Nonsteroidal Anti-inflammatory Drugs (NSAIDS) Inhibit the Growth and Reproduction of Chaetomium globosum and Other Fungi Associated with Water-Damaged Buildings.

Indoor mold due to water damage causes serious human respiratory disorders, and the remediation to homes, schools, and businesses is a major expense. Prevention of mold infestation of building materials would reduce health problems and building remediation costs. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit yeasts and a limited number of filamentous fungi. The purpose of this research was to determine the possible inhibitory activity of nonsteroidal anti-inflammatory drugs (NSAIDs) on germination, fungal growth, and reproduction of Chaetomium globosum and other important filamentous fungi that occur in water-damaged buildings. Several NSAIDs were found to inhibit C. globosum germination, growth, and reproduction. The most effective NSAIDs inhibiting C. globosum were ibuprofen, diflunisal, and diclofenac. Fusarium oxysporum, Fusarium solani, Aspergillus niger, and Stachybotrys atra were also tested on the various media with similar results obtained. However, F. oxysporum and A. niger exhibited a higher level of resistance to aspirin and NaSAL when compared to the C. globosum isolates. The inhibition exhibited by NSAIDs was variable depending on growth media and stage of fungal development. These compounds have a great potential of inhibiting fungal growth on building materials such as gypsum board. Formulations of sprays or building materials with NSAID-like chemical treatments may hold promise in reducing mold in homes and buildings.

Is monitoring of plasma 5-fluorouracil levels in metastatic / advanced colorectal cancer clinically effective? A systematic review.

BACKGROUND: Pharmacokinetic guided dosing of 5-fluorouracil chemotherapies to bring plasma 5-fluorouracil into a desired therapeutic range may lead to fewer side effects and better patient outcomes. High performance liquid chromatography and a high throughput nanoparticle immunoassay (My5-FU) have been used in conjunction with treatment algorithms to guide dosing. The objective of this study was to assess accuracy, clinical effectiveness and safety of plasma 5-fluorouracil guided dose regimen(s) versus standard regimens based on body surface area in colorectal cancer. METHODS: We undertook a systematic review. MEDLINE; MEDLINE In-Process & Other Non-Indexed Citations; EMBASE; Cochrane Library; Science Citation Index and Conference Proceedings (Web of Science); and NIHR Health Technology Assessment Programme were searched from inception to January 2014. We reviewed evidence on accuracy of My5-FU for estimating plasma 5-fluorouracil and on the clinical effectiveness of pharmacokinetic dosing compared to body surface area dosing. Estimates of individual patient data for overall survival and progression-free survival were reconstructed from published studies. Survival and adverse events data were synthesised and examined for consistency across studies. RESULTS: My5-FU assays were found to be consistent with reference liquid chromatography tandem mass spectrometry. Comparative studies pointed to gains in overall survival and in progression-free survival with pharmacokinetic dosing, and were consistent across multiple studies. CONCLUSIONS: Although our analyses are encouraging, uncertainties remain because evidence is mainly from outmoded 5-fluorouracil regimens; a randomised controlled trial is urgently needed to investigate new dose adjustment methods in modern treatment regimens.

Methods for specifying the target difference in a randomised controlled trial: the Difference ELicitation in TriAls (DELTA) systematic review.

BACKGROUND: Randomised controlled trials (RCTs) are widely accepted as the preferred study design for evaluating healthcare interventions. When the sample size is determined, a (target) difference is typically specified that the RCT is designed to detect. This provides reassurance that the study will be informative, i.e., should such a difference exist, it is likely to be detected with the required statistical precision. The aim of this review was to identify potential methods for specifying the target difference in an RCT sample size calculation. METHODS AND FINDINGS: A comprehensive systematic review of medical and non-medical literature was carried out for methods that could be used to specify the target difference for an RCT sample size calculation. The databases searched were MEDLINE, MEDLINE In-Process, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Methodology Register, PsycINFO, Science Citation Index, EconLit, the Education Resources Information Center (ERIC), and Scopus (for in-press publications); the search period was from 1966 or the earliest date covered, to between November 2010 and January 2011. Additionally, textbooks addressing the methodology of clinical trials and International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) tripartite guidelines for clinical trials were also consulted. A narrative synthesis of methods was produced. Studies that described a method that could be used for specifying an important and/or realistic difference were included. The search identified 11,485 potentially relevant articles from the databases searched. Of these, 1,434 were selected for full-text assessment, and a further nine were identified from other sources. Fifteen clinical trial textbooks and the ICH tripartite guidelines were also reviewed. In total, 777 studies were included, and within them, seven methods were identified-anchor, distribution, health economic, opinion-seeking, pilot study, review of the evidence base, and standardised effect size. CONCLUSIONS: A variety of methods are available that researchers can use for specifying the target difference in an RCT sample size calculation. Appropriate methods may vary depending on the aim (e.g., specifying an important difference versus a realistic difference), context (e.g., research question and availability of data), and underlying framework adopted (e.g., Bayesian versus conventional statistical approach). Guidance on the use of each method is given. No single method provides a perfect solution for all contexts.

