Adaptation to ex vivo culture reduces human hematopoietic stem cell activity independently of cell cycle.

Loss of long-term hematopoietic stem cell (LT-HSC) function ex vivo hampers the success of clinical protocols reliant on culture. However, the kinetics and mechanisms by which this occurs remain incompletely characterized. Here, through time-resolved scRNA-Seq, matched in vivo functional analysis and the use of a reversible in vitro system of early G1 arrest, we define the sequence of transcriptional and functional events occurring during the first ex vivo division of human LT-HSCs. We demonstrate that the sharpest loss of LT-HSC repopulation capacity happens early on, between 6 and 24 hours of culture, before LT-HSCs commit to cell cycle progression. During this time window, LT-HSCs adapt to the culture environment, limiting global variability in gene expression and transiently upregulating gene networks involved in signaling and stress responses. From 24 hours, LT-HSC progression past early G1 contributes to the establishment of differentiation programmes in culture. However, contrary to current assumptions, we demonstrate that loss of HSC function ex vivo is independent of cell cycle progression. Finally, we show that targeting LT-HSC adaptation to culture by inhibiting early activation of JAK/STAT signaling improves HSC long-term repopulating function ex vivo. Collectively, our study demonstrates that controlling early LT-HSC adaptation to ex vivo culture, for example via JAK inhibition, is of critical importance to improve HSC gene therapy and expansion protocols.

"This is real", "this is hard" and "I'm not making it up": Experience of diagnosis and living with non-epileptic attack disorder.

PURPOSE: To use a qualitative research approach to explore adults' experience of living with non-epileptic attack disorder. OBJECTIVE: The objective was to explore the experience of adults (18 years+) with a confirmed diagnosis of non-epileptic attack disorder (NEAD) across the trajectory of the disorder. The topics investigated included the onset of symptoms, the experience of non-epileptic attacks, the diagnostic process and living with NEAD. METHOD: Twelve people diagnosed with NEAD who attended a tertiary hospital neurology department took part in semi-structured interviews. The data generated were analysed using reflexive thematic analysis. RESULTS: Eleven women and one man with median age of 25 years took part. Three themes were developed: mind-body (dis)connect, a stigmatised diagnosis and a role for containment. Adults spoke about their experience of nonepileptic attacks, the diagnostic and management process and the impact of both nonepileptic attacks and the NEAD diagnosis on their lives. CONCLUSIONS: Adults' experience's within the healthcare system across the trajectory of NEAD influenced their own understanding and trust in their NEAD experience, how they shared this with others in their social and work lives and how they managed their NEAD symptoms on a daily basis. The research suggests the need for a consistent, timely implementation of a rule-in diagnostic approach and multi-disciplinary management of NEAD. It is recommended that lessons be taken from theoretical models including the common-sense model and a modified version of the reattribution model to support the de-stigmatisation of this diagnosis to inform psychoeducation and professionally facilitated peer-support groups.

'No one else understands', 'I wouldn't want to pity myself over something that's not really my problem': siblings' experiences of their adolescent brothers and sisters' inpatient treatment for mental health difficulties.

BACKGROUND: Family life is disrupted when a child experiences mental health difficulties. This can have long-standing effects on sibling relationships. This study explores the lived experiences of young people who have an adolescent sibling hospitalised for treatment of a mental health difficulty. METHOD: Semi-structured interviews of 45-60 min were conducted to explore the experiences of 10 siblings (6 sisters/4 brothers aged 13-22) of nine patients (5 sisters/4 brothers aged 15-17) receiving treatment for a mental health difficulty in a child and adolescent inpatient unit (IPU). Interpretative phenomenological analysis was used to analyse the data. RESULTS: Two superordinate themes were identified: 'Who am I if I'm not supporting them?' and 'On the fringes: actively involved but from the outside'. The interplay of these two super-ordinate themes was found to influence the five sub-ordinate themes: 'Confusion and disbelief', 'Don't worry about me, focus on them.', 'Powerless when I need to be powerful.', 'Helping or hindering- what is this place??' and 'Knowledge is power.' CONCLUSION: Siblings described experiencing conflicting and confusing emotions which may impact their attendance in IPU and engagement in siblings' treatment. Siblings of adolescents in inpatient treatment for mental health difficulties may be at increased risk of experiencing psychological distress. The mental well-being of siblings must be borne in mind by child and adolescent inpatient services supporting families in crisis.

