Household Air Pollution Interventions to Improve Health in Low- and Middle-Income Countries: An Official American Thoracic Society Research Statement.

Background: An estimated 3 billion people, largely in low- and middle-income countries, rely on unclean fuels for cooking, heating, and lighting to meet household energy needs. The resulting exposure to household air pollution (HAP) is a leading cause of pneumonia, chronic lung disease, and other adverse health effects. In the last decade, randomized controlled trials of clean cooking interventions to reduce HAP have been conducted. We aim to provide guidance on how to interpret the findings of these trials and how they should inform policy makers and practitioners.Methods: We assembled a multidisciplinary working group of international researchers, public health practitioners, and policymakers with expertise in household air pollution from within academia, the American Thoracic Society, funders, nongovernmental organizations, and global organizations, including the World Bank and the World Health Organization. We performed a literature search, convened four sessions via web conference, and developed consensus conclusions and recommendations via the Delphi method.Results: The committee reached consensus on 14 conclusions and recommendations. Although some trials using cleaner-burning biomass stoves or cleaner-cooking fuels have reduced HAP exposure, the committee was divided (with 55% saying no and 45% saying yes) on whether the studied interventions improved measured health outcomes.Conclusions: HAP is associated with adverse health effects in observational studies. However, it remains unclear which household energy interventions reduce exposure, improve health, can be scaled, and are sustainable. Researchers should engage with policy makers and practitioners working to scale cleaner energy solutions to understand and address their information needs.

Organized cervical cancer screening: A randomized controlled trial assessing the effect of sending invitation letters.

OBJECTIVE: To evaluate the effect of implementing two modalities of organized Cervical Cancer Screening (CCS) program on screening uptake after a six-month delay. METHODS: A three-armed cluster randomized control trial was conducted in France between January 8 and July 2, 2021, involving148 510 women aged 40 to 65 and 1070 general practitioners. In the Optimized screening group, an invitation letter was posted to non-adherent women, and general practitioners were sent a list of their non-adherent patients. In the Organized screening group, an invitation letter was posted to non-adherent women. In the Usual care group, no invitation was sent. The endpoint was cervical cancer screening uptake after a six months period a) among all eligible women (primary endpoint); and b) among initially non-adherent women (post-hoc analysis). Statistical analysis was based on a logistic mixed model that compared between-group percentages of adherent women. A hierarchical comparison successively tested differences between the three arms (alpha 5 % risk). RESULTS: Among all 148,510 eligible women, screening uptake was 63.6 % (31,731/49910) in the Optimized screening group vs 61.8 % (30,210/48847) in the Usual care group (OR [IC95 %] = 1.05[0.93; 1.18]). Among the 64,370 initially non-adherent women, screening uptake was 17.9 % (3955/22134) in the Optimized screening group vs 11.6 % (5321/20995) in the Usual care group (OR [IC95 %] = 1.70[1.56;1.86]). There was no significant difference between Optimized and Organized screening groups (17.2 % vs 17.9 %; OR [IC95 %] = 1.02[0.94; 1.11]). CONCLUSIONS: The implementation of an organized screening based on an invitation letter resulted in a modest increase in participation among non-adherent women six months later.

A randomized trial on three different minimally invasive decompression techniques for lumbar spinal stenosis. Five years follow-up from the NORDSTEN-SST.

PURPOSE: The short-term clinical outcome for midline-preserving posterior decompression techniques was comparable. The aim of this study was to evaluate long-term clinical results after three different midline-preserving posterior decompression techniques. MATERIAL: In the NORDSTEN spinal stenosis trial (NORDSTEN-SST) 437 patients were randomized to three different midline-retaining posterior decompression techniques: Unilateral laminotomy with crossover (UL), bilateral laminotomy (BL) and spinous process osteotomy (SPO). Primary outcome was the mean change in Oswestry disability index (ODI) score at five-years follow-up. Secondary outcomes were the proportion of patients classified as success, mean change in EQ-5D, ZCQ-score, NRS-score for leg and low back pain, a seven-point Global Perceived Effect (GPE) Scale and proportion of subsequential spinal surgery. RESULTS: The number of patients that completed follow-up data after five years was 358 (82%): In the UL, BL and SPO group the numbers were 122, 119 and 117, respectively. Mean age at baseline was 66.7 (SD 8.2) years, mean BMI was 27.8 (SD 4.1), and 172/358 (48%) were female. In the UL group the mean change was -18.2 (95% CI -21.0 -5.4), in the BL group it was -19.0 (95% CI -21.9-16.1) and in the SPO it was -18.6 (95% CI -21.6-15.7) (p = 0.917). No significant differences in the secondary outcomes between the three surgical groups were found, also the subsequent spinal surgery rates were similar. CONCLUSION: There were no significant differences in patient reported outcomes and subsequent spinal surgery rates after the three different decompression techniques at five-year follow-up.

