Patient characteristics associated with risk of first hospital admission and readmission for acute exacerbation of chronic obstructive pulmonary disease (COPD) following primary care COPD diagnosis: a cohort study using linked electronic patient records.

OBJECTIVES: To investigate patient characteristics of an unselected primary care population associated with risk of first hospital admission and readmission for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). DESIGN: Retrospective open cohort using pseudonymised electronic primary care data linked to secondary care data. SETTING: Primary care; Lothian (population approximately 800,000), Scotland. PARTICIPANTS: Data from 7002 patients from 72 general practices with a COPD diagnosis date between 2000 and 2008 recorded in their primary care record. Patients were followed up until 2010, death or they left a participating practice. MAIN OUTCOME MEASURES: First and subsequent admissions for AECOPD (International Classification of Diseases (ICD) 10 codes J44.0, J44.1 in any diagnostic position) after COPD diagnosis in primary care. RESULTS: 1756 (25%) patients had at least 1 AECOPD admission; 794 (11%) had at least 1 readmission and the risk of readmission increased with each admission. Older age at diagnosis, more severe COPD, low body mass index (BMI), current smoking, increasing deprivation, COPD admissions and interventions for COPD prior to diagnosis in primary care, and comorbidities were associated with higher risk of first AECOPD admission in an adjusted Cox proportional hazards regression model. More severe COPD and COPD admission prior to primary care diagnosis were associated with increased risk of AECOPD readmission in an adjusted Prentice-Williams-Peterson model. High BMI was associated with a lower risk of first AECOPD admission and readmission. CONCLUSIONS: Several patient characteristics were associated with first AECOPD admission in a primary care cohort of people with COPD but fewer were associated with readmission. Prompt diagnosis in primary care may reduce the risk of AECOPD admission and readmission. The study highlights the important role of primary care in preventing or delaying a first AECOPD admission.

Insights into the pathophysiology of catch-up compared with non-catch-up growth in children born small for gestational age: an integrated analysis of metabolic and transcriptomic data.

Small for gestational age (SGA) children exhibiting catch-up (CU) growth have a greater risk of cardiometabolic diseases in later life compared with non-catch-up (NCU) SGA children. The aim of this study was to establish differences in metabolism and gene expression profiles between CU and NCU at age 4-9 years. CU children (n=22) had greater height, weight and body mass index standard deviation scores along with insulin-like growth factor-I (IGF-I) and fasting glucose levels but lower adiponectin values than NCU children (n=11; all P<0.05). Metabolic profiling demonstrated a fourfold decrease of urine myo-inositol in CU compared with NCU (P<0.05). There were 1558 genes differentially expressed in peripheral blood mononuclear cells between the groups (P<0.05). Integrated analysis of data identified myo-inositol related to gene clusters associated with an increase in insulin, growth factor and IGF-I signalling in CU children (P<0.05). Metabolic and transcriptomic profiles in CU SGA children showed changes that may relate to cardiometabolic risk.

Development and validation of an ankle brachial index risk model for the prediction of cardiovascular events.

BACKGROUND: The ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS. DESIGN: An analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events. METHODS: Subjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS + ABI, were fitted for the primary outcome of major coronary events. RESULTS: In predicting events in the external validation dataset, C-index for the FRS was 0.672 (95% CI 0.599 to 0.737) in men and 0.578 (95% CI 0.492 to 0.661) in women. The FRS + ABI led to a small increase in C-index in men to 0.685 (95% CI 0.612 to 0.749) and large increase in women to 0.690 (95% CI 0.605 to 0.764) with net reclassification improvement (NRI) of 4.3% (95% CI 0.0 to 7.6%, p = 0.050) and 9.6% (95% CI 6.1 to 16.4%, p < 0.001), respectively. Restricting the FRS + ABI model to those with FRS intermediate 10-year risk of 10 to 19% resulted in higher NRI of 15.9% (95% CI 6.1 to 20.6%, p < 0.001) in men and 23.3% (95% CI 13.8 to 62.5%, p = 0.002) in women. However, incorporating ABI in an improved newly fitted risk factor model had a nonsignificant effect: NRI 2.0% (95% CI 2.3 to 4.2%, p = 0.567) in men and 1.1% (95% CI 1.9 to 4.0%, p = 0.483) in women. CONCLUSIONS: An ABI risk model may improve prediction especially in individuals at intermediate risk and when performance of the base risk factor model is modest.

