms, 4.0% and 3.8% respectively with moderate harms, and 0.9% and 1.0% respectively with severe harms. Most patients enrolled in HCC screening were detected at an early stage, and a minority experienced physical harms. A mailed outreach strategy did not significantly increase early HCC detection or physical harms compared to usual care. NCT02582918 and NCT03756051.

Artificial intelligence guided screening for cardiomyopathies in an obstetric population: a pragmatic randomized clinical trial.

Nigeria has the highest reported incidence of peripartum cardiomyopathy worldwide. This open-label, pragmatic clinical trial randomized pregnant and postpartum women to usual care or artificial intelligence (AI)-guided screening to assess its impact on the diagnosis left ventricular systolic dysfunction (LVSD) in the perinatal period. The study intervention included digital stethoscope recordings with point of-care AI predictions and a 12-lead electrocardiogram with asynchronous AI predictions for LVSD. The primary end point was identification of LVSD during the study period. In the intervention arm, the primary end point was defined as the number of identified participants with LVSD as determined by a positive AI screen, confirmed by echocardiography. In the control arm, this was the number of participants with clinical recognition and documentation of LVSD on echocardiography in keeping with current standard of care. Participants in the intervention arm had a confirmatory echocardiogram at baseline for AI model validation. A total of 1,232 (616 in each arm) participants were randomized and 1,195 participants (587 intervention arm and 608 control arm) completed the baseline visit at 6 hospitals in Nigeria between August 2022 and September 2023 with follow-up through May 2024. Using the AI-enabled digital stethoscope, the primary study end point was met with detection of 24 out of 587 (4.1%) versus 12 out of 608 (2.0%) patients with LVSD (intervention versus control odds ratio 2.12, 95% CI 1.05-4.27; P = 0.032). With the 12-lead AI-electrocardiogram model, the primary end point was detected in 20 out of 587 (3.4%) versus 12 out of 608 (2.0%) patients (odds ratio 1.75, 95% CI 0.85-3.62; P = 0.125). A similar direction of effect was observed in prespecified subgroup analysis. There were no serious adverse events related to study participation. In pregnant and postpartum women, AI-guided screening using a digital stethoscope improved the diagnosis of pregnancy-related cardiomyopathy. ClinicalTrials.gov registration: NCT05438576.

Effectiveness of direct patient outreach with a narrative naloxone and overdose prevention video to patients prescribed long-term opioid therapy in the USA: the Naloxone Navigator randomised clinical trial

IntroductionPublic health efforts to reduce opioid overdose fatalities include educating people at risk and expanding access to naloxone, a medication that reverses opioid-induced respiratory depression. People receiving long-term opioid therapy...

The professional perception of the International Caries Classification and Management System (ICCMS): a pragmatic randomised clinical trial.

Introduction The International Caries Classification and Management System (ICCMS) was developed to standardise caries diagnosis, risk assessment and treatment decisions based on overall evidence. To evaluate its criteria in practice, a clinical trial assessed professionals' perceptions of two caries management systems.Methods A perception questionnaire was administered to two groups: one using ICCMS criteria and the other based on professional experience criteria (non-ICCMS group). The online questionnaire included quantitative scale questions to measure effort and satisfaction and two open-ended questions to collect the positive and negative perceptions of dentists by using either criteria system. The questionnaires were administered six months after the study's implementation.Results Both groups showed high levels of effort and satisfaction. Professionals using ICCMS reported more positive perceptions by citing improved diagnosis (71.4%) and standardised patient care (43%). However, they also noted negative aspects, such as increased number of questionnaires and records (58%), longer clinical sessions (43%) and higher rates of patient absenteeism (29%).Conclusion Professionals who used the ICCMS had a positive outlook on the system, with benefits seen in diagnosis and patient monitoring. However, there is room for improvement in terms of automation and simplification to enhance the professional use of the system in the clinical setting.