A Novel Smartphone-Based Intervention Aimed at Increasing Future Orientation via the Future Self: a Pilot Randomized Controlled Trial of a Prototype Application.

We developed and tested a smartphone-based intervention, FutureU, that aims to stimulate future-oriented thinking and behavior by strengthening the degree to which people identify with their future self. In order to examine the potential of this intervention prototype and opportunities for further optimization, we evaluated 1) the immediate and long-term efficacy of the intervention, and 2) intervention effects after each of three intervention modules. To this end, we conducted a randomized controlled pilot study among first-year university students (N = 176). Results showed a decrease in goal commitment immediately after the intervention. At 3-months follow-up, trends showed an increase in future orientation and in self-efficacy. During the intervention, there was a positive effect on vividness of the future self after the first module. Although there is scope for improvement, the findings highlight the potential of the intervention to increase people's future-oriented thinking and behavior.

Evaluation of an SMS Based Alcohol Intervention for Same Sex Attracted Women: A Randomized Controlled Trial to Examine Feasibility, Acceptability, and Efficacy.

PURPOSE: The purpose of this randomized controlled trial (Trial registration ID: redacted) was to examine the feasibility, acceptability, and efficacy of the Step One program, an SMS-based alcohol intervention for same-sex attracted women (SSAW). METHODS: Ninety-seven SSAW who scored ≥8 on the Alcohol Use Disorders Identification Test (AUDIT) were randomly allocated to receive the Step One program (n = 47; mean age = 36.79) or a weekly message containing a link to a website with health information and support services for LGBT individuals (n = 50; mean age = 34.08). Participants completed questionnaires on alcohol use, wellbeing, and help-seeking at baseline (T1), intervention completion (T2; 4 wk after baseline) and 12 wk post-intervention (T3). In addition, participants in the intervention condition completed feasibility and accessibility measures at T2, and a subsample (n = 10) was interviewed about acceptability at T3. RESULTS: Across conditions, participants significantly reduced their alcohol intake and improved their wellbeing and help-seeking over time. However, there were no significant differences between the intervention and control condition. Furthermore, frequency of help-seeking was low; only four intervention group participants and three control group participants began accessing support between T1 and T3. Overall, our findings indicate the intervention would benefit from revision prior to implementation. CONCLUSIONS: Our approach was consistent with best practice in the development of an ecologically valid intervention; however, this intervention, in its current form, lacks the complexity desired by its users to optimally facilitate alcohol reduction among SSAW. Keywords: Alcohol intervention; Intervention mapping framework; Randomized controlled trial (RCT); Same-sex attracted women; Short-message service (SMS).

Promoting motivation and reducing stress in medical students by utilizing self-determination theory - a randomized controlled trial in practical psychiatry courses.

BACKGROUND: Medical students experience high levels of stress and related mental health problems. Students' autonomous and controlled motivation and their mental well-being are interconnected. This study aimed to investigate whether an innovative teaching concept based on self-determination theory (SDT) could improve students' motivation and thereby reduce their stress levels, ultimately providing a healthier framework for learning. METHODS: In a week-long practical psychiatry course for medical students, a new didactic concept was implemented in half the groups (n = 73) and compared with the preexisting concept (n = 75) as a randomized controlled trial (RCT). To promote the SDT-target factors of perceived autonomy, competence, and relatedness, the methods used included team building, exclusively positive feedback, group discussions, and choice in task distribution. Significant group differences in motivation, stress, performance, and their relationships were analyzed through t-tests, multiple linear regression analyses, mediation analyses, and hierarchical linear modeling (HLM) using questionnaires collected before (t0) and after (t1) the course, and students' exam results (t2). RESULTS: In the innovation group (n = 53), intrinsic motivation/interest (d = 0.41; p = .019) and perceived choice/autonomy (d = 0.33; p = .048) were greater than in the control group (n = 52). While autonomous regulation remained stable, the innovation group showed reduced controlled regulation (d = -0.36; p = .033) and reported significantly lower stress (d = -0.55; p = .003). The observed changes in motivation collectively mediated the stress reduction. However, students in the innovation group achieved lower exam scores, which seemed to result from the absence of critical feedback, but not from the observed differences in motivation or stress. CONCLUSIONS: This study demonstrated that enhancing intrinsic motivation through SDT-based teaching can effectively reduce stress in medical students. Exclusively strengths-based positive feedback may have hindered exam performance, but optimizing educational concepts to promote motivation and reduce stress will be a valuable step toward improving medical students' mental well-being.

