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The objective of this article is to investigate adherence to reporting standards and methodological quality in systematic reviews on burns care published in peer-reviewed journals to determine their utility for guiding evidence-based burns care. PubMed, Embase, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, and the Joanna Briggs Institute (JBI) Database of Systematic Reviews and Implementation Reports were searched from 2009. Any systematic review on any question on therapeutic interventions in burns care was eligible for inclusion. Critical appraisal and data extraction were performed using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist by two independent reviewers. The overall quality of the 44 included burns care systematic reviews was low, with an average methodological quality of 55% and an average compliance with reporting guidelines of 70%. Correlation analysis showed that adherence to reporting guidelines has been relatively stable, but methodological quality has deteriorated (r = -.32, P < .05). Cochrane reviews had lower citation rates than reviews published in other journals, whereas reviews that included meta-analyses had more citations. Quality did not have a significant effect on citation rate. Health professionals working in burns should be able to expect that systematic reviews published in their field are of a high standard. Unfortunately, this is not the case. To address this problem, established guidelines on the conduct and reporting of systematic reviews should be adhered to by researchers and editors.

Purpose: Methotrexate chemotherapy is associated with various toxicities which can result in the interruption or discontinuation of treatment and a subsequently raised risk of relapse. This umbrella systematic review was conducted to synthesize the results of all existing systematic reviews that investigate the pharmacogenetics of methotrexate-induced toxicity, with the aim of developing a comprehensive reference for personalized medicine. Methods: Databases searched were PubMed, Embase, JBI Database of Systematic Reviews and Implementation Reports, DARE, and ProQuest. Papers were critically appraised by two reviewers, and data were extracted using a standardized tool. Results: Three systematic reviews on methotrexate-induced toxicity were included in the review. Meta-analyses were reported across Asian, Caucasian, pediatric and adult patients for the MTHFR C677T and A1298C polymorphisms. Toxicity outcomes included different forms of hematologic, ectodermal and hepatic toxicities. Results varied considerably depending on the patient groups and subgroups investigated in the different systematic reviews, as well as the genetic models utilized. However, significant associations were found between the MTHFR C677T allele and; hepatic toxicity, myelosuppression, oral mucositis, gastrointestinal toxicity, and skin toxicity. Additionally, limited evidence suggests that the MTHFR A1298C polymorphism may be associated with decreased risk of skin toxicity and leukopenia. Conclusion: This umbrella systematic review has synthesized the best available evidence on the pharmacogenetics of methotrexate toxicity. The next step in making personalized medicine for methotrexate therapy a clinical reality is research on the effectiveness and cost-effectiveness of MTHFR genotype testing to enable the close monitoring of at-risk patients for the timely initiation of rescue therapies. Refereed/Peer-reviewed

Fluoropyrimidine (FU) and platinum-based chemotherapies are greatly complicated by their associated toxicities. This umbrella systematic review synthesized all systematic reviews that investigated associations between germline variations and toxicity, with the aim of informing personalized medicine. Systematic reviews are important in pharmacogenetics where false positives are common. Four systematic reviews were identified for FU-induced toxicity and three for platinum. Polymorphisms of DPYD and TYMS, but not MTHFR, were statistically significantly associated with FU-induced toxicity (although only DPYD had clinical significance). For platinum, GSTP1 was found to not be associated with toxicity. This umbrella systematic review has synthesized the best available evidence on the pharmacogenetics of FU and platinum toxicity. It provides a useful reference for clinicians and identifies important research gaps. Refereed/Peer-reviewed

Engineered nanomaterials that produce reactive oxygen species on exposure to X‐ and gamma‐rays used in radiation therapy offer promise of novel cancer treatment strategies. Similar to photodynamic therapy but suitable for large and deep tumors, this new approach where nanomaterials acting as sensitizing agents are combined with clinical radiation can be effective at well‐tolerated low radiation doses. Suitably engineered nanomaterials can enhance cancer radiotherapy by increasing the tumor selectivity and decreasing side effects. Additionally, the nanomaterial platform offers therapeutically valuable functionalities, including molecular targeting, drug/gene delivery, and adaptive responses to trigger drug release. The potential of such nanomaterials to be combined with radiotherapy is widely recognized. In order for further breakthroughs to be made, and to facilitate clinical translation, the applicable principles and fundamentals should be articulated. This review focuses on mechanisms underpinning rational nanomaterial design to enhance radiation therapy, the understanding of which will enable novel ways to optimize its therapeutic efficacy. A roadmap for designing nanomaterials with optimized anticancer performance is also shown and the potential clinical significance and future translation are discussed., Engineered nanomaterials that produce reactive oxygen species on exposure to X‐ and gamma‐rays used in radiation therapy offer promise of novel cancer treatment strategies including in deep tissue. This review focuses on mechanisms underpinning rational nanomaterial design to enhance radiation therapy, the understanding of which will enable novel ways to optimize its therapeutic efficacy.

The ISUP (Internal Society of Urologic Pathology) recently adopted a five-tiered prognostication system. There is evidence to suggest that the ISUP grade group 4 is a heterogeneous entity regarding prognosis. Our aim was to systematically examine the existing evidence to determine if outcome differences exist within the ISUP grade group 4. A systematic search of the literature for all studies examining the heterogeneity of the ISUP grade group 4 was conducted. Available studies were combined with meta-analysis to evaluate prognostic differences within the ISUP grade group 4 measured by all-cause mortality (ACM) and the prostate cancer-specific mortality (PCSM). Eight studies were identified and utilised a variety of outcome measures to answer the question of heterogeneity within the ISUP grade group 4. Four of these studies examined prognosis using both ACM and PCSM. These were combined into a meta-analysis. The combined group of 5 + 3/3 + 5 had statistically significant higher ACM (hazard ratio [HR] 1.23, 95% confidence internal [Cl] 1.08–1.41) when compared to the 4 + 4 group. There was no difference in the PCSM between the two groups (HR 1.34, 95% CI 0.89–2.01). However, heterogeneity was high for this analysis secondary to a range of methodological differences. Our meta-analysis showed that Gleason grade 3 + 5/5 + 3 had higher ACM than Gleason grade group 4 + 4. Measures of PCSM were statistically insignificant, although heterogeneity was high. Evidence suggests that heterogeneity is likely, although inconclusive. Further studies with consistent methodologies are required to answer this question.