Relative effectiveness of robot-assisted and standard laparoscopic prostatectomy as alternatives to open radical prostatectomy for treatment of localised prostate cancer: a systematic review and mixed treatment comparison meta-analysis.

OBJECTIVE: To compare the effectiveness of robot-assisted and standard laparoscopic prostatectomy. METHODS: A care pathway was described. We performed a systematic literature review based on a search of Medline, Medline in Process, Embase, Biosis, Science Citation Index, Cochrane Controlled Trials Register, Current Controlled Trials, Clinical Trials, WHO International Clinical Trials Registry and NIH Reporter, the Health Technology Assessment databases, the Database of Abstracts of Reviews of Effects, and relevant conference abstracts up to 31st October 2010). Additionally, reference lists were scanned, an expert panel consulted, and websites of manufacturers, professional organisations, and regulatory bodies were checked. We selected randomised controlled trials (RCTs) and non-randomised comparative studies, published after 1st January 1995, including men with localised prostate cancer undergoing robot-assisted or laparoscopic prostatectomy compared with the other procedure or with open prostatectomy. Studies where at least 90% of included men had clinical tumour stages T1 to T2 and which reported at least one of our specified outcomes were eligible for inclusion. A mixed-treatment comparison meta-analysis was performed to generate comparative statistics on specified outcomes. RESULTS: We included data from 19 064 men across one RCT and 57 non-randomised comparative reports. Robotic prostatectomy had a lower risk of major intra-operative harms such as organ injury [0.4% robotic vs 2.9% laparoscopic], odds ratio ([OR] {95% credible interval [CrI]} 0.16 [0.03 to 0.76]), and a lower rate of surgical margins positive for cancer [17.6% robotic vs 23.6% laparoscopic], OR [95% CrI] 0.69 [0.51 to 0.96]). There was no evidence of a difference in the proportion of men with urinary incontinence at 12 months (OR [95% CrI] 0.55 [0.09 to 2.84]). There were insufficient data on sexual dysfunction. Surgeon learning rates for the procedures did not differ, although data were limited. CONCLUSIONS: Men undergoing robotic prostatectomy appear to have reduced surgical morbidity, and a lower risk of a positive surgical margin, which may reduce rates of cancer recurrence and the need for further treatment, but considerable uncertainty surrounds these results. We found no evidence that men undergoing robotic prostatectomy are disadvantaged in terms of early outcomes. We were unable to determine longer-term relative effectiveness.

Using behavioural science to explore impact and implementation of obstetric anaesthesia training in Tanzania, Nepal and Bangladesh: a qualitative evaluation study with obstetric anaesthesia providers.

Objective: High quality obstetric anaesthetic care is integral to reducing preventable maternal deaths in Low-and-Middle-Income-Countries (LMICs). We applied behavioural science to evaluate SAFE Obstetrics, a 3-day Continuing Professional Development (CPD) course, on physician and non-physician anaesthetists' practice behaviours across 3 LMICs.Methods: Seven anaesthetist Fellows from Bangladesh, Nepal and Tanzania were trained in qualitative methods and behavioural science. Structured interviews were undertaken by Fellows and two UK behavioural scientists with course participants. Interviews were based on the Theoretical Domains Framework: a comprehensive framework of influences on behaviour change. Interviews were recorded, transcribed and analysed using content and thematic analysis.Results: 78 physician and non-physician anaesthetists participated (n = 26 Bangladesh, n = 24 Nepal and n = 28 Tanzania). Participants reported positive improvements in patient-centered working, safety, teamwork and confidence. Across countries, we found similar barriers and facilitators: environmental resources, a strong professional identity and positive social influences were key facilitators of change.Conclusion: This multi-country theory-based evaluation highlighted the impact of SAFE Obstetrics on participants' clinical practice. A supportive work environment was crucial for implementing learning following training; CPD courses in LMICs must furnish participants with skills and equipment to address training implementation challenges. Building local behavioural science capacity can strengthen LMIC health intervention evaluations.

