Kieran Rothnie

Ablative therapy for people with localised prostate cancer: a systematic review and economic evaluation.

BACKGROUNDnFor people with localised prostate cancer, active treatments are effective but have significant side effects. Minimally invasive treatments that destroy (or ablate) either the entire gland or the part of the prostate with cancer may be as effective and cause less side effects at an acceptable cost. Such therapies include cryotherapy, high-intensity focused ultrasound (HIFU) and brachytherapy, among others.nnnOBJECTIVESnThis study aimed to determine the relative clinical effectiveness and cost-effectiveness of ablative therapies compared with radical prostatectomy (RP), external beam radiotherapy (EBRT) and active surveillance (AS) for primary treatment of localised prostate cancer, and compared with RP for salvage treatment of localised prostate cancer which has recurred after initial treatment with EBRT.nnnDATA SOURCESnMEDLINE (1946 to March week 3, 2013), MEDLINE In-Process & Other Non-Indexed Citations (29 March 2013), EMBASE (1974 to week 13, 2013), Bioscience Information Service (BIOSIS) (1956 to 1 April 2013), Science Citation Index (1970 to 1 April 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (issue 3, 2013), Cochrane Database of Systematic Reviews (CDSR) (issue 3, 2013), Database of Abstracts of Reviews of Effects (DARE) (inception to March 2013) and Health Technology Assessment (HTA) (inception to March 2013) databases were searched. Costs were obtained from NHS sources.nnnREVIEW METHODSnEvidence was drawn from randomised controlled trials (RCTs) and non-RCTs, and from case series for the ablative procedures only, in people with localised prostate cancer. For primary therapy, the ablative therapies were cryotherapy, HIFU, brachytherapy and other ablative therapies. The comparators were AS, RP and EBRT. For salvage therapy, the ablative therapies were cryotherapy and HIFU. The comparator was RP. Outcomes were cancer related, adverse effects (functional and procedural) and quality of life. Two reviewers extracted data and carried out quality assessment. Meta-analysis used a Bayesian indirect mixed-treatment comparison. Data were incorporated into an individual simulation Markov model to estimate cost-effectiveness.nnnRESULTSnThe searches identified 121 studies for inclusion in the review of patients undergoing primary treatment and nine studies for the review of salvage treatment. Cryotherapy [3995 patients; 14 case series, 1 RCT and 4 non-randomised comparative studies (NRCSs)], HIFU (4000 patients; 20 case series, 1 NRCS) and brachytherapy (26,129 patients; 2 RCTs, 38 NRCSs) studies provided limited data for meta-analyses. All studies were considered at high risk of bias. There was no robust evidence that mortality (4-year survival 93% for cryotherapy, 99% for HIFU, 91% for EBRT) or other cancer-specific outcomes differed between treatments. For functional and quality-of-life outcomes, the paucity of data prevented any definitive conclusions from being made, although data on incontinence rates and erectile dysfunction for all ablative procedures were generally numerically lower than for non-ablative procedures. The safety profiles were comparable with existing treatments. Studies reporting the use of focal cryotherapy suggested that incontinence rates may be better than for whole-gland treatment. Data on AS, salvage treatment and other ablative therapies were too limited. The cost-effectiveness analysis confirmed the uncertainty from the clinical review and that there is no technology which appears superior, on the basis of current evidence, in terms of average cost-effectiveness. The probabilistic sensitivity analyses suggest that a number of ablative techniques are worthy of further research.nnnLIMITATIONSnThe main limitations were the quantity and quality of the data available on cancer-related outcomes and dysfunction.nnnCONCLUSIONSnThe findings indicate that there is insufficient evidence to form any clear recommendations on the use of ablative therapies in order to influence current clinical practice. Research efforts in the use of ablative therapies in the management of prostate cancer should now be concentrated on the performance of RCTs and the generation of standardised outcomes.nnnSTUDY REGISTRATIONnThis study is registered as PROSPERO CRD42012002461.nnnFUNDINGnThe National Institute for Health Research Health Technology Assessment programme.

Benefits of Incentives for Breastfeeding and Smoking cessation in pregnancy (BIBS): a mixed-methods study to inform trial design.