Background Cardiovascular disease (CVD), cancer, diabetes and chronic respiratory disease are noncommunicable diseases (NCDs) that cause extensive social and economic burden worldwide, particularly in low-income and middle-income countries. There is growing recognition of the importance of the disabilities that individuals experience as a consequence of these NCDs. Objectives This systematic review examined the prevalence of disabilities associated with cancer, CVD, chronic respiratory disease and diabetes. Methods A comprehensive literature search was conducted in PubMed, CINAHL, Embase, Web of Science, PsycINFO, CIRRIE, WHO database, LILACS and AIM. Studies were included if their samples were representative of people with at least one of these four conditions and if prevalence estimates of disability were provided. As random sampling was not feasible in the majority of cases, studies were included where they offered evidence that their sample was representative of the general population being investigated. Results A total of 105 articles were included in the review. Most studies were conducted in high-income countries. The prevalence of difficulties with activities of daily living (i.e. eating, bathing, dressing) was reported to be 10.4-34.5% amongst cancer survivors, 21.1-64.1% in those with CVD, 7.4-49.8% in those with chronic respiratory disease and 12.2-54.5% for those with diabetes. The prevalence of a range of other physical, cognitive and psychological impairments (systemic or structural) was additionally described for each disease. Conclusion Substantial proportions of people with cancer, CVD, chronic respiratory disease or diabetes experience some form of disability - although there was great variance in prevalence and definitions. The findings of this review support the evidence base of global impact associated with NCD, indicate frequency measures for specific disabilities and inabilities associated with each NCD and provide direction for future systematic reviews. What is known about the topic WHAT THIS ARTICLE ADDS.

REVIEW QUESTION / OBJECTIVE Does pancreatic enzyme replacement therapy improve nutritional status such as body mass index and fat-soluble vitamins associated with improved fat absorption and better control of gastrointestinal symptoms associated with fat malabsorption in patients with pancreatic exocrine insufficiency? Does the timing of pancreatic enzyme administration and adjuvant therapy with proton pump inhibitor influence the effectiveness of pancreatic enzyme replacement therapy for patients with pancreatic exocrine insufficiency? The objectives of this review are to identify the effect of pancreatic enzyme replacement therapy on: Fat absorption in patients with pancreatic exocrine insufficiency Nutritional impact such as weight change and nutritional markers Improvement in gastrointestinal symptoms Treatment related adverse events in patients with pancreatic exocrine insufficiency. In addition to these, the timing of pancreatic enzyme administration and adjuvant therapy with proton pump inhibitors will also be investigated for its effectiveness in pancreatic enzyme replacement therapy. INCLUSION CRITERIA Types of participants This review will consider studies that include all patients with pancreatic exocrine insufficiency, including patients with chronic pancreatitis, pancreatic cancer, and a history of pancreatic surgical resection and cystic fibrosis in acute and community settings. Studies on patients with celiac disease, diabetes mellitus, human immunodeficiency virus, irritable bowel syndrome, post gastric and bowel resections will not be included as the use of pancreatic enzyme replacement therapy in these populations has not been fully accepted. Studies on patients of any age will be included. Types of intervention(s)/phenomena of interest This review will consider studies that evaluate pancreatic enzyme replacement therapy without TRUNCATED AT 250 WORDS

Objective Clinicians and other healthcare professionals need access to summaries of evidence-based information in order to provide effective care to their patients at the point-of-care. Evidence-based practice (EBP) point-of-care resources have been developed and are available online to meet this need. This study aimed to develop a comprehensive list of available EBP point-of-care resources and evaluate their processes and policies for the development of content, in order to provide a critical analysis based upon rigor, transparency and measures of editorial quality to inform healthcare providers and promote quality improvement amongst publishers of EBP resources. Design A comprehensive and systematic search (Pubmed, CINAHL, and Cochrane Central) was undertaken to identify available EBP point-of-care resources, defined as “web-based medical compendia specifically designed to deliver predigested, rapidly accessible, comprehensive, periodically updated, and evidence-based information (and possibly also guidance) to clinicians.” Main Outcome Measures A pair of investigators independently extracted information on general characteristics, content presentation, editorial quality, evidence-based methodology, and breadth and volume. Results Twenty-seven summary resources were identified, of which 22 met the predefined inclusion criteria for EBP point-of-care resources, and 20 could be accessed for description and assessment. Overall, the upper quartile of EBP point-of-care providers was assessed to be UpToDate, Nursing Reference Centre, Mosby's Nursing Consult, BMJ Best Practice, and JBI COnNECT+. Linking Evidence to Action The choice of which EBP point-of-care resources are suitable for an organization is a decision that depends heavily on the unique requirements of that organization and the resources it has available. However, the results presented in this study should enable healthcare providers to make that assessment in a clear, evidence-based manner, and provide a comprehensive list of the available options.