Investigation Into the Effects of Intra-Articular Steroid on Post-Traumatic Osteoarthritis in Distal Radius Fractures: A Randomized Controlled Pilot Study.

PURPOSE: The aim of this prospective, randomized, controlled, double-blinded pilot study was to determine the rates of post-traumatic osteoarthritis and assess joint space width in the presence or absence of a single intra-articular injection of corticosteroid after an acute, intra-articular distal radius fracture (DRF). METHODS: Forty patients received a single, intra-articular, radiocarpal joint injection of 4 mg of dexamethasone (DEX) (n = 19) or normal saline placebo (n = 21) within 2 weeks of a surgically or nonsurgically treated intra-articular DRF. The primary outcome measure was minimum radiocarpal joint space width (mJSW) on noncontrast computed tomography scans at 2 years postinjection. Secondary outcomes were obtained at 3 months, 6 months, 1 year, and 2 years postinjection and included Disabilities of the Arm, Shoulder, and Hand; Michigan Hand Questionnaire; Patient-Rated Wrist Evaluation; wrist range of motion; and grip strength. RESULTS: At 2-year follow-up, there was no difference in mean mJSW between the DEX group (2.2 mm; standard deviation, 0.6; range, 1.4-3.2) and the placebo group (2.3 mm; standard deviation, 0.7; range, 0.9-3.9). Further, there were no differences in any secondary outcome measures at any postinjection follow-up interval. CONCLUSIONS: Radiocarpal joint injection of corticosteroid within 2 weeks of an intra-articular DRF does not appear to affect the development of post-traumatic osteoarthritis within 2 years follow-up in a small pilot cohort. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

LEAP! Rx: A randomized trial of a pragmatic approach to lifestyle medicine.

INTRODUCTION: Clinicians lack the tools to incorporate physical activity into clinical care for Alzheimer's disease prevention. We tested a 52-week exercise and health education program (Lifestyle Empowerment for Alzheimer's Prevention [LEAP! Rx]) that integrates clinician referrals and community-based fitness resources. METHODS: We randomized 219 participants to the LEAP! Rx (ie, exercise and monthly brain health education) or a standard-of-care control group and tested the effects on cardiorespiratory fitness, insulin resistance, body composition, lipids, and cognitive performance. RESULTS: Physicians were able to connect their patients to a community lifestyle intervention. The intervention group increased in cardiorespiratory fitness at 12 and 52 weeks (p = 0.005). We observed no effects on secondary measures. Participants meeting 80% of weekly goals (150 min, moderate to vigorous activity) saw greater fitness improvements than those with less than 80% (p < 0.001). DISCUSSION: These results hold promise for broad implementation of exercise interventions into larger healthcare systems and have implications for improved research recruitment strategies. TRIAL REGISTRATION: NCT No. NCT03253341. HIGHLIGHTS: Our community-based exercise program increased cardiorespiratory fitness. Our digital physician referral method increased the diversity of the participant sample. Our findings have implications for personalized dementia risk reduction strategies.

Effectiveness and Safety of IPN-20-SENSE LIDOCAINE for Lip Volume Augmentation and/or Redefinition (SMILE Study): A Non-inferiority Randomized Double-Blinded Controlled Study.

