Exploring the impact of music on response to ketamine/esketamine: A scoping review.

Music and ketamine are both known to affect therapeutic outcomes, but few studies have investigated their co-administration. This scoping review describes the existing literature on the joint use of music and ketamine-or esketamine (the S(+) enantiomer of ketamine)-in humans. The review considers that extant studies have explored the intersection of ketamine/esketamine and music in healthy volunteers and in patients of various age groups, at different dosages, through different treatment processes, and have varied the sequence of playing music relative to ketamine/esketamine administration. Studies investigating the use of music during ketamine anesthesia are also included in the review because anesthesia and sedation were the early drivers of ketamine use. Studies pertaining to recreational ketamine use were omitted. The review was limited to articles published in the English language but not restricted by publication year. To the best of our knowledge, this scoping review is the first comprehensive exploration of the interplay between music and ketamine/esketamine and offers valuable insights to researchers interested in designing future studies.

Self-reporting of psychoneurophysical (PNP) symptoms in adults with four chronic diseases: a protocol for a scoping review.

BACKGROUND: Patient self-reporting of health-specific information, including symptoms, allows healthcare providers to provide more timely, personalized, and patient-centered care to meet their needs. It is critical to acknowledge that symptom reporting draws from the individual's unique sociocultural background influencing how one perceives health and illness. This scoping review will explore whether racial groups with 4 chronic diseases (cardiovascular diseases, respiratory diseases, cancers, and diabetes) differ in self-reporting of psychoneurophysical (PNP) symptoms. The PNP symptoms of interest include depressive symptoms, fatigue, anxiety, pain, cognitive impairment, sleep impairment, mood impairment, irritability, and shortness of breath. METHODS: Four databases will be searched by a biomedical librarian: CINAHL Plus (EBSCOhost), Embase (Elsevier), PubMed (NLM), Web of Science: Core Collection (Clarivate Analytics), and limited to publications written in the English language. Two independent reviewers will screen the records' title, abstract, and then full text and extract the data from included articles using Covidence. A third reviewer will be used for resolving disagreements. Included articles must comprise adult patients with at least one of the specified chronic diseases who self-report at least one of the specified PNP symptoms. Studies that used clinician-administered questionnaires or obtained symptom responses from primary caregiver or patient designee will be excluded. Articles on patient-reported functionality or perceived quality of life will also be excluded from the review. Two reviewers will independently extract data (e.g., demographics, study design, racial group, chronic disease, measure/scale used for self-report) from each included article using Covidence and Microsoft Excel for data cleaning and analyses. DISCUSSION: This scoping review may potentially identify the relevant and practical implications related to clinical decision-making and health outcomes for patients experiencing the psychoneurophysical symptoms included in this study. The authors will present how the results can be utilized in clinical practice, health policy, and research planning. SYSTEMATIC REVIEW REGISTRATION: The protocol was registered on Open Science Framework (OSF) at: https://osf.io/ps7aw.

A scoping review exploring cure definitions and language for inherited hemoglobinopathies.

Purpose: Sickle cell disease and beta thalassemia are some of the first targets for potentially curative cell-based therapies. Currently, bone marrow transplants, stem cell transplants, and gene therapy are being researched and utilized for people living with these hemoglobinopathies. Although these therapies are often described as curative, there is not a clear definition of what cure means for these hemoglobinopathies. Methods: Five databases were searched for this scoping review. Two reviewers screened each article at the title/abstract and full text levels using Covidence. Articles were included if they were (1) about bone marrow transplants, stem cell transplants, or gene therapy; (2) conditions of focus were sickle cell disease or beta thalassemia; and (3) reported original data on clinical outcomes, psychosocial outcomes, or key stakeholder perspectives and opinions. Data were collected by 2 reviewers also using Covidence, and analyses were conducted in Excel and R. Results: We found that, although cure is widely and indiscriminately used, it is not often defined, and when cure is defined, there is no clear convergence or consensus on the definition. Furthermore, cure is often qualified and undefined euphemisms for cure are often used. We also report the major ways in which the success and complications of these treatment modalities are described. Conclusion: We frame the significance of our findings by discussing their scientific, ethical, and social implications and focus on the need for precise and clear terminology that centers lived experience and acknowledges the interplay between scientific and lay expertise and perceptions.