This systematic review investigated the effect of paternal obesity on reproductive potential. Databases searched were Pubmed, Ovid, Web of Science, Scopus, Cinahl and Embase. Papers were critically appraised by two reviewers, and data were extracted using a standardized tool. Outcomes were: likelihood of infertility, embryo development, clinical pregnancy, live birth, pregnancy viability, infant development, sperm; concentration, morphology, motility, volume, DNA fragmentation, chromatin condensation, mitochondrial membrane potential (MMP), and seminal plasma factors. Thirty papers were included, with a total participant number of 115,158. Obese men were more likely to experience infertility (OR = 1.66, 95% CI 1.53-1.79), their rate of live birth per cycle of assisted reproduction technology (ART) was reduced (OR = 0.65, 95% CI 0.44-0.97) and they had a 10% absolute risk increase of pregnancy non-viability. Additionally, obese men had an increased percentage of sperm with low MMP, DNA fragmentation, and abnormal morphology. Clinically significant differences were not found for conventional semen parameters. From these findings it can be concluded that male obesity is associated with reduced reproductive potential. Furthermore, it may be informative to incorporate DNA fragmentation analysis and MMP assessment into semen testing, especially for obese men whose results suggest they should have normal fertility.

BACKGROUND Primary research, including qualitative research, as well as experts working in social services and aged care have identified the mixed feelings carers experience when the person they have been caring for is admitted into a residential aged care facility permanently. They have raised the importance of understanding these experiences as a means to implementing policies and programs that enhance carers’ well-being. This systematic review was motivated by the need to use evidence to inform effective and feasible interventions to support carers, and the absence of a systematic review synthesizing the qualitative evidence on how carers experience this transition. OBJECTIVES The objective of this qualitative systematic review was to identify and synthesize the evidence on the experiences of carers of older people when the person they had been providing care for is admitted permanently into a residential aged care facility, and to draw recommendations from the synthesis of the evidence on these experiences to enhance policy and programming aimed at supporting affected caregivers. INCLUSION CRITERIA Types of participants: All carers of people who had experienced the person they had been caring for at home being moved into a residential aged care facility permanently. Phenomena of interest: Experiences of the caregiver of the older person when the person they have been caring for at home is admitted into a residential aged care facility permanently. Types of studies: The review considered qualitative studies, including but not limited to designs such as phenomenology, grounded theory, ethnography and action research. Types of outcomes: The outcomes are in the form of synthesized findings pertaining to carers’ experiences when the person they have been caring for is admitted into a residential aged care facility permanently. SEARCH STRATEGY A comprehensive search of leading databases which are sources of qualitative published and unpublished studies was conducted between 18 September 2013 and 10 November 2013. The search considered studies reported in English and published from the database inception to 10 November 2013. METHODOLOGICAL QUALITY Papers selected for retrieval were assessed by two independent reviewers for methodological validity prior to inclusion in the review using the Joanna Briggs Institute Qualitative Assessment and Review Instrument. DATA EXTRACTION Data were extracted from identified papers using the standardized data extraction tool from the Joanna Briggs Institute Qualitative Assessment and Review Instrument. The data extracted included descriptive details about the phenomena of interest, populations and study methods. DATA SYNTHESIS The Joanna Briggs Institute meta-aggregative approach for synthesizing qualitative evidence was used. Research findings were pooled using the Joanna Briggs Institute Qualitative Assessment and Review Instrument. Study findings that were supported by the data in primary studies were organized into categories on the basis of similarity of meaning. These categories were then subjected to a meta-synthesis to produce a set of synthesized findings. RESULTS Fourteen studies matched the inclusion criteria and were included in the review. From these 14 studies a total of 71 study findings about how carers experience the transition when the person they have been caring for is TRUNCATED AT 500 WORDS

Review question/objective The objective of this review is to identify the effectiveness of curcumin on musculoskeletal pain. More specifically, the objectives are to identify the effectiveness of the use of turmeric, turmeric extract, and/or curcuminoids to modulate musculoskeletal pain. Inclusion criteria Types of participants This review will consider studies that include any humans (children, adults and older people) experiencing musculoskeletal pain, including experimentally induced pain. Types of intervention(s) This review will consider studies that evaluate the use of turmeric, turmeric extract or curcuminoids on subjects experiencing pain of clinical or experimental origin. Where turmeric or curcumin is delivered as one component of a combination of bioactive agents and is not individually controlled for; studies will be included but considered separately. Types of controls Studies with any form of control including placebo, treatment as usual and before and after measurements will be considered in this review. Types of outcomes This review will consider studies that include the following outcome measures: pain diaries, visual analogue scales, or pain questionnaires. As a secondary outcome measures of functionality including activities of daily living and range of motion will be included. Additionally, any reports or data in selected studies on adverse events will be included.

BACKGROUND Pain management is a significant issue in health facilities in Ghana. For burn patients, this is even more challenging as burn pain has varied facets. Despite the existence of pharmacological agents for pain management, complaints of pain still persist. OBJECTIVES The aim of this project was to identify pain management practices in the burns units of Komfo Anokye Teaching Hospital, compare these approaches to best practice, and implement strategies to enhance compliance to standards. METHODS Ten evidence-based audit criteria were developed from evidence summaries. Using the Joanna Briggs Institute Practical Application of Clinical Evidence Software (PACES), a baseline audit was undertaken on a convenience sample of ten patients from the day of admission to the seventh day. Thereafter, the Getting Research into Practice (GRiP) component of PACES was used to identify barriers, strategies, resources and outcomes. After implementation of the strategies, a follow-up audit was undertaken using the same sample size and audit criteria. RESULTS The baseline results showed poor adherence to best practice. However, following implementation of strategies, including ongoing professional education and provision of assessment tools and protocols, compliance rates improved significantly. Atlhough the success of this project was almost disrupted by an industrial action, collaboration with external bodies enabled the successful completion of the project. CONCLUSION Pain management practices in the burns unit improved at the end of the project which reflects the importance of an audit process, education, providing feedback, group efforts and effective collaboration.