Hypergonadotropic hypogonadism and chromosomal aberrations: clinical heterogeneity and implications on the health of elderly men, case series.

BACKGROUND: Hypogonadism in older men is often considered as late onset hypogonadism. However, this clinical condition results from primary testicular failure which could be of genetic origin with Klinefelter syndrome being the most common chromosomal abnormality associated with it. CASE PRESENTATION: We report a heterogeneous group of cases who were diagnosed with hypergonadotropic hypogonadism in their adulthood and were found to have rare chromosomal aberrations. All were elderly men (in their 70 s and 80 s) for whom the diagnosis was made during the evaluation of incidental symptoms suggestive of endocrinopathy. The first had hyponatremia; the other two had gynaecomastia and features of hypogonadism noted during admission for various acute medical problems. With respect to their genetic results; the first had a male karyotype with balanced reciprocal translocation between the long arm of chromosome 4 and the short arm of chromosome 7. The second case had a male karotype with one normal X chromosome and an isochrome for the short arm of the Y chromosome. The third case was an XX male with unbalanced translocation between the X & Y chromosomes with retention of the SRY locus. CONCLUSION: Hypergonadotrophic hypogonadism in the elderly, may be due to chromosomal aberrations, resulting in heterogeneous and diverse clinical phenotypes. Vigilance must be exercised when seeing cases with subtle clinical findings. This report suggests that in selected cases of adult hypergonadotropic hypogonadism, chromosomal analysis may be indicated.

Parents Plus parenting programme for parents of adolescents with intellectual disabilities: A cluster randomised controlled trial.

OBJECTIVE: This study evaluated the effectiveness of the Parents Plus Special Needs (PPSN) programme, a seven-week parenting group intervention for parents of adolescents with intellectual disabilities. METHOD: In a cluster randomised controlled trial, 24 intellectual disability services supporting families of adolescents with an intellectual disability were assigned to PPSN (12 services; 141 parents) or waitlist control group (12 services; 136 parents). Primary outcomes were parent-reported parenting practices, family adjustment, problem behaviours, emotional problems, and prosocial behaviours. Secondary outcomes were parental satisfaction, parental self-efficacy, and goal attainment. RESULTS: Compared to the waitlist group, participants in the PPSN group reported improvements in parenting practices, problem behaviours, parental satisfaction, parental self-efficacy and goal attainment, which were retained at 3-month follow-up. There were additional gains for family adjustment at follow-up. CONCLUSION: The PPSN is effective in improving parenting behaviour, family relationships, and problem behaviours in adolescents, but not in improving emotional difficulties.

Mental health and resilience in the Irish defense forces during the COVID-19 global pandemic.

The Irish Defense Forces (DF) responded to the COVID-19 pandemic and national public health crisis by deploying personnel to aid domestic civil authorities in medical and care settings, contact tracing, logistics, and operations. Current research on COVID-19 reveals increased psychological distress among frontline workers and the general public. Resilience has previously been associated with lower levels of psychological distress. This study sets out to test these associations, and to examine mental health differences between DF personnel deployed in Ireland on pandemic-related duties (DIPD) and non-DIPD. Participants were 231 DF members who completed the: Connor-Davidson Resilience Scale-10, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Perceived Coronavirus Threat Questionnaire, Brief Trauma Questionnaire, Post-traumatic Stress Disorder Checklist-5, and Alcohol Use Disorder Identification Test. Independent t-tests revealed no differences between DIPD and non-DIPD on measures of psychological distress or on self-rated mental health prior to COVID-19 (PC19) and during COVID-19 (DC19). Results of multiple hierarchical regression analyses revealed that depression predicted lower levels of resilience, while multiple traumatic events predicted higher levels of resilience. The total adjusted variance explained by the model was 25%. Clinical and policy implications for improving access to psychological support within the DF and military populations are discussed.

Parents' Experiences of Their Child's Solid-Organ Transplant: A Meta-Ethnography of Qualitative Studies.