BACKGROUNDnSmoking in pregnancy and/or not breastfeeding have considerable negative health outcomes for mother and baby.nnnAIMnTo understand incentive mechanisms of action for smoking cessation in pregnancy and breastfeeding, develop a taxonomy and identify promising, acceptable and feasible interventions to inform trial design.nnnDESIGNnEvidence syntheses, primary qualitative survey, and discrete choice experiment (DCE) research using multidisciplinary, mixed methods. Two mother-and-baby groups in disadvantaged areas collaborated throughout.nnnSETTINGnUK.nnnPARTICIPANTSnThe qualitative study included 88 pregnant women/recent mothers/partners, 53 service providers, 24 experts/decision-makers and 63 conference attendees. The surveys included 1144 members of the general public and 497 health professionals. The DCE study included 320 women with a history of smoking.nnnMETHODSn(1) Evidence syntheses: incentive effectiveness (including meta-analysis and effect size estimates), delivery processes, barriers to and facilitators of smoking cessation in pregnancy and/or breastfeeding, scoping review of incentives for lifestyle behaviours; (2) qualitative research: grounded theory to understand incentive mechanisms of action and a framework approach for trial design; (3) survey: multivariable ordered logit models; (4) DCE: conditional logit regression and the log-likelihood ratio test.nnnRESULTSnOut of 1469 smoking cessation and 5408 breastfeeding multicomponent studies identified, 23 smoking cessation and 19 breastfeeding studies were included in the review. Vouchers contingent on biochemically proven smoking cessation in pregnancy were effective, with a relative risk of 2.58 (95% confidence interval 1.63 to 4.07) compared with non-contingent incentives for participation (four studies, 344 participants). Effects continued until 3 months post partum. Inconclusive effects were found for breastfeeding incentives compared with no/smaller incentives (13 studies) but provider commitment contracts for breastfeeding show promise. Intervention intensity is a possible confounder. The acceptability of seven promising incentives was mixed. Women (for vouchers) and those with a lower level of education (except for breastfeeding incentives) were more likely to disagree. Those aged ≤u200944 years and ethnic minority groups were more likely to agree. Agreement was greatest for a free breast pump and least for vouchers for breastfeeding. Universal incentives were preferred to those targeting low-income women. Initial daily text/telephone support, a quitting pal, vouchers for >u2009£20.00 per month and values up to £80.00 increase the likelihood of smoking cessation. Doctors disagreed with provider incentives. A ladder logic model emerged through data synthesis and had face validity with service users. It combined an incentive typology and behaviour change taxonomy. Autonomy and well-being matter. Personal difficulties, emotions, socialising and attitudes of others are challenges to climbing a metaphorical ladder towards smoking cessation and breastfeeding. Incentive interventions provide opportunity rungs to help, including regular skilled flexible support, a pal, setting goals, monitoring and outcome verification. Individually tailored and non-judgemental continuity of care can bolster womens capabilities to succeed. Rigid, prescriptive interventions placing the onus on women to behave healthily risk them feeling pressurised and failing. To avoid losing face, women may disengage.nnnLIMITATIONSnIncluded studies were heterogeneous and of variable quality, limiting the assessment of incentive effectiveness. No cost-effectiveness data were reported. In surveys, selection bias and confounding are possible. The validity and utility of the ladder logic model requires evaluation with more diverse samples of the target population.nnnCONCLUSIONSnIncentives provided with other tailored components show promise but reach is a concern. Formal evaluation is recommended. Collaborative service-user involvement is important.nnnSTUDY REGISTRATIONnThis study is registered as PROSPERO CRD42012001980.nnnFUNDINGnThe National Institute for Health Research Health Technology Assessment programme.

Risk of myocardial infarction (MI) and death following MI in people with chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis.