REVIEW QUESTION/OBJECTIVE The objective of this systematic review is to assess the effectiveness of aggressive treatment of oligometastatic breast cancer (OMBC) on survival outcomes by conducting a meta-analysis of current available evidence.More specifically, the objectives are to identify the effectiveness of intensified multidisciplinary treatment with aggressive locoregional therapies on survival time, five-year survival rates and disease free survival. The population is adult women (18 years and over) with OMBC defined as single or few (five or less) metastases limited to a single organ and the comparative group is conventional palliative treatment aimed at disease control. Secondary objectives to be assessed will be adverse outcomes associated with intensified treatment regimes.

REVIEW QUESTION/OBJECTIVE The gold standard for the diagnosis of pre-diabetes is the measurement of fasting plasma glucose and the oral glucose tolerance test. The objective of this systematic review is to identify all alternative tests currently in use for the diagnosis of type 2 pre-diabetes mellitus in children and establish their accuracy relative to this gold standard.

REVIEW OBJECTIVE The objective of this systematic review is to synthesize the best available evidence on the predictors of change in the severity of untreated lower urinary tract symptoms in men in a non-hospital setting.

Background Prostate cancer can be treated with several different modalities, including radiation treatment. Various prognostic tools have been developed to aid decision making by providing estimates of the probability of different outcomes. Such tools have been demonstrated to have better prognostic accuracy than clinical judgment alone. Methods A systematic review was undertaken to identify papers relating to the prediction of clinical outcomes (biochemical failure, metastasis, survival) in patients with prostate cancer who received radiation treatment, with the particular aim of identifying whether published tools are adequately developed, validated, and provide accurate predictions. PubMed and EMBASE were searched from July 2007. Title and abstract screening, full text review, and critical appraisal were conducted by two reviewers. A review protocol was published in advance of commencing literature searches. Results The search strategy resulted in 165 potential articles, of which 72 were selected for full text review and 47 ultimately included. These papers described 66 models which were newly developed and 31 which were external validations of already published predictive tools. The included studies represented a total of 60,457 patients, recruited between 1984 and 2009. Sixty five percent of models were not externally validated, 57% did not report accuracy and 31% included variables which are not readily accessible in existing datasets. Most models (72, 74%) related to external beam radiation therapy with the remainder relating to brachytherapy (alone or in combination with external beam radiation therapy). Conclusions A large number of prognostic models (97) have been described in the recent literature, representing a rapid increase since previous reviews (17 papers, 1966–2007). Most models described were not validated and a third utilised variables which are not readily accessible in existing data collections. Where validation had occurred, it was often limited to data taken from single institutes in the US. While validated and accurate models are available to predict prostate cancer specific mortality following external beam radiation therapy, there is a scarcity of such tools relating to brachytherapy. This review provides an accessible catalogue of predictive tools for current use and which should be prioritised for future validation. Electronic supplementary material The online version of this article (doi:10.1186/s13014-017-0786-z) contains supplementary material, which is available to authorized users.

This systematic review investigated the effectiveness and safety of intensive insulin therapy (IIT), insulin secretagogues and sensitisers in burn patients. PubMed, Embase, clinicaltrials.gov and Cochrane central were searched from 1990 to 2016. Title/abstract screening, full-text review, critical appraisal and data extraction were carried out by two independent reviewers. Inclusion criteria were hospitalised burn patients, IIT, insulin sensitisers or secretagogues and the outcomes mortality, length of stay, resting energy expenditure, blood glucose, catabolism, or complications. We identified 594 potential studies of which 13 were included. Five studies investigated IIT in paediatric patients, 3 investigated IIT in adults and 5 investigated sensitisers or secretagogues. Glycaemic targets differed with age group - paediatric studies compared IIT to loose glycaemic control while adult studies compared IIT to more moderate control. Meta-analyses were limited by differences in outcome reporting, however mortality was increased in children by loose glycaemic control (OR=3.78, 95%CI 1.19-12.02) but not significantly affected in adults by moderate compared to tight control. Meta-analyses could not be performed for sensitisers or secretagogues. These findings support recommendations that moderate insulin administration (130-150mg/dL) is the prudent approach in burn patients. The evidence is relatively sparse and further research is warranted.

REVIEW QUESTION/OBJECTIVE The objective of this review is to enhance understanding of the experiences of the carers of older people when the person they have been providing care for is admitted permanently into a residential aged care facility. A secondary objective is to use the review findings to draw recommendations for enhancing policy and programming aimed at supporting caregivers of older individuals who have moved into a residential aged care facility in Australia. The review question is: What is it like for carers when the person they have been caring for is moved into a residential aged care facility permanently? INCLUSION CRITERIA Types of participants This review will consider carers of older people (65 years and over) from all countries who have experienced an individual they have been caring for move into a residential aged care facility permanently, as well as carers of people who have been caring for some-one under 65 years of age, who move permanently into a residential aged care facility with an age related condition. Whilst most individuals who enter a residential aged care facility will be adults 65 years and over, there are exemptions when people are under 65 years within Australia but have an age related condition requiring them to reside in a residential aged care facility, and carers of these people will be included. Aboriginal and Torres Strait Islander people are deemed eligible for aged care assessments at 50 years of age due to their shorter life expectancy. Their TRUNCATED AT 250 WORDS