OBJECTIVE: The aim of this paper was to conduct a systematic review and meta-ethnography of qualitative studies examining the experiences of parents adjusting to life after the solid organ transplant (SOT) of their child. METHODS: A systematic review of the literature was conducted to identify qualitative studies that examined this topic. The search retrieved 4,964 studies to review against inclusion criteria. A total of 21 studies were included in the meta-ethnography. A reciprocal translation was conducted to compare themes identified in each study. A line of argument synthesis was then conducted in order to integrate the similarities and differences between all of the studies into a new interpretative context. RESULTS: The synthesis identified four themes: (a) adjusting to life after transplant, (b) factors that facilitate adjustment, (c) factors that disrupt adjustment, and (d) changes caused by transplant. As a result of the synthesis, a new interpretation of parents' experiences of adjusting to life after the SOT of their child was constructed. A summary figure is presented. CONCLUSION: This review found that while parents may struggle to adapt to life post-transplant and the demands of caring for their child, the experience can also result in the development of new skills, a new appreciation for life, and viewing the self in a more positive manner. A better understanding of parental experiences will promote the development of more effective interventions for the adjustment of parents and families to post-transplant life.

Beliefs About Worry and Pain Amongst Adolescents With and Without Chronic Pain.

OBJECTIVE: To explore beliefs about worries, beliefs about pain, and worries about pain held by adolescents with and without chronic pain. METHODS: Adolescents with and without chronic pain aged 14-19 completed an online survey with free text questions about pain and worry. We collected demographics and used the Penn State Worry Questionnaire and Pain Catastrophizing Scale for Children to contextualize the qualitative data, which was analyzed with reflexive thematic analysis. RESULTS: Eighty-one participants completed the survey, 36 with chronic pain and 45 without (mean age: 16.73). Compared to adolescents without chronic pain, adolescents living with chronic pain reported significantly higher general worry and pain catastrophizing. Thematic analysis generated two themes, "Worry changes perceptions of selfhood" and "Pain changes perceptions of selfhood." Each theme comprised two sub-themes showing how current and future identity trajectories were distorted by worry and pain. The theme "Pain changes perceptions of selfhood" also included a third sub-theme: "Pain impedes future working choices." Worry content as well as process was problematic in all adolescents. Adolescents experiencing chronic pain had specific, additional worries that pain reduces future career progression. These worries appeared highly salient and challenging. CONCLUSIONS: Adolescents may need greater support in recognizing worry as part of normative development. Adolescents in pain may benefit from specific support identifying and reducing how pain-related worries interact with their futures and careers, and from school-based and vocational interventions to reduce the realistic risks they face negotiating modern labor markets.

"Why Isn't It Going Away?": A Qualitative Exploration of Worry and Pain Experiences in Adolescents with Chronic Pain.

INTRODUCTION: The role of cognition is central to the fear avoidance (FA) model of chronic pain (CP), which emphasizes the importance of catastrophic pain interpretations and has been shown to be applicable to pediatric CP populations. However, while we know that pain catastrophizing plays a distinct role in influencing outcomes for children with CP, we know little about the specifics of how young people with CP experience catastrophizing and worry, as well as their general pain beliefs. OBJECTIVE: To qualitatively explore beliefs about and experiences of worry and pain among a purposeful sample of adolescents with CP. METHODS: Individual semistructured interviews with 12 adolescents (aged 12-17) with varying forms of CP attending an outpatient pain clinic in a general children's hospital. Relevant psychometric measures were administered orally to further inform the data. Data were analyzed using critical realist thematic analysis. RESULTS: Three themes and one subtheme were identified. Themes were 1) the worry ripple: mind, body, and behavior (subtheme: worry content: personal competence and health); 2) the pain mystery: living in a "scribble of black"; and 3) the resist or avoid conundrum. CONCLUSIONS: The findings highlight the need for psychological interventions targeting acceptance of uncertainty and also informing education on mind/body connections in adolescents with CP.

Quality improvement strategies to prevent falls in older adults: a systematic review and network meta-analysis.

