Screening for lung cancer with computed tomography: protocol for systematic reviews for the Canadian Task Force on Preventive Health Care.

PURPOSE: Lung cancer is the leading cause of cancer deaths in Canada, and because early cancers are often asymptomatic screening aims to prevent mortality by detecting cancer earlier when treatment is more likely to be curative. These reviews will inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening for lung cancer. METHODS: We will update the review on the benefits and harms of screening with CT conducted for the task force in 2015 and perform de novo reviews on the comparative effects between (i) trial-based selection criteria and use of risk prediction models and (ii) trial-based nodule classification and different nodule classification systems and on patients' values and preferences. We will search Medline, Embase, and Cochrane Central (for questions on benefits and harms from 2015; comparative effects from 2012) and Medline, Scopus, and EconLit (for values and preferences from 2012) via peer-reviewed search strategies, clinical trial registries, and the reference lists of included studies and reviews. Two reviewers will screen all citations (including those in the previous review) and base inclusion decisions on consensus or arbitration by another reviewer. For benefits (i.e., all-cause and cancer-specific mortality and health-related quality of life) and harms (i.e., overdiagnosis, false positives, incidental findings, psychosocial harms from screening, and major complications and mortality from invasive procedures as a result of screening), we will include studies of adults in whom lung cancer is not suspected. We will include randomized controlled trials comparing CT screening with no screening or alternative screening modalities (e.g., chest radiography) or strategies (e.g., CT using different screening intervals, classification systems, and/or patient selection via risk models or biomarkers); non-randomized studies, including modeling studies, will be included for the comparative effects between trial-based and other selection criteria or nodule classification methods. For harms (except overdiagnosis) we will also include non-randomized and uncontrolled studies. For values and preferences, the study design may be any quantitative design that either directly or indirectly measures outcome preferences on outcomes pertaining to lung cancer screening. We will only include studies conducted in Very High Human Development Countries and having full texts in English or French. Data will be extracted by one reviewer with verification by another, with the exception of result data on mortality and cancer incidence (for calculating overdiagnosis) where duplicate extraction will occur. If two or more studies report on the same comparison and it is deemed suitable, we will pool continuous data using a mean difference or standardized mean difference, as applicable, and binary data using relative risks and a DerSimonian and Laird model unless events are rare (< 1%) where we will pool odds ratios using Peto's method or (if zero events) the reciprocal of the opposite treatment arm size correction. For pooling proportions, we will apply suitable transformation (logit or arcsine) depending on the proportions of events. If meta-analysis is not undertaken we will synthesize the data descriptively, considering clinical and methodological differences. For each outcome, two reviewers will independently assess within- and across-study risk of bias and rate the certainty of the evidence using GRADE (Grading of Recommendations Assessment, Development, and Evaluation), and reach consensus. DISCUSSION: Since 2015, additional trials and longer follow-ups or additional data (e.g., harms, specific patient populations) from previously published trials have been published that will improve our understanding of the benefits and harms of screening. The systematic review of values and preferences will allow fulsome insights that will inform the balance of benefits and harms. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022378858.

Modelling in vitro gametogenesis using induced pluripotent stem cells: a review.

In vitro gametogenesis (IVG) has been a topic of great interest in recent years not only because it allows for further exploration of mechanisms of germ cell development, but also because of its prospect for innovative medical applications especially for the treatment of infertility. Elucidation of the mechanisms underlying gamete development in vivo has inspired scientists to attempt to recapitulate the entire process of gametogenesis in vitro. While earlier studies have established IVG methods largely using pluripotent stem cells of embryonic origin, the scarcity of sources for these cells and the ethical issues involved in their use are serious limitations to the progress of IVG research especially in humans. However, with the emergence of induced pluripotent stem cells (iPSCs) due to the revolutionary discovery of dedifferentiation and reprogramming factors, IVG research has progressed remarkably in the last decade. This paper extensively reviews developments in IVG using iPSCs. First, the paper presents key concepts from groundwork studies on IVG including earlier researches demonstrating that IVG methods using embryonic stem cells (ESCs) also apply when using iPSCs. Techniques for the derivation of iPSCs are briefly discussed, highlighting the importance of generating transgene-free iPSCs with a high capacity for germline transmission to improve efficacy when used for IVG. The main part of the paper discusses recent advances in IVG research using iPSCs in various stages of gametogenesis. In addition, current clinical applications of IVG are presented, and potential future applications are discussed. Although IVG is still faced with many challenges in terms of technical issues, as well as efficacy and safety, novel IVG methodologies are emerging, and IVG using iPSCs may usher in the next era of reproductive medicine sooner than expected. This raises both ethical and social concerns and calls for the scientific community to cautiously develop IVG technology to ensure it is not only efficacious but also safe and adheres to social and ethical norms.

