Clinical RNA sequencing clarifies variants of uncertain significance identified by prior testing.

Purpose: Sequencing-based genetic testing often identifies variants of uncertain significance (VUS) or fails to detect pathogenic variants altogether. We evaluated the utility of RNA sequencing (RNA-seq) to clarify VUS or identify missing variants in a clinical setting. Methods: Over a 2-year period, genetics providers at a single institution referred 26 cases for clinical RNA-seq. Cases had either no candidate variant identified by prior testing or a VUS suspected to impact splicing or expression. A committee reviewed each submission to ensure it met study criteria. Results: Among 26 cases, 8 could not be sequenced because of poor expression in an accessible tissue, 2 did not meet inclusion criteria, 3 were solved prior to collection, and 4 families declined participation or did not complete sample collection. For the 9 cases sequenced, the clinical laboratory reported two positive, four negative, and three "indeterminate." For all three indeterminate cases, original RNA-seq data was manually evaluated and deemed explanatory. Conclusion: Clinical RNA-seq can clarify VUS, especially splice variants, but laboratory-specific interpretation guidelines may lead to indeterminate results. Identifying individuals likely to benefit from RNA-seq and providing appropriate counseling poses unique challenges.

Telehealth versus face-to-face delivery of speech language pathology services: A systematic review and meta-analysis.

BACKGROUND: There is an increasing demand for the provision of speech language pathology (SLP) services via telehealth. Therefore, we systematically reviewed randomized controlled trials comparing telehealth to face-to-face provision of SLP services. METHODS: We searched Medline, Embase and Cochrane, clinical trial registries, and conducted a citation analysis to identify trials. We included randomized trials comparing similar care delivered live via telehealth (phone or video), to face-to-face. Primary outcomes included: % syllables stuttered (%SS) (for individuals who stutter); change in sound pressure levels monologue (for individuals with Parkinson's disease); and key function scores (for other areas). Where data were sufficient, mean differences were calculated. RESULTS: Nine randomized controlled trials were included; eight evaluated video and one evaluated phone telehealth. Risk of bias was generally low or unclear, excepting blinding. There were no significant differences at any time-point up to 18 months for %SS (mean difference, MD 0.1, 95% CI -0.4 to 0.6, p = 0.70). For people with Parkinson's disease, there was no difference between groups in change in sound pressure levels (monologue) (MD 0.6, 95% CI -1.2 to 2.5, p = 0.49). Four trials investigated interventions for speech sound disorder, voice disorder and post-stroke dysphagia and aphasia; they found no differences between telehealth service delivery and face-to-face delivery. CONCLUSIONS: Evidence suggests that the telehealth provision of SLP services may be a viable alternative to their provision face-to-face, particularly to people who stutter and people with Parkinson's disease. The key limitation is the small number of randomized controlled trials, as well as evidence on the quality of life, well-being and satisfaction and economic outcomes.

Perceptions of genomic newborn screening: a cross-sectional survey conducted with UK medical students.

BACKGROUND: With the potential to identify a vast number of rare diseases soon after birth, genomic newborn screening (gNBS) could facilitate earlier interventions and improve health outcomes. Designing a gNBS programme will involve balancing stakeholders' opinions and addressing concerns. The views of medical students-future clinicians who would deliver gNBS-have not yet been explored. METHODS: We conducted a nationwide online survey of UK medical students via the REDCap platform. Perceptions of gNBS, including scope of testing and potential benefits and drawbacks, were explored using a mix of multiple-choice questions, Likert scales, visual analogue scales and free-text questions. RESULTS: In total, 116 medical students across 16 universities participated. Overall, 45% supported gNBS, with a positively skewed mean support score of 3.24 (SD 1.26, range: 1.0-5.0), and 55% felt it relevant to their future practice. Almost all agreed that infant-onset and childhood-onset diseases and conditions with effective treatments should be included. Most felt that earlier interventions and personalised care would be the most important benefit of gNBS. Other perceived benefits included earlier diagnoses, diagnosing more patients and enabling research for new treatments. However, several perceived challenges were highlighted: risk of genomic discrimination, incidental or uncertain findings, data security and breaching children's future autonomy. Students expressed conflicting opinions on the psychological impact on families, but most were concerned about a lack of support due to current resource limitations in health services. Students frequently reported having insufficient knowledge to form an opinion, which may reflect gaps in genomics education at medical school and the current lack of evidence base for gNBS. CONCLUSION: Although some support for gNBS was demonstrated, ethicolegal and social challenges were raised, emphasising a need for ongoing discussions about the implications of gNBS.

