Physical Therapies for Delayed Onset Muscle Soreness: A Protocol for an Umbrella and Mapping Systematic Review with Meta-Meta-Analysis.

BACKGROUND: Delayed onset muscle soreness (DOMS), also known as exercise-induced muscle damage (EIMD), is typically caused by strenuous and/or unaccustomed physical exercise. DOMS/EIMD manifests itself in reduced muscle strength and performance levels, increased muscle soreness, swelling, and elevated levels of inflammatory biomarkers. Numerous randomised controlled trials (RCTs) and systematic reviews (SRs) of a wide variety of physiotherapy interventions for reducing the signs and symptoms of DOMS/EIMD have been published. However, these SRs often arrive at contradictory conclusions, impeding decision-making processes. OBJECTIVE: We will systematically review the current evidence on clinical outcomes (efficacy, safety) of physiotherapy interventions for the treatment of DOMS/EIMD in healthy adults. We will also assess the quality of the evidence and identify, map, and summarise data from the available SRs. METHOD: Umbrella review with evidence map and meta-meta-analyses. MEDLINE, Embase, Cochrane Database of Systematic Reviews, Epistemonikos and PEDro will be searched from January 1998 until February 2024. SRs of RCTs of any treatment used by physiotherapists (e.g., low-level laser therapy, electrical stimulation, heat/cold therapy, ultrasound, magnets, massage, manual therapies) to treat DOMS/EIMD in healthy adults will be eligible. Narrative/non-systematic reviews, studies of adolescents/children and medically compromised individuals, of complementary therapies, dietary, nutritional, or pharmacological interventions, as well as self-administered interventions, or those published before 1998, will be excluded. AMSTAR 2 will be used to evaluate the methodological quality of the included SRs. Corrected covered area, will be computed for assessing overlaps among included SRs, and an evidence map will be prepared to describe the credibility of evidence for interventions analysed in the relevant SRs. DISCUSSION: DOMS/EIMD is a complex condition, and there is no consensus regarding the standard of clinical/physiotherapeutic care. By critically evaluating the existing evidence, we aim to inform clinicians about the most promising therapies for DOMS/EIMD. This umbrella review has the potential to identify gaps in the existing evidence base that would inform future research. The protocol has been registered at PROSPERO (CRD42024485501].

KardiaMobile 6L for measuring QT interval in people having antipsychotic medication to inform early value assessment: a systematic review.

Background: The indication for this assessment is the use of the KardiaMobile six-lead electrocardiogram device for the assessment of QT interval-based cardiac risk in service users prior to the initiation of, or for the monitoring of, antipsychotic medications, which are associated with an established risk of QT interval prolongation. Objectives: To provide an early value assessment of whether KardiaMobile six-lead has the potential to provide an effective and safe alternative to 12-lead electrocardiogram for initial assessment and monitoring of QT interval-based cardiac risk in people taking antipsychotic medications. Review methods: Twenty-seven databases were searched to April/May 2022. Review methods followed published guidelines. Where appropriate, study quality was assessed using appropriate risk of bias tools. Results were summarised by research question; accuracy/technical performance; clinical effects (on cardiac and psychiatric outcomes); service user acceptability/satisfaction; costs of KardiaMobile six-lead. Results: We did not identify any studies which provided information about the diagnostic accuracy of KardiaMobile six-lead, for the detection of corrected QT-interval prolongation, in any population. All studies which reported information about agreement between QT interval measurements (corrected and/or uncorrected) with KardiaMobile six-lead versus 12-lead electrocardiogram were conducted in non-psychiatric populations, used cardiologists and/or multiple readers to interpret electrocardiograms. Where reported or calculable, the mean difference in corrected QT interval between devices (12-lead electrocardiogram vs. KardiaMobile six-lead) was generally small (≤ 10 ms) and corrected QT interval measured using KardiaMobile six-lead was consistently lower than that measured using 12-lead electrocardiogram. All information about the use of KardiaMobile six-lead, in the context of QT interval-based cardiac risk assessment for service users who require antipsychotic medication, was taken from retrospective surveys of staff and service users who had chosen to use KardiaMobile six-lead during pilots, described in two unpublished project reports. It is important to note that both these project reports relate to pilot studies which were not intended to be used in wider evaluations of KardiaMobile six-lead for use in the NHS. Both reports included survey results which indicated that the use of KardiaMobile six-lead may be associated with reductions in the time taken to complete an electrocardiogram and costs, relative to 12-lead electrocardiogram, and that KardiaMobile six-lead was preferred over 12-lead electrocardiogram by almost all responding staff and service users. Limitations: There was a lack of published evidence about the efficacy of KardiaMobile six-lead for initial assessment and monitoring of QT interval-based cardiac risk in people taking antipsychotic medications. Conclusions: There is insufficient evidence to support a full diagnostic assessment evaluating the clinical and cost effectiveness of KardiaMobile six-lead, in the context of QT interval-based cardiac risk assessment for service users who require antipsychotic medication. The evidence to inform the aims of this early value assessment (i.e. to assess whether the device has the potential to be clinically effective and cost-effective) was also limited. This report includes a comprehensive list of research recommendations, both to reduce the uncertainty around this early value assessment and to provide the additional data needed to inform a full diagnostic assessment, including cost-effectiveness modelling. Study registration: This study is registered as PROSPERO CRD42022336695. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR135520) and is published in full in Health Technology Assessment; Vol. 28, No. 19. See the NIHR Funding and Awards website for further award information.