BACKGROUND: Hyaluronic acid (HA) is a widely used dermal filler for lip augmentation. IPN-20-SENSE LIDOCAINE (Laboratoires VIVACY) is a monophasic gel consisting of cross-linked HA and includes lidocaine hydrochloride for the reduction of injection-associated pain. AIMS: The SMILE study was designed to assess the non-inferiority of IPN-20-SENSE LIDOCAINE compared to HA-RK-Lido in improving aesthetic lip appearance. The secondary objectives were to evaluate the effectiveness and safety of IPN-20-SENSE LIDOCAINE against the chosen similar active control device. PATIENTS/METHODS: This was a prospective, multicenter, double-blinded, randomized active controlled parallel group study undertaken in two investigational sites between May 2021 and July 2022 (14 months). The primary endpoint of this study was the proportion of subjects reporting an improvement on the Global Aesthetic Improvement Scale (GAIS) 3 months after treatment initiation. RESULTS: Regarding the primary endpoint, the difference between the treatment arms in the proportion of improved subjects was +7.0 [-2.2; 17.7]. The lower limit of this 90% CI, being above the non-inferiority margin of -15 and below zero, demonstrated the non-inferiority of IPN-20-SENSE LIDOCAINE vs. HA-RK-Lido. The secondary outcomes reported by subjects and the blinded live evaluators supported this result. All injection site reactions and device-related adverse events reported in this study were expected, already described and were mostly mild and transient. CONCLUSIONS: The study demonstrated the non-inferiority of IPN-20-SENSE LIDOCAINE to HA-RK-Lido in the aesthetic improvement of the lips. The effect of both treatments decreased over time. Nonetheless, aesthetic improvement was sustained longer in the IPN-20-SENSE LIDOCAINE arm. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Internet-Based Cognitive Behavioural Treatments for Obsessive-Compulsive Disorder: A Systematic Review and Meta-Analysis.

Obsessive-compulsive disorder (OCD) is a common mental health condition characterized by distressing, intrusive thoughts (obsessions) and repetitive behaviours (compulsions) aimed at reducing anxiety. Internet-based cognitive behavioural therapy (ICBT) has emerged as an effective treatment modality for various mental health disorders. This meta-analysis evaluates the efficacy of guided self-help ICBT (GSH ICBT) and unguided self-help ICBT (SH ICBT) against active and passive control conditions in adults with OCD. A comprehensive systematic literature search yielded 12 randomized controlled trials (RCTs) comprising 15 comparison arms (N = 1416) that met the inclusion criteria. Results indicate that GSH ICBT significantly reduced OCD symptomatology posttreatment compared to active controls (g = 0.378, k = 9), with no significant effects maintained at follow-up (g = 0.153, k = 4). GSH ICBT was also found to be as effective as active CBT interventions in reducing comorbid anxiety and depression symptoms posttreatment (g = 0.278, k = 6) and at follow-up (g = 0.124, k = 4). However, improvements in quality of life were not significant posttreatment (g = 0.115, k = 4) nor at follow-up (g = 0.179, k = 3). Combined GSH and SH ICBT demonstrated large effects on reducing OCD symptoms (g = 0.754, k = 6), medium effects on comorbid symptoms (g = 0.547, k = 6) and small effects on quality of life (g = 0.227, k = 2) when compared to inactive controls. No significant differences were found between GSH and SH ICBT in all measured outcomes posttreatment (OCD: g = 0.098, k = 3; AD: g = 0.070, k = 3; QoL: g = -0.030, k = 1) and at follow-up (OCD: g = 0.265, k = 2; AD: g = 0.084, k = 2; QoL: g = 0.00, k = 1). Sample size was identified as a significant moderator of treatment effects. This paper further explores clinical significance, treatment adherence, therapist time investment and moderator influences of the ICBT. The limitations of the study and recommendations for future research are thoroughly discussed.

[Experience with an international study on standard-risk relapsed childhood acute lymphoblastic leukemia (IntReALL SR 2010 study) in Japan].

Many effective new agents for relapsed childhood acute lymphoblastic leukemia (ALL) are now becoming available, and international standard chemotherapy should be developed to optimize use of these agents. Randomized controlled trials (RCTs) are needed to establish a standard treatment, but few have been conducted for relapsed childhood ALL in Japan due to the small patient population. Participation in international RCTs is necessary to access sufficient patients for informative study results, but differences in approved drugs and healthcare systems between countries make this challenging. In 2014, the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) participated in an international study on standard-risk relapsed childhood ALL (IntReALL SR 2010) involving two RCTs and multiple drugs not approved in Japan, which was addressed by replacing the unapproved drugs with alternative approved drugs with the same or similar efficacy. This article discusses the historical background of treatment development for relapsed childhood ALL, our experience in participating in the IntReALL SR 2010 trial, and prospects for treating relapsed childhood ALL.

Systematic review and meta-analysis of the efficacy of exercise intervention in kidney transplant recipients.