Review question/objective This review will aim to answer the following questions: 1. What are the resident risk factors associated with antimicrobial resistant organism carriage in the residential aged care setting? 2. What are the institutional risk factors associated with antimicrobial resistant organism carriage in the residential aged care setting? 3. What are the environmental risk factors associated with antimicrobial resistant organism carriage in the residential aged care setting? The objective of this systematic review is to synthesize the best available evidence of the risk factors associated with antimicrobial resistant organism carriage in residents of residential aged care facilities. More specifically, the objective is to identify the factors that make some residents more at risk than others to either colonization or infection with an antimicrobial resistant organism. These may include patient/resident factors (predisposing medical conditions, immune status, functional capacity), institutional factors (staffing ratios, clinical policies and procedures, antibiotic use, indwelling devices) or environmental factors (cleaning of environment, cleaning of equipment, ward layout, hand hygiene facilities, shared and community living). Inclusion criteria Types of participants This review will consider studies that include permanent residents of residential aged care Facilities, both male and female. Carriage of an antimicrobial resistant organism will be defined as the presence of such an organism confirmed via a culture positive result from any site on the body. The carrier status must be clearly defined in included studies. Studies that report either antimicrobial resistant organism colonization or infection will be included. Studies that only look at a specific disease sub-population of residents who are under 65 years of age will be excluded. Studies that focus exclusively on residents under the age of 65 will also be excluded. Residents under the age of 65 included within studies that are not stratified by age will be included. Types of intervention(s)/phenomena of interest All risk factors associated with carriage of any antimicrobial resistant organism in residents of residential aged care facilities will be considered in this review. A risk factor is a condition that is associated with the presence of an antimicrobial resistant organism in a resident. Examples of risk factors include, but are not limited to predisposing medical conditions, immune status, functional capacity (resident factors); staffing ratios, clinical policies and procedures, antibiotic use, indwelling devices (institutional factors); and cleaning of environment, cleaning of equipment, ward layout, hand hygiene facilities, shared and community living (environmental factors). Types of outcomes Outcomes of interest include the characteristics of residents with antimicrobial resistant organism carriage. These will be associated with the resident, the facility, and/or the environment (i.e. immune status, clinical policies, ward layout etc.). The measurement of these outcomes may include a risk ratio (RR),likelihood ratio (LR), or odds ratio (OR) of risk factors in comparison to residents who do not have an antimicrobial resistant organism.

Review question/objective The objective of this review is to identify the factors associated with an increased risk for developing recurrent raised intracranial pressure in nonsyndromic children who have had previous cranial vault remodelling surgery. Inclusion criteria Types of participants This review will consider studies that include: 1. Male and female children up to the age of 18 years old who have had previous cranial vault remodelling surgery for craniosynostosis. 2. Patients diagnosed with primary, nonsyndromic craniosynostosis. 3. Patients who have undergone reoperation for signs and symptoms of raised intracranial pressure. This review will exclude studies that include: 1. Patients with any genetic abnormalities. Types of intervention(s)/phenomena of interest This review will consider studies that evaluate the factors that may be associated with increased risk for developing recurrent raised intracranial pressure, including: 1. Patient's age at the time of first surgery 2. The extent of cranial vault remodelling surgery undertaken. 3. The involvement of single or multiple sutures. 4. The specific suture involved. 5. The timing of initial suture closure (antenatal vs postnatal). Other risk factors identified during the course of the review will also be considered. Types of outcomes Recurrent raised intracranial pressure leading to repeat cranial vault operation. We will consider studies that report raised ICP by objective measures such as papilloedema which is swelling of the optic discs caused by raised ICP and/or 24 hour ICP monitoring via any intracranial pressure monitoring device.

Review question/objective The objective of this review is to identify the effect that paternal obesity compared with normal weight has on semen quality, seminal plasma composition, embryo development, pregnancy outcomes and trans-generational effects in adult males. Inclusion criteria Types of participants This review will consider studies that include adults (>18 years of age), with no upper age limit. Studies that include men with a history of reproductive disorders (eg androgen deficiency, varicocele, cryptorchidism, trauma, vasectomy, testicular torsion) will be excluded. In addition, studies in which frozen or donor sperm have been used will also be excluded. Studies where the majority of males have azoospermia will also be excluded. Additionally, studies focusing on men who have been exposed to environmental toxins such as pesticide exposure will be excluded. Studies will be excluded due to the above conditions because of their significant influence on the measured outcomes. These conditions could introduce confounding factors due to their potential to influence the measured outcomes differently between the populations of interest. Types of subpopulations This review will consider studies that evaluate obese males (BMI > or ≥ 30) compared with normal weight males (BMI < or ≤25; studies which exclude or separately evaluate men below a certain BMI as underweight will also be considered). Where different categories of obesity are used, data will be standardized to obese versus non-obese. Types of outcomes This review will consider studies that include the following outcome measures: clinical semen parameters, sperm DNA integrity and other cellular and molecular characteristics, seminal plasma composition, embryo development, pregnancy outcomes (including live birth), and trans-generational effects.