Diagnostic Assessment via Live Telehealth (Phone or Video) Versus Face-to-Face for the Diagnoses of Psychiatric Conditions: A Systematic Review.

Objective: To determine the validity of telephone or video interviews, compared to face-to-face, for psychiatric diagnosis.Data Sources: We searched MEDLINE, Embase, and PsycINFO from inception to June 22, 2023, and performed backward and forward citation analysis on all included studies on August 3, 2023.Study Selection: We included primary studies comparing live telehealth (via telephone or videoconferencing) with face-to-face interviews using the same standardized diagnostic criteria for a mental health condition. Each patient had to undergo both modes of interviewing. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2.Results: This review included 35 studies. Seven are clinical studies that compare telehealth with face-to-face consultations for initial psychiatric diagnosis; telehealth via video or telephone is a reliable alternative for some specific disorders or for use in some specific populations that were studied. The other 28 studies compared telehealth to face-to-face interviews for the use of mental health standardized diagnostic instruments for a broad range of conditions, including depression, bipolar disorder, posttraumatic stress disorder, social anxiety disorder, and autism spectrum disorder, demonstrating good agreement and reliability. Telehealth holds promise for psychiatric assessments, especially when in-person evaluations are not feasible.Conclusions: From the limited studies primarily conducted before the expansion of telehealth during the COVID-19 pandemic, several small studies suggest that telehealth's psychiatric diagnoses or assessments of various psychiatric conditions seem to be a viable option and should be considered for certain patients during situations, settings, or environments. More research is needed, as telehealth has become more broadly utilized.

Sphingosine-1-Phosphate-Cathelicidin Axis Plays a Pivotal Role in the Development of Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer caused by mutagenesis resulting from excess UVR or other types of oxidative stress. These stressors also upregulate the production of a cutaneous innate immune element, cathelicidin antimicrobial peptide (CAMP), through endoplasmic reticulum stress-initiated, sphingosine-1-phosphate (S1P) signaling pathway. Although CAMP has beneficial antimicrobial activities, it also can be proinflammatory and procarcinogenic. We addressed whether and how S1P-induced CAMP production leads to cSCC development. Our study demonstrated that (i) CAMP expression is increased in cSCC cells and skin from patients with cSCC; (ii) S1P levels are elevated in cSCC cells, whereas inhibition of S1P production attenuates CAMP-stimulated cSCC growth; (iii) exogenous CAMP stimulates cSCC but not normal human keratinocyte growth; (iv) blockade of FPRL1 protein, a CAMP receptor, attenuates cSCC growth as well as the growth and invasion of cSCC cells mediated by CAMP into an extracellular matrix-containing fibroblast substrate; (v) FOXP3+ regulatory T-cell (which decreases antitumor immunity) levels increase in cSCC skin; and (vi) CAMP induces endoplasmic reticulum stress in cSCC cells. Together, the endoplasmic reticulum stress-S1P-CAMP axis forms a vicious circle, creating a favorable environment for cSCC development, that is, cSCC growth and invasion impede anticancer immunity.

Tools, techniques, methods, and processes for the detection and mitigation of fraudulent or erroneous data in evidence synthesis: a scoping review protocol.