BACKGROUND AND OBJECTIVE: There is uncertainty about the beneficial effects of exercise intervention for kidney transplant recipients. The purpose of our meta-analysis is to estimate the efficacy of exercise intervention in kidney transplant recipients. METHODS: A database search according to the PICOS framework was performed for all published randomized, double-blind, placebo-controlled trials (RCTs) about exercise intervention for kidney transplant recipients. The databases involved include PubMed, Embase, and Cochrane Library. RESULTS: A total of 16 RCTs (involving 827 patients) in compliance with inclusion criteria were included in our study. The results demonstrated that adequate exercise intervention improved statistically in creatinine clearance [mean difference (MD) = - 0.29, 95% confidence interval (CI) - 0.46 to - 0.11, p = 0.001], serum urea (MD = - 21.57, 95% CI - 35.84 to - 7.29, p = 0.003), VO2 peak (MD = 3.20, 95% CI 1.97-4.43, p < 0.00001), high-density lipoprotein-cholesterol (HDL-C) (MD = 0.21, 95% CI 0.04-0.37, p = 0.01), 60-s sit to stand test (60-STS) (MD = 14.47, 95% CI 8.89-20.04, p < 0.00001), 6-min walk distance (6-MWD) (MD = 91.87, 95% CI 38.34-145.39, p = 0.0008), and 6-min walk test (6-MWT) (MD = 44.08, 95% CI 20.30-67.87, p = 0.0003) of patients after kidney transplantation. No between-groups differences (p > 0.05) were observed for anthropometric characteristics, body composition, serum cytokine levels, and quality of life short form-36 questionnaire (SF-36). CONCLUSIONS: In kidney transplant recipients, appropriate exercise intervention improved renal function, cardiopulmonary function, physical performance. TRIAL REGISTRATION: The PROSPERO registration number is CRD42022357574.

Causalgia: A Review of Nerve Resection, Amputation, Immunotherapy, and Amputated Limb CRPS II Pathology.

BACKGROUND: Causalgia and complex regional pain syndrome (CRPS) type II with nerve injury can be difficult to treat. Surgical peripheral nerve denervation for causalgia has been largely abandoned by pain clinicians because of a perception that this may aggravate a central component (anesthesia dolorosa). METHODS: We selectively searched Pubmed, Cochrane, MEDLINE, EMBASE, CINAHL Plus, and Scopus from 1947 for articles, books, and book chapters for evidence of surgical treatments (nerve resection and amputation) and treatment related to autoimmunity and immune deficiency with CRPS. RESULTS: Reviews were found for the treatment of causalgia or CRPS type II (n = 6), causalgia relieved by nerve resection (n = 6), and causalgia and CRPS II treated by amputation (n = 8). Twelve reports were found of autoimmunity with CRPS, one paper of these on associated immune deficiency and autoimmunity, and two were chosen for discussion regarding treatment with immunoglobulin and one by plasma exchange. We document a report of a detailed and unique pathological examination of a CRPS type II affected amputated limb and related successful treatment with immunoglobulin. CONCLUSIONS: Nerve resection, with grafting, and relocation may relieve uncomplicated causalgia and CRPS type II in some patients in the long term. However, an unrecognized and treatable immunological condition may underly some CRPS II cases and can lead to the ultimate failure of surgical treatments.

Improving eye care quality through brief verbal intervention on optometry service provider by using unannounced standardized patient with refractive error: study protocol for a randomized controlled trial.

BACKGROUND: Improper refractive correction can be harmful to eye health, aggravating the burden of vision impairment. During most optometry clinical consultations, practitioner-patient interactions play a key role. Maybe it is feasible for patients themselves to do something to get high-quality optometry. But the present empirical research on the quality improvement of eye care needs to be strengthened. The study aims to test the effect of the brief verbal intervention (BVI) through patients on the quality of optometry service. METHODS: This study will take unannounced standardized patient (USP) with refractive error as the core research tool, both in measurement and intervention. The USP case and the checklist will be developed through a standard protocol and assessed for validity and reliability before its full use. USP will be trained to provide standardized responses during optical visits and receive baseline refraction by the skilled study optometrist who will be recruited within each site. A multi-arm parallel-group randomized trial will be used, with one common control and three intervention groups. The study will be performed in four cities, Guangzhou and three cities in Inner Mongolia, China. A total of 480 optometry service providers (OSPs) will be stratified and randomly selected and divided into four groups. The common control group will receive USP usual visits (without intervention), and three intervention groups will separately receive USP visits with three kinds of BVI on the patient side. A detailed outcome evaluation will include the optometry accuracy, optometry process, patient satisfaction, cost information and service time. Descriptive analysis will be performed for the survey results, and the difference in outcomes between interventions and control providers will be compared and statistically tested using generalized linear models (GLMs). DISCUSSION: This research will help policymakers understand the current situation and influencing factors of refractive error care quality, and then implement precise policies; at the same time, explore short and easy interventions for patients to improve the quality of optometry service. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200062819. Registered on August 19, 2022.