Impact of mHealth Interventions on Supporting Dietary Adherence in Cardiovascular Disease: A Systematic Review.

INTRODUCTION: A systematic review was conducted to determine if mobile health (mHealth) interventions, and which intervention characteristics, effectively support dietary adherence and reduce risk factors in patients with cardiovascular disease (CVD). METHOD: Using 7 databases, studies involving adult participants with specific CVD diagnoses, mHealth intervention testing, and dietary adherence assessment were identified. Systematic reviews, qualitative studies, or studies testing interventions involving open dialogue between participants and health care providers or researchers were excluded. Two independent reviewers conducted screening and assessed the risk of bias. RESULTS: Thirteen studies involved participants with prehypertension (n = 1), hypertension (n = 9), coronary artery disease (n = 2), and heart failure (n = 1). mHealth interventions in 8 studies improved dietary adherence, 4 showed mixed results, and 1 showed no improvements. Eight studies found interactive text and/or application-based mHealth intervention features effectively improved dietary adherence. One study had a low risk of bias, 2 had some concerns/moderate risk, and 10 had a high/critical or serious risk. DISCUSSION: In most included studies, mHealth interventions positively impacted dietary adherence for patients with CVD. IMPLICATIONS FOR RESEARCH AND PRACTICE: Clinicians may recommend mHealth interventions to support nutrition education and self-management for their patients with CVD.

Associations between SARS-CoV-2 infection and incidence of new chronic condition diagnoses: a systematic review.

Because of the large number of infected individuals, an estimate of the future burdens of the long-term consequences of SARS-CoV-2 infection is needed. This systematic review examined associations between SARS-CoV-2 infection and incidence of categories of and selected chronic conditions, by age and severity of infection (inpatient vs. outpatient/mixed care). MEDLINE and EMBASE were searched (1 January 2020 to 4 October 2022) and reference lists scanned. We included observational studies from high-income OECD countries with a control group adjusting for sex and comorbidities. Identified records underwent a two-stage screening process. Two reviewers screened 50% of titles/abstracts, after which DistillerAI acted as second reviewer. Two reviewers then screened the full texts of stage one selections. One reviewer extracted data and assessed risk of bias; results were verified by another. Random-effects meta-analysis estimated pooled hazard ratios (HR). GRADE assessed certainty of the evidence. Twenty-five studies were included. Among the outpatient/mixed SARS-CoV-2 care group, there is high certainty of a small-to-moderate increase (i.e. HR 1.26-1.99) among adults ≥65 years of any cardiovascular condition, and of little-to-no difference (i.e. HR 0.75-1.25) in anxiety disorders for individuals <18, 18-64, and ≥65 years old. Among 18-64 and ≥65 year-olds receiving outpatient/mixed care there are probably (moderate certainty) large increases (i.e. HR ≥2.0) in encephalopathy, interstitial lung disease, and respiratory failure. After SARS-CoV-2 infection, there is probably an increased risk of diagnoses for some chronic conditions; whether the magnitude of risk will remain stable into the future is uncertain.

Advancing Cardio-Oncology in Asia.

