Developing 'high impact' guideline-based quality indicators for UK primary care: a multi-stage consensus process.

BACKGROUND: Quality indicators (QIs) are an important tool for improving clinical practice and are increasingly being developed from evidence-based guideline recommendations. We aimed to identify, select and apply guideline recommendations to develop a set of QIs to measure the implementation of evidence-based practice using routinely recorded clinical data in United Kingdom (UK) primary care. METHODS: We reviewed existing national clinical guidelines and QIs and used a four-stage consensus development process to derive a set of 'high impact' QIs relevant to primary care based upon explicit prioritisation criteria. We then field tested the QIs using remotely extracted, anonymised patient records from 89 randomly sampled primary care practices in the Yorkshire region of England. RESULTS: Out of 2365 recommendations and QIs originally reviewed, we derived a set of 18 QIs (5 single, 13 composites - comprising 2-9 individual recommendations) for field testing. QIs predominantly addressed chronic disease management, in particular diabetes, cardiovascular and renal disease, and included both processes and outcomes of care. Field testing proved to be critical for further refinement and final selection. CONCLUSIONS: We have demonstrated a rigorous and transparent methodology to develop a set of high impact, evidence-based QIs for primary care from clinical guideline recommendations. While the development process was successful in developing a limited set of QIs, it remains challenging to derive robust new QIs from clinical guidelines in the absence of established systems for routine, structured recording of clinical care.

Composition of the bovine uterine proteome is associated with stage of cycle and concentration of systemic progesterone.

Early embryonic loss accounts for over 70% of total embryonic and foetal loss in dairy cattle. Early embryonic development and survival is associated with the concentration of systemic progesterone. To determine if the uterine proteome is influenced by stage of cycle or systemic progesterone concentrations, uterine flushings were collected from the ipsi- and contralateral uterine horns of beef heifers on Days 7 (n = 10) and 15 (n = 10) of the oestrous cycle. Animals were separated into low or high progesterone groups based on plasma progesterone concentrations on Day 5 of the cycle. Samples were albumin depleted before iTRAQ R labeling and subsequent strong cation exchange-LC-MS/MS analyses. A total of 20 proteins were up to 5.9-fold higher (p<0.05) and 20 were up to 2.3-fold lower on Day 15 compared toDay 7. In addition, the expression of a number of proteins on Day 7 and/or 15 of the cycle was correlated with progesterone concentrations during Days 3­7 or the rate of change in progesterone between Days 3 and 7. This study highlights the dynamic changes occurring in the microenvironment surrounding the embryo during this period. The findings here also support the hypothesis that progesterone supports embryonic development by altering the maternal uterine environment.

A comparison of the bovine uterine and plasma proteome using iTRAQ proteomics.

Early embryo loss is a key factor affecting fertility in dairy and beef herds. Prior to implantation, the bovine embryo spends around 16 days free-floating in the uterine environment and is dependent on the composition of uterine fluid for normal growth and development. However, there is a lack of information regarding the protein composition of the bovine uterus and how it relates to plasma. In this study, uterine flushings (UF) (n = 6) and blood plasma (n = 4) were collected from beef heifers on day 7 of the oestrous cycle, albumin depleted and compared using iTRAQ proteomics. A total of 35 proteins were higher and 18 were lower in UF including metabolic enzymes, proteins with anti-oxidant activity and those involved in modulation of the immune response. This study confirms the dynamic nature of the bovine uterine proteome and that it differs from plasma. Factors affecting the uterine proteome and how it impacts on embryo survival warrant further study.

Immunodepletion of albumin and immunoglobulin G from bovine plasma.

Current MS-based proteomics has facilitated the identification of large numbers of proteins from complex mixtures. The bovine plasma proteome has the potential to provide a wealth of information concerning the biological state of an animal. However, during MS-based experiments, higher abundance proteins such as albumin and immunoglobulin G (IgG) can hinder the identification of potentially important proteins that are present in much lower abundance. While a variety of readily available technologies exist for the depletion of multiple high-abundance proteins from human, mouse and rat samples, there are few available for bovine. In this study, we report the depletion of >97% of albumin and >92% of IgG from bovine plasma.