Regional anesthesia as a safe option in patient with limb girdle muscular dystrophy undergoing total abdominal hysterectomy: A case report and case review.

Regional anesthesia can be a very safe option in patients with limb girdle muscular dystrophy undergoing lower abdominal surgeries as general anesthesia and volatile anesthetic agents are associated with increased risk of malignant hyperthermia and rhabdomyolysis.

Knowledge and Attitude Regarding Patients Right among Nurses in a Teaching Hospital: A Descriptive Cross-sectional Study.

INTRODUCTIONS: It is important to maintain trust and satisfaction among patients. The health personnel take an important role to overcome their right. The objective of this study was to find out knowledge and attitude regarding patients' rights among nurses in Teaching Hospital. METHODS: A descriptive cross sectional study was conducted among 122 nurses in different wards of Teaching Hospital. Nurses were selected by using simple random sampling technique for data collection. Ethical clearance was taken from Chitwan Medical College institutional reviewers Committee (CMC-IRC) to conduct the study. A structured, self- administered questionnaire and five-point Likert scale were used to analyze the collected data. Data was collected from 27th Ashadh to 9th Shrawan 2075. RESULTS: This study revealed that out of 122 respondents, 30 (24.6%) of respondents have an adequate level of knowledge whereas about half 62 (50.8%) of respondents had favorable and 60 (49.2%) had an unfavorable level of attitude regarding patients right. Sixty-one (50%) of the nurses were from the age group <22 years, 27 (77.9%) were unmarried, about 93 (76.2%) of nurses had completed Proficiency Certificate Level Nursing, 101 (82.2%) had work experience less than 24 months. CONCLUSIONS: According to the study, it concluded that one-fourth of the respondents have an adequate level of knowledge, one-half of the respondents had a favorable attitude. Therefore, knowledge and attitude regarding patients' rights should be increase through in-service education and seminars should be organized by the administration to promote quality health care service.

Accurate diagnosis of latent tuberculosis in children, people who are immunocompromised or at risk from immunosuppression and recent arrivals from countries with a high incidence of tuberculosis: systematic review and economic evaluation.