Cardio-oncology is an emerging multi-disciplinary field, which aims to reduce morbidity and mortality of cancer patients by preventing and managing cancer treatment-related cardiovascular toxicities. With the exponential growth in cancer and cardiovascular diseases in Asia, there is an emerging need for cardio-oncology awareness among physicians and country-specific cardio-oncology initiatives. In this state-of-the-art review, we sought to describe the burden of cancer and cardiovascular disease in Asia, a region with rich cultural and socio-economic diversity. From describing the uniqueness and challenges (such as socio-economic disparity, ethnical and racial diversity, and limited training opportunities) in establishing cardio-oncology in Asia, and outlining ways to overcome any barriers, this article aims to help advance the field of cardio-oncology in Asia.

Decompensated cirrhosis: targeted training of acute medical teams to improve quality of care in first 24 hours.

BACKGROUND: A quality improvement project in a secondary care centre was initiated to investigate and evaluate the impact of staff education and the use of the British Society of Gastroenterology/British Association for the Study of the Liver cirrhosis care bundle in improving care of patients admitted to hospital with decompensated liver cirrhosis. METHOD: A staff training programme was implemented, involving around 30 health professionals consisting of consultants, junior doctors, physician associates and nurses from the acute medical unit. A review of electronic documentation and analysis of key clinical parameters, pre- and post-intervention, was carried out. RESULTS: The data show that the intervention has led to an improvement in patient management and clinical outcomes. CONCLUSION: This project illustrates that collaboration between hepatology and medical teams, with emphasis on education and training, benefits patients who present to hospital with decompensated liver cirrhosis.

Anthracycline-Induced Cardiotoxicity in Breast Cancer Patients: A Five-Year Retrospective Study in 10 Centers.

Background: Cardiotoxicity as a result of anthracycline chemotherapy has been linked to increased morbidity and mortality in breast cancer patients. There is a need for early detection through risk factor identification. To date, no large multicenter study has been conducted to describe the incidence, risk factors and clinical and demographic profiles of breast cancer patients with anthracycline-induced cardiotoxicity (AIC) in the Philippines. Methods: This was a nationwide multicenter retrospective cohort study among adult breast cancer patients who underwent anthracycline chemotherapy from 2015 to 2020 in 10 sites in the Philippines. Baseline characteristics and possible risk factors for AIC were retrieved from medical records and cancer registries. AIC was defined as a reduction of left ventricular ejection fraction (LVEF) by > 10% from baseline to a value of < 53% or the development of overt left ventricular systolic dysfunction or heart failure (HF). Odds ratios from logistic regression were computed to determine risk factors associated with AIC using STATA-15.0 software. Results: Out of 341 patients included, 33 had AIC, accounting for an incidence of 9.68%. Nine patients (2.6%) had clinical HF. AIC patients had a mean age of 53.91 ± 10.84 years. Breast cancer AIC patients were significantly older and had lower body mass index (BMI) than those without AIC. AIC patients had significantly more comorbidities, especially hypertension and atrial fibrillation. Multivariate analysis showed that patients with any preexisting comorbidity are approximately 12.37 times as likely to have AIC, while those with concurrent chemotherapy are 0.07 times or 93% less likely to have AIC. Conclusion: Among adult breast cancer patients undergoing anthracycline chemotherapy, we determined a high incidence of cardiotoxicity at 9.68%. Having preexisting comorbidities gave patients 12 times increased odds of developing anthracycline cardiotoxicity. The presence of concurrent non-anthracycline chemotherapy showed an inverse association with the development of AIC which we attribute largely to patient selection in a retrospective study. The significantly higher propensity for AIC development in patients with preexisting comorbidities may warrant closer monitoring and control of patient comorbidities such as hypertension among patients undergoing anthracycline chemotherapy.

Move It or Lose It? The Effect of Early Active Movement on Clinical Outcomes Following Rotator Cuff Repair: A Systematic Review With Meta-analysis.