Meta-analysis: Incidence of cirrhosis and hepatocellular carcinoma in patients with Fontan palliation.

BACKGROUND AND AIMS: The Fontan palliation is the final stage of surgery for many children born with univentricular physiology. Almost all Fontan patients develop liver fibrosis which may eventually lead to cirrhosis and hepatocellular carcinoma (HCC). These are important causes of morbidity and mortality in these patients. We performed a systematic review and meta-analysis to assess the incidence of cirrhosis and HCC in Fontan patients and stratify it based on time since surgery. METHODS: A literature search of seven databases identified 1158 records. Studies reporting the number of cirrhosis and HCC cases in Fontan patients and time since Fontan surgery were included. In the cirrhosis cohort, we included only those studies where all patients underwent liver biopsy. RESULTS: A total of 23 studies were included: 12 and 13 studies in the cirrhosis and HCC cohorts, respectively, with two studies included in both cohorts. The incidence of cirrhosis was 0.97 per 100 patient-years (95% CI 0.57-1.63), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 1.61 per 100 patient-years (95% CI 1.24-2.08) and 32.2% (95% CI 25.8%-39.4%), respectively. The incidence of HCC was 0.12 per 100 patient-years (95% CI 0.07-0.21), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 0.20 per 100 patient-years (95% CI 0.12-0.35) and 3.9% (95% CI 2.2%-6.8%), respectively. Only about 70% of patients with HCC (20/28) had underlying cirrhosis. CONCLUSION: The incidence of cirrhosis and HCC increases over time, especially at ≥20 years post Fontan surgery. Studies are needed to further identify at-risk patients in order to streamline surveillance for these highly morbid conditions.

Examining allergy related diseases in Africa: A scoping review protocol.

During recent decades, allergy related diseases have emerged as a growing area of concern in developing regions of the world, including Africa. Worldwide prevalence of allergic diseases has grown to an estimated 262 million for asthma, 400 million for allergic rhinitis (or hay fever), 171 million with atopic dermatitis (or eczema), and over 200 million for food allergy. In Africa, considerable variability exists in the data surrounding prevalence at the continent-wide, regional, and study site levels. Furthermore, research conducted in many rural areas and underdeveloped countries in Africa remains limited, and presently, little has been done to characterize and map the extremely heterogeneous body of literature which confounds research efforts. This scoping review will seek to identify studies examining the prevalence, management strategies, outcomes, and associated risk factors for allergy related diseases in Africa. The Joanna Briggs Institute's scoping review methods will be followed, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review (PRISMA-ScR) was used for writing the protocol. Four databases (Embase, Global Health, PubMed, African Journals Online) will be searched for literature published from 2003 to 2023 in any language. Title and abstract screening and full-text screening will be completed by two independent reviewers using Covidence; conflicts resolved by a third reviewer. Data will be extracted using Covidence by two reviewers independently. To report the results, we will follow the PRISMA-ScR checklist and report descriptive statistics and a narrative summary.

Proteomics for heart failure risk stratification: a systematic review.