OBJECTIVE: This scoping review aims to identify, catalogue, and characterize previously reported tools, techniques, methods, and processes that have been recommended or used by evidence synthesizers to detect fraudulent or erroneous data and mitigate its impact. INTRODUCTION: Decision-making for policy and practice should always be underpinned by the best available evidence-typically peer-reviewed scientific literature. Evidence synthesis literature should be collated and organized using the appropriate evidence synthesis methodology, best exemplified by the role systematic reviews play in evidence-based health care. However, with the rise of "predatory journals," fraudulent or erroneous data may be invading this literature, which may negatively affect evidence syntheses that use this data. This, in turn, may compromise decision-making processes. INCLUSION CRITERIA: This review will include peer-reviewed articles, commentaries, books, and editorials that describe at least 1 tool, technique, method, or process with the explicit purpose of identifying or mitigating the impact of fraudulent or erroneous data for any evidence synthesis, in any topic area. Manuals, handbooks, and guidance from major organizations, universities, and libraries will also be considered. METHODS: This review will be conducted using the JBI methodology for scoping reviews and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Databases and relevant organizational websites will be searched for eligible studies. Title and abstract, and subsequently full-text screening will be conducted in duplicate using Covidence. Data from identified full texts will be extracted using a pre-determined checklist, while the findings will be summarized descriptively and presented in tables. THIS SCOPING REVIEW PROTOCOL WAS REGISTERED IN OPEN SCIENCE FRAMEWORK: https://osf.io/u8yrn.

Reduction of neuroinflammation and seizures in a mouse model of CLN1 batten disease using the small molecule enzyme mimetic, N-Tert-butyl hydroxylamine.

Infantile neuronal ceroid lipofuscinosis (CLN1 Batten Disease) is a devastating pediatric lysosomal storage disease caused by pathogenic variants in the CLN1 gene, which encodes the depalmitoylation enzyme, palmitoyl-protein thioesterase 1 (PPT1). CLN1 patients present with visual deterioration, psychomotor dysfunction, and recurrent seizures until neurodegeneration results in death, typically before fifteen years of age. Histopathological features of CLN1 include aggregation of lysosomal autofluorescent storage material (AFSM), as well as profound gliosis. The current management of CLN1 is relegated to palliative care. Here, we examine the therapeutic potential of a small molecule PPT1 mimetic, N-tert-butyl hydroxylamine (NtBuHA), in a Cln1-/- mouse model. Treatment with NtBuHA reduced AFSM accumulation both in vitro and in vivo. Importantly, NtBuHA treatment in Cln1-/- mice reduced neuroinflammation, mitigated epileptic episodes, and normalized motor function. Live cell imaging of Cln1-/- primary cortical neurons treated with NtBuHA partially rescued aberrant synaptic calcium dynamics, suggesting a potential mechanism contributing to the therapeutic effects of NtBuHA in vivo. Taken together, our findings provide supporting evidence for NtBuHA as a potential treatment for CLN1 Batten Disease.

Leadership development programmes in healthcare research: a systematic review, meta-analysis and meta-aggregation.

BACKGROUND: Academic institutions benefit from researchers adopting leadership positions and, subsequently, leadership development programmes are of increasing importance. Despite this, no evaluation of the evidence basis for leadership development programmes for healthcare researchers has been conducted. In this study, the authors reviewed leadership development programmes for healthcare researchers and aimed to identify their impact and the factors which influenced this impact. METHODS: The authors searched MEDLINE, EMBASE, CINAHL and PsycINFO between January 2000 and January 2023 for evaluations of leadership development programmes with healthcare researchers. The authors synthesised results through exploratory meta-analysis and meta-aggregation and used the Medical Education Research Study Quality Instrument (MERSQI) and Joanna Briggs Institute (JBI) Checklist for Qualitative Studies to identify higher-reliability studies. RESULTS: 48 studies met inclusion criteria, of which approximately half (22) met the criteria for higher reliability. The median critical appraisal score was 10.5/18 for the MERSQI and 3.5/10 for the JBI. Common causes of low study quality appraisal related to study design, data analysis and reporting. Evaluations principally consisted of questionnaires measuring self-assessed outcomes. Interventions were primarily focused on junior academics. Overall, 163/168 categorised programme outcomes were positive. Coaching, experiential learning/project work and mentoring were associated with increased organisational outcomes. CONCLUSION: Educational methods appeared to be more important for organisational outcomes than specific educational content. To facilitate organisational outcomes, educational methods should include coaching, project work and mentoring. Programmes delivered by external faculty were less likely to be associated with organisational outcomes than those with internal or mixed faculty, but this needs further investigation. Finally, improving evaluation design will allow educators and evaluators to more effectively understand factors which are reliably associated with organisational outcomes of leadership development.