Objectives Cardiovascular disease is an important comorbidity in patients with chronic obstructive pulmonary disease (COPD). We aimed to systematically review the evidence for: (1) risk of myocardial infarction (MI) in people with COPD; (2) risk of MI associated with acute exacerbation of COPD (AECOPD); (3) risk of death after MI in people with COPD. Design Systematic review and meta-analysis. Methods MEDLINE, EMBASE and SCI were searched up to January 2015. Two reviewers screened abstracts and full text records, extracted data and assessed studies for risk of bias. We used the generic inverse variance method to pool effect estimates, where possible. Evidence was synthesised in a narrative review where meta-analysis was not possible. Results Searches yielded 8362 records, and 24 observational studies were included. Meta-analysis showed increased risk of MI associated with COPD (HR 1.72, 95% CI 1.22 to 2.42) for cohort analyses, but not in case–control studies: OR 1.18 (0.80 to 1.76). Both included studies that investigated the risk of MI associated with AECOPD found an increased risk of MI after AECOPD (incidence rate ratios, IRR 2.27, 1.10 to 4.70, and IRR 13.04, 1.71 to 99.7). Meta-analysis showed weak evidence for increased risk of death for patients with COPD in hospital after MI (OR 1.13, 0.97 to 1.31). However, meta-analysis showed an increased risk of death after MI for patients with COPD during follow-up (HR 1.26, 1.13 to 1.40). Conclusions There is good evidence that COPD is associated with increased risk of MI; however, it is unclear to what extent this association is due to smoking status. There is some evidence that the risk of MI is higher during AECOPD than stable periods. There is poor evidence that COPD is associated with increased in hospital mortality after an MI, and good evidence that longer term mortality is higher for patients with COPD after an MI.

Closing the mortality gap after a myocardial infarction in people with and without chronic obstructive pulmonary disease

Objective Patients with chronic obstructive pulmonary disease (COPD) have increased mortality following myocardial infarction (MI) compared with patients without COPD. We investigated the extent to which differences in recognition and management after MI could explain the mortality difference. Methods 300u2005161 patients with a first MI between 2003 and 2013 were identified in the UK Myocardial Ischaemia National Audit Project database. Logistic regression was used to compare mortality in hospital and at 180u2005days postdischarge between patients with and without COPD. Variables relating to inhospital factors (delay in diagnosis, use of reperfusion and time to reperfusion/use of angiography) and use of secondary prevention were sequentially added to models. Results Mortality was higher for patients with COPD both inhospital (4.6% vs 3.2%) and at 180u2005days (12.8% vs 7.7%). After adjusting for inhospital factors, the effect of COPD on inhospital mortality after MI was reduced for both ST-elevation myocardial infarctions (STEMIs) and non-STEMIs (STEMIs OR 1.24 (95% CI 1.10 to 1.41) to 1.13 (95% CI 0.99 to 1.29); non-STEMIs OR 1.34 (95% CI 1.24 to 1.45) to 1.16 (95% CI 1.07 to 1.26)). Adjusting for inhospital factors reduced the effect of COPD on mortality after non-STEMI at 180u2005days (OR 1.56 (95% CI 1.47 to 1.65) to 1.37 (95% CI 1.31 to 1.44)). Adjusting for use of secondary prevention also reduced the effect of COPD on mortality at 180u2005days for STEMIs and non-STEMIs (STEMIs OR 1.45 (95% CI 1.31 to 1.61) to 1.25 (95% CI 1.11 to 1.41); non-STEMIs OR 1.37 (95% CI 1.31 to 1.44) to 1.26 (95% CI 1.17 to 1.35). Conclusions Delayed diagnosis, timing and use of reperfusion of a STEMI, use of angiography after a non-STEMI and use of secondary prevention medicines are all potential explanations for the mortality gap after MI in people with COPD.

Validation of the recording of acute exacerbations of COPD in UK primary care electronic healthcare records

Background Acute Exacerbations of COPD (AECOPD) identified from electronic healthcare records (EHR) are important for research, public health and to inform healthcare utilisation and service provision. However, there is no standardised method of identifying AECOPD in UK EHR. We aimed to validate the recording of AECOPD in UK EHR. Methods We randomly selected 1385 patients with COPD from the Clinical Practice Research Datalink. We selected dates of possible AECOPD based on 15 different algorithms between January 2004 and August 2013. Questionnaires were sent to GPs asking for confirmation of their patients’ AECOPD on the dates identified and for any additional relevant information. Responses were reviewed independently by two respiratory physicians. Positive predictive value (PPV) and sensitivity were calculated. Results The response rate was 71.3%. AECOPD diagnostic codes, lower respiratory tract infection (LRTI) codes, and prescriptions of antibiotics and oral corticosteroids (OCS) together for 5–14 days had a high PPV (>75%) for identifying AECOPD. Symptom-based algorithms and prescription of antibiotics or OCS alone had lower PPVs (60–75%). A combined strategy of antibiotic and OCS prescriptions for 5–14 days, or LRTI or AECOPD code resulted in a PPV of 85.5% (95% CI, 82.7–88.3%) and a sensitivity of 62.9% (55.4–70.4%). Conclusion Using a combination of diagnostic and therapy codes, the validity of AECOPD identified from EHR can be high. These strategies are useful for understanding health-care utilisation for AECOPD, informing service provision and for researchers. These results highlight the need for common coding strategies to be adopted in primary care to allow easy and accurate identification of events.