BACKGROUND: Heart failure (HF) is a complex clinical syndrome with persistently high mortality. High-throughput proteomic technologies offer new opportunities to improve HF risk stratification, but their contribution remains to be clearly defined. We aimed to systematically review prognostic studies using high-throughput proteomics to identify protein signatures associated with HF mortality. METHODS: We searched four databases and two clinical trial registries for articles published from 2012 to 2023. HF proteomics studies measuring high numbers of proteins using aptamer or antibody-based affinity platforms on human plasma or serum with outcomes of all-cause or cardiovascular death were included. Two reviewers independently screened articles, extracted data, and assessed the risk of bias. A third reviewer resolved conflicts. We assessed the risk of bias using the Risk Of Bias In Non-randomized Studies-of Exposure tool. RESULTS: Out of 5131 unique articles identified, nine articles were included in the review. The nine studies were observational; three used the aptamer platform, and six used the antibody platform. We found considerable heterogeneity across studies in measurement panels, HF definitions, ejection fraction categorization, follow-up duration, and outcome definitions, and a lack of risk estimates for most protein associations. Hence, we proceeded with a systematic review rather than a meta-analysis. In two comparable aptamer studies in patients with HF with reduced ejection fraction, 21 proteins were identified in common for the association with all-cause death. Among these, one protein, WAP four-disulfide core domain protein 2 was also reported in an antibody study on HFrEF and for the association with CV death. We proposed standardized reporting criteria to facilitate the interpretation of future studies. CONCLUSIONS: In this systematic review of nine studies evaluating the association of proteomics with mortality in HF, we identified a limited number of proteins common across several studies. Heterogeneity across studies compromised drawing broad inferences, underscoring the importance of standardized approaches to reporting.

Key Findings from Mental Health Research During the Menopause Transition for Racially and Ethnically Minoritized Women Living in the United States: A Scoping Review.

Background: Racially and ethnically minoritized (REM) women experience social and structural factors that may affect their response to mental health treatment and menopausal symptoms during the menopause transition (MT). This scoping review on mental health during the MT for REM women in the United States was conducted to characterize factors associated with mental health challenges. Materials and Methods: Five databases were searched. Articles were included if focused on MT in REM women in the United States and its territories with specific mental illnesses and published in English from 2005 to 2021. Titles and abstracts and full text were screened. Screening and data collection were completed in duplicate by two reviewers in Covidence. Results: Sixty-five articles were included and indicate that REM women experience a disproportionate burden of depressive symptoms during the MT. Less evidence is reported about anxiety, Post-Traumatic Stress Disorder, psychosis, schizophrenia, and other mental illnesses. The risk factors associated with mental illness during MT are social, structural, and biological. Treatment response to therapeutic interventions is often underpowered to explain REM differences. Conclusion: Depression during the MT is associated with negative outcomes that may impact REM women differentially. Incorporating theoretical frameworks (e.g., intersectionality, weathering) into mental health research will reduce the likelihood that scientists mislabel race as the cause of these inequities, when racism and intersecting systems of oppression are the root causes of differential expression of mental illness among REM women during the MT. There is a need for interdisciplinary research to advance the mental health of REM women.

COVID-19 pandemic and mental health among Hispanic/Latino/a immigrants in the USA: protocol for a scoping review.

INTRODUCTION: The COVID-19 pandemic has had drastic effects on worldwide mental health and laid bare health disparities and inequities among marginalised groups and racial/ethnic minoritised communities in the USA. This is especially the case among Hispanic/Latino/a immigrants who face numerous structural and socioeconomic barriers to well-being. The increased mental health burden on Hispanic/Latino/a immigrants may have far reaching effects if left unaddressed. Thus, by understanding further Hispanic/Latino/a immigrant mental health during the pandemic, communities and health providers may be able to better address this growing issue. This scoping review aims to assess and outline the current literature on the pandemic's effects on Hispanic/Latino/a immigrant mental health in the USA, identify research gaps and areas of urgent concern, and inform future research and public health interventions and guidelines. METHODS AND ANALYSIS: A scoping review following the Joanna Briggs Institute methodology will be conducted. The PsycINFO, PubMed, Scopus and Web of Science: Core Collection databases and five grey literature sources will be searched for articles published in English from 1 January 2020 to 31 December 2022. Two independent reviewers will screen the search results at title and abstract and then full text using Covidence with conflicts resolved by a third reviewer. Data collection will also be performed in duplicate using Microsoft Excel with discrepancies resolved by a third reviewer and consensus discussion. ETHICS AND DISSEMINATION: Ethics approval is not required for this scoping review. Results will be published in a peer-reviewed journal as well as presented at local and national conferences and meetings relevant to our field. Furthermore, to make our findings accessible to non-scientific audiences, we will use various mediums, such as graphical abstracts, policy briefs and fact sheets to share the results in both English and Spanish on different platforms.