Cranberry Juice, Cranberry Tablets, or Liquid Therapies for Urinary Tract Infection: A Systematic Review and Network Meta-analysis.

BACKGROUND AND OBJECTIVE: With over 50% of women suffering from at least one episode of urinary tract infection (UTI) each year and an increasing prevalence of antimicrobial resistance, efforts need to be made to clearly identify the evidence supporting potential non-drug interventions. This study aims to compare the effects of cranberry juice, cranberry tablets, and increased liquids for the management of UTIs. METHODS: PubMed, Embase, and Cochrane CENTRAL were searched for randomised controlled trials. The primary outcome was the number of UTIs, and the secondary outcomes were UTI symptoms and antimicrobial consumption. A risk of bias assessment was performed using the Cochrane risk of bias tool, and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. KEY FINDINGS AND LIMITATIONS: A total of 20 trials (3091 participants) were included, with 18 studies highlighting a 54% lower rate of UTIs with cranberry juice consumption than no treatment and a 27% lower rate than placebo liquid. Cranberry juice also resulted in a 49% lower rate of antibiotic use than placebo liquid and a 59% lower rate than no treatment, based on a network meta-analysis of six studies. The use of cranberry compounds also reduced the prevalence of symptoms associated with UTIs. CONCLUSIONS AND CLINICAL IMPLICATIONS: With moderate to low certainty, the evidence supports the use of cranberry juice for the prevention of UTIs. While increased liquids reduce the rate of UTIs compared with no treatment, cranberry in liquid form provides even better clinical outcomes in terms of reduction in UTIs and antibiotic use and should be considered for the management of UTIs. PATIENT SUMMARY: With the increasing prevalence of antimicrobial-resistant UTIs, alternate non-drug treatment options for its management are required. Available evidence supports the use of cranberry compounds and increases in fluid intake for managing UTIs.

The impact of telehealth care on escalation to emergency care: A systematic review and meta-analysis.

OBJECTIVE: We compared the impact of accessing healthcare (1) by telehealth (via telephone or video) vs face-to-face; and (2) by telephone vs video telehealth care, on escalation to emergency care. METHODS: We searched Medline, Embase and Cochrane CENTRAL to 24 July 2023; and conducted a citation analysis on 19 September 2023. We included randomised controlled trials. Risk of bias was assessed using Cochrane Tool 2. We calculated risk ratios for dichotomous outcomes and standardised mean difference for continuous outcomes. RESULTS: Ten trials compared telehealth (five telephone, four video, one both) to face-to-face care. Six were overall low, three some concerns and one high risk of bias. There were no differences between telehealth and face-to-face for visits to the emergency department (RR 1.07, 95% CI 0.89 to 1.29), hospitalisations up to 12 months (RR 0.89, 95% CI 0.56 to 1.41), deaths or other adverse events. Costs of care were similar, as were patient satisfaction scores.Six trials compared telephone to video telehealth: three were overall low, two some concerns, and one high risk of bias. There were no differences between telephone and video for visits to the emergency department (RR 0.67, 95% CI 0.41 to 1.12), hospitalisations (RR 1.04, 95% CI 0.73 to 1.48), deaths, other adverse events, costs, or patient satisfaction. Healthcare provider satisfaction was high. CONCLUSIONS: Telehealth care - delivered by telephone or by video - may be an appropriate alternative to face-to-face provision of care, as it does not increase the likelihood of escalation of care to the emergency department for patients in primary care, hospital outpatients, post-discharge patients or residents in aged care.