BACKGROUND: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB) [(Zopf 1883) Lehmann and Neumann 1896], is a major cause of morbidity and mortality. Nearly one-third of the world's population is infected with MTB; TB has an annual incidence of 9 million new cases and each year causes 2 million deaths worldwide. OBJECTIVES: To investigate the clinical effectiveness and cost-effectiveness of screening tests [interferon-gamma release assays (IGRAs) and tuberculin skin tests (TSTs)] in latent tuberculosis infection (LTBI) diagnosis to support National Institute for Health and Care Excellence (NICE) guideline development for three population groups: children, immunocompromised people and those who have recently arrived in the UK from high-incidence countries. All of these groups are at higher risk of progression from LTBI to active TB. DATA SOURCES: Electronic databases including MEDLINE, EMBASE, The Cochrane Library and Current Controlled Trials were searched from December 2009 up to December 2014. REVIEW METHODS: English-language studies evaluating the comparative effectiveness of commercially available tests used for identifying LTBI in children, immunocompromised people and recent arrivals to the UK were eligible. Interventions were IGRAs [QuantiFERON(®)-TB Gold (QFT-G), QuantiFERON(®)-TB Gold-In-Tube (QFT-GIT) (Cellestis/Qiagen, Carnegie, VA, Australia) and T-SPOT.TB (Oxford Immunotec, Abingdon, UK)]. The comparator was TST 5 mm or 10 mm alone or with an IGRA. Two independent reviewers screened all identified records and undertook a quality assessment and data synthesis. A de novo model, structured in two stages, was developed to compare the cost-effectiveness of diagnostic strategies. RESULTS: In total, 6687 records were screened, of which 53 unique studies were included (a further 37 studies were identified from a previous NICE guideline). The majority of the included studies compared the strength of association for the QFT-GIT/G IGRA with the TST (5 mm or 10 mm) in relation to the incidence of active TB or previous TB exposure. Ten studies reported evidence on decision-analytic models to determine the cost-effectiveness of IGRAs compared with the TST for LTBI diagnosis. In children, TST (≥ 5 mm) negative followed by QFT-GIT was the most cost-effective strategy, with an incremental cost-effectiveness ratio (ICER) of £18,900 per quality-adjusted life-year (QALY) gained. In immunocompromised people, QFT-GIT negative followed by the TST (≥ 5 mm) was the most cost-effective strategy, with an ICER of approximately £18,700 per QALY gained. In those recently arrived from high TB incidence countries, the TST (≥ 5 mm) alone was less costly and more effective than TST (≥ 5 mm) positive followed by QFT-GIT or T-SPOT.TB or QFT-GIT alone. LIMITATIONS: The limitations and scarcity of the evidence, variation in the exposure-based definitions of LTBI and heterogeneity in IGRA performance relative to TST limit the applicability of the review findings. CONCLUSIONS: Given the current evidence, TST (≥ 5 mm) negative followed by QFT-GIT for children, QFT-GIT negative followed by TST (≥ 5 mm) for the immunocompromised population and TST (≥ 5 mm) for recent arrivals were the most cost-effective strategies for diagnosing LTBI that progresses to active TB. These results should be interpreted with caution given the limitations identified. The evidence available is limited and more high-quality research in this area is needed including studies on the inconsistent performance of tests in high-compared with low-incidence TB settings; the prospective assessment of progression to active TB for those at high risk; the relative benefits of two-compared with one-step testing with different tests; and improved classification of people at high and low risk for LTBI. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014009033. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

A novel, long-acting glucagon-like peptide receptor-agonist: dulaglutide.

BACKGROUND: Dulaglutide is a new, long-acting glucagon-like peptide analogue in the treatment of type 2 diabetes. It is available in two doses, 0.75 and 1.5 mg, given by injection once weekly. This systematic review reports the effectiveness and safety of dulaglutide in type 2 diabetes in dual and triple therapy. METHODS: MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, and conference abstracts were searched from 2005 to August 2014, and updated in January 2015. Company websites and references of included studies were checked for potentially relevant studies. European Medicines Agency and US Food and Drug Administration websites were searched. RESULTS: Four trials were included. All were manufacturer-funded randomized controlled trials from the Assessment of Weekly Administration of Dulaglutide in Diabetes (AWARD) program. AWARD-1 compared dulaglutide 1.5 mg against exenatide 10 µg twice daily and placebo, AWARD-2 compared dulaglutide 0.75 and 1.5 mg against insulin glargine, AWARD-5 compared dulaglutide 0.75 and 1.5 mg against sitagliptin 100 mg and placebo, and AWARD-6 compared dulaglutide 1.5 mg against liraglutide 1.8 mg. The duration of follow-up in the trials ranged from 26 to 104 weeks. The primary outcome of all the included trials was change in HbA1c. At 26 weeks, greater HbA1c reductions were seen with dulaglutide than with twice daily exenatide (dulaglutide 1.5/0.75 mg: -1.5%/-1.3%; exe: 0.99%) and sitagliptin (1.5/0.75 mg -1.22%/-1.01%; sitagliptin: -0.6%). HbA1c change was greater with dulaglutide 1.5 mg (-1.08%) than with glargine (-0.63%), but not with dulaglutide 0.75 mg (-0.76%). Dulaglutide 1.5 mg was found to be noninferior to liraglutide 1.8 mg. More patients treated with dulaglutide achieved HbA1c targets of <7% and ≤6.5%. Reduction in weight was greater with dulaglutide than with sitagliptin and exenatide. Hypoglycemia was infrequent. The main adverse events were nausea, diarrhea, and vomiting. CONCLUSION: Dulaglutide is effective in the treatment of patients with type 2 diabetes but we need long follow-up data for safety concerns.

Clinical effectiveness and cost-effectiveness of elemental nutrition for the maintenance of remission in Crohn's disease: a systematic review and meta-analysis.