OBJECTIVE: To assess the effect of early active shoulder movement after rotator cuff repair, compared to delayed active shoulder movement, on clinical outcomes, rotator cuff integrity, and return to work. STUDY DESIGN: Intervention systematic review. LITERATURE SEARCH: We searched 14 databases in November 2017 and updated the search in December 2018 and February 2020. STUDY SELECTION CRITERIA: We included comparative studies that assessed the effect of early active shoulder movement versus delayed active shoulder movement following rotator cuff repair. DATA SYNTHESIS: Means and SDs were used to calculate weighted mean differences and 95% confidence intervals for outcomes of interest. The sensitivity analysis included only randomized controlled trials and was performed when heterogeneity among studies was statistically significant. RESULTS: Eight studies with a total of 756 participants (early active shoulder movement, n = 379; delayed active shoulder movement, n = 377) were included. There was high-certainty evidence favoring early active movement for forward flexion (6 weeks), abduction (6 weeks), and external rotation (6 weeks and 3 and 6 months) postsurgery. There was moderate-certainty evidence of worse Western Ontario Rotator Cuff Index score (6 weeks) for the early active movement group, and no difference in rotator cuff integrity between the early and delayed active movement groups. There were no group differences for all other outcomes. CONCLUSION: Patients who commenced active shoulder movement early after rotator cuff repair had greater shoulder range of motion and worse shoulder-specific quality of life after surgery than patients who delayed active shoulder movement. However, the group differences did not appear to be clinically important, and rotator cuff integrity was similar. J Orthop Sports Phys Ther 2021;51(7):331-344. Epub 15 May 2021. doi:10.2519/jospt.2021.9634.

Quorum quenching activity of Andrographis paniculata (Burm f.) Nees andrographolide compounds on metallo-ß-lactamase-producing clinical isolates of Pseudomonas aeruginosa PA22 and PA247 and their effect on lasR gene expression.

Andrographis paniculata (Burm f.) Nees is a tropical plant native to Southeast Asia that has been used as an effective remedy for a wide variety of illnesses in traditional Chinese and Ayurvedic medicine. The antimicrobial activity of its crude extract had been shown to be due to its quorum quenching activity. The study determined the effect of purified extracted compounds from the leaf of A. paniculata, namely: andrographolide, 14-deoxyandrographolide, 14-deoxy-12-hydroxyandrographolide and neoandrographolide on quorum sensing-mediated virulence mechanisms in clinical isolates of metallo-ß-lactamase (MßL)-producing Pseudomonas aeruginosa. Their effect on the expression of the lasR gene, which codes for LasR, a transcription activator protein of the quorum sensing system in P. aeruginosa was also determined using RT-qPCR. All the pure compounds significantly decreased the biofilm formation, protease production and swarming motility of the P. aeruginosa isolates compared to the untreated controls (p < 0.05). Results of the RT-qPCR assay showed that all compounds significantly downregulated the expression of lasR compared to the untreated control (p < 0.05), supporting the position that the lower virulence activities of the treated group were due to quorum quenching activity of the pure compounds. Multiple comparisons using Tukey's HSD analysis revealed that the means of the relative expression of lasR of the isolates treated with the different compounds were not significantly different from each other (p > 0.05), suggesting equal potencies. Results show the potential of the isolated pure compounds from A. paniculata for use as antimicrobial agents as a result of their quorum quenching activities.

Comparison of Chemical Composition and Biological Activities of Eight Selaginella Species.