Validity and interpretation of spirometric recordings to diagnose COPD in UK primary care

Background The diagnosis of COPD is dependent upon clinical judgment and confirmation of the presence of airflow obstruction using spirometry. Spirometry is now routinely available; however, spirometry incorrectly performed or interpreted can lead to misdiagnosis. We aimed to determine whether spirometry undertaken in primary care for patients suspected to have COPD was of sufficient quality and whether their spirometry was correctly interpreted. Methods Two chest physicians re-read all spirometric readings for both quality of the procedure and interpretation, received as a part of COPD validation studies using data from the Clinical Practice Research Datalink (CPRD). We then used logistic regression to investigate predictors of correct interpretation. Results Spirometry traces were obtained for 306 patients, of which 221 (72.2%) were conducted in primary care. Of those conducted in primary care, 98.6% (n=218) of spirometry traces were of adequate quality. Of those traces that were of adequate quality and conducted in primary care, and in whom a general practitioner (GP) diagnosis of COPD had been made, 72.5% (n=218) were consistent with obstruction. Historical records for asthma diagnosis significantly decreased odds of correct interpretation. Conclusion The quality of the spirometry procedure undertaken in primary care is high. However, this was not reflected in the quality of interpretation, suggesting an unmet training in primary care. The quality of the spirometry procedure as demonstrated by spirometric tracings provides a re-assurance for the use of spirometric values available in the electronic health care record databases for research purposes.

Effects of Pulmonary Rehabilitation on Exacerbation Number and Severity in People With COPD: An Historical Cohort Study Using Electronic Health Records

BACKGROUND: In previous systematic reviews (predominantly of randomized controlled trials), pulmonary rehabilitation (PR) has been shown to reduce hospital admissions for acute exacerbations of COPD (AECOPD). However, findings have been less consistent for cohort studies. The goal of this study was to compare rates of hospitalized and general practice (GP)‐treated AECOPD prior to and following PR. METHODS: Using anonymized data from the Clinical Practice Research Datalink and Hospital Episode Statistics, hospital admissions and GP visits for AECOPD were compared 1 year prior to and 1 year following PR in patients referred for PR. Exacerbation rates were also compared between individuals eligible and referred for PR vs those eligible and not referred. RESULTS: A total of 69,089 (64%) of the patients with COPD in the cohort were eligible for PR. Of these, only 6,436 (9.3%) were recorded as having been referred for rehabilitation. A total of 62,019 (89.8%) were not referred, and 634 (0.98%) declined referral. When combining GP and hospital exacerbations, patients who were eligible and referred for PR had a slightly higher but not statistically significant exacerbation rate (2.83 exacerbations/patient‐year; 95% CI, 2.66–3.00) than those who were eligible but not referred (2.17 exacerbations/patient‐year; 95% CI, 2.11–2.24). CONCLUSIONS: This study found that < 10% of patients who were eligible for PR were actually referred. Patients who were eligible and referred for (but not necessarily completed) PR did not have fewer GP visits and hospitalizations for AECOPD in the year following PR compared with those not referred or compared with the year prior to PR.