BACKGROUND: Although enteral nutrition has been shown to be a viable treatment option for the management of active Crohn's disease (CD), the evidence regarding its clinical benefits compared with standard treatments (e.g. steroids) for maintaining remission in patients with CD has been inconsistent. If enteral nutrition was to be effective, the use of drugs such as steroids and immunosuppressive drugs could be reduced, thereby reducing the likelihood of adverse events associated with these medications. OBJECTIVES: This systematic review aimed to assess the clinical effectiveness and cost-effectiveness of elemental nutrition (a type of enteral nutrition) for maintenance of remission in patients with CD. DATA SOURCES: Major bibliographic databases (e.g. MEDLINE, EMBASE, Cochrane Database of Systematic Reviews) were searched from inception to August/September 2013. Searches were not limited by study design, language or publication date. Websites for relevant organisations and references of included studies were checked. METHODS: Experimental randomised and non-randomised controlled trials (RCTs and nRCTs) reporting clinical effectiveness and cost-effectiveness of elemental nutrition in the maintenance of remission in patients with CD were eligible. Study selection, data extraction and risk of bias (RoB) assessment were performed independently. Risk ratios (RRs) and mean differences (MDs) were pooled using a random-effects model. Heterogeneity was assessed via forest plots, Cochran's Q and the I2 statistics. Overall, quality of evidence for each outcome was rated using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: Eight studies (three RCTs and five nRCTs) were included in the review. RCTs indicated a significant benefit of elemental nutrition vs. no intervention (an unrestricted diet) in maintaining remission at 24 months [one RCT; RR 2.06, 95% confidence interval (CI) 1.00 to 4.43; very low-grade evidence] and preventing relapse at 12-24 months post baseline (two RCTs; pooled RR 0.57, 95% CI 0.38 to 0.84; I2 = 0%; high-grade evidence). Similarly, three nRCTs showed significant benefits of elemental nutrition over no intervention in maintaining remission at 12-48 months and preventing relapse at 12 months post baseline (MD 1.20 months, 95% CI 0.35 to 2.04 months). The incidence of mucosal healing was not significantly different in the intervention and control groups (RR 2.70, 95% CI 0.62 to 11.72). Adherence to an elemental nutrition regime was significantly worse than adherence to polymeric nutrition (RR 0.68, 95% CI 0.50 to 0.92) and, when compared with other active treatments (medications, polymeric nutrition or a combination), elemental nutrition yielded non-significant results with wide 95% CIs, rendering these results inconclusive. Complications and adverse events were too sparse to allow meaningful comparisons. None of the studies reported cost-effectiveness of elemental nutrition. Owing to scarcity of data, subgroup and sensitivity analyses could not be performed to explore methodological and clinical sources of heterogeneity. LIMITATIONS: The findings warrant cautious interpretation given the limitations of the evidence in methodological quality (small samples, short follow-up) and the RoB in individual studies (lack of blinding, confounding). CONCLUSIONS: Limited evidence indicates potential benefits of elemental nutrition against no intervention in the maintenance of remission and prevention of relapse in adult patients with CD. There was a lack or insufficient evidence on adverse events and complications. Future large and long-term randomised trials are warranted to draw more definitive conclusions regarding the effects of elemental nutrition in maintaining remission in CD. TRIAL REGISTRATION: This study is registered as PROSPERO CRD42013005134. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Identifying potential moderators for response to treatment in low back pain: A systematic review.

BACKGROUND: Identifying which patients with non-specific low back pain are likely to gain the greatest benefit from different treatments is an important research priority. Few studies are large enough to produce data on sub-group effects from different treatments. Data from existing large studies may help identify potential moderators to use in future individual patient data meta-analyses. OBJECTIVE: To systematically review papers of therapist delivered interventions for low back pain to identify potential moderators to inform an individual patient data meta-analysis. DATA SOURCES: We searched MEDLINE, EMBASE, Web of Science and Citation Index and Cochrane Register of Controlled Trials (CENTRALhttp://www.cochrane.org/editorial-and-publishing-policy-resource/cochrane-central-register-controlled-trials-central) for relevant papers. DATA EXTRACTION AND DATA SYNTHESIS: We screened for randomised controlled trials with ≥500 or more participants, and cohort studies of ≥1000 or more participants. We examined all publications related to these studies for any reported moderator analyses. Two reviewers independently did risk of bias assessment of main results and quality assessment of any moderator analyses. RESULTS: We included four randomised trials (n=7208). Potential moderators with strong evidence (p<0.05) in one or more studies were age, employment status and type, back pain status, narcotic medication use, treatment expectations and education. Potential moderators with weaker evidence (0.05

Fluorouracil plasma monitoring: systematic review and economic evaluation of the My5-FU assay for guiding dose adjustment in patients receiving fluorouracil chemotherapy by continuous infusion.