Selaginella P. Beauv. is a group of vascular plants in the family Selaginellaceae Willk., found worldwide and numbering more than 700 species, with some used as foods and medicines. The aim of this paper was to compare methanolic (MeOH) and dichloromethane (DCM) extracts of eight Selaginella species on the basis of their composition and biological activities. Six of these Selaginella species are underinvestigated. Using ultra-high performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) analysis, we identified a total of 193 compounds among the tested Selaginella species, with flavonoids predominating. MeOH extracts recovered more constituents that were detected, including selaginellins, the occurrence of which is only typical for this plant genus. Of all the tested species, Selaginella apoda contained the highest number of identified selaginellins. The majority of the compounds were identified in S. apoda, the fewest compounds in Selaginella cupressina. All the tested species demonstrated antioxidant activity using oxygen radical absorption capacity (ORAC) assay, which showed that MeOH extracts had higher antioxidant capacity, with the half maximal effective concentration (EC50) ranging from 12 ± 1 (Selaginella myosuroides) to 124 ± 2 (Selaginella cupressina) mg/L. The antioxidant capacity was presumed to be correlated with the content of flavonoids, (neo)lignans, and selaginellins. Inhibition of acetylcholinesterase (AChE) was mostly discerned in DCM extracts and was only exhibited in S. myosuroides, S. cupressina, Selaginella biformis, and S. apoda extracts with the half maximal inhibitory concentration (IC50) in the range of 19 ± 3 to 62 ± 1 mg/L. Substantial cytotoxicity against cancer cell lines was demonstrated by the MeOH extract of S. apoda, where the ratio of the IC50 HEK (human embryonic kidney) to IC50 HepG2 (hepatocellular carcinoma) was 7.9 ± 0.2. MeOH extracts inhibited the production of nitrate oxide and cytokines in a dose-dependent manner. Notably, S. biformis halved the production of NO, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 at the following concentrations: 105 ± 9, 11 ± 1, and 10 ± 1 mg/L, respectively. Our data confirmed that extracts from Selaginella species exhibited cytotoxicity against cancer cell lines and AChE inhibition. The activity observed in S. apoda was the most promising and is worth further exploration.

Evidence-based Medicine Simulation: A Novel and Practice-relevant Approach to Teaching Real-time Literature Searching to Emergency Medicine Residents.

INTRODUCTION: Evidence-based medicine (EBM) and literature searching skills are competencies within the emergency medicine (EM) residency curriculum. Previously in our residency program, a librarian taught literature searching instruction, including a classroom-based overview of search engines. Learners reported low engagement and poor retention. To improve engagement, interest, and skill retention, we used a novel approach: simulation to teach real-time literature searching. METHODS: Based on a needs assessment of our EM residents, we created a literature searching workshop using a flipped classroom approach and high-fidelity simulation. Goals of the session were to be interactive, engaging, and practice-relevant. With a librarian, we developed a brief list of EM-relevant databases, including tips for searching and links to sites/apps. Prereadings also covered the hierarchy of evidence and formulating a good clinical (PICO) question. Residents (12 junior residents) participated in a high-fidelity simulation involving a stable patient whose management required a literature search to inform decisions. Feedback was collected on the simulation experience. RESULTS: Residents received the list of EM-relevant databases 7 days prior and were instructed to set up and test the resources on their smartphones. The day of the session, one resident volunteered to lead the simulation; all residents participated in the search on their smart phones. Collectively, it took 4.5 minutes to find a study that adequately addressed the clinical question and to manage the patient accordingly. Feedback on the simulation was positive. Students found it "very real and practical" and "immediately institutable into practice." It helped residents learn to efficiently and effectively search the literature while managing a stable patient. CONCLUSION: A flipped-classroom simulation-based teaching strategy made learning literature searching more interesting, engaging, and applicable to EM practice. Based on popular demand, we will continue to use this teaching method.

Prone cardiopulmonary resuscitation: A scoping and expanded grey literature review for the COVID-19 pandemic.

AIM: To identify and summarize the available science on prone resuscitation. To determine the value of undertaking a systematic review on this topic; and to identify knowledge gaps to aid future research, education and guidelines. METHODS: This review was guided by specific methodological framework and reporting items (PRISMA-ScR). We included studies, cases and grey literature regarding prone position and CPR/cardiac arrest. The databases searched were MEDLINE, Embase, CINAHL, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, Scopus and Google Scholar. Expanded grey literature searching included internet search engine, targeted websites and social media. RESULTS: Of 453 identified studies, 24 (5%) studies met our inclusion criteria. There were four prone resuscitation-relevant studies examining: blood and tidal volumes generated by prone compressions; prone compression quality metrics on a manikin; and chest computed tomography scans for compression landmarking. Twenty case reports/series described the resuscitation of 25 prone patients. Prone compression quality was assessed by invasive blood pressure monitoring, exhaled carbon dioxide and pulse palpation. Recommended compression location was zero-to-two vertebral segments below the scapulae. Twenty of 25 cases (80%) survived prone resuscitation, although few cases reported long term outcome (neurological status at hospital discharge). Seven cases described full neurological recovery. CONCLUSION: This scoping review did not identify sufficient evidence to justify a systematic review or modified resuscitation guidelines. It remains reasonable to initiate resuscitation in the prone position if turning the patient supine would lead to delays or risk to providers or patients. Prone resuscitation quality can be judged using end-tidal CO2, and arterial pressure tracing, with patients turned supine if insufficient.