Process evaluation of a kindergarten-based intervention for obesity prevention in early childhood: the Toybox study Malaysia.

BACKGROUND: Toybox is a kindergarten-based intervention program that targets sedentary behavior, snacking and drinking habits, as well as promoting physical activity in an effort to improve healthy energy balance-related behaviors among children attending kindergartens in Malaysia. The pilot of this program was conducted as a randomized controlled trial (RCT) involving 837 children from 22 intervention kindergartens and 26 control kindergartens respectively. This paper outlines the process evaluation of this intervention. METHODS: We assessed five process indicators: recruitment, retention, dosage, fidelity, and satisfaction for the Toybox program. Data collection was conducted via teachers' monthly logbooks, post-intervention feedback through questionnaires, and focus group discussions (FGD) with teachers, parents, and children. Data were analyzed using quantitative and qualitative data analysis methods. RESULTS: A total of 1072 children were invited. Out of the 1001 children whose parents consented to join, only 837 completed the program (Retention rate: 88.4%). As high as 91% of the 44 teachers and their assistants engaged positively in one or more of the process evaluation data collection methods. In terms of dosage and fidelity, 76% of parents had received newsletters, tip cards, and posters at the appropriate times. All teachers and their assistants felt satisfied with the intervention program. However, they also mentioned some barriers to its implementation, including the lack of suitable indoor environments to conduct activities and the need to make kangaroo stories more interesting to captivate the children's attention. As for parents, 88% of them were satisfied with the family-based activities and enjoyed them. They also felt that the materials provided were easy to understand and managed to improve their knowledge. Lastly, the children showed positive behaviors in consuming more water, fruits, and vegetables. CONCLUSIONS: The Toybox program was deemed acceptable and feasible to implement by the parents and teachers. However, several factors need to be improved before it can be expanded and embedded as a routine practice across Malaysia.

Physiotherapy with integrated virtual reality for patients with complex chronic low back pain: protocol for a pragmatic cluster randomized controlled trial (VARIETY study).

BACKGROUND: Chronic low back pain (CLBP) is the most common chronic pain condition worldwide. Currently, primary care physiotherapy is one of the main treatment options, but effects of this treatment are small. Virtual Reality (VR) could be an adjunct to physiotherapy care, due to its multimodal features. The primary aim of this study is to assess the (cost-)effectiveness of physiotherapy with integrated multimodal VR for patients with complex CLBP, compared to usual primary physiotherapy care. METHODS: A multicenter, two-arm, cluster randomized controlled trial (RCT) including 120 patients with CLBP from 20 physiotherapists will be conducted. Patients in the control group will receive 12 weeks of usual primary physiotherapy care for CLBP. Patients in the experimental group will receive treatment consisting of 12 weeks of physiotherapy with integrated, immersive, multimodal, therapeutic VR. The therapeutic VR consists of the following modules: pain education, activation, relaxation and distraction. The primary outcome measure is physical functioning. Secondary outcome measures include pain intensity, pain-related fears, pain self-efficacy and economic measures. Effectiveness of the experimental intervention compared to the control intervention on primary and secondary outcome measures will be analyzed on an intention-to-treat principle, using linear mixed-model analyses. DISCUSSION: This pragmatic, multicenter cluster randomized controlled trial, will determine the clinical and cost-effectiveness of physiotherapy with integrated, personalized, multimodal, immersive VR in favor of usual physiotherapy care for patients with CLBP. TRIAL REGISTRATION: This study is prospectively registered at ClinicalTrials.gov (identifier: NCT05701891).

A protocol for a randomized-controlled trial to investigate the effect of infant sign training on the speech-language development in young children born with cleft palate.

