Does evidence-based practice improve patient outcomes

Background Evidence based practice (EBP) is widely promoted, but does EBP practice produce better patient outcomes? We report a natural experiment when part of the internal medicine service in a hospital was reorganized in 2003 to form an EBP unit, the rest of the service remaining unchanged. The units attended similar patients until 2012 permitting comparisons of outcomes and activity. Methods We used routinely collected statistics (2004 11) to compare the two different methods of practice and test whether patients being seen by the EBP unit differed from standard practice (SP) patients. Data were available by doctor and year. To check for differences between the EBP and SP doctors prior to reorganization, we used statistics from 2000 2003. We looked for changes in patient outcomes or activity following reorganization and whether the EBP unit was achieving significantly different results from SP. Data across the periods were combined and tested using Mann-Whitney. Results No statistically significant differences in outcomes were detected between the EBP and the SP doctors prior to reorganization. Following the unit’s establishment, the mortality of patients being treated by EBP doctors compared to their previous performance dropped from 7.4% to 6.3% (P<0.02) and length of stay from 9.15 to 6.01 days (P=0.002). No statistically significant improvements were seen in SP physicians’ performance. No differences in the proportion of patients admitted or their complexity between the services were detected. Despite this, EBP patients had a clinically significantly lower risk of death 6.27% vs 7.75% (P<0.001) and a shorter length of stay 6.01 vs 8.46 days (P<0.001) than SP patients. Readmission rates were similar: 14.4% (EBP); 14.5% (SP). EBP doctors attended twice as many patients/doctor as SP doctors. Conclusion The EBP unit was associated with better patient outcomes and more efficient performance than achieved by the same physicians previously or by SP concurrently

Green Care: a Conceptual Framework. A Report of the Working Group on the Health Benefits of Green Care

‘Green Care’ is a range of activities that promotes physical and mental health and well-being through contact with nature. It utilises farms, gardens and other outdoor spaces as a therapeutic intervention for vulnerable adults and children. Green care includes care farming, therapeutic horticulture, animal assisted therapy and other nature-based approaches. These are now the subject of investigation by researchers from many different countries across the world

SMOOTH (Self-Management of Open Online Trials in Health) analysis found improvements were needed for reporting methods of internet-based trials

Background The growth of trials conducted over the internet has increased, but with little practical guidance for their conduct and it is sometimes challenging for researchers to adapt the conventions used in face-to-face trials and maintain the validity of the work. Aim To systematically explore existing self-recruited online randomized trials of self-management interventions and analyze the trials to assess their strengths and weaknesses, the quality of reporting and the involvement of lay persons as collaborators in the research process. Methods The Online Randomized Controlled Trials of Health Information Database (ORCHID) was used as the sampling frame to identify a subset of self-recruited online trials of self-management interventions. The authors cataloged what these online trials were assessing, appraised study quality, extracted information on how trials were run and assessed the potential for bias. We searched out how public and patient participation was integrated into online trial design and how this was reported. We recorded patterns of use for registration, reporting, settings, informed consent, public involvement, supplementary materials, and dissemination planning. Results The sample included 41 online trials published from 2002-2015. The barriers to replicability and risk of bias in online trials included inadequate reporting of blinding in 28/41 (68%) studies; high attrition rates with incomplete or unreported data in 30/41 (73%) of trials; and 26/41 (63%) of studies were at high risk for selection bias as trial registrations were unreported. The methods for (23/41, 56%) trials contained insufficient information to replicate the trial, 19/41 did not report piloting the intervention. Only 2/41 studies were cross-platform compatible. Public involvement was most common for advisory roles (n=9, 22%), and in the design, usability testing and piloting of user materials (n=9, 22%) Conclusions This study catalogs the state of online trials of self-management in the early 21st century and provides insights for online trials development as early as the protocol planning stage. Reporting of trials was generally poor and, in addition to recommending that authors report their trials in accordance with CONSORT guidelines, we make recommendations for researchers writing protocols, reporting on and evaluating online trials. The research highlights considerable room for improvement in trial registration, reporting of methods, data management plans, and public and patient involvement in self-recruited online trials of self-management interventions