Reversing the trend: a scoping review of health innovation transfer or exchange from low- and middle-income countries to high-income countries.

The transfer of innovations from low and middle-income countries (LMICs) to high-income countries (HICs) has received little attention, leaving gaps in the understanding of the process, its benefits and the factors influencing it. This scoping review, part of a National Institutes of Health (NIH) project and the focus for a 2022 NIH-sponsored workshop on Global Health Reciprocal Innovation, sought to identify publications describing health innovations that were researched, developed and implemented in LMICs and adapted to address similar health challenges in HICs. A protocol was written a priori and registered on Open Science Framework. Four databases were searched for articles published in English from 2000 to 2022 and described health innovations developed in LMICs and were transferred to HICs. Using Covidence, two reviewers initially screened the title and abstract and then the full text; discrepancies were resolved through discussion. Two reviewers collected the data from each article using Covidence and Microsoft Excel; discrepancies were resolved by a separate third reviewer. 7191 records were retrieved and screened of which 12 studies were included. Various frameworks and methodologies were employed in these studies, with a particular emphasis on adaptation and adoption of innovations. The review uncovered different paradigms of LMIC to HIC innovation transfer and exchange, including unidirectional transfers from LMICs to HICs as well as bidirectional or multidirectional mutually beneficial exchanges. The use of both qualitative and quantitative data collection methods was common across all the included articles. Facilitators for innovation transfers included stakeholder engagement, relevance of local context, simplicity, and sufficient funding, promotion and branding. Barriers to transfers were mostly the opposite of the facilitators. Our results highlighted the underexplored field of LMIC to HIC innovation transfer and exchange and lay the foundation for future research studies.

The National Cancer Institute's Cancer Disparities Research Partnership Program: a unique funding model 20 years later.

The burden of cancer and access to effective treatment are not experienced equally by all in the United States. For underserved populations that often access the health-care system when their cancers are in advanced disease stages, radiation oncology services are essential. In 2001, the National Cancer Institute's (NCI's) Radiation Research Program created and implemented the Cancer Disparities Research Partnership Program (CDRP). CDRP was a pioneering funding model whose goal was to increase participation of medically underserved populations in NCI clinical trials. CDRP's Cooperative Agreement funding supported for awardees the planning, development, and conduct of radiation oncology clinical research in institutions not traditionally involved in NCI-sponsored research and cared for a disproportionate number of medically underserved, health-disparities populations. The awardee secured and provided support for mentorship from 1 of 2 NCI comprehensive cancer centers named in its application. Six CDRP awards were made over two 5-year funding periods ending in 2013, with the end-of-program accomplishments previously reported. With the current focus on addressing equity, diversity, and inclusion, the 6 principal investigators were surveyed, 5 of whom responded about the impact of CDRP on their institutions, communities, and personal career paths. The survey that was emailed included 10 questions on a 5-point Likert scale. It was not possible to collect patient data this long after completion of the program. This article provides a 20-year retrospective of the experiences and observations from those principal investigators that can inform those now planning, building, and implementing equity, diversity, and inclusion programs.

Characteristics of Cancer Epidemiology Studies That Employ Metabolomics: A Scoping Review.

An increasing number of cancer epidemiology studies use metabolomics assays. This scoping review characterizes trends in the literature in terms of study design, population characteristics, and metabolomics approaches and identifies opportunities for future growth and improvement. We searched PubMed/MEDLINE, Embase, Scopus, and Web of Science: Core Collection databases and included research articles that used metabolomics to primarily study cancer, contained a minimum of 100 cases in each main analysis stratum, used an epidemiologic study design, and were published in English from 1998 to June 2021. A total of 2,048 articles were screened, of which 314 full texts were further assessed resulting in 77 included articles. The most well-studied cancers were colorectal (19.5%), prostate (19.5%), and breast (19.5%). Most studies used a nested case-control design to estimate associations between individual metabolites and cancer risk and a liquid chromatography-tandem mass spectrometry untargeted or semi-targeted approach to measure metabolites in blood. Studies were geographically diverse, including countries in Asia, Europe, and North America; 27.3% of studies reported on participant race, the majority reporting White participants. Most studies (70.2%) included fewer than 300 cancer cases in their main analysis. This scoping review identified key areas for improvement, including needs for standardized race and ethnicity reporting, more diverse study populations, and larger studies.