BACKGROUND: 5-Fluorouracil (5-FU) is a chemotherapy used in colorectal, head and neck (H&N) and other cancers. Dose adjustment is based on body surface area (BSA) but wide variations occur. Pharmacokinetic (PK) dosing is suggested to bring plasma levels into the therapeutic range to promote fewer side effects and better patient outcomes. We investigated the clinical effectiveness and cost-effectiveness of the My5-FU assay for PK dose adjustment to 5-FU therapy. OBJECTIVES: To systematically review the evidence on the accuracy of the My5-FU assay compared with gold standard methods [high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS)]; the effectiveness of My5-FU PK dosing compared with BSA; the effectiveness of HPLC and/or LC-MS compared with BSA; the generalisability of published My5-FU and PK studies; costs of using My5-FU; to develop a cost-effectiveness model. DATA SOURCES: We searched MEDLINE, EMBASE, Science Citation Index and other databases between January and April 2014. METHODS: Two reviewers independently screened titles and abstracts with arbitration and consensus agreement. We undertook quality assessment. We reconstructed Kaplan-Meier plots for progression-free survival (PFS) and overall survival (OS) for comparison of BSA and PK dosing. We developed a Markov model to compare My5-FU with BSA dosing which modelled PFS, OS and adverse events, using a 2-week cycle over a 20 year time horizon with a 3.5% discount rate. Health impacts were evaluated from the patient perspective, while costs were evaluated from the NHS and Personal Social Services perspective. RESULTS: A total of 8341 records were identified through electronic searches and 35 and 54 studies were included in the clinical effectiveness and cost-effectiveness reviews respectively. There was a high apparent correlation between My5-FU, HPLC and LC-MS/mass spectrometer but upper and lower limits of agreement were -18% to 30%. Median OS were estimated as 19.6 [95% confidence interval (CI) 17.0 to 21.0] months for PK versus 14.6 (95% CI 14.1 to 15.3) months for BSA for 5-FU+folinic acid (FA); and 27.4 (95% CI 23.2 to 38.8) months for PK versus 20.6 (95% CI 18.4 to 22.9) months for BSA for FOLFOX6 in metastatic colorectal cancer (mCRC). PK versus BSA studies were generalisable to the relevant populations. We developed cost-effectiveness models for mCRC and H&N cancer. The base case assumed a cost per My5-FU assay of £ 61.03. For mCRC for 12 cycles of a oxaliplatin in combination with 5-fluorouracil and FA (FOLFOX) regimen, there was a quality-adjusted life-year (QALY) gain of 0.599 with an incremental cost-effectiveness ratio of £ 4148 per QALY. Probabilistic and scenario analyses gave similar results. The cost-effectiveness acceptability curve showed My5-FU to be 100% cost-effective at a threshold of £ 20,000 per QALY. For H&N cancer, again, given caveats about the poor evidence base, we also estimated that My5-FU is likely to be cost-effective at a threshold of £ 20,000 per QALY. LIMITATIONS: Quality and quantity of evidence were very weak for PK versus BSA dosing for all cancers with no randomised controlled trials (RCTs) using current regimens. For H&N cancer, two studies of regimens no longer in use were identified. CONCLUSIONS: Using a linked evidence approach, My5-FU appears to be cost-effective at a willingness to pay of £ 20,000 per QALY for both mCRC and H&N cancer. Considerable uncertainties remain about evidence quality and practical implementation. RCTs are needed of PK versus BSA dosing in relevant cancers.

Practicalities of using a modified version of the Cochrane Collaboration risk of bias tool for randomised and non-randomised study designs applied in a health technology assessment setting.