Immunoprophylaxis against respiratory syncytial virus (RSV) with palivizumab in children: a systematic review and economic evaluation

Objectives: To systematically review the effectiveness and cost-effectiveness of palivizumab for the prevention of respiratory syncytial virus (RSV) in children and examine prognostic factors to determine whether subgroups can be identified with important differences in cost-effectiveness. Data sources: Bibliographic databases were searched from inception to March 2007 for literature on the effectiveness and cost-effectiveness of prophylaxis with palivizumab. Review methods: The literature was systematically reviewed and current economic evaluations were analysed to identify which parameters were driving the different cost-effectiveness estimates. A probabilistic decision-analytical model was built to assess the cost-effectiveness of prophylaxis with palivizumab for children at risk of RSV infection and the parameters populated with the best estimates thought most applicable to the UK. We also constructed a new model, the Birmingham Economic Evaluation (BrumEE). Cost-effectiveness analyses were undertaken from both NHS and societal perspectives. Results: Two randomised controlled trials (RCTs) were identified. Prophylaxis with palivizumab for preterm infants without chronic lung disease (CLD) or children with CLD resulted in a 55% reduction in RSV hospital admission: 4.8% (48/1002) in the palivizumab group and 10.6% (53/500) in the no prophylaxis group (p=0.0004). Prophylaxis with palivizumab was associated with a 45% reduction in hospitalisation rate RSV among children with coronary heart disease (CHD). Hospitalisation rates for RSV were 5.3% (34/639) in the palivizumab group and 9.7% (63/648) in the no prophylaxis group (p=0.003). Of existing economic evaluations, 3 systematic reviews and 18 primary studies were identified. All the systematic reviews concluded that the potential costs of palivizumab were far in excess of any potential savings achieved by decreasing hospital admission rates, and that the use of palivizumab was unlikely to be cost-effective in all children for whom it is recommended, but that its continued use for particularly high-risk children may be justified. The incremental cost-effectiveness ratios (ICERs) of the primary studies varied 17-fold for life-years gained (LYG), from £25,800/ LYG to £404,900/LYG, and several hundred-fold for quality-adjusted life years (QALYs), from £3200/QALY to £1,489,700/QALY for preterm infants without CLD or children with CLD. For children with CHD, the ICER varied from £5300/LYG to £7900/LYG and from £7500/ QALY to £68,700/QALY. An analysis of what led to the discrepant ICERs showed that the assumed mortality rate for RSV infection was the most important driver. The results of the BrumEE confirm that palivizumab does not reach conventional levels of cost-effectiveness in any of the licensed indications if used for all eligible children. Conclusions: Prophylaxis with palivizumab is clinically effective for the reducing the risk of serious lower respiratory tract infection caused by RSV infection and requiring hospitalisation in high-risk children, but if used unselectively in the licensed population, the ICER is double that considered to represent good value for money in the UK. The BrumEE shows that prophylaxis with palivizumab may be cost-effective (based on a threshold of £30,000/QALY) for children with CLD when the children have two or more additional risk factors. Future research should initially focus on reviewing systematically the major uncertainties for patient subgroups with CLD and CHD and then on primary research to address the important uncertainties that remain

Systematic review and meta-analysis on certolizumab pegol for rheumatoid arthritis in adults