BACKGROUND: Falls are a common occurrence and the most effective quality improvement (QI) strategies remain unclear. METHODS: We conducted a systematic review and network meta-analysis (NMA) to elucidate effective quality improvement (QI) strategies for falls prevention. Multiple databases were searched (inception-April 2017). We included randomised controlled trials (RCTs) of falls prevention QI strategies for participants aged ≥65 years. Two investigators screened titles and abstracts, full-text articles, conducted data abstraction and appraised risk of bias independently. RESULTS: A total of 126 RCTs including 84,307 participants were included after screening 10,650 titles and abstracts and 1210 full-text articles. NMA including 29 RCTs and 26,326 patients found that team changes was statistically superior in reducing the risk of injurious falls relative to usual care (odds ratio [OR] 0.57 [0.33 to 0.99]; absolute risk difference [ARD] -0.11 [95% CI, -0.18 to -0.002]). NMA for the outcome of number of fallers including 61 RCTs and 40 128 patients found that combined case management, patient reminders and staff education (OR 0.18 [0.07 to 0.47]; ARD -0.27 [95% CI, -0.33 to -0.15]) and combined case management and patient reminders (OR, 0.36 [0.13 to 0.97]; ARD -0.19 [95% CI, -0.30 to -0.01]) were both statistically superior compared to usual care. CONCLUSIONS: Team changes may reduce risk of injurious falls and a combination of case management, patient reminders, and staff education, as well as case management and patient reminders may reduce risk of falls. Our results can be tailored to decision-maker preferences and availability of resources. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42013004151).

A network analysis of the causal attributions for obesity in children and adolescents and their parents.

Illness attributions inform how people understand illness and relate to psychological outcomes. Parental attributions may impact children's adjustment to illness. This study investigated child, adolescent and parental causal attributions in paediatric obesity and illustrates the relationships between these attributions using network analysis. A cross-sectional design using the diagram network analytic method. Thirty children and 25 parents generated individual causal attribution maps. Network theory was used to analyse causal effects and results were visualised using network models. The results indicated large individual variation in the networks. Activity and eating-related variables featured strongly in child and parent networks. Children viewed their activity while parents regarded their child's eating behaviours as the main drivers of obesity. The characterisation of some children along an internalising dimension was supported in both networks. Habitual cluster behaviours and difficulties in regulation were identified in the child network. Parents ascribed significance to the future impact of obesity on body image and mood. Challenges in parent management were also indicated. Obesity is a heterogeneous condition, requiring a tailored treatment approach. Therapeutic directions were identified in the areas of activity, food intake, sleep hygiene and parent management. Attributional processes represent a potential mechanism to tailor obesity treatment. Further research is needed to establish the relationship between attributions, treatment engagement and outcome.

Development and maturation of the fibrous components of the arterial roots in the mouse heart.

The arterial roots are important transitional regions of the heart, connecting the intrapericardial components of the aortic and pulmonary trunks with their ventricular outlets. They house the arterial (semilunar) valves and, in the case of the aorta, are the points of coronary arterial attachment. Moreover, because of the semilunar attachments of the valve leaflets, the arterial roots span the anatomic ventriculo-arterial junction. By virtue of this arrangement, the interleaflet triangles, despite being fibrous, are found on the ventricular aspect of the root and located within the left ventricular cavity. Malformations and diseases of the aortic root are common and serious. Despite the mouse being the animal model of choice for studying cardiac development, few studies have examined the structure of their arterial roots. As a consequence, our understanding of their formation and maturation is incomplete. We set out to clarify the anatomical and histological features of the mouse arterial roots, particularly focusing on their walls and the points of attachment of the valve leaflets. We then sought to determine the embryonic lineage relationships between these tissues, as a forerunner to understanding how they form and mature over time. Using histological stains and immunohistochemistry, we show that the walls of the mouse arterial roots show a gradual transition, with smooth muscle cells (SMC) forming the bulk of wall at the most distal points of attachments of the valve leaflets, while being entirely fibrous at their base. Although the interleaflet triangles lie within the ventricular chambers, we show that they are histologically indistinguishable from the arterial sinus walls until the end of gestation. Differences become apparent after birth, and are only completed by postnatal day 21. Using Cre-lox-based lineage tracing technology to label progenitor populations, we show that the SMC and fibrous tissue within the walls of the mature arterial roots share a common origin from the second heart field (SHF) and exclude trans-differentiation of myocardium as a source for the interleaflet triangle fibrous tissues. Moreover, we show that the attachment points of the leaflets to the walls, like the leaflets themselves, are derived from the outflow cushions, having contributions from both SHF-derived endothelial cells and neural crest cells. Our data thus show that the arterial roots in the mouse heart are similar to the features described in the human heart. They provide a framework for understanding complex lesions and diseases affecting the aortic root.