UNLABELLED: We describe our experience of using a modified version of the Cochrane risk of bias (RoB) tool for randomised and non-randomised comparative studies. OBJECTIVES: To assess time to complete RoB assessment. To assess inter-rater agreement. To explore the association between RoB and treatment effect size METHODS: Cochrane risk of bias assessment was performed on a sample of full text primary reports included in a systematic review comparing operative techniques for radical prostatectomy. Inter-rater agreement was assessed using the kappa statistic. RESULTS: Twenty-four studies were judged as high overall RoB, 13 were judged as low RoB and 11 were unclear. The weighted Kappa value was 0.35 indicating fair agreement. The median (range) time taken to rate each study was 30 min (10-49). The effect estimate for all studies was 0.61 (95% credible interval (CrI) 0.46-0.83) and 0.73 (95% CrI 0.29-1.75) for low risk studies. CONCLUSIONS: Although the process was time consuming, using a modified version of the RoB tool proved useful for demonstrating conservative effect estimates. That we only achieved a fair agreement between reviewers demonstrates the urgent need for further validation to improve inter-rater agreement. We suggest additional RoB levels could improve inter-rater reliability.

Women's knowledge of and attitude towards disability in rural Nepal.

PURPOSE: What is perceived to be a disability is both culturally specific and related to levels of development and modernity. This paper explores knowledge and attitudes towards people with disabilities among rural women in Nepal, one of the poorer countries in South Asia. METHOD: Four hundred and twelve married women of reproductive age (aged 15-49 years), from four villages in two different parts of Nepal, who had delivered a child within the last 24 months preceding the study, completed a standard questionnaire. RESULTS: The majority of the participants only considered physical conditions that limit function of an individual and are visible to naked eyes, such as missing a leg or arm, to be disability. Attitudes towards people with disability were generally positive, for example most women believed that disabled people should have equal rights and should be allowed to sit on committees or get married. Most respondents thought that disability could result from: (i) accidents; (ii) medical conditions; or (iii) genetic inheritance. Fewer women thought that disability was caused by fate or bad spirits. CONCLUSIONS: There is need to educate the general population on disability, especially the invisible disabilities. There is also a need for further research on disability and its social impact. IMPLICATIONS FOR REHABILITATION: • There is need to educate the general population on disability, especially the invisible disabilities and its rehabilitation. There is also a need for further research on disability and its social impact.

Aspirin in primary prevention of cardiovascular disease and cancer: a systematic review of the balance of evidence from reviews of randomized trials.

BACKGROUND: Aspirin has been recommended for primary prevention of cardiovascular disease (CVD) and cancer, but overall benefits are unclear. We aimed to use novel methods to re-evaluate the balance of benefits and harms of aspirin using evidence from randomised controlled trials, systematic reviews and meta-analyses. METHODS AND FINDINGS: Data sources included ten electronic bibliographic databases, contact with experts, and scrutiny of reference lists of included studies. Searches were undertaken in September 2012 and restricted to publications since 2008. Of 2,572 potentially relevant papers 27 met the inclusion criteria. Meta-analysis of control arms to estimate event rates, modelling of all-cause mortality and L'Abbé plots to estimate heterogeneity were undertaken. Absolute benefits and harms were low: 60-84 major CVD events and 34-36 colorectal cancer deaths per 100,000 person-years were averted, whereas 46-49 major bleeds and 68-117 gastrointestinal bleeds were incurred. Reductions in all-cause mortality were minor and uncertain (Hazard Ratio 0.96; 95% CI: 0.90-1.02 at 20 years, Relative Risk [RR] 0.94, 95% CI: 0.88-1.00 at 8 years); there was a non-significant change in total CVD (RR 0.85, 95% CI: 0.69-1.06) and change in total cancer mortality ranged from 0.76 (95% CI: 0.66-0.88) to 0.93 (95% CI: 0.84-1.03) depending on follow-up time and studies included. Risks were increased by 37% for gastrointestinal bleeds (RR 1.37, 95% CI: 1.15-1.62), 54%-66% for major bleeds (Rate Ratio from IPD analysis 1.54, 95% CI: 1.30-1.82, and RR 1.62, 95% CI: 1.31-2.00), and 32%-38% for haemorrhagic stroke (Rate Ratio from IPD analysis 1.32; 95% CI: 1.00-1.74; RR 1.38; 95% CI: 1.01-1.82). CONCLUSIONS: Findings indicate small absolute effects of aspirin relative to the burden of these diseases. When aspirin is used for primary prevention of CVD the absolute harms exceed the benefits. Estimates of cancer benefit rely on selective retrospective re-analysis of RCTs and more information is needed.