Anti-inflammatories as adjunct treatment for cellulitis: a systematic review and meta-analysis.

OBJECTIVES: Existing guideline recommendations suggest considering corticosteroids for adjunct treatment of cellulitis, but this is based on a single trial with low certainty of evidence. The objective was to determine if anti-inflammatory medication (non-steroidal anti-inflammatory drugs [NSAIDs], corticosteroids) as adjunct cellulitis treatment improves clinical response and cure. METHODS: Systematic review and meta-analysis including randomized controlled trials of patients with cellulitis treated with antibiotics irrespective of age, gender, severity and setting, and an intervention of anti-inflammatories (NSAIDs or corticosteroids) vs. placebo or no intervention. Medline (PubMed), Embase (via Elsevier), and Cochrane CENTRAL were searched from inception to August 1, 2023. Data extraction was conducted independently in pairs. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2. Data were pooled using a random effects model. Primary outcomes are time to clinical response and cure. RESULTS: Five studies (n = 331) were included, all were adults. Three trials reported time to clinical response. There was a benefit with use of an oral NSAID as adjunct therapy at day 3 (risk ratio 1.81, 95%CI 1.42-2.31, I2 = 0%). There was no difference between groups at day 5 (risk ratio 1.19, 95%CI 0.62-2.26), although heterogeneity was high (I2 = 96%). Clinical cure was reported by three trials, and there was no difference between groups at all timepoints up to 22 days. Statistical heterogeneity was moderate to low. Adverse events (N = 3 trials) were infrequent. CONCLUSIONS: For patients with cellulitis, the best available data suggest that oral nonsteroidal anti-inflammatory drugs (NSAIDs) as adjunct therapy to antibiotics may lead to improved early clinical response, although this is not sustained beyond 4 days. There is insufficient data to comment on the role of corticosteroids for clinical response. These results must be interpreted with caution due to the small number of included studies. REGISTRATION: Open Science Framework:   https://osf.io/vkxae?view_only=fb4f8ca438a048cb9ca83c5f47fd4d81 .

RéSUMé: OBJECTIFS: Les recommandations existantes suggèrent d'envisager des corticostéroïdes pour le traitement complémentaire de la cellulite, mais cela est basé sur un seul essai avec une faible certitude des preuves. L'objectif était de déterminer si les anti-inflammatoires (anti-inflammatoires non stéroïdiens [AINS], corticostéroïdes) comme traitement d'appoint de la cellulite améliorent la réponse clinique et la guérison. MéTHODES: Revue systématique et méta-analyse comprenant des essais contrôlés randomisés de patients atteints de cellulite traités avec des antibiotiques, indépendamment de l'âge, du sexe, de la gravité et du contexte, et une intervention d'anti-inflammatoires (AINS ou corticostéroïdes) contre placebo ou sans intervention. Medline (PubMed), Embase (via Elsevier) et Cochrane CENTRAL ont été recherchés de la création au 1er août 2023. L'extraction des données a été effectuée indépendamment par paires. Le risque de biais a été évalué à l'aide de l'outil Cochrane sur le risque de biais 2. Les données ont été regroupées à l'aide d'un modèle à effets aléatoires. Les principaux résultats sont le temps de réponse clinique et de guérison. RéSULTATS: Cinq études (n = 331) ont été incluses, toutes des études adultes. Trois essais ont indiqué le délai de réponse clinique. Il y avait un avantage avec l'utilisation d'un AINS par voie orale comme traitement d'appoint au jour 3 (risque ratio 1,81, 95%CI 1,42 à 2,31, I2 = 0%). Il n'y avait pas de différence entre les groupes au jour 5 (rapport de risque 1,19, IC à 95% 0,62 à 2,26), bien que l'hétérogénéité était élevée (I2 = 96 %). La guérison clinique a été rapportée par trois essais, et il n'y avait aucune différence entre les groupes à tous les points de temps jusqu'à 22 jours. L'hétérogénéité statistique était modérée à faible. Les événements indésirables (N = 3 essais) étaient peu fréquents. CONCLUSIONS: Pour les patients atteints de cellulite, les meilleures données disponibles suggèrent que les anti-inflammatoires non stéroïdiens oraux (AINS) comme traitement d'appoint aux antibiotiques peuvent entraîner une amélioration de la réponse clinique précoce, bien que cela ne soit pas soutenu au-delà de quatre jours. Les données sont insuffisantes pour commenter le rôle des corticostéroïdes dans la réponse clinique. Ces résultats doivent être interprétés avec prudence en raison du petit nombre d'études incluses. ENREGISTREMENT: Cadre de la science ouverte:   https://osf.io/vkxae?view_only=fb4f8ca438a048cb9ca83c5f47fd4d81 .

