Sherie Smith

Clinical pathways for patients with newly diagnosed hepatitis C - what actually happens.

Summary.  Management of hepatitis C virus (HCV)‐infected individuals requires referral to specialist care. To determine whether patients newly diagnosed as anti‐HCV positive are appropriately referred for further investigation and management, and if not, to determine why not. We studied patients tested for antibodies to HCV by Nottingham Public Health Laboratory in a 2‐year period (2000–2002). The progress of newly diagnosed anti‐HCV positive patients into specialist clinics for further management was documented. For patients not referred for specialist care, a questionnaire was sent to the clinician requesting the initial anti‐HCV test, to identify reasons for nonreferral. Eleven thousand one hundred and seventy‐seven patients were tested for anti‐HCV. Two hundred and fifty‐six (2.3%) were newly diagnosed as being anti‐HCV positive. Two per cent of samples sent from primary care were anti‐HCV positive, compared to 18.8, 18.9 and 1.3% sent from prison, drug and alcohol units, and secondary care, respectively. About 64.3% of positive patients diagnosed in primary care were referred to specialist care, compared to 18.4, 42.4 and 62.6% of patients diagnosed in the other three settings. One hundred and twenty‐five (49%) newly diagnosed patients were referred appropriately for further management. 68 of these attended clinic, 45 underwent liver biopsy and 26 (10%) began treatment. One hundred and thirty‐one patients (51%) were not referred. In 54 cases, there was no evidence that the anti‐HCV positive result reached the patient. In 15, referral was considered but rejected, and 20 patients were referred to non‐HCV‐specialists (their general practitioners or to genito‐urinary medicine). Hence less than 50% of newly diagnosed anti‐HCV positive patients are referred to an appropriate clinic for further investigation and management. Reasons for this are multifarious and complex, reflecting both systems failure and patient choice. Unless these are understood and addressed, the Department of Health Hepatitis C Strategy (2002) and Action Plan for England (2004) will fail to achieve their intended objectives.

Effect of education and safety equipment on poisoning-prevention practices and poisoning: systematic review, meta-analysis and meta-regression

Objective: To assess (a) the effect of home safety education and the provision of safety equipment on poison-prevention practices and poisoning rates, and (b) whether the effect of interventions differs by social group. Data sources: Medline, Embase, Cinahl, ASSIA, Psychinfo, Web of Science, plus other electronic sources and hand searching of conference abstracts and reference lists. Authors of included studies were asked to supply individual participant data. Review methods: Randomised controlled trials, non-randomised controlled trials and controlled before-and-after studies, with participants aged ⩽19 years, providing home safety education with or without free or subsidised safety equipment and reporting poison-prevention practices or poisoning incidents were included. Pooled odds ratios and pooled rate ratios were estimated, and meta-regression estimated intervention effects by child age, gender and social variables. Results: Home safety interventions increased safe storage of medicines (OR 1.57, 95% CI 1.22 to 2.02) and cleaning products (OR 1.63, 95% CI 1.22 to 2.17), the possession of syrup of ipecac (OR 3.34, 95% CI 1.50 to 7.41), and having poison control centre numbers accessible (OR 3.67, 95% CI 1.84 to 7.33). There was a lack of evidence on poisoning rates (rate ratio 1.03, 95% CI 0.78 to 1.36) and no consistent evidence that intervention effects differed by child age, gender or social group. Conclusions: Home safety education and the provision of safety equipment improve poison-prevention practices, but the impact on poisoning rates is unclear. Such interventions are unlikely to widen inequalities in childhood poisoning-prevention practices.

Preventing Childhood Falls at Home. Meta-Analysis and Meta-Regression

BACKGROUND Childhood falls are an important global public health problem, but evidence on their prevention has not been quantitatively synthesized. Despite social inequalities in childhood injury rates, there is a lack of evidence examining the effect of fall-prevention practices by social group. METHODS A systematic review of literature was conducted up to June 2004 and meta-analysis using individual patient data to evaluate the effect of home-safety interventions on fall-prevention practices and fall-injury rates. Meta-regression examined the effect of interventions by child age, gender, and social variables. Included were 21 studies, 13 of which contributed to meta-analyses. RESULTS Home-safety interventions increased stair-gate use (OR=1.26; 95% CI=1.05, 1.51), and there was some evidence of reduced baby-walker use (OR=0.66; 95% CI=0.43, 1.00), but little evidence of increased possession of window locks, screens, or windows with limited opening (OR=1.16, 95% CI=0.84, 1.59) or of nonslip bath mats or decals (OR=1.15; 95% CI=0.51, 2.62). Two studies reported nonsignificant effects on falls (baby-walker-related falls on flat ground [OR=1.35; 95% CI=0.64, 2.83] or down steps or stairs [OR=0.70; 95% CI=0.14, 3.49]) and medically attended falls (OR=0.78; 95% CI=0.61, 1.00). CONCLUSIONS Home-safety education and the provision of safety equipment improved some fall-prevention practices, but the impact on fall-injury rates is unclear. There was some evidence that the effect of home-safety interventions varied by social group.