Chronic Obstructive Pulmonary Disease and the Risk of Stroke

Rationale: Chronic obstructive pulmonary disease (COPD) has been identified as a risk factor for cardiovascular diseases such as myocardial infarction. The role of COPD in cerebrovascular disease is, however, less certain. Although earlier studies have suggested that the risk for stroke is also increased in COPD, more recent investigations have generated mixed results. Objectives: The primary objective of our review was to quantify the magnitude of the association between COPD and stroke. We also sought to clarify the nature of the relationship between COPD and stroke by investigating whether the risk of stroke in COPD varies with age, sex, smoking history, and/or type of stroke and whether stroke risk is modified in particular COPD phenotypes. Results: The MEDLINE and EMBASE databases were searched in May 2016 to identify articles that compared stroke outcomes in people with and without COPD. Studies were grouped by study design to distinguish those that reported prevalence of stroke (cross‐sectional studies) from those that estimated incidence (cohort or case‐control studies). In addition, studies were stratified according to study population characteristics, the nature of COPD case definitions, and adjustment for confounding (smoking). Heterogeneity was assessed using the I2 statistic. We identified 5,493 studies, of which 30 met our predefined inclusion criteria. Of the 25 studies that reported prevalence ratios, 11 also estimated prevalence odds ratios. The level of heterogeneity among the included cross‐sectional studies did not permit the calculation of pooled ratios, save for a group of four studies that estimated prevalence odds ratios adjusted for smoking (prevalence odds ratio, 1.51; 95% confidence interval, 1.09‐2.09; I2 = 45%). All 11 studies that estimated relative risk for nonfatal incident stroke reported increased risk in COPD. Adjustment for smoking invariably reduced the magnitude of the associations. Conclusions: Although both prevalence and incidence of stroke are increased in people with COPD, the weight of evidence does not support the hypothesis that COPD is an independent risk factor for stroke. The possibility remains that COPD is causal in certain subsets of patients with COPD and for certain stroke subtypes.

Chronic obstructive pulmonary disease and acute myocardial infarction: effects on presentation, management, and outcomes

Abstract Cardiovascular disease is a common cause of death in patients with chronic obstructive pulmonary disease (COPD) and is a key target for improving outcomes. However, there are concerns that patients with COPD may not have enjoyed the same mortality reductions from acute myocardial infarction (AMI) in recent decades as the general population. This has raised questions about differences in presentation, management and outcomes in COPD patients compared to non-COPD patients. The evidence points to an increased risk of death after AMI in patients with COPD, but it is unclear to what extent this is attributable to COPD itself or to modifiable factors including under-treatment with guideline-recommended interventions and drugs. We review the evidence for differences between COPD and non-COPD patients in terms of the presentation of AMI, its treatment, and outcomes both in hospital and in the longer term.

The push me, pull you of financial incentives and health inequalities: a mixed methods study investigating smoking cessation in pregnancy and breastfeeding

Abstract Background Financial incentives are increasingly considered to address socially patterned behaviours like smoking in pregnancy and breastfeeding. We investigated their mechanisms of action in relation to health inequalities to inform incentive intervention design. Methods The evidence syntheses we undertook were incentive effectiveness, delivery processes, barriers and facilitators to smoking cessation in pregnancy and also breastfeeding; and incentives for lifestyle behaviours. We searched Medline, Embase, CINAHL, PsycINFO, Web of Science, the Cochrane Library (all sections), MIDIRS, ASSIA, and the Trials Register of Promoting Health Interventions for studies published in English between Jan 1, 1990, and March 31, 2012, using a range of natural language, MeSH, and other index terms. Surveys were done with 1144 respondents from the general public and with 497 maternity and early-years health professionals. Qualitative interviews and focus groups were conducted with pregnant women, recent mothers, and partners in three UK settings (n=88); and with 53 service providers, 24 experts and decision makers, and 63 conference attendees. A discrete choice experiment (DCE) was conducted with 320 female current or ex-smokers. Findings Systematic reviews raised concerns about the reach of incentives, particularly to marginalised groups. Baseline characteristics for people who were eligible, approached, and recruited to studies were under-reported. Sample sizes were mostly small. Surveys revealed mixed acceptability. Less educated, white British, and women general public respondents disagreed (odds ratios [OR] 0·5≤OR Interpretation Financial incentives can help some women, but whether they will address inequalities is unclear because of concerns about reach and resistance to being pushed and pulled. Funding The project was funded by the Health Technology Assessment programme (10/31/02) and will be published in full in Health Technology Assessment . The Chief Scientist Office of the Scottish Government Health and Social Care Directorates funds the Nursing Midwifery and Allied Health Professional Research Unit, University of Stirling; and the Health Services Research Unit and the Health Economics Research Unit, University of Aberdeen.