How COVID-19 exposed pre-existing roadblocks for cancer control in Africa: strategies, lessons and recommendations from the 2019-2020 Africa Cancer Research and Control ECHO.

Background: The COVID-19 related mitigation measures adversely affected various cancer control activities in Africa, with cancer prevention and screening activities amongst the most significantly impacted. When the COVID-19 pandemic struck, the Africa Cancer Research and Control ECHO utilised their virtual platform to share experiences and knowledge of how to continue cancer service delivery during the pandemic. This analysis describes the evolved strategies, dilemmas, and recommendations to strengthen the health systems for cancer control in Africa. Methods: Eleven 1-hour-long sessions about the then newly emerging coronavirus infection and its impact on cancer control in Africa were held from April 2020 to August 2020, using Zoom®. An average of 39 participants attended the sessions including scientists, clinicians, policymakers and global partners. Sessions were analysed thematically. Results: Most strategies to maintain cancer services during the COVID-19 pandemic centred around cancer treatment, with few strategies on maintaining cancer prevention services, early detection, palliative care and research services. The most mentioned challenge during the pandemic was fear of exposure to COVID-19 infection at the health facility during diagnosis, treatment or follow-up for cancer care. Other challenges were disruptions to service delivery, inaccessibility of cancer treatment, disruption of research activities and a lack of psychosocial support for COVID-19 related fear/anxiety. Significantly, this analysis shows that the COVID-19 related mitigation measures exacerbated existing predicaments in Africa, such as inadequate attention to cancer prevention strategies, psychosocial and palliative services and cancer research. The Africa Cancer ECHO recommends African countries to leverage the infrastructure developed in response to COVID-19 pandemic to strengthen the health system along the entire cancer control continuum. This calls for urgent action to develop and implement evidence-based frameworks and comprehensive National Cancer Control Plans that will withstand any future disruptions.

Ionising radiation and cardiovascular disease: systematic review and meta-analysis.

OBJECTIVE: To systematically review and perform a meta-analysis of radiation associated risks of cardiovascular disease in all groups exposed to radiation with individual radiation dose estimates. DESIGN: Systematic review and meta-analysis. MAIN OUTCOME MEASURES: Excess relative risk per unit dose (Gy), estimated by restricted maximum likelihood methods. DATA SOURCES: PubMed and Medline, Embase, Scopus, Web of Science Core collection databases. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Databases were searched on 6 October 2022, with no limits on date of publication or language. Animal studies and studies without an abstract were excluded. RESULTS: The meta-analysis yielded 93 relevant studies. Relative risk per Gy increased for all cardiovascular disease (excess relative risk per Gy of 0.11 (95% confidence interval 0.08 to 0.14)) and for the four major subtypes of cardiovascular disease (ischaemic heart disease, other heart disease, cerebrovascular disease, all other cardiovascular disease). However, interstudy heterogeneity was noted (P<0.05 for all endpoints except for other heart disease), possibly resulting from interstudy variation in unmeasured confounders or effect modifiers, which is markedly reduced if attention is restricted to higher quality studies or those at moderate doses (<0.5 Gy) or low dose rates (<5 mGy/h). For ischaemic heart disease and all cardiovascular disease, risks were larger per unit dose for lower dose (inverse dose effect) and for fractionated exposures (inverse dose fractionation effect). Population based excess absolute risks are estimated for a number of national populations (Canada, England and Wales, France, Germany, Japan, USA) and range from 2.33% per Gy (95% confidence interval 1.69% to 2.98%) for England and Wales to 3.66% per Gy (2.65% to 4.68%) for Germany, largely reflecting the underlying rates of cardiovascular disease mortality in these populations. Estimated risk of mortality from cardiovascular disease are generally dominated by cerebrovascular disease (around 0.94-1.26% per Gy), with the next largest contribution from ischaemic heart disease (around 0.30-1.20% per Gy). CONCLUSIONS: Results provide evidence supporting a causal association between radiation exposure and cardiovascular disease at high dose, and to a lesser extent at low dose, with some indications of differences in risk between acute and chronic exposures, which require further investigation. The observed heterogeneity complicates a causal interpretation of these findings, although this heterogeneity is much reduced if only higher quality studies or those at moderate doses or low dose rates are considered. Studies are needed to assess in more detail modifications of radiation effect by lifestyle and medical risk factors. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020202036.