Randomised controlled trial of thermostatic mixer valves in reducing bath hot tap water temperature in families with young children in social housing

Objectives To assess the effectiveness of thermostatic mixing valves (TMVs) in reducing bath hot tap water temperature, assess acceptability of TMVs to families and impact on bath time safety practices. Design Pragmatic parallel arm randomised controlled trial. Setting A social housing organisation in Glasgow, Scotland, UK. Participants 124 families with at least one child under 5 years. Intervention A TMV fitted by a qualified plumber and educational leaflets before and at the time of TMV fitting. Main outcome measures Bath hot tap water temperature at 3-month and 12-month post-intervention or randomisation, acceptability, problems with TMVs and bath time safety practices. Results Intervention arm families had a significantly lower bath hot water temperature at 3-month and 12-month follow-up than families in the control arm (3 months: intervention arm median 45.0°C, control arm median 56.0°C, difference between medians, −11.0, 95% CI −14.3 to −7.7); 12 months: intervention arm median 46.0°C, control arm median 55.0°C, difference between medians −9.0, 95% CI −11.8 to −6.2) They were significantly more likely to be happy or very happy with their bath hot water temperature (RR 1.43, 95% CI 1.05 to 1.93), significantly less likely to report the temperature as being too hot (RR 0.33, 95% CI 0.16 to 0.68) and significantly less likely to report checking the temperature of every bath (RR 0.84, 95% CI 0.73 to 0.97). Seven (15%) intervention arm families reported problems with their TMV. Conclusions TMVs and accompanying educational leaflets are effective at reducing bath hot tap water temperatures in the short and longer term and are acceptable to families. Housing providers should consider fitting TMVs in their properties and legislators should consider mandating their use in refurbishments as well as in new builds.

What is the evidence-base for atopic eczema treatments? A summary of published randomised controlled trials

Atopic eczema (AE) is a common chronic inflammatory skin condition. While many AE treatment options are available, the evidence to support their efficacy varies in depth and quality. In 2000, a National Institute for Health Research (NIHR) Health Technology Assessment systematic review identified and evaluated existing randomized controlled trials (RCTs) of AE treatments. To ensure continuing utility, the NIHR commissioned an update to the review. Here, we present an overview of the updated report and its key findings. Systematic reviews and RCTs of AE treatments that included participants with AE (criteria based or diagnosed) were identified using Medline, Embase, CENTRAL, Latin American and Caribbean Health Sciences, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature and Cochrane Skin Group Specialised Register [searched to 31 August 2013 (RCTs) and 31 December 2015 (systematic reviews)]. Outcome measures included symptoms, AE severity, quality of life and adverse effects. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Of the 287 new RCTs identified, only 22 (8%) were judged to have a low risk of bias. When combined with RCTs from the previous review (n = 254), we found ‘reasonable evidence of benefit’ for corticosteroids, calcineurin inhibitors, Atopiclair®, ciclosporin, azathioprine, ultraviolet radiation and education programmes. Interventions with reasonable evidence of ‘no benefit’ included some dietary interventions, ion exchange water softeners, multiple daily applications of topical corticosteroids and antibiotic‐containing corticosteroids for noninfected AE. Many common treatments lack evidence of efficacy and warrant further evaluation. The evidence base for AE is still hampered by poor trial design and reporting. The trials included in this review were used to establish the Global Resource of EczemA Trials (GREAT) database.

How are eczema ‘flares’ defined? A systematic review and recommendation for future studies†

Eczema is an important public health problem due to high prevalence and associated morbidity. As a chronic, relapsing disease, the ability to capture disease flares is important when evaluating treatment success, yet it is unclear how flares should be defined. This study systematically reviews and critically appraises the literature defining flares in eczema, and explores methodological and practical aspects of including eczema flares as outcome measures in trials to inform developing an international consensus definition adding details of our own recent experience. A systematic review was undertaken of flare definitions in prospective intervention studies of eczema published up until 14 February 2013. Data were double‐extracted. We pre‐specified that important characteristics of a good flare definition should include (i) being feasible to collect and (ii) being recorded at the time flare symptoms were experienced. Three hundred and fourteen papers were identified of which 26 included some description of eczema flares. Overall, 22 different flare definitions were used. Flares were included as the primary outcome in 17 studies (65%). Only four studies (15%) used a patient‐reported flare definition. No studies fulfilled all of our pre‐specified essential characteristics. No validation studies were identified. The wide variation and lack of validation of flare definitions hampers comparison of findings between studies for this chronic, relapsing disease. None of the currently used definitions seem fit for purpose. Further research should establish which aspects of worsening of disease are most important to patients, and how best to capture these data in a way that is valid, reliable and feasible in all clinical and research settings.