Some medicines used for people with certain mental health problems can increase the risk of developing serious heart conditions. Although these heart conditions are rare, it is generally recommended that people have an electrocardiogram examination before starting to take these medicines. People who need to continue these medications over a period of time may need additional electrocardiograms every so often, to check for any heart problems that have developed recently. KardiaMobile six-lead (or 6-lead) is a portable electrocardiogram that may offer a less intrusive way to take electrocardiogram measurements. This is because less undressing is needed as the electrodes are only applied to fingers of the left and right hand and the left ankle or knee and the cold gel is not needed. Testing using the KardiaMobile six-lead device can be carried out at the patient's home. These features might mean that the KardiaMobile six-lead device could be more acceptable than the 12-lead electrocardiogram to some patients. This assessment considered whether the KardiaMobile six-lead device has the potential to provide an effective and safe alternative to 12-lead electrocardiogram for initial assessment and monitoring of the risk of heart problems in people taking antipsychotic medications. Based on the available evidence, it remains unclear whether KardiaMobile six-lead has adequately demonstrated sufficient evidence of potential advantage(s) over current practice to justify further research to inform assessment of its clinical effectiveness and cost effectiveness. Our report provides detailed recommendations about the research needed, to provide further information about potential benefits so that a decision can be made about whether it should be used in the NHS in England, after further research has been completed.

Pralsetinib for RET Fusion-Positive Advanced Non-small-Cell Lung Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Roche) of pralsetinib (Gavreto®), as part of the single technology appraisal (STA) process, to submit evidence for the clinical effectiveness and cost effectiveness of pralsetinib for the treatment of adult patients with rearranged during transfection (RET) fusion-positive advanced non-small-cell lung cancer (NSCLC) not previously treated with a RET inhibitor. Kleijnen Systematic Reviews Ltd, in collaboration with University Medical Center Groningen, was commissioned to act as the independent Evidence Review Group (ERG). This paper summarizes the company submission (CS), presents the ERG's critical review of the clinical and cost-effectiveness evidence in the CS, highlights the key methodological considerations, and describes the development of the NICE guidance by the Appraisal Committee. The CS reported data from the ARROW trial. ARROW is a single-arm, multicenter, non-randomized, open-label, multi-cohort study in patients with RET fusion-positive NSCLC and other advanced solid tumors. The CS included both untreated and pre-treated RET fusion-positive NSCLC patients, among other disease types. The comparators in the untreated population were pembrolizumab + pemetrexed + chemotherapy and pembrolizumab monotherapy. The comparators for the pre-treated population were docetaxel monotherapy, docetaxel + nintedanib, and platinum-based chemotherapy ± pemetrexed. As no comparators were included in ARROW, an indirect treatment comparison was conducted to estimate relative effectiveness. The ERG's concerns included the immaturity of data, small sample size, and lack of comparative safety evidence. The ERG considers the clinical evidence presented to be insufficiently robust to inform the economic model. Even when all the ERG preferred assumptions were implemented in the model, uncertainty remained on a number of issues, such as the appropriateness of the hazard ratios and the methods and data used to derive them, long-term efficacy of pralsetinib, and direct evidence for health-related quality of life (HRQoL). NICE did not recommend pralsetinib within its marketing authorization for treating RET fusion-positive advanced non-small-cell lung cancer (NSCLC) in adults who have not had a RET inhibitor before. The uncertainty of the clinical evidence and the estimates of cost effectiveness were too high to be considered a cost-effective use of NHS resources. Therefore, pralsetinib was not recommended for routine use.

Fenfluramine for Treating Dravet Syndrome: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