Mono-Substituted Hydrocarbon Diastereomer Combinations Reveal Stapled Peptides with High Structural Fidelity.

Modified peptides, such as stapled peptides, which replicate the structure of α-helical protein segments, represent a potential therapeutic advance. However, the 3D solution structure of these stapled peptides is rarely explored beyond the acquisition of circular dichroism (CD) data to quantify bulk peptide helicity; the detailed backbone structure, which underlies this, is typically undefined. Diastereomeric stapled peptides based on helical sections of three proteins (αSyn, Cks1 and CK1α) were generated; their overall helicity was quantified by CD; and the most helical peptide from each series was selected for structural analysis. Solution-phase models for the optimised peptides were generated using NMR-derived restraints and a modified CHARMM22 force field. Comparing these models with PDB structures allowed deviation between the stapled peptides and critical helical regions to be evaluated. These studies demonstrate that CD alone is not sufficient to assess the structural fidelity of a stapled peptide.

Pharmacist-led depression screening and intervention in an underserved, rural, and multi-ethnic diabetic population.

OBJECTIVES: To test the feasibility of implementation and integration of community pharmacist-led depression screening for patients with diabetes in an underserved rural area and to assess the response rate of prescribers to pharmacist-led depression screening and treatment recommendation. SETTING: Independent community pharmacy-run diabetes education center. PRACTICE DESCRIPTION: Clinical community pharmacy site on Maryland's Eastern Shore. PRACTICE INNOVATION: All patients with uncontrolled diabetes (A1C >7%) 18 years of age and older attending one or both diabetes self-management classes and diabetic counseling completed the Patient Health Questionnaire 9 (PHQ-9). Those with moderate to severe cognitive impairment or preexisting mental illness except for anxiety or untreated/undertreated depression were excluded from the results. A copy of the screening was faxed to the referring provider with an accompanying letter. Positive screening reports included a suggestion for further evaluation and possible pharmacologic treatment. EVALUATION: Data collected (PHQ-9 scores, provider response rate, and A1C) were analyzed with the use of appropriate evaluation tools. RESULTS: Of the 57 patients who took the screening, 11 (19.3%) were positive and 46 (80.7%) negative for possible depression. Responses were received from providers on 3 of the 11 patients who screened positive, and no providers initiated depression treatment. The site plans to continue data collection following this residency's completion to assess clinical impact. CONCLUSION: This model may be replicated at many community pharmacies to integrate a depression screening. Based on prescribers' response rate, faxing alone is not recommended as the primary communication with the provider, and an alternate method should be assessed to effectively recommend pharmacologic therapy for patients with positive depression screenings.

Anatomical Examination of Mandibular Condyle Protrusion Into the Middle Cranial Fossa.

Trauma to the mandible can occasionally be a life-threatening event. Although extremely rare with only 56 reported patients in the English language, fracture of the floor of the middle cranial fossa with protrusion of the mandibular condyle into the middle cranial fossa was first reported in 1963 by Dingman. The authors review the anatomy of the temporomandibular joint in relation to the middle cranial fossa and demonstrate the possible complications due to condylar intrusion with anatomical dissection.

Engaging with and navigating limbo: Lived experiences of siblings of adults with autism spectrum disorders.

BACKGROUND: Supporting an adult with autism spectrum disorder (ASD) can be associated with family stress but also with personal growth and resilience. Research providing insight into how typically developing siblings make sense of their unique sibling relationships in adulthood remains limited. METHOD: Using interpretative phenomenological analysis, this study explored subjective experiences of eight siblings of adults with ASD and co-occurring intellectual disability. RESULTS: Analysis of interview transcripts revealed a complex lived experience explained by the overarching theme "engaging with and navigating limbo", which was characterized by commitment to the sibling relationship, power tensions in the family, uncertainty about the future and negotiating the tension between relational closeness and distance. CONCLUSION: Using family systems theory, overregulation and closed communication emerged as processes relevant to families living with ASD. Clinical opportunities to support family communication, change tolerance and belonging are discussed.

LacI Transcriptional Regulatory Networks in Clostridium thermocellum DSM1313.