Effectiveness of 2009 pandemic influenza A(H1N1) vaccines: A systematic review and meta-analysis

BACKGROUND The clinical effectiveness of monovalent influenza A(H1N1)pdm09 vaccines has not been comprehensively summarised. We undertook a systematic review and meta-analysis to assess vaccine effectiveness (VE) for adjuvanted and unadjuvanted vaccines. METHODS We searched healthcare databases and grey literature from 11 June 2009 to 12 November 2014. Two researchers independently assessed titles and abstracts to identify studies for full review. Random effects meta-analyses estimated the pooled effect size of vaccination compared to placebo or no vaccination for crude and adjusted odds ratios (OR) to prevent laboratory confirmed influenza illness (LCI) and related hospitalization. VE was calculated as (1-pooled OR)∗100. Narrative synthesis was undertaken where meta-analysis was not possible. RESULTS We identified 9229 studies of which 38 at moderate risk of bias met protocol eligibility criteria; 23 were suitable for meta-analysis. Pooled adjusted VE against LCI with adjuvanted and unadjuvanted vaccines both reached statistical significance (adjuvanted: VE=80%; 95% confidence interval [CI] 59-90%; unadjuvanted: VE=66%; 95% CI 47-78%); in planned secondary analyses, VE in adults often failed to reach statistical significance and pooled point estimates were lower than observed in children. Overall pooled adjusted VE against hospitalization was 61% (95% CI 14-82%); in planned secondary analyses, adjusted VE attained statistical significance in adults aged 18-64years and children for adjuvanted vaccines. Adjuvanted vaccines were significantly more effective in children compared to adults for both outcomes. CONCLUSIONS Adjuvanted and unadjuvanted monovalent influenza A(H1N1)pdm09 vaccines were both effective in preventing LCI. Overall, the vaccines were also effective against influenza-related hospitalization. For both outcomes adjuvanted vaccines were more effective in children than in adults.

The top 10 research priorities in cystic fibrosis developed by a partnership between people with CF and healthcare providers

There remain many treatment uncertainties in cystic fibrosis (CF). With limited resources, research should focus on questions which are most important to the CF community. We conducted a James Lind Alliance Priority Setting Partnership in CF. Research questions were elicited and then prioritised in successive surveys. A workshop agreed the final top 10. Online methods avoided cross infection and widened participation. The elicitation survey had 482 respondents (1080 questions) and prioritisation survey 677 respondents. Participants were drawn equally from the patient and clinical communities globally. We have achieved a consensus on 10 research priorities which will be attractive to funders.

Protective efficacy of BCG vaccine against leprosy in southern Malaŵi.

This paper describes a matched case-control study to determine the efficacy of BCG vaccine in preventing the occurrence of leprosy in southern Malaŵi, a previously unstudied area. The BCG immunization rate amongst 145 individuals with leprosy was 44.8%, compared to 62.5% in 290 matched controls. The protective efficacy of BCG vaccine against leprosy in this region was estimated to be 63.6%; smallpox immunization had no effect. These findings support the view that BCG vaccine should be considered as a control measure in areas where leprosy is endemic.

Validation of the global resource of eczema trials (GREAT database)

BackgroundEczema (syn. Atopic Eczema or Atopic Dermatitis) is a chronic, relapsing, itchy skin condition which probably results from a combination of genetic and environmental factors. The Global Resource of EczemA Trials (GREAT) is a collection of records of randomised controlled trials (RCTs) for eczema treatment produced from a highly sensitive search of six reference databases. We sought to assess the sensitivity of the GREAT database as a tool to save future researchers repeating extensive bibliographic searches.MethodsAll Cochrane systematic review on treatments for eczema and five non-Cochrane systematic reviews on eczema were identified as a reference set to assess the utility of the GREAT database in identifying randomised controlled trials (RCTs). RCTs included in the systematic reviews were checked for inclusion in the GREAT database by two independent authors. A third author resolved any disagreements.ResultsFive Cochrane and six non-Cochrane systematic reviews containing a total of 105 RCTs of eczema treatments were included. Of these, 95 fitted the inclusion criteria for the GREAT database and 88 were published from 2000 onwards. Of the 88 eligible studies, 92% were found in the GREAT database. Seven trials were not included in the GREAT database - two of these were reported within a review paper and one as an abstract with no trial results.ConclusionsThe sensitivity of the GREAT database for trials from 2000 onwards was high (75/88 trials, 94%). Sensitivity for the period prior to 2000 was less sensitive, due to differences in how the trials were identified prior to this time.‘Dual’ filtering for new records has recently become part of the GREAT database methodology and should further improve the sensitivity of the database in time. The GREAT database can be considered as a primary source for future systematic reviews including randomised controlled trials of eczema treatments, but searches should be supplemented by checking reference lists for eligible trials, searching trial registries and contacting pharmaceutical companies for unpublished studies.