Fenfluramine, tradename Fintepla®, was appraised within the National Institute for Health and Care Excellence (NICE) single technology appraisal (STA) process as Technology Appraisal 808. Within the STA process, the company (Zogenix International) provided NICE with a written submission and a mathematical health economic model, summarising the company's estimates of the clinical effectiveness and cost-effectiveness of fenfluramine for patients with Dravet syndrome (DS). This company submission (CS) was reviewed by an evidence review group (ERG) independent of NICE. The ERG, Kleijnen Systematic Reviews in collaboration with Maastricht University Medical Centre, produced an ERG report. This paper presents a summary of the ERG report and the development of the NICE guidance. The CS included a systematic review of the evidence for fenfluramine. From this review the company identified and presented evidence from two randomised trials (Study 1 and Study 1504), an open-label extension study (Study 1503) and 'real world evidence' from a prospective and retrospective study. Both randomised trials were conducted in patients up to 18 years of age with DS, whose seizures were incompletely controlled with previous anti-epileptic drugs. A Bayesian network meta-analysis was performed to compare fenfluramine with cannabidiol plus clobazam. There was no evidence of a difference between any doses of fenfluramine and cannabidiol in the mean convulsive seizure frequency (CSF) rate during treatment. However, fenfluramine increased the number of patients achieving ≥ 50% reduction in CSF frequency from baseline compared to cannabidiol. The company used an individual-patient state-transition model (R version 3.5.2) to model cost-effectiveness of fenfluramine. The CSF and convulsive seizure-free days were estimated using patient-level data from the placebo arm of the fenfluramine registration studies. Subsequently, a treatment effect of either fenfluramine or cannabidiol was applied. Utility values for the economic model were obtained by mapping Pediatric Quality of Life Inventory data from the registration studies to EuroQol-5D-3L Youth (EQ-5D-Y-3L). The company included caregiver utilities in their base-case, as the severe needs of patients with DS have a major impact on parents and caregivers. There were several key issues. First, the company included caregiver utilities in the model in a way that when patients in the economic model died, the corresponding caregiver utility was also set to zero. Second, the model was built in R statistical software, resulting in transparency issues. Third, the company assumed the same percentage reduction for convulsive seizure days as was estimated for CSF. Fourth, during the final appraisal committee meeting, influential changes were made to the model that were not in line with the ERG's preferences (but were accepted by the appraisal committee). The company's revised and final incremental cost effectiveness ratio (ICER) in line with committee preferences resulted in fenfluramine dominating cannabidiol. Fenfluramine was recommended as an add-on to other antiepileptic medicines for treating seizures associated with DS in people aged 2 years and older in the National Health Service (NHS).

Lack of Rigour in the Review. Comment on Kuligowski et al. Manual Therapy in Cervical and Lumbar Radiculopathy: A Systematic Review of the Literature. Int. J. Environ. Res. Public Health 2021, 18, 6176.

I read with interest the article by Kuligowski et al., 2021 published in the Journal [...].

Osteopathic Manipulative Treatment for Pediatric Conditions: An Update of Systematic Review and Meta-Analysis.

Osteopathic manipulative treatment (OMT) continues to be used for a range of diseases in children. OBJECTIVES: The aim of this paper is to update our previous systematic review (SR) initially published in 2013 by critically evaluating the evidence for or against this treatment. METHODS: Eleven databases were searched (January 2012 to November 2021). STUDY SELECTION AND DATA EXTRACTION: Only randomized clinical trials (RCTs) of OMT in pediatric patients compared with any type of controls were considered. The Cochrane risk-of-bias tool was used. In addition, the quality of the evidence was rated using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria, as recommended by the Cochrane Collaboration. RESULTS: Thirteen trials met the eligibility criteria, of which four could be subjected to a meta-analysis. The findings show that, in preterm infants, OMT has little or no effect on reducing the length of hospital stay (standardized mean difference (SMD) -0.03; 95% confidence interval (CI) -0.44 to 0.39; very low certainty of evidence) when compared with usual care alone. Only one study (8.3%) was judged to have a low risk of bias and showed no effects of OMT on improving exclusive breastfeeding at 1 month. The methodological quality of RCTs published since 2013 has improved. However, adverse effects remain poorly reported. CONCLUSIONS: The quality of the primary trials of OMT has improved during recent years. However, the quality of the totality of the evidence remains low or very low. Therefore, the effectiveness of OMT for selected pediatric populations remains unproven.

Lenalidomide with Rituximab for Previously Treated Follicular Lymphoma and Marginal Zone Lymphoma: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Celgene) of lenalidomide (Revlimid®), as part of the Single Technology Appraisal (STA) process, to submit evidence for the clinical effectiveness and cost-effectiveness of lenalidomide in combination with rituximab (MabThera®), together referred to as R2, for the treatment of adults with treated follicular lymphoma (FL) or marginal zone lymphoma (MZL). Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre+, was commissioned to act as the independent Evidence Review Group (ERG). This paper summarises the company submission (CS), presents the ERG's critical review on the clinical and cost-effectiveness evidence in the CS, highlights the key methodological considerations, and describes the development of the NICE guidance by the Appraisal Committee. The CS included one relevant study, for the comparison of R2 versus rituximab monotherapy (R-mono): the AUGMENT trial. In addition, the company performed an unanchored indirect comparison of R2 versus rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) and rituximab combined with cyclophosphamide, vincristine, and prednisolone (R-CVP), using data for R2 from the AUGMENT trial and pooled data for R-CHOP/R-CVP from the Haematological Malignancy Research Network (HMRN) database. During the STA process, the company provided an addendum containing evidence on only the FL population, in line with the marketing authorisation obtained at that time, which did not include MZL. The probabilistic incremental cost-effectiveness ratios (ICERs) presented by the company were £27,768 per quality-adjusted life year (QALY) gained for R2 versus R-CHOP, £41,602 per QALY gained for R2 versus R-CVP, and £23,412 per QALY gained for R2 versus R-mono. The ERG's concerns included the validity of the unanchored comparison, the unavailability of a state transition model to verify the outcomes of the partitioned survival model, substantial uncertainty in survival curves, and potential over-estimation of utility values. The revised ERG base case resulted in ICERs ranging from £16,874 to £44,888 per QALY gained for R2 versus R-CHOP, from £23,135 to £59,810 per QALY gained for R2 versus R-CVP, and from £18,779 to £27,156 per QALY gained for R2 versus R-mono. Substantial uncertainty remained around these ranges. NICE recommended R2 within its marketing authorisation, as an option for previously treated FL (grade 1-3A) in adults, contingent on the company providing lenalidomide according to the commercial arrangement.