BACKGROUND: Children born with a cleft palate with or without cleft lip (CP ± L) are known to be at risk for speech-language disorders that impact educational and social-emotional growth. It is hypothesized that speech-language intervention delivered before the age of 3 years could decrease the impact of CP ± L on speech-language development. Infant sign training in combination with verbal input expands the natural communication of young children including multimodal speech-language input (i.e., verbal and manual input) via caregivers who act as co-therapists. AIMS: To determine the effectiveness of infant sign training in 1-year-old children with CP ± L by comparing different interventions. METHODS & PROCEDURES: This is a two-centre, randomized, parallel-group, longitudinal, controlled trial. Children are randomized to either an infant sign training group (IST group), a verbal training group (VT group) or no intervention control group (C group). Caregivers of children who are assigned to the IST group or VT group will participate in three caregiver training meetings to practise knowledge and skills to stimulate speech-language development. Outcome measures include a combination of questionnaires, language tests and observational analyses of communicative acts. OUTCOMES & RESULTS: It is hypothesized that speech-language development of children with CP ± L will benefit more from IST compared with VT and no intervention. Additionally, the number and quality of communicative acts of both children and caregivers are expected to be higher after IST. CONCLUSIONS & IMPLICATIONS: This project will contribute to the development of evidence-based clinical practice guidelines regarding early speech-language intervention in children with CP ± L under the age of 3 years. WHAT THIS PAPER ADDS: What is already known on the subject Children with CP ± L are known to be at risk for speech-language delays that impact educational and social emotional growth. Given the limited scientific prove of the impact of early speech-language intervention, no standardized clinical practice guidelines are available yet for children with CP ± L under the age of 3 years. Early intervention in this population mostly focuses on improving verbal input via caregivers or professionals without including a multimodal language input. A growing scientific interest has been seen in the use of infant signs to support speech-language development and caregiver-child interaction in typically developing children and children with developmental delays. What this study adds to existing knowledge No evidence is yet available for the effectiveness and feasibility of early intervention based on infant sign training in combination with verbal input to improve speech-language skills in young children with CP ± L. The current project will investigate the effect of infant sign training on the speech-language development in this population. Outcome measures are compared with those of two control groups: verbal training only and no intervention. It is hypothesized that infant signs may support the intelligibility of verbal utterances produced by children with CP ± L. Improving children's intelligibility may increase the opportunities for these children to engage in early, frequent and high-quality interactions with their caregivers resulting in a richer social and linguistic environment. As a result, infant sign training may result in better speech-language skills compared with the control interventions. What are the potential or actual clinical implications of this work? If providing early intervention based on infant sign training is effective, there is the potential for improved speech-language outcomes in early childhood, resulting in increased speech intelligibility, increased well-being of the child and family and less need for speech-language therapy on the long-term. This project will contribute to the development of evidence-based clinical practice guidelines regarding early speech-language intervention in children with CP ± L under the age of 3 years.

Scandcleft randomized trials of primary surgery for unilateral cleft lip and palate: Speech proficiency at 10 years of age.

BACKGROUND & AIM: To assess consonant proficiency and velopharyngeal function in 10-year-old children born with unilateral cleft lip and palate (UCLP) within the Scandcleft project. METHODS & PROCEDURES: Three parallel group, randomized, clinical trials were undertaken as an international multicentre study by nine cleft teams in five countries. Three different surgical protocols for primary palate repair (Arm B-Lip and soft palate closure at 3-4 months, hard palate closure at 36 months, Arm C-Lip closure at 3-4 months, hard and soft palate closure at 12 months, and Arm D-Lip closure at 3-4 months combined with a single-layer closure of the hard palate using a vomer flap, soft palate closure at 12 months) were tested against a common procedure (Arm A-Lip and soft palate closure at 3-4 months followed by hard palate closure at 12 months) in the total cohort of 431 children born with a non-syndromic UCLP. Speech audio and video recordings of 399 children were available and perceptually analysed. Percentage of consonants correct (PCC) from a naming test, an overall rating of velopharyngeal competence (VPC) (VPC-Rate), and a composite measure (VPC-Sum) were reported. OUTCOMES & RESULTS: The mean levels of consonant proficiency (PCC score) in the trial arms were 86-92% and between 58% and 83% of the children had VPC (VPC-Sum). Only 50-73% of the participants had a consonant proficiency level with their peers. Girls performed better throughout. Long delay of the hard palate repair (Arm B) indicated lower PCC and simultaneous hard and soft palate closure higher (Arm C). However, the proportion of participants with primary VPC (not including velopharyngeal surgeries) was highest in Arm B (68%) and lowest in Arm C (47%). CONCLUSIONS & IMPLICATIONS: The speech outcome in terms of PCC and VPC was low across the trials. The different protocols had their pros and cons and there is no obvious evidence to recommend any of the protocols as superior. Aspects other than primary surgical method, such as time after velopharyngeal surgery, surgical experience, hearing level, language difficulties and speech therapy, need to be thoroughly reviewed for a better understanding of what has affected speech outcome at 10 years. WHAT THIS PAPER ADDS: What is already known on the subject Speech outcomes at 10 years of age in children treated for UCLP are sparse and contradictory. Previous studies have examined speech outcomes and the relationship with surgical intervention in 5-year-olds. What this study adds to the existing knowledge Speech outcomes based on standardized assessment in a large group of 10-year-old children born with UCLP and surgically treated according to different protocols are presented. While speech therapy had been provided, a large proportion of the children across treatment protocols still needed further speech therapy. What are the potential or actual clinical implications of this work? Aspects other than surgery and speech function might add to the understanding of what affects speech outcome. Effective speech therapy should be available for children in addition to primary surgical repair of the cleft and secondary surgeries if needed.