Antioxidant, Cytotoxicity, and Antiophidian Potential of Alstonia macrophylla Bark.

The objective of this research was to find the possible pharmacognosy of the bark of the Philippine Alstonia macrophylla Wall. ex G.Don (AM). Gas chromatographic-mass spectral (GC-EI-MS) characterization and energy dispersive X-ray spectroscopy (EDX) were performed to detect the bioactive constituents. EDX analysis of AM bark displayed a high content of potassium (3.26%) and calcium (2.96%). Eight constituents were detected in AM crude dichloromethane (DCM) extracts, which consisted of a long-chain unsaturated fatty acid (17:0) and fatty acid esters such as ethyl hexadecanoate and methyl hexadecanoate. Extraction of AM bark using methanol and dimethyl sulfoxide (MeOH/DMSO) solvents resulted in the identification of 17 constituents, principally alkaloids (alstonerine, 34.38%; strictamin, 5.23%; rauvomitin, 4.29%; and brucine, 3.66%) and triterpenoids (γ-sitosterol, 3.85%; lupeol, 3.00%; 24-methylenecycloartanol, 2.81%; campesterol, 2.71%; ß-amyrin, 2.30%; and stigmasterol, 2.13%). MeOH/DMSO samples of AM were used in the selected bioassays. The samples exhibited efficient free radical scavenging activity (IC50 = 0.71 mg/mL) and were noncytotoxic to normal HDFn (IC50 > 100 µg/mL) and neoplastic THP-1 cell lines (IC50 = 67.22 µg/mL) while highly degenerative to MCF-7 (IC50 = 6.34 µg/mL), H69PR (IC50 = 7.05 µg/mL), and HT-29 (IC50 = 9.10 µg/mL). Most interestingly, the AM samples inhibited the northern Philippine Cobra's (Naja philippinensis Taylor) venom (IC50 = 297.27 ± 9.33 µg/mL) through a secretory phospholipase A2 assay.

Cognitive and behavioral improvement in adults with fragile X syndrome treated with metformin-two cases.

BACKGROUND: The majority of individuals with fragile X syndrome (FXS) have intellectual disability, behavioral problems, autism, and language deficits. IQ typically declines with age in boys with the full mutation. The results of preclinical studies demonstrated that metformin, a biguanide used to treat type 2 diabetes, rescues multiple phenotypes of FXS in both Drosophila and mouse models. Preliminary studies of patients with FXS demonstrated improvements in behavior. METHODS: Here, we present two cases of individuals who have been treated with metformin clinically for one year. RESULTS: Both patients demonstrated significant cognitive and behavioral improvements. They also improved eating habits and normalization of their weight percentiles. CONCLUSION: Metformin may be a candidate drug for treatment of several types of symptoms in individuals with FXS.

The role of exercise in improving patient-reported outcomes in individuals on dialysis: A scoping review.