Exercise/physical activity and health outcomes: an overview of Cochrane systematic reviews.

BACKGROUND: Sedentary lifestyle is a major risk factor for noncommunicable diseases such as cardiovascular diseases, cancer and diabetes. It has been estimated that approximately 3.2 million deaths each year are attributable to insufficient levels of physical activity. We evaluated the available evidence from Cochrane systematic reviews (CSRs) on the effectiveness of exercise/physical activity for various health outcomes. METHODS: Overview and meta-analysis. The Cochrane Library was searched from 01.01.2000 to issue 1, 2019. No language restrictions were imposed. Only CSRs of randomised controlled trials (RCTs) were included. Both healthy individuals, those at risk of a disease, and medically compromised patients of any age and gender were eligible. We evaluated any type of exercise or physical activity interventions; against any types of controls; and measuring any type of health-related outcome measures. The AMSTAR-2 tool for assessing the methodological quality of the included studies was utilised. RESULTS: Hundred and fifty CSRs met the inclusion criteria. There were 54 different conditions. Majority of CSRs were of high methodological quality. Hundred and thirty CSRs employed meta-analytic techniques and 20 did not. Limitations for studies were the most common reasons for downgrading the quality of the evidence. Based on 10 CSRs and 187 RCTs with 27,671 participants, there was a 13% reduction in mortality rates risk ratio (RR) 0.87 [95% confidence intervals (CI) 0.78 to 0.96]; I2 = 26.6%, [prediction interval (PI) 0.70, 1.07], median effect size (MES) = 0.93 [interquartile range (IQR) 0.81, 1.00]. Data from 15 CSRs and 408 RCTs with 32,984 participants showed a small improvement in quality of life (QOL) standardised mean difference (SMD) 0.18 [95% CI 0.08, 0.28]; I2 = 74.3%; PI -0.18, 0.53], MES = 0.20 [IQR 0.07, 0.39]. Subgroup analyses by the type of condition showed that the magnitude of effect size was the largest among patients with mental health conditions. CONCLUSION: There is a plethora of CSRs evaluating the effectiveness of physical activity/exercise. The evidence suggests that physical activity/exercise reduces mortality rates and improves QOL with minimal or no safety concerns. TRIAL REGISTRATION: Registered in PROSPERO ( CRD42019120295 ) on 10th January 2019.

Correction: Offline Digital Education for Postregistration Health Professions: Systematic Review and Meta-Analysis by the Digital Health Education Collaboration.

[This corrects the article DOI: 10.2196/12968.].

Effectiveness of Digital Education on Communication Skills Among Medical Students: Systematic Review and Meta-Analysis by the Digital Health Education Collaboration.