Variations in achievement of evidence-based, high-impact quality indicators in general practice: An observational study.

BACKGROUND: There are widely recognised variations in the delivery and outcomes of healthcare but an incomplete understanding of their causes. There is a growing interest in using routinely collected 'big data' in the evaluation of healthcare. We developed a set of evidence-based 'high impact' quality indicators (QIs) for primary care and examined variations in achievement of these indicators using routinely collected data in the United Kingdom (UK). METHODS: Cross-sectional analysis of routinely collected, electronic primary care data from a sample of general practices in West Yorkshire, UK (n = 89). The QIs covered aspects of care (including processes and intermediate clinical outcomes) in relation to diabetes, hypertension, atrial fibrillation, myocardial infarction, chronic kidney disease (CKD) and 'risky' prescribing combinations. Regression models explored the impact of practice and patient characteristics. Clustering within practice was accounted for by including a random intercept for practice. RESULTS: Median practice achievement of the QIs ranged from 43.2% (diabetes control) to 72.2% (blood pressure control in CKD). Considerable between-practice variation existed for all indicators: the difference between the highest and lowest performing practices was 26.3 percentage points for risky prescribing and 100 percentage points for anticoagulation in atrial fibrillation. Odds ratios associated with the random effects for practices emphasised this; there was a greater than ten-fold difference in the likelihood of achieving the hypertension indicator between the lowest and highest performing practices. Patient characteristics, in particular age, gender and comorbidity, were consistently but modestly associated with indicator achievement. Statistically significant practice characteristics were identified less frequently in adjusted models. CONCLUSIONS: Despite various policy and improvement initiatives, there are enduring inappropriate variations in the delivery of evidence-based care. Much of this variation is not explained by routinely collected patient or practice variables, and is likely to be attributable to differences in clinical and organisational behaviour.

Prescribed opioids in primary care: cross-sectional and longitudinal analyses of influence of patient and practice characteristics.

OBJECTIVES: To examine trends in opioid prescribing in primary care, identify patient and general practice characteristics associated with long-term and stronger opioid prescribing, and identify associations with changes in opioid prescribing. DESIGN: Trend, cross-sectional and longitudinal analyses of routinely recorded patient data. SETTING: 111 primary care practices in Leeds and Bradford, UK. PARTICIPANTS: We observed 471 828 patient-years in which all patients represented had at least 1 opioid prescription between April 2005 and March 2012. A cross-sectional analysis included 99 847 patients prescribed opioids between April 2011 and March 2012. A longitudinal analysis included 49 065 patient-years between April 2008 and March 2012. We excluded patients with cancer or treated for substance misuse. MAIN OUTCOME MEASURES: Long-term opioid prescribing (4 or more prescriptions within 12 months), stronger opioid prescribing and stepping up to or down from stronger opioids. RESULTS: Opioid prescribing in the adult population almost doubled for weaker opioids over 2005-2012 and rose over sixfold for stronger opioids. There was marked variation among general practices in the odds of patients stepping up to stronger opioids compared with those not stepping up (range 0.31-3.36), unexplained by practice-level variables. Stepping up to stronger opioids was most strongly associated with being underweight (adjusted OR 3.26, 1.49 to 7.17), increasing polypharmacy (4.15, 3.26 to 5.29 for 10 or more repeat prescriptions), increasing numbers of primary care appointments (3.04, 2.48 to 3.73 for over 12 appointments in the year) and referrals to specialist pain services (5.17, 4.37 to 6.12). Compared with women under 50 years, men under 50 were less likely to step down once prescribed stronger opioids (0.53, 0.37 to 0.75). CONCLUSIONS: While clinicians should be alert to patients at risk of escalated opioid prescribing, much prescribing variation may be attributable to clinical behaviour. Effective strategies targeting clinicians and patients are needed to curb rising prescribing, especially of stronger opioids.