Amanda Farrin

Patient risk factors for pressure ulcer development: Systematic review

OBJECTIVE To identify risk factors independently predictive of pressure ulcer development in adult patient populations? DESIGN A systematic review of primary research was undertaken, based upon methods recommended for effectiveness questions but adapted to identify observational risk factor studies. DATA SOURCES Fourteen electronic databases were searched, each from inception until March 2010, with hand searching of specialist journals and conference proceedings; contact with experts and a citation search. There was no language restriction. REVIEW METHODS Abstracts were screened, reviewed against the eligibility criteria, data extracted and quality appraised by at least one reviewer and checked by a second. Where necessary, statistical review was undertaken. We developed an assessment framework and quality classification based upon guidelines for assessing quality and methodological considerations in the analysis, meta-analysis and publication of observational studies. Studies were classified as high, moderate, low and very low quality. Risk factors were categorised into risk factor domains and sub-domains. Evidence tables were generated and a summary narrative synthesis by sub-domain and domain was undertaken. RESULTS Of 5462 abstracts retrieved, 365 were identified as potentially eligible and 54 fulfilled the eligibility criteria. The 54 studies included 34,449 patients and acute and community patient populations. Seventeen studies were classified as high or moderate quality, whilst 37 studies (68.5%) had inadequate numbers of pressure ulcers and other methodological limitations. Risk factors emerging most frequently as independent predictors of pressure ulcer development included three primary domains of mobility/activity, perfusion (including diabetes) and skin/pressure ulcer status. Skin moisture, age, haematological measures, nutrition and general health status are also important, but did not emerge as frequently as the three main domains. Body temperature and immunity may be important but require further confirmatory research. There is limited evidence that either race or gender is important. CONCLUSIONS Overall there is no single factor which can explain pressure ulcer risk, rather a complex interplay of factors which increase the probability of pressure ulcer development. The review highlights the limitations of over-interpretation of results from individual studies and the benefits of reviewing results from a number of studies to develop a more reliable overall assessment of factors which are important in affecting patient susceptibility.

A new pressure ulcer conceptual framework.

Aim This paper discusses the critical determinants of pressure ulcer development and proposes a new pressure ulcer conceptual framework. Background Recent work to develop and validate a new evidence-based pressure ulcer risk assessment framework was undertaken. This formed part of a Pressure UlceR Programme Of reSEarch (RP-PG-0407-10056), funded by the National Institute for Health Research. The foundation for the risk assessment component incorporated a systematic review and a consensus study that highlighted the need to propose a new conceptual framework. Design Discussion Paper. Data Sources The new conceptual framework links evidence from biomechanical, physiological and epidemiological evidence, through use of data from a systematic review (search conducted March 2010), a consensus study (conducted December 2010–2011) and an international expert group meeting (conducted December 2011). Implications for Nursing A new pressure ulcer conceptual framework incorporating key physiological and biomechanical components and their impact on internal strains, stresses and damage thresholds is proposed. Direct and key indirect causal factors suggested in a theoretical causal pathway are mapped to the physiological and biomechanical components of the framework. The new proposed conceptual framework provides the basis for understanding the critical determinants of pressure ulcer development and has the potential to influence risk assessment guidance and practice. It could also be used to underpin future research to explore the role of individual risk factors conceptually and operationally. Conclusion By integrating existing knowledge from epidemiological, physiological and biomechanical evidence, a theoretical causal pathway and new conceptual framework are proposed with potential implications for practice and research.

Hepatic metabolism and transporter gene variants enhance response to rosuvastatin in patients with acute myocardial infarction: the GEOSTAT-1 Study.

Background—Pharmacogenetics aims to maximize benefits and minimize risks of drug treatment. Our objectives were to examine the influence of common variants of hepatic metabolism and transporter genes on the lipid-lowering response to statin therapy. Methods and Results—The Genetic Effects On STATins (GEOSTAT-1) Study was a genetic substudy of Secondary Prevention of Acute Coronary Events—Reduction of Cholesterol to Key European Targets (SPACE ROCKET) (a randomized, controlled trial comparing 40 mg of simvastatin and 10 mg of rosuvastatin) that recruited 601 patients after myocardial infarction. We genotyped the following functional single nucleotide polymorphisms in the genes coding for the cytochrome P450 (CYP) metabolic enzymes, CYP2C9*2 (430C>T), CYP2C9*3 (1075A>C), CYP2C19*2 (681G>A), CYP3A5*1 (6986A>G), and hepatic influx and efflux transporters SLCO1B1 (521T>C) and breast cancer resistance protein (BCRP; 421C>A). We assessed 3-month LDL cholesterol levels and the proportion of patients reaching the current LDL cholesterol target of <70 mg/dL (<1.81 mmol/L). An enhanced response to rosuvastatin was seen for patients with variant genotypes of either CYP3A5 (P=0.006) or BCRP (P=0.010). Furthermore, multivariate logistic-regression analysis revealed that patients with at least 1 variant CYP3A5 and/or BCRP allele (n=186) were more likely to achieve the LDL cholesterol target (odds ratio: 2.289; 95% CI: 1.157, 4.527; P=0.017; rosuvastatin 54.0% to target vs simvastatin 33.7%). There were no differences for patients with variants of CYP2C9, CYP2C19, or SLCO1B1 in comparison with their respective wild types, nor were differential effects on statin response seen for patients with the most common genotypes for CYP3A5 and BCRP (n=415; odds ratio: 1.207; 95% CI: 0.768, 1.899; P=0.415). Conclusion—The LDL cholesterol target was achieved more frequently for the 1 in 3 patients with CYP3A5 and/or BCRP variant genotypes when prescribed rosuvastatin 10 mg, compared with simvastatin 40 mg. Clinical Trial Registration—URL: http://isrctn.org. Unique identifier: ISRCTN 89508434.