An Adaptive Pragmatic Randomized Controlled Trial of Emergency Department Acupuncture for Acute Musculoskeletal Pain Management

Acute musculoskeletal pain in emergency department (ED) patients is frequently severe and challenging to treat with medications alone. The purpose of this study was to determine the feasibility, acceptability, and effectiveness of adding ED acupuncture to treat acute episodes of musculoskeletal pain in the neck, back, and extremities. In this pragmatic 2-stage adaptive open-label randomized clinical trial, Stage 1 identified whether auricular acupuncture (AA; based on the battlefield acupuncture protocol) or peripheral acupuncture (PA; needles in head, neck, and extremities only), when added to usual care was more feasible, acceptable, and efficacious in the ED. Stage 2 assessed effectiveness of the selected acupuncture intervention(s) on pain reduction compared to usual care only (UC). Licensed acupuncturists delivered AA and PA. They saw and evaluated but did not deliver acupuncture to the UC group as an attention control. All participants received UC from blinded ED providers. Primary outcome was 1-hour change in 11-point pain numeric rating scale. Stage 1 interim analysis found both acupuncture styles similar, so Stage 2 continued all 3 treatment arms. Among 236 participants randomized, demographics and baseline pain were comparable across groups. When compared to UC alone, reduction in pain was 1.6 (95% confidence interval [CI]: 0.7 to 2.6) points greater for AA+UC and 1.2 (95% CI: 0.3 to 2.1) points greater for PA+UC patients. Participants in both treatment arms reported high satisfaction with acupuncture. ED acupuncture is feasible and acceptable and can reduce acute musculoskeletal pain better than UC alone.

Effect of Adding Personalized Instant Messaging Apps to a Brief Smoking Cessation Model in Community Smokers in Hong Kong: Pragmatic Randomized Clinical Trial.

While text messaging has proven effective for smoking cessation (SC), engagement in the intervention remains suboptimal. This study aims to evaluate whether using more interactive and adaptive instant messaging (IM) apps on smartphones, which enable personalization and chatting with SC advisors, can enhance SC outcomes beyond the provision of brief SC advice and active referral (AR) to SC services. From December 2018 to November 2019, we proactively recruited 700 adult Chinese daily cigarette users in Hong Kong. Participants were randomized in a 1:1 ratio. At baseline, all participants received face-to-face brief advice on SC. Additionally, they were introduced to local SC services and assisted in selecting one. The intervention group received an additional 26 personalized regular messages and access to interactive chatting through IM apps for 3 months. The regular messages aimed to enhance self-efficacy, social support, and behavioral capacity for quitting, as well as to clarify outcome expectations related to cessation. We developed 3 sets of messages tailored to the planned quit date (within 30 days, 60 days, and undecided). Participants in the intervention group could initiate chatting with SC advisors on IM themselves or through prompts from regular messages or proactive inquiries from SC advisors. The control group received 26 SMS text messages focusing on general health. The primary outcomes were smoking abstinence validated by carbon monoxide levels of <4 parts per million at 6 and 12 months after the start of the intervention. Of the participants, 505/700 (72.1%) were male, and 450/648 (69.4%) were aged 40 or above. Planning to quit within 30 days was reported by 500/648 (77.2%) participants, with fewer intervention group members (124/332, 37.3%) reporting previous quit attempts compared with the control group (152/335, 45.4%; P=.04). At the 6- and 12-month follow-ups (with retention rates of 456/700, 65.1%, and 446/700, 63.7%, respectively), validated abstinence rates were comparable between the intervention (14/350, 4.0%, and 19/350, 5.4%) and control (11/350, 3.1% and 21/350, 6.0%) groups. Compared with the control group, the intervention group reported greater utilization of SC services at 12 months (RR 1.26, 95% CI 1.01-1.56). Within the intervention group, engaging in chat sessions with SC advisors predicted better validated abstinence at 6 months (RR 3.29, 95% CI 1.13-9.63) and any use of SC services (RR 1.66, 95% CI 1.14-2.43 at 6 months; RR 1.67, 95% CI 1.26-2.23 at 12 months). An IM-based intervention, providing support and assistance alongside brief SC advice and AR, did not yield further increases in quitting rates but did encourage the utilization of SC services. Future research could explore whether enhanced SC service utilization leads to improved long-term SC outcomes. ClinicalTrials.gov NCT03800719; https://clinicaltrials.gov/ct2/show/NCT03800719.