Cancer in Costello syndrome: a systematic review and meta-analysis.

BACKGROUND: Costello syndrome (CS) is a cancer-predisposition disorder caused by germline pathogenic variants in HRAS. We conducted a systematic review using case reports and case series to characterise cancer risk in CS. METHODS: We conducted a systematic review to identify CS cases to create a retrospective cohort. We tested genotype-phenotype correlations and calculated cumulative incidence and hazard rates (HR) for cancer and cancer-free death, standardised incidence rates (SIR) and survival after cancer. RESULTS: This study includes 234 publications reporting 621 patients from 35 countries. Over nine percent had cancer, including rhabdomyosarcoma, bladder, and neuroblastoma. The rate of cancer and death associated with p.Gly12Ser were lower when compared to all other variants (P < 0.05). Higher mortality for p.Gly12Cys, p.Gly12Asp, p.Gly12Val and p.Gly60Val and higher malignancy rate for p.Gly12Ala were confirmed (P < 0.05). Cumulative incidence by age 20 was 13% (cancer) and 11% (cancer-free death). HR (death) was 3-4% until age 3. Statistically significant SIRs were found for rhabdomyosarcoma (SIR = 1240), bladder (SIR = 1971), and neuroblastoma (SIR = 60). Survival after cancer appeared reduced. CONCLUSIONS: This is the largest investigation of cancer in CS to date. The high incidence and SIR values found to highlight the need for rigorous surveillance and evidence-based guidelines for this high-risk population.

The impact of caregiving for children with chronic conditions on the HPA axis: A scoping review.

Caregiving has been robustly linked to caregiver health through the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in the context of caregiving for an adult with a chronic illness. However, little research examines the physiological impact of caregiving for a child with a chronic illness despite high burden and unique stressors. In this review, we explore the links of caregiving for a child with a congenital, chromosomal, or genetic disorder to the regulation or dysregulation of the HPA axis. A search was conducted in PubMed, Embase, and the Web of Science and 15 studies met inclusion criteria. Overall, there were inconsistent links of caregiving to HPA axis functioning, perhaps due to the heterogeneity across disease contexts, study designs, and biomarker measurement. Future research should standardize measurement and study designs, increase participant diversity, and examine moderators of the links of caregiving to the HPA axis.

A systematic review of the biological mediators of fat taste and smell.

Taste and smell play a key role in our ability to perceive foods. Overconsumption of highly palatable energy-dense foods can lead to increased caloric intake and obesity. Thus there is growing interest in the study of the biological mediators of fat taste and associated olfaction as potential targets for pharmacologic and nutritional interventions in the context of obesity and health. The number of studies examining mechanisms underlying fat taste and smell has grown rapidly in the last 5 years. Therefore, the purpose of this systematic review is to summarize emerging evidence examining the biological mechanisms of fat taste and smell. A literature search was conducted of studies published in English between 2014 and 2021 in adult humans and animal models. Database searches were conducted using PubMed, EMBASE, Scopus, and Web of Science for key terms including fat/lipid, taste, and olfaction. Initially, 4,062 articles were identified through database searches, and a total of 84 relevant articles met inclusion and exclusion criteria and are included in this review. Existing literature suggests that there are several proteins integral to fat chemosensation, including cluster of differentiation 36 (CD36) and G protein-coupled receptor 120 (GPR120). This systematic review will discuss these proteins and the signal transduction pathways involved in fat detection. We also review neural circuits, key brain regions, ingestive cues, postingestive signals, and genetic polymorphism that play a role in fat perception and consumption. Finally, we discuss the role of fat taste and smell in the context of eating behavior and obesity.