Exercise improves objective measures of physical function in individuals on hemodialysis, but its effect on patient-reported outcomes (PROs) is largely unknown. We performed a scoping review to characterize the existing knowledge base on exercise and PROs in dialysis patients to make recommendations for future research. We searched Medline, Embase, Cochrane Database of Systematic Reviews; Cochrane Central Register of Controlled Trials, CINAHL, and SPORT Discus from inception to November 28, 2018 and then screened results for randomized controlled trials comparing aerobic/resistance exercise, or both, with no exercise in individuals on dialysis that reported results of any PRO. Of 1374 eligible studies, 25 studies met inclusion criteria. Study interventions included aerobic exercise (11 intradialytic and 3 home-based trials); intradialytic resistance exercise (seven studies) and combined aerobic and resistance exercise (six intradialytic and one facility-based trial). The PROs measured included health-related quality of life (n = 19), depression (n = 6), anxiety (n = 3), symptom burden (n = 4), sleep quality (n = 2), restless legs syndrome (n = 2), disability (n = 2), and self-reported physical activity level (n = 4). Only five studies included a PRO as a primary outcome. Studies primarily used broad/generic measures of health-related quality of life and the effect of exercise on symptoms remains relatively unexplored, particularly in peritoneal dialysis populations. Although limited, the role of exercise in improving restless legs was consistent and is a promising outcome for future study. A critical step to improving the quality of the research on this topic includes the use of validated and consistent PRO measures.

Fragile X- associated Neuropsychiatric Disorders: A Case Report.

Mutations in the Fragile X Mental Retardation 1 (FMR1) gene create a spectrum of developmental disorders in children in addition to neurodegenerative problems in older populations. Two types of mutations are recognized in the FMR1 gene. The full mutation (>200 CGG repeats) in the FMR1 gene leads to Fragile X Syndrome which is the most common inherited cause of intellectual disability and autism, while the premutation (55 to 200 CGG repeats) identified among carriers leads to a range of problems linked to elevated levels of the FMR1 mRNA leading to mRNA toxicity and occasionally mildly deficient FMRP levels. Two disorders among premutation carriers have been recognized namely: the Fragile X-associated Primary Ovarian Insufficiency (FXPOI) and Fragile X-associated Tremor/Ataxia Syndrome (FXTAS). Recently, in order to recognize a group of associated disorders commonly found in premutation carriers and extensively reported in co-morbidities studies, a new distinctive name was proposed: Fragile X-associated Neuropsychiatric Disorders (FXAND). This paper will present a case report of a female premutation carrier who has encountered predominantly psychiatric problems, but also chronic pain and sleep disturbances consistent with FXAND.

Global Perspectives on Children's Digital Opportunities: An Emerging Research and Policy Agenda.

Diverse international perspectives show that children can benefit greatly from digital opportunities. Despite widespread optimism about the potential of digital technologies, especially for information and education, the research reveals an insufficient evidence base to guide policy and practice across all continents of the world, especially in middle- and low-income countries. Beyond revealing pressing and sizeable gaps in knowledge, this cross-national review also reveals the importance of understanding local values and practices regarding the use of technologies. This leads us to stress that future researchers must take into account local contexts and existing inequalities and must share best practices internationally so that children can navigate the balance between risks and opportunities. This article documents the particular irony that while the world's poorer countries look to research to find ways to increase access and accelerate the fair distribution of digital educational resources, the world's wealthier countries look to research for guidance in managing excessive screen time, heavily commercial content, and technologies that intrude on autonomy and privacy. We conclude by recommending that digital divides should be carefully bridged with contextual sensitivity to avoid exacerbating existing disparities; that the provision of technological resources is complemented by a focus on skills enhancement, for teachers as well as students; that a keen eye is needed to ensure the balance of children's protection and participation rights, with protection now including data abuses as well as safety considerations; and that we forge collaborations among all stakeholders in seeking to enhance children's digital opportunities worldwide.

The impact on patients of a nurse-led clinical service in gastroenterology.

Higher rates of chronic liver disease have resulted in a significant increase in the number of patients needing regular abdominal paracentesis for ascites. Waiting times for admission at the Royal Wolverhampton NHS Trust had become longer and delays in intervention and treatment became inevitable. In 2014, the Trust developed a nurse-led abdominal paracentesis day-case service. A qualitative evaluation of the service was conducted using in-depth patient interviews and surveys to determine the impact of the service, including how the new nursing role affected the patient experience. The results show that the nurse-led clinical service in gastroenterology positively impacts patients' experiences. Following this innovation, the service was extended to provide intravenous infusions for gastroenterology patients via the day-case unit. With appropriate training and competency assessments, nurses can now perform selected medical procedures safely and effectively, thereby facilitating nursing staff to expand and develop their roles. This development has substantial implications for nursing and is an important contribution to the debate on the future direction of the nursing profession.