Background The appearance of tumor necrosis factor-alpha (TNFalpha) inhibitors dramatically changed the prognosis of rheumatoid arthritis. Certolizumab pegol (CZP) is a human Fab fragment of anti-TNFalpha monoclonal antibody which is approved for the treatment of rheumatoid arthritis. We performed a systematic review and meta-analysis, with Cochrane methodology, of the effects of CZP in rheumatoid arthritis. Objectives To assess the clinical benefits and harms of CZP in patients with rheumatoid arthritis. Methods We performed a search of electronic database (Cochrane Database, MEDLINE, EMBASE, Web of Knowledge and clinicaltrials.gov) until 26th September 2016. We searched for randomized controlled trials of CZP in rheumatoid arthritis compared to any other agent including placebo. Results 14 trials were included for the meta-analysis, 12 (5422 patients) in the pooled analysis for benefits and 14 (5499 patients) in the pooled analysis for safety. The overall possibility of bias seemed to be low but the quality of the evidence was low due to the risk of attrition bias. With the approved dose - CZP 200 mg subcutaneous every other week with the first three doses of 400 mg - CZP showed statistically significant improvements at 24 weeks compared to placebo in: ACR50 absolute improvement 27% (95% CI 20% to 33%), RR 3.8 (95% CI 2.42 to 5.95) and NNT=4 (95% CI 3 to 8); DAS28 <2.6 - original definition of remission - with RR 3.79 (95% CI 1.90 to 7.56); HAQ with -12% absolute improvement (95% CI -9% to -14%); and erosion score with -0.29% (95% CI -0.42% to -0.17%). There are also data available at 12 weeks with RR of 1.99 (95% CI 1.44 to 2.76) of achieving DAS28<2.6 with CZP 200 mg dose. The proportion of patients achieving DAS28<2.6 was still higher with CZP at 52 weeks with RR of 1.83 (95% CI 1.53 to 2.18). Serious adverse events were more frequent for CZP 200 mg dose with a RR of 1.47 (95% CI 1.13 to 1.91) and NNH of 32. There have been eight adverse events leading to death in CZP 200 mg group versus two in the control group (not statistically significant) and 10 patients developing tuberculosis versus two in the control group (not statistically significant). Conclusions There is low level evidence from randomized controlled trials that CZP as monotherapy or combined with methotrexate improved ACR50, DAS28, HAQ and joint damaged on x-ray. Adverse events were more frequent with active treatment

Publication bias – teaching materials

The attached slides can be used to teach people about publication bias. There are notes beneath the slides with suggestions of how they might be used Prepared by Professor Amanda Burls and available from www.testingtreatments.org. Task purpose: to help people understand publication bias by working through a real concrete example. Key slides can be used usefully in a five minute slot in a session on appraising systematic reviews. However the extended use of the slides with group work could take up to an hour depending on how the teacher organises the session. Assumes no prior knowledge but can be used for quite a high level of prior skill group (i.e. those with previous training in the critical appraisal of systematic reviews) and indeed works well for a group with heterogenous skill levels. Skill area: making sense of the evidence from systematic review