Prostate cancer is a heterogeneous disease whose therapies frequently have adverse effects. Informed patient counseling regarding likely clinical outcomes is therefore important. In this systematic review we aimed to identify all external validations of tools that are used to predict clinical outcomes in patients undergoing radical prostatectomy and evaluate which are optimum for clinical implementation. PubMed and EMBASE were searched from 2007 to 2016. Search terms related to the inclusion criteria were: prostate cancer, clinical outcomes, radical prostatectomy, and prognosis. Titles and abstracts were screened and relevant studies were advanced to full-text review. Reference lists were reviewed for further studies. The Centre for Evidence Based Medicine prognostic tool was used for critical appraisal. Seventy-three studies externally validated 13 pre- and 41 postoperative tools for the prediction of biochemical recurrence (BCR), aggressive BCR, metastasis, and prostate cancer-specific mortality (PCSM). Recommendations for clinical implementation were made on the basis of accuracy, cohort sizes, and consistency. The accuracy of recommended tools ranged from 68% to 79% and 72% to 92% among the largest validation cohorts for pre- and postoperative tools. For preoperative prognosis we recommended the Cancer of the Prostate Risk Assessment (CAPRA) and Stephenson nomograms for BCR, the CAPRA nomogram for aggressive BCR as well as metastasis, and the D'Amico criteria for PCSM. For postoperative prognosis we recommended the CAPRA-Surgery (CAPRA-S), Stephenson, Kattan, Duke prostate cancer (DPC), and the Suardi nomograms for the prediction of BCR, the DPC nomogram for aggressive BCR, the CAPRA-S and Eggener nomograms for metastasis, and the Eggener nomogram for PCSM. Use of these tools should help clinicians deliver accurate, evidence-based counseling to patients undergoing prostatectomy. Refereed/Peer-reviewed

Background:Radical prostatectomy is a common surgical procedure performed to treat prostate cancer. Patient-reported outcomes after surgery include urinary incontinence, erectile dysfunction, decreased quality of life and psychological effects. Predictive tools to assess the likelihood of an individual experiencing various patient-reported outcomes have been developed to aid decision-making when selecting treatment. METHODS: A systematic review was undertaken to identify all papers describing tools for the prediction of patient-reported outcome measures in men with prostate cancer treated with radical prostatectomy. To be eligible for inclusion, papers had to provide a summary measure of accuracy. PubMed and EMBASE were searched from July 2007. Title/abstract screening, and full-text review were undertaken by two reviewers, while data extraction and critical appraisal was performed by a single reviewer. RESULTS: The search strategy identified 3217 potential studies, of which 191 progressed to full-text review and 14 were included.From these studies, 27 tools in total were identified, of which 18 predicted urinary symptoms, six predicted erectile function and one predicted freedom from a group of three outcomes (‘trifecta’) (biochemical recurrence, incontinence and erectile dysfunction). On the basis of tool accuracy (470%) and external validation, two tools predicting incontinence and two tools predicting erectile dysfunction are ready for implementation CONCLUSIONS: A small number of tools for the prediction of patient-reported outcomes following radical prostatectomy have been developed. Four tools were found to have adequate accuracy and validation and are ready for implementation for the prediction of urinary incontinence and erectile dysfunction Refereed/Peer-reviewed

Irinotecan chemotherapy toxicities can be severe, and may result in treatment delay, morbidity and in some rare cases death. This systematic review of systematic reviews synthesises all meta-analyses on biomarkers for irinotecan toxicity across all genetic models for Asians, Caucasians, low dose, medium/high dose and regimens with and without fluorouracil. False-positive findings are a problem in pharmacogenetics, increasing the importance of systematic reviews. Four systematic reviews that investigated the effect of the polymorphisms UGT1A1∗6 and/or∗28 on neutropenia or diarrhoea toxicity were included. Both UGT1A1∗6 and ∗28 were reliably demonstrated to be risk factors for irinotecan-induced neutropenia, with tests for both polymorphisms potentially being particularly useful in Asian cancer patients. UGT1A1∗6 and ∗28 were also related to diarrhoea toxicity; however, at low doses of irinotecan there was evidence that UGT1A1∗28 was not. In synthesising the best available evidence, this umbrella systematic review provides a novel reference for clinicians applying personalised medicine and identifies important research gaps. Refereed/Peer-reviewed

Human embryos for hESC derivation are often donated at the cleavage stage and of reduced quality. Poor quality embryos have lower efficiency for hESC derivation. However, cleavage stage mouse embryos develop into higher quality expanded blastocysts if they are cultured with insulin, suggesting that this approach could be used to improve hESC derivation from poor quality cleavage stage embryos. The present study used a mouse model to examine this approach. In particular we examined the effect of insulin on the number of epiblast cells in blastocysts on days 4, 5 and 6 using Oct4 and Nanog co-expression. Second we examined the effect of insulin on the frequency with which outgrowths can be derived from these. Finally, we tested whether prior culture in the presence of insulin results in blastocysts with increased capacity to generate ESC colonies. Culture of cleavage stage embryos with insulin increased the number of Oct4 and Nanog positive cells in blastocysts at all time points examined. Prior culture with insulin had no effect on outgrowths generated from blastocysts plated on days 4 or 5. However, insulin treatment of blastocysts plated on day 6 resulted in increased numbers of outgrowths with larger epiblasts compared with controls. 13% of insulin treated day 6 blastocysts produced primary ESC colonies compared with 6% of controls. In conclusion, treatment with insulin can improve epiblast cell number in mice leading to an increase with which primary ESC colonies can be generated and may improve hESC isolation from reduced quality embryos donated at the cleavage stage.

Human embryos donated for embryonic stem cell (ESC) derivation have often been cryopreserved for 5–10 years. As a consequence, many of these embryos have been cultured in media now known to affect embryo viability and the number of ESC progenitor epiblast cells. Historically, these conditions supported only low levels of blastocyst development necessitating their transfer or cryopreservation at the 4–8-cell stage. As such, these embryos are donated at the cleavage stage and require further culture to the blastocyst stage before hESC derivation can be attempted. These are generally of poor quality, and, consequently, the efficiency of hESC derivation is low. Recent work using a mouse model has shown that the culture of embryos from the cleavage stage with insulin to day 6 increases the blastocyst epiblast cell number, which in turn increases the number of pluripotent cells in outgrowths following plating, and results in an increased capacity to give rise to ESCs. These findings suggest that culture with insulin may provide a strategy to improve the efficiency with which hESCs are derived from embryos donated at the cleavage stage.