Organisms regulate gene expression in response to the environment to coordinate metabolic reactions. Clostridium thermocellum expresses enzymes for both lignocellulose solubilization and its fermentation to produce ethanol. One LacI regulator termed GlyR3 in C. thermocellum ATCC 27405 was previously identified as a repressor of neighboring genes with repression relieved by laminaribiose (a ß-1,3 disaccharide). To better understand the three C. thermocellum LacI regulons, deletion mutants were constructed using the genetically tractable DSM1313 strain. DSM1313 lacI genes Clo1313_2023, Clo1313_0089, and Clo1313_0396 encode homologs of GlyR1, GlyR2, and GlyR3 from strain ATCC 27405, respectively. Growth on cellobiose or pretreated switchgrass was unaffected by any of the gene deletions under controlled-pH fermentations. Global gene expression patterns from time course analyses identified glycoside hydrolase genes encoding hemicellulases, including cellulosomal enzymes, that were highly upregulated (5- to 100-fold) in the absence of each LacI regulator, suggesting that these were repressed under wild-type conditions and that relatively few genes were controlled by each regulator under the conditions tested. Clo1313_2022, encoding lichenase enzyme LicB, was derepressed in a ΔglyR1 strain. Higher expression of Clo1313_1398, which encodes the Man5A mannanase, was observed in a ΔglyR2 strain, and α-mannobiose was identified as a probable inducer for GlyR2-regulated genes. For the ΔglyR3 strain, upregulation of the two genes adjacent to glyR3 in the celC-glyR3-licA operon was consistent with earlier studies. Electrophoretic mobility shift assays have confirmed LacI transcription factor binding to specific regions of gene promoters.IMPORTANCE Understanding C. thermocellum gene regulation is of importance for improved fundamental knowledge of this industrially relevant bacterium. Most LacI transcription factors regulate local genomic regions; however, a small number of those genes encode global regulatory proteins with extensive regulons. This study indicates that there are small specific C. thermocellum LacI regulons. The identification of LacI repressor activity for hemicellulase gene expression is a key result of this work and will add to the small body of existing literature on the area of gene regulation in C. thermocellum.

Comparisons of Interventions for Preventing Falls in Older Adults: A Systematic Review and Meta-analysis.

Importance: Falls result in substantial burden for patients and health care systems, and given the aging of the population worldwide, the incidence of falls continues to rise. Objective: To assess the potential effectiveness of interventions for preventing falls. Data Sources: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Ageline databases from inception until April 2017. Reference lists of included studies were scanned. Study Selection: Randomized clinical trials (RCTs) of fall-prevention interventions for participants aged 65 years and older. Data Extraction and Synthesis: Pairs of reviewers independently screened the studies, abstracted data, and appraised risk of bias. Pairwise meta-analysis and network meta-analysis were conducted. Main Outcomes and Measures: Injurious falls and fall-related hospitalizations. Results: A total of 283 RCTs (159 910 participants; mean age, 78.1 years; 74% women) were included after screening of 10 650 titles and abstracts and 1210 full-text articles. Network meta-analysis (including 54 RCTs, 41 596 participants, 39 interventions plus usual care) suggested that the following interventions, when compared with usual care, were associated with reductions in injurious falls: exercise (odds ratio [OR], 0.51 [95% CI, 0.33 to 0.79]; absolute risk difference [ARD], -0.67 [95% CI, -1.10 to -0.24]); combined exercise and vision assessment and treatment (OR, 0.17 [95% CI, 0.07 to 0.38]; ARD, -1.79 [95% CI, -2.63 to -0.96]); combined exercise, vision assessment and treatment, and environmental assessment and modification (OR, 0.30 [95% CI, 0.13 to 0.70]; ARD, -1.19 [95% CI, -2.04 to -0.35]); and combined clinic-level quality improvement strategies (eg, case management), multifactorial assessment and treatment (eg, comprehensive geriatric assessment), calcium supplementation, and vitamin D supplementation (OR, 0.12 [95% CI, 0.03 to 0.55]; ARD, -2.08 [95% CI, -3.56 to -0.60]). Pairwise meta-analyses for fall-related hospitalizations (2 RCTs; 516 participants) showed no significant association between combined clinic- and patient-level quality improvement strategies and multifactorial assessment and treatment relative to usual care (OR, 0.78 [95% CI, 0.33 to 1.81]). Conclusions and Relevance: Exercise alone and various combinations of interventions were associated with lower risk of injurious falls compared with usual care. Choice of fall-prevention intervention may depend on patient and caregiver values and preferences.