Cost-effectiveness of shared pharmaceutical care for older patients: RESPECT trial findings

BACKGROUND Pharmaceutical care serves as a collaborative model for medication review. Its use is advocated for older patients, although its cost-effectiveness is unknown. Although the accompanying article on clinical effectiveness from the RESPECT (Randomised Evaluation of Shared Prescribing for Elderly people in the Community over Time) trial finds no statistically significant impact on prescribing for older patients undergoing pharmaceutical care, economic evaluations are based on an estimation, rather than hypothesis testing. AIM To evaluate the cost-effectiveness of pharmaceutical care for older people compared with usual care, according to National Institute for Health and Clinical Excellence (NICE) reference case standards. METHODS An economic evaluation was undertaken in which NICE reference case standards were applied to data collected in the RESPECT trial. RESULTS On average, pharmaceutical care is estimated to cost an incremental 10 000 UK pounds per additional quality-adjusted life year (QALY). If the NHSs cost-effectiveness threshold is between 20 000 and 30 000 UK pounds per extra QALY, then the results indicate that pharmaceutical care is cost-effective despite a lack of statistical significance to this effect. However, the statistical uncertainty surrounding the estimates implies that the probability that pharmaceutical care is not cost-effective lies between 0.22 and 0.19. Although results are not sensitive to assumptions about costs, they differ between subgroups: in patients aged >75 years pharmaceutical care appears more cost-effective for those who are younger or on fewer repeat medications. CONCLUSION Although pharmaceutical care is estimated to be cost-effective in the UK, the results are uncertain and further research into its long-term benefits may be worthwhile.

Differential recruitment in a cluster randomized trial in primary care: the experience of the UK Back pain, Exercise, Active management and Manipulation (UK BEAM) feasibility study

Background Cluster randomized trials, which randomize groups of patients rather than individuals, are commonly used to evaluate healthcare interventions such as training programmes targeted at health professionals. This article reports the dangers of randomizing entire primary care practices when participants cannot be identified before randomization, as shown by a UK national trial. Method The UK BEAM trial, a national cluster randomized 322 factorial trial, was designed to evaluate three treatments for back pain in primary care: “active management”; randomized by practice; and spinal manipulation and exercise classes, both randomized by individual. Results Two hundred and thirty-one participants were recruited in the feasibility study, 165 (141% of expected recruitment) from active (management) practices but only 66 (54% of expected recruitment) from traditional (management) practices. The participants in active practices were significantly different from those in traditional practices, notably in suffering from milder back pain. Conclusions The feasibility study highlighted the dangers of randomizing clusters when individuals cannot be identified beforehand. Different numbers and types of participants were recruited in the two types of cluster. This differential recruitment led us to change the main trial design by abandoning practice level randomization. Instead all practices were trained in active management to maximize recruitment. Ideally cluster randomized trials should identify patients beforehand, to minimize the chance of selection bias. If this is not possible, patient recruitment should be independent in both intervention and control clusters. Pilot studies are especially important for cluster randomized trials, to identify unforeseen problems.