Preparing tomorrow's doctors for the genomics era: A nationwide survey of UK medical students.

Introduction: Low confidence in genomics knowledge among clinicians is a major barrier to the integration of genomics into mainstream medicine. Here, we assessed the genomics confidence of UK medical students approaching graduation. Methods: We conducted a web-based nationwide survey of UK medical students in the final 2 years of study where participants rated their confidence in genomics concepts. Results: In total, 145 medical students across 19 medical schools participated. The amount of genomics teaching students reported receiving was positively associated with genomics confidence, with the amount of basic science teaching having the strongest influence. While confidence was high in core genomics principles, such as the difference between DNA, genes and chromosomes (95%), confidence dropped in clinical applications of genomics - only 50% reported a good understanding of the genetic contribution to disease and 28% reported good knowledge of clinically used genomic tests. Overall, 59% reported a poor understanding of variant interpretation; however, over half who reported receiving 'lots' of genomic medicine teaching reported a good understanding of this topic. Conclusion: Gaps in genomics knowledge and drivers in confidence have been identified herein, highlighting the need for improvements in undergraduate genomics education to prepare future doctors to confidently practise in the genomics era.

Cardiovascular disease risk communication and prevention: a meta-analysis.

BACKGROUND AND AIMS: Knowledge of quantifiable cardiovascular disease (CVD) risk may improve health outcomes and trigger behavioural change in patients or clinicians. This review aimed to investigate the impact of CVD risk communication on patient-perceived CVD risk and changes in CVD risk factors. METHODS: PubMed, Embase, and PsycINFO databases were searched from inception to 6 June 2023, supplemented by citation analysis. Randomized trials that compared any CVD risk communication strategy versus usual care were included. Paired reviewers independently screened the identified records and extracted the data; disagreements were resolved by a third author. The primary outcome was the accuracy of risk perception. Secondary outcomes were clinician-reported changes in CVD risk, psychological responses, intention to modify lifestyle, and self-reported changes in risk factors and clinician prescribing of preventive medicines. RESULTS: Sixty-two trials were included. Accuracy of risk perception was higher among intervention participants (odds ratio = 2.31, 95% confidence interval = 1.63 to 3.27). A statistically significant improvement in overall CVD risk scores was found at 6-12 months (mean difference = -0.27, 95% confidence interval = -0.45 to -0.09). For primary prevention, risk communication significantly increased self-reported dietary modification (odds ratio = 1.50, 95% confidence interval = 1.21 to 1.86) with no increase in intention or actual changes in smoking cessation or physical activity. A significant impact on patients' intention to start preventive medication was found for primary and secondary prevention, with changes at follow-up for the primary prevention group. CONCLUSIONS: In this systematic review and meta-analysis, communicating CVD risk information, regardless of the method, reduced the overall risk factors and enhanced patients' self-perceived risk. Communication of CVD risk to patients should be considered in routine consultations.