Certolizumab pegol (CDP870) for rheumatoid arthritis in adults

Background Tumour necrosis factor (TNF)-alpha inhibitors are beneficial for the treatment of rheumatoid arthritis (RA) for reducing the risk of joint damage, improving physical function and improving the quality of life. This review is an update of the 2014 Cochrane Review of the treatment of RA with certolizumab pegol. Objectives To assess the clinical benefits and harms of certolizumab pegol (CZP) in people with RA who have not responded well to conventional disease-modifying anti-rheumatic drugs (DMARDs). Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL: Cochrane Library 2016, Issue 9), MEDLINE, Embase, Web of Knowledge, reference lists of articles, clinicaltrials.gov and ICTRP of WHO. The searches were updated from 2014 (date of the last search for the previous version) to 26 September 2016. Selection criteria Randomised controlled trials that compared certolizumab pegol with any other agent, including placebo or methotrexate (MTX), in adults with active RA, regardless of current or prior treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs), such as MTX. Data collection and analysis Two review authors independently checked search results, extracted data and assessed trial quality. We resolved disagreements by discussion or referral to a third review author. Main results We included 14 trials in this update, three more than previously. Twelve trials (5422 participants) included measures of benefit. We pooled 11 of them, two more than previously. Thirteen trials included information on harms, (5273 participants). The duration of follow-up varied from 12 to 52 weeks and the range of doses of certolizumab pegol varied from 50 to 400 mg given subcutaneously. In Phase III trials, the comparator was placebo plus MTX in seven trials and placebo in five. In the two Phase II trials the comparator was only placebo. The approved dose of certolizumab pegol, 200 mg every other week, produced clinically important improvements at 24 weeks for the following outcomes: - American College of Rheumatology (ACR) 50% improvement (pain, function and other symptoms of RA): 25% absolute improvement (95% confidence interval (CI) 20% to 33%); number need to treat for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 5); risk ratio (RR) 3.80 (95% CI 2.42 to 5.95), 1445 participants, 5 studies. - The Health Assessment Questionnaire (HAQ): -12% absolute improvement (95% CI -9% to -14%); NNTB of 8 (95% CI 7 to 11); mean difference (MD) - 0.35 (95% CI -0.43 to -0.26; 1268 participants, 4 studies) (scale 0 to 3; lower scores mean better function). - Proportion of participants achieving remission (Disease Activity Score (DAS) < 2.6) absolute improvement 10% (95% CI 8% to 16%); NNTB of 8 (95% CI 6 to 12); risk ratio (RR) 2.94 (95% CI 1.64 to 5.28), 2420 participants, six studies. - Radiological changes: erosion score (ES) absolute improvement -0.29% (95% CI -0.42% to -0.17%); NNTB of 6 (95% CI 4 to 10); MD -0.67 (95% CI -0.96 to -0.38); 714 participants, two studies (scale 0 to 230), but not a clinically important difference. -Serious adverse events (SAEs) were statistically but not clinically significantly more frequent for certolizumab pegol (200 mg every other week) with an absolute rate difference of 3% (95% CI 1% to 4%); number needed to treat for an additional harmful outcome (NNTH) of 33 (95% CI 25 to 100); Peto odds ratio (OR) 1.47 (95% CI 1.13 to 1.91); 3927 participants, nine studies. There was a clinically significant increase in all withdrawals in the placebo groups (for all doses and at all follow-ups) with an absolute rate difference of -29% (95% CI -16% to -42%), NNTH of 3 (95% CI 2 to 6), RR 0.47 (95% CI 0.39 to 0.56); and there was a clinically significant increase in withdrawals due to adverse events in the certolizumab groups (for all doses and at all follow-ups) with an absolute rate difference of 2% (95% CI 0% to 3%); NNTH of 58 (95% CI 28 to 329); Peto OR 1.45 (95% CI 1.09 to 1.94) 5236 participants Twelve studies. We judged the quality of evidence to be high for ACR50, DAS remission, SAEs and withdrawals due to adverse events, and moderate for HAQ and radiological changes, due to concerns about attrition bias. For all withdrawals we judged the quality of evidence to be moderate, due to inconsistency. Authors' conclusions The results and conclusions did not change from the previous review. There is a moderate to high certainty of evidence from randomised controlled trials that certolizumab pegol, alone or combined with methotrexate, is beneficial in the treatment of RA for improved ACR50 and health-related quality of life, an increased chance of remission of RA, and reduced joint damage as seen on x-ray. Fewer people stopped taking their treatment, but most of these who did stopped due to serious adverse events. Adverse events were more frequent with active treatment. We found a clinically but not statistically significant risk of serious adverse events

Heparin versus 0.9% sodium chloride locking for prevention of occlusion in central venous catheters in adults