The Effect of Regularly Dosed Acetaminophen vs No Acetaminophen on Renal Function in Plasmodium knowlesi Malaria (PACKNOW): A Randomized, Controlled Trial.

BACKGROUND: Acetaminophen inhibits cell-free hemoglobin-induced lipid peroxidation and improves renal function in severe falciparum malaria but has not been evaluated in other infections with prominent hemolysis, including Plasmodium knowlesi malaria. METHODS: PACKNOW was an open-label, randomized, controlled trial of acetaminophen (500 mg or 1000 mg every 6 hours for 72 hours) vs no acetaminophen in Malaysian patients aged ≥5 years with knowlesi malaria of any severity. The primary end point was change in creatinine at 72 hours. Secondary end points included longitudinal changes in creatinine in patients with severe malaria or acute kidney injury (AKI), stratified by hemolysis. RESULTS: During 2016-2018, 396 patients (aged 12-96 years) were randomized to acetaminophen (n = 199) or no acetaminophen (n = 197). Overall, creatinine fell by a mean (standard deviation) 14.9% (18.1) in the acetaminophen arm vs 14.6% (16.0) in the control arm (P = .81). In severe disease, creatinine fell by 31.0% (26.5) in the acetaminophen arm vs 20.4% (21.5) in the control arm (P = .12), and in those with hemolysis by 35.8% (26.7) and 19% (16.6), respectively (P = .07). No difference was seen overall in patients with AKI; however, in those with AKI and hemolysis, creatinine fell by 34.5% (20.7) in the acetaminophen arm vs 25.9% (15.8) in the control arm (P = .041). Mixed-effects modeling demonstrated a benefit of acetaminophen at 72 hours (P = .041) and 1 week (P = .002) in patients with severe malaria and with AKI and hemolysis (P = .027 and P = .002, respectively). CONCLUSIONS: Acetaminophen did not improve creatinine among the entire cohort but may improve renal function in patients with severe knowlesi malaria and in those with AKI and hemolysis. CLINICAL TRIALS REGISTRATION: NCT03056391.

Rationale, Strengths, and Limitations of Real-World Evidence in Oncology: A Canadian Review and Perspective.

Randomized controlled trials (RCTs) continue to be the basis for essential evidence regarding the efficacy of interventions such as cancer therapies. Limitations associated with RCT designs, including selective study populations, strict treatment regimens, and being time-limited, mean they do not provide complete information about an intervention's safety or the applicability of the trial's results to a wider range of patients seen in real-world clinical practice. For example, recent data from Alberta showed that almost 40% of patients in the province's cancer registry would be trial-ineligible per common exclusion criteria. Real-world evidence (RWE) offers an opportunity to complement the RCT evidence base with this kind of information about safety and about use in wider patient populations. It is also increasingly recognized for being able to provide information about an intervention's effectiveness and is considered by regulators as an important component of the evidence base in drug approvals. Here, we examine the limitations of RCTs in oncology research, review the different types of RWE available in this area, and discuss the strengths and limitations of RWE for complementing RCT oncology data.