Prevalence of abnormal plasma liver enzymes in older people with Type 2 diabetes.

AIMS: To determine the prevalence and distribution of abnormal plasma liver enzymes in a representative sample of older adults with Type 2 diabetes. METHODS: Plasma concentrations of alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase were measured in a randomly selected, population-based cohort of 1066 men and women aged 60-75 years with Type 2 diabetes (the Edinburgh Type 2 Diabetes Study). RESULTS: Overall, 29.1% (95% CI 26.1-31.8) of patients had one or more plasma liver enzymes above the upper limit of the normal reference range. Only 10.1% of these patients had a prior history of liver disease and a further 12.4% reported alcohol intake above recommended limits. Alanine aminotransferase was the most commonly raised liver enzyme (23.1% of patients). The prevalence of abnormal liver enzymes was significantly higher in men (odds ratio 1.40, 95% CI 1.07-1.83), in the youngest 5-year age band (odds ratio 2.02, 95% CI 1.44-2.84), in patients with diabetes duration < 5 years (odds ratio 1.38, 95% CI 1.01-1.90), plasma HbA(1c) ≥ 58 mmol/mol (7.5%) (odds ratio 1.43, 95% CI 1.09-1.88), obese BMI (odds ratio 2.84, 95% CI 1.59-3.06) and secondary care management for their diabetes (odds ratio 1.40, 95% CI 1.05-1.87). However, all these factors combined accounted for only 7.6% of the variation in liver enzyme abnormality. CONCLUSIONS: The prevalence of elevated liver enzymes in people with Type 2 diabetes is high, with only modest variation between clinically defined patient groups. Further research is required to determine the prognostic value of raised, routinely measured liver enzymes to inform decisions on appropriate follow-up investigations.

Clinically relevant fatigue in recurrence-free prostate cancer survivors.

BACKGROUND: Little is known about the prevalence and associations of clinically relevant fatigue (CRF) in recurrence-free prostate cancer survivors. PATIENTS AND METHODS: Four hundred and sixteen recurrence-free prostate cancer survivors who were >1 year post-radiotherapy or radical prostatectomy were surveyed. The prevalence of CRF (defined as Brief Fatigue Inventory >3) was determined and compared with a noncancer control group. Other measures included the Hospital Anxiety and Depression Scale, International Prostate Symptom Score, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Relationships between these factors and CRF were explored in univariate and multivariate analyses. RESULTS: Analyzable data were obtained from 91% (377/416) of patients. The prevalence of CRF was 29% (108/377) versus 16% (10/63) in the controls (P=0.031). CRF was more common in post-radiotherapy than in post-prostatectomy 33% (79/240) versus 22% (29/133), P=0.024. However, when other factors (current depression, anxiety, urinary symptoms, medical comorbidities, pain and insomnia) were controlled for, previous treatment did not predict CRF. Current depression [Hospital Anxiety and Depression Scale≥8 was by far the strongest association [odds ratio 9.9, 95% confidence interval 4.2-23.5)]. CONCLUSIONS: Almost one-third of recurrence-free prostate cancer survivors report CRF. Depression, anxiety, urinary symptoms, pain and insomnia measured at outcome are more strongly associated than type of cancer treatment previously received.

Severe hypoglycaemia and late-life cognitive ability in older people with Type 2 diabetes: the Edinburgh Type 2 Diabetes Study.