Effectiveness of nurse delivered endoscopy: findings from randomised multi-institution nurse endoscopy trial (MINuET)

Objective To compare the cost effectiveness of nurses and doctors in performing upper gastrointestinal endoscopy and flexible sigmoidoscopy. Design As part of a pragmatic randomised trial, the economic analysis calculated incremental cost effectiveness ratios, and generated cost effectiveness acceptability curves to address uncertainty. Setting 23 hospitals in the United Kingdom. Participants 67 doctors and 30 nurses, with a total of 1888 patients, from July 2002 to June 2003. Intervention Diagnostic upper gastrointestinal endoscopy and flexible sigmoidoscopy carried out by doctors or nurses. Main outcome measure Estimated health gains in QALYs measured with EQ-5D. Probability of cost effectiveness over a range of decision makers’ willingness to pay for an additional quality adjusted life year (QALY). Results Although differences did not reach traditional levels of significance, patients in the doctor group gained 0.015 QALYs more than those in the nurse group, at an increased cost of about £56 (€59,

Clinical evaluation of magnetic resonance imaging in coronary heart disease: The CE-MARC study

78) per patient. This yields an incremental cost effectiveness ratio of £3660 (€3876,

Effectiveness of nurse delivered endoscopy: findings from randomised multi-institution nurse endoscopy trial (MINuET) - art. no. b231

5097) per QALY. Though there is uncertainty around these results, doctors are probably more cost effective than nurses for plausible values of a QALY. Conclusions Though upper gastrointestinal endoscopies and flexible sigmoidoscopies carried out by doctors cost slightly more than those by nurses and improved health outcomes only slightly, our analysis favours endoscopies by doctors. For plausible values of decision makers’ willingness to pay for an extra QALY, endoscopy delivered by nurses is unlikely to be cost effective compared with endoscopy delivered by doctors. Trial registration International standard RCT 82765705

Trials in primary care: statistical issues in the design, conduct and evaluation of complex interventions

BackgroundSeveral investigations are currently available to establish the diagnosis of coronary heart disease (CHD). Of these, cardiovascular magnetic resonance (CMR) offers the greatest information from a single test, allowing the assessment of myocardial function, perfusion, viability and coronary artery anatomy. However, data from large scale studies that prospectively evaluate the diagnostic accuracy of multi-parametric CMR for the detection of CHD in unselected populations are lacking, and there are few data on the performance of CMR compared with current diagnostic tests, its prognostic value and cost-effectiveness.Methods/designThis is a prospective diagnostic accuracy cohort study of 750 patients referred to a cardiologist with suspected CHD. Exercise tolerance testing (ETT) will be preformed if patients are physically able. Recruited patients will then undergo CMR and single photon emission tomography (SPECT) followed in all patients by invasive X-ray coronary angiography. The order of the CMR and SPECT tests will be randomised. The CMR study will comprise rest and adenosine stress perfusion, cine imaging, late gadolinium enhancement and whole-heart MR coronary angiography. SPECT will use a gated stress/rest protocol. The primary objective of the study is to determine the diagnostic accuracy of CMR in detecting significant coronary stenosis, as defined by X-ray coronary angiography. Secondary objectives include an assessment of the prognostic value of CMR imaging, a comparison of its diagnostic accuracy against SPECT and ETT, and an assessment of cost-effectiveness.DiscussionThe CE-MARC study is a prospective, diagnostic accuracy cohort study of 750 patients assessing the performance of a multi-parametric CMR study in detecting CHD using invasive X-ray coronary angiography as the reference standard and comparing it with ETT and SPECT.Trial RegistrationCurrent Controlled Trials ISRCTN77246133

Validation of a Scale for Rating the Delivery of Psycho-Social Treatments for Alcohol Dependence and Misuse : The UKATT Process Rating Scale (PRS)

Objective To compare the clinical effectiveness of doctors and nurses in undertaking upper and lower gastrointestinal endoscopy. Design Pragmatic trial with Zelen’s randomisation before consent to minimise distortion of existing practice. Setting 23 hospitals in the United Kingdom. In six hospitals, nurses undertook both upper and lower gastrointestinal endoscopy, yielding a total of 29 centres. Participants 67 doctors and 30 nurses. Of 4964 potentially eligible patients, we randomised 4128 (83%) and recruited 1888 (38%) from July 2002 to June 2003. Interventions Diagnostic upper gastrointestinal endoscopy and flexible sigmoidoscopy, undertaken with or without sedation, with the standard preparation, techniques, and protocols of participating hospitals. After referral for either procedure, patients were randomised between doctors and nurses. Main outcome measures Gastrointestinal symptom rating questionnaire (primary outcome), gastrointestinal endoscopy satisfaction questionnaire and state-trait anxiety inventory (all analysed by intention to treat); immediate and delayed complications; quality of examination and corresponding report; patients’ preferences for operator; and new diagnoses at one year (all analysed according to who carried out the procedure). Results There was no significant difference between groups in outcome at one day, one month, or one year after endoscopy, except that patients were more satisfied with nurses after one day. Nurses were also more thorough than doctors in examining the stomach and oesophagus. While quality of life scores were slightly better in patients the doctor group, this was not statistically significant. Conclusions Diagnostic endoscopy can be undertaken safely and effectively by nurses. Trial registration International standard RCT 82765705