Implementation Science for the Prevention and Treatment of HIV among Adolescents and Young Adults in Sub-Saharan Africa: A Scoping Review.

Despite many evidence-based adolescent and young adult (AYA) HIV interventions, few are implemented at scale in sub-Saharan Africa (SSA). A growing implementation science literature provides important context for scaling up AYA HIV interventions in this high HIV-burden region. This scoping review examined the use of implementation research in AYA HIV studies conducted in SSA. We searched five databases and included articles which focused on AYA (10-24 years old), addressed HIV prevention or treatment, were conducted exclusively in SSA countries, and included an implementation science outcome. We included 44 articles in 13 SSA countries. Most were in East (52.3%) and South Africa (27.3%), and half focused exclusively on HIV prevention components of the care continuum. Acceptability and feasibility were the most cited implementation science outcomes. Only four articles used an established implementation science framework. The findings informed our recommendations to guide the design, implementation, and dissemination of further studies and health policymaking.

The influence of telehealth-based cancer rehabilitation interventions on disability: a systematic review.

PURPOSE: To characterize delivery features and explore effectiveness of telehealth-based cancer rehabilitation interventions that address disability in adult cancer survivors. METHODS: A systematic review of electronic databases (CINAHL Plus, Cochrane Library: Database of Systematic Reviews, Embase, National Health Service's Health Technology Assessment, PubMed, Scopus, Web of Science) was conducted in December 2019 and updated in April 2021. RESULTS: Searches identified 3,499 unique studies. Sixty-eight studies met inclusion criteria. There were 81 unique interventions across included studies. Interventions were primarily delivered post-treatment and lasted an average of 16.5 weeks (SD = 13.1). They were most frequently delivered using telephone calls (59%), administered delivered by nursing professionals (35%), and delivered in a one-on-one format (88%). Risk of bias of included studies was primarily moderate to high. Included studies captured 55 measures of disability. Only 54% of reported outcomes had data that allowed calculation of effect sizes ranging -3.58 to 15.66. CONCLUSIONS: The analyses suggest small effects of telehealth-based cancer interventions on disability, though the heterogeneity seen in the measurement of disability makes it hard to draw firm conclusions. Further research using more diverse samples, common measures of disability, and pragmatic study designs is needed to advance telehealth in cancer rehabilitation. IMPLICATIONS FOR CANCER SURVIVORS: Telehealth-based cancer rehabilitation interventions have the potential to increase access to care designed to reduce disability across the cancer care continuum.

Cancer incidence and surveillance strategies in individuals with RASopathies.

RASopathies are a set of clinical syndromes that have molecular and clinical overlap. Genetically, these syndromes are defined by germline pathogenic variants in RAS/MAPK pathway genes resulting in activation of this pathway. Clinically, their common molecular signature leads to comparable phenotypes, including cardiac anomalies, neurologic disorders and notably, elevated cancer risk. Cancer risk in individuals with RASopathies has been estimated from retrospective reviews and cohort studies. For example, in Costello syndrome, cancer incidence is significantly elevated over the general population, largely due to solid tumors. In some forms of Noonan syndrome, cancer risk is also elevated over the general population and is enriched for hematologic malignancies. Thus, cancer surveillance guidelines have been developed to monitor for the occurrence of such cancers in individuals with some RASopathies. These include abdominal ultrasound and urinalyses for individuals with Costello syndrome, while complete blood counts and splenic examination are recommended in Noonan syndrome. Improved cancer risk estimates and refinement of surveillance recommendations will improve the care of individuals with RASopathies.

Statins for Smith-Lemli-Opitz syndrome.

BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital malformations syndrome caused by defective cholesterol biosynthesis. Affected individuals show cholesterol deficiency and accumulation of various precursor molecules, mainly 7-dehydrocholesterol and 8-dehydrocholesterol. There is currently no cure for SLOS, with cholesterol supplementation being primarily a biochemical therapy of limited evidence. However, several anecdotal reports and preclinical studies have highlighted statins as a potential therapy for SLOS. OBJECTIVES: To evaluate the effects of statins, either alone or in combination with other non-statin therapies (e.g. cholesterol, bile acid, or vitamin co-supplementation), compared to cholesterol supplementation alone or in combination with other non-statin therapies (e.g. bile acid or vitamin supplementation) on several important outcomes including overall survival, neurobehavioral features, and adverse effects in individuals with SLOS. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, five other databases and three trials registers on 15 February 2022, together with reference checking, citation searching and contact with study authors to identify additional studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs with parallel or cross-over designs, and non-randomized studies of interventions (NRSIs) including non-randomized trials, cohort studies, and controlled before-and-after studies, were eligible for inclusion in this review if they met our prespecified inclusion criteria, i.e. involved human participants with biochemically or genetically diagnosed SLOS receiving statin therapy or cholesterol supplementation, or both. DATA COLLECTION AND ANALYSIS: Two authors screened titles and abstracts and subsequently full-texts for all potentially-relevant references. Both authors independently extracted relevant data from included studies and assessed the risks of bias. We analyzed the data extracted from the included NRSIs and cohort studies separately from the data extracted from the single included RCT. We used a random-effects model to account for the inherent heterogeneity and methodological variation between these different study designs. We used GRADE to assess the certainty of evidence. MAIN RESULTS: We included six studies (61 participants with SLOS); one RCT (N = 18), three prospective NRSIs (N = 20), and two retrospective NRSIs (N = 22). Five studies included only children, and two limited their participant inclusion by disease severity. Overall, there were nearly twice as many males as females. All six studies compared add-on statin therapy to cholesterol supplementation alone. However, the dosages, formulations, and durations of treatment were highly variable across studies. We judged the RCT as having a high risk of bias due to missing data and selective reporting. All included NRSIs had a serious or critical overall risk of bias assessed by the Risk Of Bias In Non-randomized Studies of Interventions tool (ROBINS-I). None of the included studies evaluated survival or reported quality of life (QoL). Only the included RCT formally assessed changes in the neurobehavioral manifestations of SLOS, and we are uncertain whether statin therapy improves this outcome (very low-certainty evidence). We are also uncertain whether the adverse events reported in the RCT were statin-related (very low-certainty evidence). In contrast, the adverse events reported in the NRSIs seem to be possibly due to statin therapy (risk ratio 13.00, 95% confidence interval 1.85 to 91.49; P = 0.01; low-certainty evidence), with only one of the NRSIs retrospectively mentioning changes in the irritability of two of their participants. We are uncertain whether statins affect growth based on the RCT or NRSI results (very low-certainty evidence). The RCT showed that statins may make little or no difference to plasma biomarker levels (low-certainty evidence), while we are uncertain of their effects on such parameters in the NRSIs (very low-certainty evidence). AUTHORS' CONCLUSIONS: Currently, there is no evidence on the potential effects of statin therapy in people with SLOS regarding survival or QoL, and very limited evidence on the effects on neurobehavioral manifestations. Likewise, current evidence is insufficient and of very low certainty regarding the effects of statins on growth parameters in children with SLOS and plasma or cerebrospinal fluid (CSF) levels of various disease biomarkers. Despite these limitations, current evidence seemingly suggests that statins may increase the risk of adverse reactions in individuals with SLOS receiving statins compared to those who are not. Given the insufficient evidence on potential benefits of statins in individuals with SLOS, and their potential for causing adverse reactions, anyone considering this therapy should take these findings into consideration. Future studies should address the highlighted gaps in evidence on the use of statins in individuals with SLOS by collecting prospective data on survival and performing serial standardized assessments of neurobehavioral features, QoL, anthropometric measures, and plasma and CSF biomarker levels after statin introduction. Future studies should also attempt to use consistent dosages, formulations and durations of cholesterol and statin therapy.