BACKGROUND: Effective communication skills are essential in diagnosis and treatment processes and in building the doctor-patient relationship. OBJECTIVE: Our aim was to evaluate the effectiveness of digital education in medical students for communication skills development. Broadly, we assessed whether digital education could improve the quality of future doctors' communication skills. METHODS: We performed a systematic review and searched seven electronic databases and two trial registries for randomized controlled trials (RCTs) and cluster RCTs (cRCTs) published between January 1990 and September 2018. Two reviewers independently screened the citations, extracted data from the included studies, and assessed the risk of bias. We also assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations assessment (GRADE). RESULTS: We included 12 studies with 2101 medical students, of which 10 were RCTs and two were cRCTs. The digital education included online modules, virtual patient simulations, and video-assisted oral feedback. The control groups included didactic lectures, oral feedback, standard curriculum, role play, and no intervention as well as less interactive forms of digital education. The overall risk of bias was high, and the quality of evidence ranged from moderate to very low. For skills outcome, meta-analysis of three studies comparing digital education to traditional learning showed no statistically significant difference in postintervention skills scores between the groups (standardized mean difference [SMD]=-0.19; 95% CI -0.9 to 0.52; I2=86%, N=3 studies [304 students]; small effect size; low-quality evidence). Similarly, a meta-analysis of four studies comparing the effectiveness of blended digital education (ie, online or offline digital education plus traditional learning) and traditional learning showed no statistically significant difference in postintervention skills between the groups (SMD=0.15; 95% CI -0.26 to 0.56; I2=86%; N=4 studies [762 students]; small effect size; low-quality evidence). The additional meta-analysis of four studies comparing more interactive and less interactive forms of digital education also showed little or no difference in postintervention skills scores between the two groups (SMD=0.12; 95% CI: -0.09 to 0.33; I2=40%; N=4 studies [893 students]; small effect size; moderate-quality evidence). For knowledge outcome, two studies comparing the effectiveness of blended online digital education and traditional learning reported no difference in postintervention knowledge scores between the groups (SMD=0.18; 95% CI: -0.2 to 0.55; I2=61%; N=2 studies [292 students]; small effect size; low-quality evidence). The findings on attitudes, satisfaction, and patient-related outcomes were limited or mixed. None of the included studies reported adverse outcomes or economic evaluation of the interventions. CONCLUSIONS: We found low-quality evidence showing that digital education is as effective as traditional learning in medical students' communication skills training. Blended digital education seems to be at least as effective as and potentially more effective than traditional learning for communication skills and knowledge. We also found no difference in postintervention skills between more and less interactive forms of digital education. There is a need for further research to evaluate the effectiveness of other forms of digital education such as virtual reality, serious gaming, and mobile learning on medical students' attitude, satisfaction, and patient-related outcomes as well as the adverse effects and cost-effectiveness of digital education.

Digital Education of Health Professionals on the Management of Domestic Violence: Systematic Review and Meta-Analysis by the Digital Health Education Collaboration.

BACKGROUND: The World Health Organization states that 35% of women experience domestic violence at least once during their lifetimes. However, approximately 80% of health professionals have never received any training on management of this major public health concern. OBJECTIVE: The objective of this study was to evaluate the effectiveness of health professions digital education on domestic violence compared to that of traditional ways or no intervention. METHODS: Seven electronic databases were searched for randomized controlled trials from January 1990 to August 2017. The Cochrane Handbook guideline was followed, and studies reporting the use of digital education interventions to educate health professionals on domestic violence management were included. RESULTS: Six studies with 631 participants met our inclusion criteria. Meta-analysis of 5 studies showed that as compared to control conditions, digital education may improve knowledge (510 participants and 5 studies; standardized mean difference [SMD] 0.67, 95% CI 0.38-0.95; I2=59%; low certainty evidence), attitudes (339 participants and 3 studies; SMD 0.67, 95% CI 0.25-1.09; I2=68%; low certainty evidence), and self-efficacy (174 participants and 3 studies; SMD 0.47, 95% CI 0.16-0.77; I2=0%; moderate certainty evidence). CONCLUSIONS: Evidence of the effectiveness of digital education on health professionals' understanding of domestic violence is promising. However, the certainty of the evidence is predominantly low and merits further research. Given the opportunity of scaled transformative digital education, both further research and implementation within an evaluative context should be prioritized.

Offline Digital Education for Postregistration Health Professions: Systematic Review and Meta-Analysis by the Digital Health Education Collaboration.

BACKGROUND: The shortage and disproportionate distribution of health care workers worldwide is further aggravated by the inadequacy of training programs, difficulties in implementing conventional curricula, deficiencies in learning infrastructure, or a lack of essential equipment. Offline digital education has the potential to improve the quality of health professions education. OBJECTIVE: The primary objective of this systematic review was to evaluate the effectiveness of offline digital education compared with various controls in improving learners' knowledge, skills, attitudes, satisfaction, and patient-related outcomes. The secondary objectives were (1) to assess the cost-effectiveness of the interventions and (2) to assess adverse effects of the interventions on patients and learners. METHODS: We searched 7 electronic databases and 2 trial registries for randomized controlled trials published between January 1990 and August 2017. We used Cochrane systematic review methods. RESULTS: A total of 27 trials involving 4618 individuals were included in this systematic review. Meta-analyses found that compared with no intervention, offline digital education (CD-ROM) may increase knowledge in nurses (standardized mean difference [SMD]=1.88; 95% CI 1.14 to 2.62; participants=300; studies=3; I2=80%; low certainty evidence). A meta-analysis of 2 studies found that compared with no intervention, the effects of offline digital education (computer-assisted training [CAT]) on nurses and physical therapists' knowledge were uncertain (SMD 0.55; 95% CI -0.39 to 1.50; participants=64; I2=71%; very low certainty evidence). A meta-analysis of 2 studies found that compared with traditional learning, a PowerPoint presentation may improve the knowledge of patient care personnel and pharmacists (SMD 0.76; 95% CI 0.29 to 1.23; participants=167; I2=54%; low certainty evidence). A meta-analysis of 4 studies found that compared with traditional training, the effects of computer-assisted training on skills in community (mental health) therapists, nurses, and pharmacists were uncertain (SMD 0.45; 95% CI -0.35 to 1.25; participants=229; I2=88%; very low certainty evidence). A meta-analysis of 4 studies found that compared with traditional training, offline digital education may have little effect or no difference on satisfaction scores in nurses and mental health therapists (SMD -0.07; 95% CI -0.42 to 0.28, participants=232; I2=41%; low certainty evidence). A total of 2 studies found that offline digital education may have little or no effect on patient-centered outcomes when compared with blended learning. For skills and attitudes, the results were mixed and inconclusive. None of the studies reported adverse or unintended effects of the interventions. Only 1 study reported costs of interventions. The risk of bias was predominantly unclear and the certainty of the evidence ranged from low to very low. CONCLUSIONS: There is some evidence to support the effectiveness of offline digital education in improving learners' knowledge and insufficient quality and quantity evidence for the other outcomes. Future high-quality studies are needed to increase generalizability and inform use of this modality of education.