A scoping review on the conduct and reporting of scoping reviews.

BACKGROUND: Scoping reviews are used to identify knowledge gaps, set research agendas, and identify implications for decision-making. The conduct and reporting of scoping reviews is inconsistent in the literature. We conducted a scoping review to identify: papers that utilized and/or described scoping review methods; guidelines for reporting scoping reviews; and studies that assessed the quality of reporting of scoping reviews. METHODS: We searched nine electronic databases for published and unpublished literature scoping review papers, scoping review methodology, and reporting guidance for scoping reviews. Two independent reviewers screened citations for inclusion. Data abstraction was performed by one reviewer and verified by a second reviewer. Quantitative (e.g. frequencies of methods) and qualitative (i.e. content analysis of the methods) syntheses were conducted. RESULTS: After searching 1525 citations and 874 full-text papers, 516 articles were included, of which 494 were scoping reviews. The 494 scoping reviews were disseminated between 1999 and 2014, with 45% published after 2012. Most of the scoping reviews were conducted in North America (53%) or Europe (38%), and reported a public source of funding (64%). The number of studies included in the scoping reviews ranged from 1 to 2600 (mean of 118). Using the Joanna Briggs Institute methodology guidance for scoping reviews, only 13% of the scoping reviews reported the use of a protocol, 36% used two reviewers for selecting citations for inclusion, 29% used two reviewers for full-text screening, 30% used two reviewers for data charting, and 43% used a pre-defined charting form. In most cases, the results of the scoping review were used to identify evidence gaps (85%), provide recommendations for future research (84%), or identify strengths and limitations (69%). We did not identify any guidelines for reporting scoping reviews or studies that assessed the quality of scoping review reporting. CONCLUSION: The number of scoping reviews conducted per year has steadily increased since 2012. Scoping reviews are used to inform research agendas and identify implications for policy or practice. As such, improvements in reporting and conduct are imperative. Further research on scoping review methodology is warranted, and in particular, there is need for a guideline to standardize reporting.

Seeking effective interventions to treat complex wounds: an overview of systematic reviews.

BACKGROUND: Numerous, often multi-faceted regimens are available for treating complex wounds, yet the evidence of these interventions is recondite across the literature. We aimed to identify effective interventions to treat complex wounds through an overview of systematic reviews. METHODS: MEDLINE (OVID interface, 1946 until October 26, 2012), EMBASE (OVID interface, 1947 until October 26, 2012), and the Cochrane Database of Systematic Reviews (Issue 10 of 12, 2012) were searched on October 26, 2012. Systematic reviews that examined adults receiving care for their complex wounds were included. Two reviewers independently screened the literature, abstracted data, and assessed study quality using the Assessment of Multiple Systematic Reviews (AMSTAR) tool. RESULTS: Overall, 99 systematic reviews were included after screening 6,200 titles and abstracts and 422 full-texts; 54 were systematic reviews with a meta-analysis (including data on over 54,000 patients) and 45 were systematic reviews without a meta-analysis. Overall, 44% of included reviews were rated as being of high quality (AMSTAR score ≥ 8). Based on data from systematic reviews including a meta-analysis with an AMSTAR score ≥ 8, promising interventions for complex wounds were identified. These included bandages or stockings (multi-layer, high compression) and wound cleansing for venous leg ulcers; four-layer bandages for mixed arterial/venous leg ulcers; biologics, ultrasound, and hydrogel dressings for diabetic leg/foot ulcers; hydrocolloid dressings, electrotherapy, air-fluidized beds, and alternate foam mattresses for pressure ulcers; and silver dressings and ultrasound for unspecified mixed complex wounds. For surgical wound infections, topical negative pressure and vacuum-assisted closure were promising interventions, but this was based on evidence from moderate to low quality systematic reviews. CONCLUSIONS: Numerous interventions can be utilized for patients with varying types of complex wounds, yet few treatments were consistently effective across all outcomes throughout the literature. Clinicians and patients can use our results to tailor effective treatment according to type of complex wound. Network meta-analysis will be of benefit to decision-makers, as it will permit multiple treatment comparisons and ranking of the effectiveness of all interventions. Please see related article: http://dx.doi.org/10.1186/s12916-015-0326-3.