Background Intermittent locking of central venous catheters (CVCs) is undertaken to help maintain their patency. There are systematic variations in care: some practitioners use heparin (at different concentrations), whilst others use 0.9% NaCl (normal saline). This review looks at the effectiveness and safety of intermittent locking with heparin compared to 0.9% NaCl to see if the evidence establishes whether one is better than the other. This work is an update of a review first published in 2014. Objectives To assess the effectiveness and safety of intermittent locking of CVCs with heparin versus normal saline (NS) in adults to prevent occlusion. Search methods The Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched 11 June 2018) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 5). Searches were also carried out in MEDLINE, Embase, CINAHL, and clinical trials databases (11 June 2018). Selection criteria We included randomised controlled trials in adults ≥ 18 years of age with a CVC that compared intermittent locking with heparin at any concentration versus NS. We applied no restriction on language. Data collection and analysis Two review authors independently selected trials, assessed quality, and extracted data. We contacted trial authors to retrieve additional information, when necessary.We carried out statistical analysis using ReviewManager 5 and assessed the overall quality of the evidence supporting assessed outcomes using GRADE. We carried out prespecified subgroup analysis. Main results We identified five new studies for this update (six prior studies were included in the original review), bringing the number of eligible studies to 11, with a total of 2392 participants. We noted differences in methods used by the included studies and variation in heparin concentrations (10 to 5000 IU/mL), time to follow-up (1 to 251.8 days), and the unit of analysis used (participant, catheter, line access). Combined results fromthese studies showed fewer occlusions with heparin than with NS (risk ratio (RR) 0.70, 95%confidence interval (CI) 0.51 to 0.95; P = 0.02; 1672 participants; 1025 catheters from 10 studies; I² = 14%) and provided very low-quality evidence. We carried out subgroup analysis by unit of analysis (testing for subgroup differences (P = 0.23; I² = 30.3%). When the unit of analysis was the participant, results show no clear differences in all occlusions between heparin and NS (RR 0.79, 95% CI 0.58 to 1.08; P = 0.15; 1672 participants; seven studies). Subgroup analysis using the catheter as the unit of analysis shows fewer occlusions with heparin use (RR 0.53, 95% CI 0.29 to 0.95; P = 0.03; 1025 catheters; three studies). When the unit of analysis was line access, results show no clear differences in occlusions between heparin and NS (RR 1.08, 95% CI 0.84 to 1.40; 770 line accesses; one study). We found no clear differences in the duration of catheter patency (mean difference (MD) 0.44 days, 95% CI -0.10 to 0.99; P = 0.11; 1036 participants; 752 catheters; six studies; low-quality evidence). We found no clear evidence of a difference in the following: CVC-related sepsis (RR 0.74, 95% CI 0.03 to 19.54; P = 0.86; 1097 participants; two studies; low-quality evidence); mortality (RR 0.76, 95% CI 0.44 to 1.31; P = 0.33; 1100 participants; three studies; low-quality evidence); haemorrhage at any site (RR 1.32, 95% CI 0.57 to 3.07; P = 0.52; 1245 participants; four studies; moderatequality evidence); or heparin-induced thrombocytopaenia (RR 0.21, 95% CI 0.01 to 4.27; P = 0.31; 443 participants; three studies; low-quality evidence). Themain reasons for downgrading the quality of evidencewere unclear allocation concealment, imprecision, and suspicion of publication bias. Authors’ conclusions Given the very low quality of the evidence, we are uncertain whether intermittent locking with heparin results in fewer occlusions than intermittent locking with NS. Low-quality evidence suggests that heparin may have little or no effect on catheter patency. Although we found no evidence of differences in safety (sepsis, mortality, or haemorrhage), the combined trials are not powered to detect rare adverse events such as heparin-induced thrombocytopaenia

What utility scores do mental health service users, healthcare professionals and members of the general public attribute to different health states? A co-produced mixed methods online survey

Utility scores are integral to health economics decision-making. Typically, utility scores have not been scored or developed with mental health service users. The aims of this study were to i) collaborate with service users to develop descriptions of five mental health states (psychosis, depression, eating disorder, medication side effects and self-harm); ii) explore feasibility and acceptability of using scenario-based health states in an e-survey; iii) evaluate which utility measures (standard gamble (SG), time trade off (TTO) and rating scale (RS)) are preferred; and iv) determine how different participant groups discriminate between the health scenarios and rank them