Offline Digital Education for Medical Students: Systematic Review and Meta-Analysis by the Digital Health Education Collaboration.

BACKGROUND: Medical schools in low- and middle-income countries are facing a shortage of staff, limited infrastructure, and restricted access to fast and reliable internet. Offline digital education may be an alternative solution for these issues, allowing medical students to learn at their own time and pace, without the need for a network connection. OBJECTIVE: The primary objective of this systematic review was to assess the effectiveness of offline digital education compared with traditional learning or a different form of offline digital education such as CD-ROM or PowerPoint presentations in improving knowledge, skills, attitudes, and satisfaction of medical students. The secondary objective was to assess the cost-effectiveness of offline digital education, changes in its accessibility or availability, and its unintended/adverse effects on students. METHODS: We carried out a systematic review of the literature by following the Cochrane methodology. We searched seven major electronic databases from January 1990 to August 2017 for randomized controlled trials (RCTs) or cluster RCTs. Two authors independently screened studies, extracted data, and assessed the risk of bias. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations criteria. RESULTS: We included 36 studies with 3325 medical students, of which 33 were RCTs and three were cluster RCTs. The interventions consisted of software programs, CD-ROMs, PowerPoint presentations, computer-based videos, and other computer-based interventions. The pooled estimate of 19 studies (1717 participants) showed no significant difference between offline digital education and traditional learning groups in terms of students' postintervention knowledge scores (standardized mean difference=0.11, 95% CI -0.11 to 0.32; small effect size; low-quality evidence). Meta-analysis of four studies found that, compared with traditional learning, offline digital education improved medical students' postintervention skills (standardized mean difference=1.05, 95% CI 0.15-1.95; large effect size; low-quality evidence). We are uncertain about the effects of offline digital education on students' attitudes and satisfaction due to missing or incomplete outcome data. Only four studies estimated the costs of offline digital education, and none reported changes in accessibility or availability of such education or in the adverse effects. The risk of bias was predominantly high in more than half of the included studies. The overall quality of the evidence was low (for knowledge, skills, attitudes, and satisfaction) due to the study limitations and inconsistency across the studies. CONCLUSIONS: Our findings suggest that offline digital education is as effective as traditional learning in terms of medical students' knowledge and may be more effective than traditional learning in terms of medical students' skills. However, there is a need to further investigate students' attitudes and satisfaction with offline digital education as well as its cost-effectiveness, changes in its accessibility or availability, and any resulting unintended/adverse effects.

Digital Education in Health Professions: The Need for Overarching Evidence Synthesis.

Synthesizing evidence from randomized controlled trials of digital health education poses some challenges. These include a lack of clear categorization of digital health education in the literature; constantly evolving concepts, pedagogies, or theories; and a multitude of methods, features, technologies, or delivery settings. The Digital Health Education Collaboration was established to evaluate the evidence on digital education in health professions; inform policymakers, educators, and students; and ultimately, change the way in which these professionals learn and are taught. The aim of this paper is to present the overarching methodology that we use to synthesize evidence across our digital health education reviews and to discuss challenges related to the process. For our research, we followed Cochrane recommendations for the conduct of systematic reviews; all reviews are reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidance. This included assembling experts in various digital health education fields; identifying gaps in the evidence base; formulating focused research questions, aims, and outcome measures; choosing appropriate search terms and databases; defining inclusion and exclusion criteria; running the searches jointly with librarians and information specialists; managing abstracts; retrieving full-text versions of papers; extracting and storing large datasets, critically appraising the quality of studies; analyzing data; discussing findings; drawing meaningful conclusions; and drafting research papers. The approach used for synthesizing evidence from digital health education trials is commonly regarded as the most rigorous benchmark for conducting systematic reviews. Although we acknowledge the presence of certain biases ingrained in the process, we have clearly highlighted and minimized those biases by strictly adhering to scientific rigor, methodological integrity, and standard operating procedures. This paper will be a valuable asset for researchers and methodologists undertaking systematic reviews in digital health education.

Online Digital Education for Postregistration Training of Medical Doctors: Systematic Review by the Digital Health Education Collaboration.