The systematic review was undertaken to investigate the effectiveness of physical therapy interventions for improving gross motor skills (GMSs) in people with an intellectual disability aged 6 years and older. There is a lack of physical therapy research for GMSs in this population, and no prior systematic review. People with an intellectual disability may require specific teaching approaches within therapy interventions to accommodate their cognitive and learning needs. People with an intellectual disability who suffer from GMS deficits can benefit from physical therapy to help improve their GMSs.Data sources were PubMed, CINAHL, Embase, and ProQuest. Reference lists of relevant identified articles were also hand searched. Papers published in English from 1 January 2008 to 22 October 2014 were considered for inclusion. This start date was chosen to reflect the tenets of the United Nations Convention on the Rights of Persons with Disabilities which was ratified in 2008.Eligible study designs for inclusion were randomized controlled trial (RCT), pseudo-RCT, repeated measures, and case report. Overall, 887 potential articles were identified, of which 42 were retrieved for full-text review, and seven were finally included. Critical appraisal was independently conducted by two reviewers using the Joanna Briggs Institute appraisal checklists; no articles were excluded following critical appraisal. Data extraction was performed using Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument data extraction instruments.High heterogeneity between the studies precluded meta-analysis of the results; a narrative synthesis was completed instead. Two RCTs, two pseudo-RCTs, two repeated measures studies, and one case report were included. Studies varied in regard to participants' intellectual disability, and the clinical interventions used. Interventions were well tolerated with negligible adverse effects. Significant improvements were reported for cadence and nondimensionalized gait velocity following body-weight-supported gait training; cadence following lower limb strengthening exercises; and the Gross Motor Function Measure-88 measures following adapted judo training. These results suggest that task-specific training may be useful. However, the overall quality of evidence was low.The evidence identified by this systematic review supporting physical therapy for improving GMSs in people with an intellectual disability was limited because of the low quality of studies (only two were RCTs) and only three statistically significant findings. Given the current paucity of evidence, a future systematic review, which sought to identify evidence regarding interventions used by a range of health and education professionals for improving GMSs in people with an intellectual disability, could provide a broader evidence base for clinical interventions which may be utilized by physical therapists.

For most of the derived human embryonic stem cell (ESC) lines thus far, the majority of human embryos used have been frozen in liquid nitrogen at or prior to the compacting stage for up to 10 years before human ESC derivation. As such they were grown in media that were relatively simple in their formulation compared with those used today. Here we report that culture of mouse embryos in media similar to these produces blastocysts in which both the inner cell mass cell number and the number of ESC progenitor cells (epiblast cells) in the inner cell mass are reduced compared with blastocysts cultured in a purpose-designed sequential (G1/G2) system commonly used today. Embryos cultured in a simple medium were less likely to attach and generate outgrowths. Further, these outgrowths had increased metabolic activity, which has been linked to differentiation, and altered gene expression. Culture of embryos in a simple medium to the compacting stage followed by culture in G2 to the blastocyst stage reduced some of these effects. However, none were improved to the level seen for culture in G1/G2. These results highlight the influence of embryo culture on embryo quality and pluripotency, which is a key factor in determining ESC isolation efficiencies.

Systematic reviews are carried out to provide an answer to a clinical question based on all available evidence (published and unpublished), to critically appraise the quality of studies, and account for and explain variations between the results of studies. The Joanna Briggs Institute specializes in providing methodological guidance for the conduct of systematic reviews and has developed methods and guidance for reviewers conducting systematic reviews of studies of diagnostic test accuracy. Diagnostic tests are used to identify the presence or absence of a condition for the purpose of developing an appropriate treatment plan. Owing to demands for improvements in speed, cost, ease of performance, patient safety, and accuracy, new diagnostic tests are continuously developed, and there are often several tests available for the diagnosis of a particular condition. In order to provide the evidence necessary for clinicians and other healthcare professionals to make informed decisions regarding the optimum test to use, primary studies need to be carried out on the accuracy of diagnostic tests and the results of these studies synthesized through systematic review. The Joanna Briggs Institute and its international collaboration have updated, revised, and developed new guidance for systematic reviews, including systematic reviews of diagnostic test accuracy. This methodological article summarizes that guidance and provides detailed advice on the effective conduct of systematic reviews of diagnostic test accuracy.

Clinicians and other healthcare professionals need access to summaries of evidence-based information in order to provide effective care to their patients at the point-of-care. Evidence-based practice (EBP) point-of-care resources have been developed and are available online to meet this need. This study aimed to develop a comprehensive list of available EBP point-of-care resources and evaluate their processes and policies for the development of content, in order to provide a critical analysis based upon rigor, transparency and measures of editorial quality to inform healthcare providers and promote quality improvement amongst publishers of EBP resources.A comprehensive and systematic search (Pubmed, CINAHL, and Cochrane Central) was undertaken to identify available EBP point-of-care resources, defined as "web-based medical compendia specifically designed to deliver predigested, rapidly accessible, comprehensive, periodically updated, and evidence-based information (and possibly also guidance) to clinicians."A pair of investigators independently extracted information on general characteristics, content presentation, editorial quality, evidence-based methodology, and breadth and volume.Twenty-seven summary resources were identified, of which 22 met the predefined inclusion criteria for EBP point-of-care resources, and 20 could be accessed for description and assessment. Overall, the upper quartile of EBP point-of-care providers was assessed to be UpToDate, Nursing Reference Centre, Mosby's Nursing Consult, BMJ Best Practice, and JBI COnNECT+.The choice of which EBP point-of-care resources are suitable for an organization is a decision that depends heavily on the unique requirements of that organization and the resources it has available. However, the results presented in this study should enable healthcare providers to make that assessment in a clear, evidence-based manner, and provide a comprehensive list of the available options.