Predatory journals and their practices present a conundrum for systematic reviewers and evidence synthesisers of health research: A qualitative descriptive study.

Predatory journals are a blemish on scholarly publishing and academia and the studies published within them are more likely to contain data that is false. The inclusion of studies from predatory journals in evidence syntheses is potentially problematic due to this propensity for false data to be included. To date, there has been little exploration of the opinions and experiences of evidence synthesisers when dealing with predatory journals in the conduct of their evidence synthesis. In this paper, the thoughts, opinions, and attitudes of evidence synthesisers towards predatory journals and the inclusion of studies published within these journals in evidence syntheses were sought. Focus groups were held with participants who were experienced evidence synthesisers from JBI (previously the Joanna Briggs Institute) collaboration. Utilising qualitative content analysis, two generic categories were identified: predatory journals within evidence synthesis, and predatory journals within academia. Our findings suggest that evidence synthesisers believe predatory journals are hard to identify and that there is no current consensus on the management of these studies if they have been included in an evidence synthesis. There is a critical need for further research, education, guidance, and development of clear processes to assist evidence synthesisers in the management of studies from predatory journals.

The 2-week systematic review (2weekSR) method was successfully blind-replicated by another team: a case study.

OBJECTIVE: To assess the replicability of a 2-week systematic review (index 2weekSR) created with the assistance of automation tools using the fidelity method. METHODS: A Preferred Reporting Items for Systematic reviews and Meta-Analyses compliant SR protocol was developed based on the published information of the index 2weekSR study. The replication team consisted of three reviewers. Two reviewers blocked off time during the replication. The total time to complete tasks and the meta-analysis results were compared with the index 2weekSR study. Review process fidelity scores (FSs) were calculated for review methods and outcomes. Barriers to completing the replication were identified. RESULTS: The review was completed over 63 person-hours (11 workdays/15 calendar days). A FS of 0.95 was achieved for the methods, with 3 (of 8) tasks only partially replicated, and an FS of 0.63 for the outcomes, with 6 (of 7) only partially replicated and one task was not replicated. Nonreplication was mainly caused by missing information in the index 2weekSR study that was not required in standard reporting guidelines. The replication arrived at the same conclusions as the original study. CONCLUSION: A 2weekSR study was replicated by a small team of three reviewers supported by automation tools. Including additional information when reporting SRs should improve their replicability.

CLN2 disease resulting from a novel homozygous deep intronic splice variant in TPP1 discovered using long-read sequencing.

Neuronal ceroid lipofuscinosis type 2 (CLN2) is an autosomal recessive neurodegenerative disorder with enzyme replacement therapy available. We present two siblings with a clinical diagnosis of CLN2 disease, but no identifiable TPP1 variants after standard clinical testing. Long-read sequencing identified a homozygous deep intronic variant predicted to affect splicing, confirmed by clinical DNA and RNA sequencing. This case demonstrates how traditional laboratory assays can complement emerging molecular technologies to provide a precise molecular diagnosis.

Comparison of Telephone and Video Telehealth Consultations: Systematic Review.