BACKGROUND: Globally, online and local area network-based (LAN) digital education (ODE) has grown in popularity. Blended learning is used by ODE along with traditional learning. Studies have shown the increasing potential of these technologies in training medical doctors; however, the evidence for its effectiveness and cost-effectiveness is unclear. OBJECTIVE: This systematic review evaluated the effectiveness of online and LAN-based ODE in improving practicing medical doctors' knowledge, skills, attitude, satisfaction (primary outcomes), practice or behavior change, patient outcomes, and cost-effectiveness (secondary outcomes). METHODS: We searched seven electronic databased for randomized controlled trials, cluster-randomized trials, and quasi-randomized trials from January 1990 to March 2017. Two review authors independently extracted data and assessed the risk of bias. We have presented the findings narratively. We mainly compared ODE with self-directed/face-to-face learning and blended learning with self-directed/face-to-face learning. RESULTS: A total of 93 studies (N=16,895) were included, of which 76 compared ODE (including blended) and self-directed/face-to-face learning. Overall, the effect of ODE (including blended) on postintervention knowledge, skills, attitude, satisfaction, practice or behavior change, and patient outcomes was inconsistent and ranged mostly from no difference between the groups to higher postintervention score in the intervention group (small to large effect size, very low to low quality evidence). Twenty-one studies reported higher knowledge scores (small to large effect size and very low quality) for the intervention, while 20 studies reported no difference in knowledge between the groups. Seven studies reported higher skill score in the intervention (large effect size and low quality), while 13 studies reported no difference in the skill scores between the groups. One study reported a higher attitude score for the intervention (very low quality), while four studies reported no difference in the attitude score between the groups. Four studies reported higher postintervention physician satisfaction with the intervention (large effect size and low quality), while six studies reported no difference in satisfaction between the groups. Eight studies reported higher postintervention practice or behavior change for the ODE group (small to moderate effect size and low quality), while five studies reported no difference in practice or behavior change between the groups. One study reported higher improvement in patient outcome, while three others reported no difference in patient outcome between the groups. None of the included studies reported any unintended/adverse effects or cost-effectiveness of the interventions. CONCLUSIONS: Empiric evidence showed that ODE and blended learning may be equivalent to self-directed/face-to-face learning for training practicing physicians. Few other studies demonstrated that ODE and blended learning may significantly improve learning outcomes compared to self-directed/face-to-face learning. The quality of the evidence in these studies was found to be very low for knowledge. Further high-quality randomized controlled trials are required to confirm these findings.

Virtual Reality for Health Professions Education: Systematic Review and Meta-Analysis by the Digital Health Education Collaboration.

BACKGROUND: Virtual reality (VR) is a technology that allows the user to explore and manipulate computer-generated real or artificial three-dimensional multimedia sensory environments in real time to gain practical knowledge that can be used in clinical practice. OBJECTIVE: The aim of this systematic review was to evaluate the effectiveness of VR for educating health professionals and improving their knowledge, cognitive skills, attitudes, and satisfaction. METHODS: We performed a systematic review of the effectiveness of VR in pre- and postregistration health professions education following the gold standard Cochrane methodology. We searched 7 databases from the year 1990 to August 2017. No language restrictions were applied. We included randomized controlled trials and cluster-randomized trials. We independently selected studies, extracted data, and assessed risk of bias, and then, we compared the information in pairs. We contacted authors of the studies for additional information if necessary. All pooled analyses were based on random-effects models. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to rate the quality of the body of evidence. RESULTS: A total of 31 studies (2407 participants) were included. Meta-analysis of 8 studies found that VR slightly improves postintervention knowledge scores when compared with traditional learning (standardized mean difference [SMD]=0.44; 95% CI 0.18-0.69; I2=49%; 603 participants; moderate certainty evidence) or other types of digital education such as online or offline digital education (SMD=0.43; 95% CI 0.07-0.79; I2=78%; 608 participants [8 studies]; low certainty evidence). Another meta-analysis of 4 studies found that VR improves health professionals' cognitive skills when compared with traditional learning (SMD=1.12; 95% CI 0.81-1.43; I2=0%; 235 participants; large effect size; moderate certainty evidence). Two studies compared the effect of VR with other forms of digital education on skills, favoring the VR group (SMD=0.5; 95% CI 0.32-0.69; I2=0%; 467 participants; moderate effect size; low certainty evidence). The findings for attitudes and satisfaction were mixed and inconclusive. None of the studies reported any patient-related outcomes, behavior change, as well as unintended or adverse effects of VR. Overall, the certainty of evidence according to the GRADE criteria ranged from low to moderate. We downgraded our certainty of evidence primarily because of the risk of bias and/or inconsistency. CONCLUSIONS: We found evidence suggesting that VR improves postintervention knowledge and skills outcomes of health professionals when compared with traditional education or other types of digital education such as online or offline digital education. The findings on other outcomes are limited. Future research should evaluate the effectiveness of immersive and interactive forms of VR and evaluate other outcomes such as attitude, satisfaction, cost-effectiveness, and clinical practice or behavior change.