Androgen deprivation therapy (ADT) can result in a range of adverse symptoms that reduce patients' quality of life. Careful patient counseling on the likely clinical outcomes and adverse effects is therefore vital. The present systematic review was undertaken to identify and characterize all the tools used for the prediction of clinical and patient-reported outcome measures (PROMs) in patients with prostate cancer undergoing ADT. PubMed and EMBASE were systematically searched from 2007 to 2016. Search terms related to the inclusion criteria were: prostate cancer, clinical outcomes, PROMs, ADT, and prognosis. Titles and abstracts were reviewed to find relevant studies, which were advanced to full-text review. The reference lists were screened for additional studies. The Centre for Evidence Based Medicine critical appraisal of prognostic studies tool was applied. The search strategy identified 8755 studies. Of the 8755 studies, 22 on clinical outcomes were identified. However, no studies of PROMs were found. Nine tools could be used to predict clinical outcomes in treatment-naive patients and 10 in patients with recurrence. The Japan Cancer of the Prostate Risk Assessment (J-CAPRA) nomogram was the best performing and validated tool for the prediction of clinical outcomes in treatment-naive patients, and the Chi and Shamash prognostic indexes have been validated for use in patients with castration-resistant disease in different clinical contexts. Using the J-CAPRA nomogram should help clinicians deliver accurate, evidence-based counseling to patients undergoing primary ADT. A strong need exists for primary studies that derive and validate tools for the prediction of PROMs in patients undergoing ADT under any circumstance because these are currently absent from the literature. Refereed/Peer-reviewed

REVIEW QUESTION/OBJECTIVE What is the association between germline polymorphisms and chemotherapy-induced toxicities in cancer patients? INCLUSION CRITERIA Types of participants This review will consider reviews that include patients with cancer of any type, stage of progression or severity, who receive or have received chemotherapy of any variety, schedule or formulation. All ages and ethnicities will be included. Reviews that include patients treated with radiotherapy or surgery will be included if they have also received chemotherapy. Types of exposure This review will consider studies that evaluate any form of germline polymorphism (i.e. SNPs, short tandem repeats and deletions), whether detected by candidate gene analysis or GWAS. Studies that investigate race, ethnicity or sex instead of defined polymorphisms will not be included. Types of outcomes This review will consider reviews that include any chemotherapy-induced toxicities, adverse events or side effects as outcome measures. This will include those defined by any edition or volume of the common terminology criteria for adverse events or National Cancer Institute common toxicity criteria, as well as any other organizational-, national- or laboratory-specific system used to define chemotherapy-induced toxicity. Criteria for defining toxicities often assign specific grades. All grades or combinations of grades will be included. Outcomes relating to tumor or cancer response, progression free and overall survival will not be included. However, measures of treatment-related mortality will be. Treatment termination or reduction due to adverse events will also be included.

REVIEW QUESTION/OBJECTIVE The objective of this systematic review is to identify and establish the effectiveness of treatments for skin tears in older people. More specifically, the objectives are: to identify the effectiveness of different treatments to promote healing and minimize infection; and to reduce secondary morbidity and mortality associated with skin tears in older adults (>60 years) in hospital, residential care, nursing home and community settings. This systematic review will address three specific questions across the healthcare contexts listed above: What are the effective interventions to promote the healing of skin tears among older adults? What are the effective interventions to minimize skin tear infection among older adults? What are the effective interventions to reduce skin tear associated secondary morbidity and mortality among older adult. INCLUSION CRITERIA Types of participants This systematic review will consider studies that include older adult participants aged 60 years and over in hospital, residential care, nursing home and community settings. Studies conducted in the general population of residential aged care centers without age restrictions will also be considered as the vast majority of participants will be aged 60 years and over. Both male and female participants will be eligible participants for this review. Participants may have one or multiple skin tears in any location from any cause and that may be classified as any degree of skin tear according to the Payne Martin or STAR skin tear classification systems. It may be necessary to subdivide the participants into TRUNCATED AT 250 WORDS

High-quality embryos give rise to embryonic stem cells (ESCs) at greater efficiencies than poor-quality embryos. However, most embryos available for human ESC derivation are of a reduced quality as a result of culture in relatively simple media up to 10 years earlier, before cryopreservation, or before compaction. In the present study, we used a mouse model to determine whether a culture with insulin from the 8-cell stage could increase the number of ESC progenitor epiblast cells in blastocysts, as well as endeavor to determine the molecular mechanism of the insulin's effect. Culture in media containing 1.7 ρM insulin increased epiblast cell number (determined by Oct4 and Nanog co-expression), and proportion in day 6 blastocysts. The inhibition of phosphoinositide 3 kinase (PI3K) (via LY294002), an early second messenger of the insulin receptor, blocked this effect. The inhibition of glycogen synthase kinase 3 (GSK3) or p53, 2 s messengers inactivated by insulin signaling (via CT99021 or pifithrin-α, respectively), increased epiblast cell numbers. When active, GSK3 and p53 block the transcription of Nanog, which is important for maintaining pluripotency. A simultaneous inhibition of GSK3 and p53 had no synergistic effects on epiblast cell number. The induced activation of GSK3 and p53, via the inhibition of proteins responsible for their inactivation (PKA via H-89 and SIRT-1 via nicotinamide, respectively), blocked the insulin's effect on the epiblast.From our findings, we conclude that insulin increases epiblast cell number via the activation of PI3K, which ultimately inactivates GSK3 and p53. Furthermore, we suggest that the inclusion of insulin in culture media could be used as a strategy for increasing the efficiency with which the ESC lines can be derived from cultured embryos.