Relationship between interpersonal trauma exposure and addictive behaviors: a systematic review.

BACKGROUND: The aim of this study was to systematically summarize knowledge on the association between exposure to interpersonal trauma and addictive behaviors. Extant reviews on this association focused on a restricted range of substance-related addictions, and/or used a narrative instead of a systematic approach. METHODS: Systematic searches of 8 databases yielded 29,841 studies, of which 3054 studies were included and subsequently classified in relation to study design (scoping review). A subset of observational studies (N = 181) prospectively investigating the relationship between exposure to interpersonal traumata and subsequent behavioral or substance-related addiction problems were characterized. Heterogeneity in study methodologies and types of addictive behaviors and traumatic experiences assessed precluded meta-analysis. Instead, the proportions of associations tested in this literature that revealed positive, negative, or null relationships between trauma exposure and subsequent addictive behaviors were recorded, along with other methodological features. RESULTS: Of 3054 included studies, 70.7% (n = 2160) used a cross-sectional design. In the 181 prospective observational studies (407,041 participants, 98.8% recruited from developed countries), 35.1% of the tested associations between trauma exposure and later addictive behaviors was positive, 1.3% was negative, and 63.6% was non-significant. These results were primarily obtained among non-treatment seeking samples (80.7% of studies; n = 146), using single and multi-item measures of addictive behaviors of unknown psychometric quality (46.4% of studies). Positive associations were more frequently observed in studies examining childhood versus adult traumatization (39.7% vs. 29.7%). CONCLUSIONS: Longitudinal research in this area emphasizes alcohol abuse, and almost no research has examined behavioral addictions. Results provide some support for a positive association between exposure to interpersonal trauma and subsequent addictive behaviors but this relationship was not consistently reported. Longitudinal studies typically assessed trauma exposure retrospectively, often after addictive behavior onset, thus precluding robust inferences about whether traumatization affects initial onset of addictive behaviors.

Physical activity in advanced cancer patients: a systematic review protocol.

BACKGROUND: Progressive, incurable cancer is associated with increased fatigue, increased muscle weakness, and reduced physical functioning, all of which negatively impact quality of life. Physical activity has demonstrated benefits on cancer-related fatigue and physical functioning in early-stage cancer patients; however, its impact on these outcomes in end-stage cancer has not been established. The aim of this systematic review is to determine the potential benefits, harms, and effects of physical activity interventions on quality of life outcomes in advanced cancer patients. METHODS/DESIGN: A systematic review of peer-reviewed literature on physical activity in advanced cancer patients will be undertaken. Empirical quantitative studies will be considered for inclusion if they present interventional or observational data on physical activity in advanced cancer patients. Searches will be conducted in the following electronic databases: CINAHL; CIRRIE Database of International Rehabilitation Research; Cochrane Database of Systematic Reviews (CDSR); Database of Abstracts of Reviews of Effects (DARE); Cochrane Central Register of Controlled Trials (CENTRAL); EMBASE; MEDLINE; PEDro: the Physiotherapy Evidence Database; PQDT; PsycInfo; PubMed; REHABDATA; Scopus; SPORTDiscus; and Web of Science, to identify relevant studies of interest. Additional strategies to identify relevant studies will include citation searches and evaluation of reference lists of included articles. Titles, abstracts, and keywords of identified studies from the search strategies will be screened for inclusion criteria. Two independent reviewers will conduct quality appraisal using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies (EPHPP) and the Cochrane risk of bias tool. A descriptive summary of included studies will describe the study designs, participant and activity characteristics, and objective and patient-reported outcomes. DISCUSSION: This systematic review will summarize the current evidence base on physical activity interventions in advanced cancer patients. The findings from this systematic review will identify gaps to be explored by future research studies and inform future practice guideline development of physical activity interventions in advanced cancer patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015026281.