Digital Education for Health Professions in the Field of Dermatology: A Systematic Review by Digital Health Education Collaboration.

Digital health education is a new approach that is receiving increasing attention with advantages such as scalability and flexibility of education. This study employed a Cochrane review approach to assess the evidence for the effectiveness of health professions' digital education in dermatology to improve knowledge, skills, attitudes and satisfaction. Twelve trials (n = 955 health professionals) met our eligibility criteria. Nine studies evaluated knowledge; of those two reported that digital education improved the outcome. Five studies evaluated skill; of those 3 studies stated that digital education improved this outcome whereas 2 showed no difference when compared with control. Of the 5 studies measuring learners' satisfaction, 3 studies claimed high satisfaction scores. Two studies reported that when compared with traditional education, digital education had little effect on satisfaction. The evidence for the effectiveness of digital health education in dermatology is mixed and the overall findings are inconclusive, mainly because of the predominantly very low quality of the evidence. More methodologically robust research is needed to further inform clinicians and policymakers.

Choice of outcomes and measurement instruments in randomised trials on eLearning in medical education: a systematic mapping review protocol.

BACKGROUND: There will be a lack of 18 million healthcare workers by 2030. Multiplying the number of well-trained healthcare workers through innovative ways such as eLearning is highly recommended in solving this shortage. However, high heterogeneity of learning outcomes in eLearning systematic reviews reveals a lack of consistency and agreement on core learning outcomes in eLearning for medical education. In addition, there seems to be a lack of validity evidence for measurement instruments used in these trials. This undermines the credibility of these outcome measures and affects the ability to draw accurate and meaningful conclusions. The aim of this research is to address this issue by determining the choice of outcomes, measurement instruments and the prevalence of measurement instruments with validity evidence in randomised trials on eLearning for pre-registration medical education. METHODS: We will conduct a systematic mapping and review to identify the types of outcomes, the kinds of measurement instruments and the prevalence of validity evidence among measurement instruments in eLearning randomised controlled trials (RCTs) in pre-registration medical education. The search period will be from January 1990 until August 2017. We will consider studies on eLearning for health professionals' education. Two reviewers will extract and manage data independently from the included studies. Data will be analysed and synthesised according to the aim of the review. DISCUSSION: Appropriate choice of outcomes and measurement tools is essential for ensuring high-quality research in the field of eLearning and eHealth. The results of this study could have positive implications for other eHealth interventions, including (1) improving quality and credibility of eLearning research, (2) enhancing the quality of digital medical education and (3) informing researchers, academics and curriculum developers about the types of outcomes and validity evidence for measurement instruments used in eLearning studies. The protocol aspires to assist in the advancement of the eLearning research field as well as in the development of high-quality healthcare professionals' digital education. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017068427.

Light Therapies for Acne.

Clinical Question: Are light therapies effective and safe for treating acne? Bottom Line: The evidence for all light therapies remains weak and inconclusive. Red-light methyl aminolevulinate-photodynamic therapy (MAL-PDT) was the only treatment associated with a small though clinically insignificant reduction in the number of inflamed lesions and in global improvement as assessed by an investigator in moderate to severe acne. Red-light MAL-PDT was not associated with higher rates of severe adverse effects than placebo or no treatment. Owing to inadequate reporting of adverse effects such as scarring or blistering, the safety of all light therapies remains uncertain.

Melatonin and health: an umbrella review of health outcomes and biological mechanisms of action.

BACKGROUND: Our aims were to evaluate critically the evidence from systematic reviews as well as narrative reviews of the effects of melatonin (MLT) on health and to identify the potential mechanisms of action involved. METHODS: An umbrella review of the evidence across systematic reviews and narrative reviews of endogenous and exogenous (supplementation) MLT was undertaken. The Oxman checklist for assessing the methodological quality of the included systematic reviews was utilised. The following databases were searched: MEDLINE, EMBASE, Web of Science, CENTRAL, PsycINFO and CINAHL. In addition, reference lists were screened. We included reviews of the effects of MLT on any type of health-related outcome measure. RESULTS: Altogether, 195 reviews met the inclusion criteria. Most were of low methodological quality (mean -4.5, standard deviation 6.7). Of those, 164 did not pool the data and were synthesised narratively (qualitatively) whereas the remaining 31 used meta-analytic techniques and were synthesised quantitatively. Seven meta-analyses were significant with P values less than 0.001 under the random-effects model. These pertained to sleep latency, pre-operative anxiety, prevention of agitation and risk of breast cancer. CONCLUSIONS: There is an abundance of reviews evaluating the effects of exogenous and endogenous MLT on health. In general, MLT has been shown to be associated with a wide variety of health outcomes in clinically and methodologically heterogeneous populations. Many reviews stressed the need for more high-quality randomised clinical trials to reduce the existing uncertainties.