BACKGROUND: Telehealth has been used for health care delivery for decades, but the COVID-19 pandemic greatly accelerated the uptake of telehealth in many care settings globally. However, few studies have carried out a direct comparison among different telehealth modalities, with very few studies having compared the effectiveness of telephone and video telehealth modalities. OBJECTIVE: This study aimed to identify and synthesize randomized controlled trials (RCTs) comparing synchronous telehealth consultations delivered by telephone and those conducted by video with outcomes such as clinical effectiveness, patient safety, cost-effectiveness, and patient and clinician satisfaction with care. METHODS: PubMed (MEDLINE), Embase, and CENTRAL were searched via the Cochrane Library from inception until February 10, 2023, for RCTs without any language restriction. Forward and backward citation searches were conducted on included RCTs. The Cochrane Risk of Bias 2 tool was used to assess the quality of the studies. We included studies carried out in any health setting-involving all types of outpatient cohorts and all types of health care providers-that compared synchronous video consultations directly with telephone consultations and reported outcomes specified in the objective. We excluded studies of clinician-to-clinician telehealth consults, hospitalized patients, and asynchronous consultations. RESULTS: Sixteen RCTs-10 in the United States, 3 in the United Kingdom, 2 in Canada, and 1 in Australia involving 1719 participants-were included in the qualitative and quantitative analyses. Most of the telehealth interventions were for hospital-based outpatient follow-ups, monitoring, and rehabilitation (n=13). The 3 studies that were conducted in the community all focused on smoking cessation. In half of the studies, nurses delivered the care (n=8). Almost all included studies had high or unclear risk of bias, mainly due to bias in the randomization process and selection of reported results. The trials found no substantial differences between telephone and video telehealth consultations with regard to clinical effectiveness, patient satisfaction, and health care use (cost-effectiveness) outcomes. None of the studies reported on patient safety or adverse events. We did not find any study on telehealth interventions for diagnosis, initiating new treatment, or those conducted in a primary care setting. CONCLUSIONS: Based on a small set of diverse trials, we found no notable differences between telephone and video consultations for the management of patients with an established diagnosis. There is also a significant lack of telehealth research in primary care settings despite its high uptake.

Telehealth versus face-to-face delivery of cognitive behavioural therapy for insomnia: A systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: This systematic review and meta-analysis compared the effectiveness of the delivery of care to patients with insomnia via telehealth to its delivery face-to-face. METHODS: We searched Medline, Embase, and Cochrane CENTRAL from inception to 11 January 2023, and conducted a citation analysis on 13 June 2023. No language restrictions were imposed. We included randomised controlled trials. Where feasible, mean differences were calculated; we used a random effects model. RESULTS: Four trials (239 patients) were included. There were no significant differences between telehealth and face-to-face for insomnia severity scores shortly post-intervention (MD 1.13, 95% CI -0.29-2.55) or at 3 months (mean difference (MD) 1.79, 95% CI -0.01-3.59). There were no differences in Short Form-36 physical and mental scores, Work and Social Adjustment scores, and sleep quality components. Depression scores did not differ post-intervention or at 3 months (MD 0.42, 95% CI -2.42-3.26). Functioning likewise did not differ post-intervention or at 3 months (standardised mean difference (SMD) 0.15, 95% CI -0.37-0.67, P = 0.58). Treatment satisfaction did not differ (one trial) or favoured the face-to-face group (one trial). CONCLUSIONS: Telehealth may be a viable alternative to the face-to-face provision of cognitive behavioural therapy for insomnia to patients with insomnia. However, the volume of the existing evidence is limited, therefore additional trials are needed, evaluating cognitive behavioural therapy for insomnia and other therapies for individuals for whom cognitive behavioural therapy for insomnia is not effective, and conducted with a wider range of populations, providers and settings.

High-Spin and Reactive Fe13 Cluster with Exposed Metal Sites.

Atomically defined large metal clusters have applications in new reaction development and preparation of materials with tailored properties. Expanding the synthetic toolbox for reactive high nuclearity metal complexes, we report a new class of Fe clusters, Tp*4 W4 Fe13 S12 , displaying a Fe13 core with M-M bonds that has precedent only in main group and late metal chemistry. M13 clusters with closed shell electron configurations can show significant stability and have been classified as superatoms. In contrast, Tp*4 W4 Fe13 S12 displays a large spin ground state of S=13. This compound performs small molecule activations involving the transfer of up to 12 electrons resulting in significant cluster rearrangements.