OBJECTIVE: To determine the association between lifetime severe hypoglycaemia and late-life cognitive ability in older people with Type 2 diabetes. METHODS: Cross-sectional, population-based study of 1066 men and women aged 60-75 years, with Type 2 diabetes. Frequency of severe hypoglycaemia over a person's lifetime and in the year prior to cognitive testing was assessed using a previously validated self-completion questionnaire. Results of age-sensitive neuropsychological tests were combined to derive a late-life general cognitive ability factor, 'g'. Vocabulary test scores, which are stable during ageing, were used to estimate early life (prior) cognitive ability. RESULTS: After age- and sex- adjustment, 'g' was lower in subjects reporting at least one prior severe hypoglycaemia episode (n = 113), compared with those who did not report severe hypoglycaemia (mean 'g'-0.34 vs. 0.05, P < 0.001). Mean vocabulary test scores did not differ significantly between the two groups (30.2 vs. 31.0, P = 0.13). After adjustment for vocabulary, difference in 'g' between the groups persisted (means -0.25 vs. 0.04, P < 0.001), with the group with severe hypoglycaemia demonstrating poorer performance on tests of Verbal Fluency (34.5 vs. 37.3, P = 0.02), Digit Symbol Testing (45.9 vs. 49.9, P = 0.002), Letter-Number Sequencing (9.1 vs. 9.8, P = 0.005) and Trail Making (P < 0.001). These associations persisted after adjustment for duration of diabetes, vascular disease and other potential confounders. CONCLUSIONS: Self-reported history of severe hypoglycaemia was associated with poorer late-life cognitive ability in people with Type 2 diabetes. Persistence of this association after adjustment for estimated prior cognitive ability suggests that the association may be attributable, at least in part, to an effect of hypoglycaemia on age-related cognitive decline.

Clinically relevant fatigue in men with hormone-sensitive prostate cancer on long-term androgen deprivation therapy.

BACKGROUND: The purpose of the study was to determine the prevalence and associations of clinically relevant fatigue (CRF) in men with biochemically controlled prostate cancer on long-term androgen deprivation therapy (ADT). PATIENTS AND METHODS: One hundred and ninety-eight men were surveyed and the prevalence of CRF (Brief Fatigue Inventory score >3) determined. Associations with other measures (Hospital Anxiety and Depression Scale; International Prostate Symptom Score; European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; Brief Pain Inventory worst pain; clinical and demographic information) were explored in univariate and multivariate analyses. RESULTS: Eight-one per cent (160 of 198) of questionnaires were analysable. CRF prevalence was 43% (68 of 160). CRF associations included moderate/severe urinary symptoms, anxiety and medical co-morbidities; the strongest associations were depression [odds ratio (OR) 9.8, 95% confidence interval (CI) 4.3-22.8] and pain (OR 9.2, 95% CI 4.0-21.5). After controlling for other factors, the independent associations were depression (OR 4.7, 95% CI 1.6-14.0) and pain (OR 3.1, 95% CI 1.0-8.9). There was no association with age, disease burden or treatment duration. CONCLUSIONS: Two-fifths of men with biochemically controlled prostate cancer on long-term ADT report CRF that interferes with function. Management aimed at improving CRF should address depression and pain.

Guided self-help for functional (psychogenic) symptoms: a randomized controlled efficacy trial.

OBJECTIVES: Functional (psychogenic or somatoform) symptoms are common in neurology clinics. Cognitive-behavioral therapy (CBT) can be an effective treatment, but there are major obstacles to its provision in practice. We tested the hypothesis that adding CBT-based guided self-help (GSH) to the usual care (UC) received by patients improves outcomes. METHODS: We conducted a randomized trial in 2 neurology services in the United Kingdom. Outpatients with functional symptoms (rated by the neurologist as "not at all" or only "somewhat" explained by organic disease) were randomly allocated to UC or UC plus GSH. GSH comprised a self-help manual and 4 half-hour guidance sessions. The primary outcome was self-rated health on a 5-point clinical global improvement scale (CGI) at 3 months. Secondary outcomes were measured at 3 and 6 months. RESULTS: In this trial, 127 participants were enrolled, and primary outcome data were collected for 125. Participants allocated to GSH reported greater improvement on the primary outcome (adjusted common odds ratio on the CGI 2.36 [95% confidence interval 1.17-4.74; p = 0.016]). The absolute difference in proportion "better" or "much better" was 13% (number needed to treat was 8). At 6 months the treatment effect was no longer statistically significant on the CGI but was apparent in symptom improvement and in physical functioning. CONCLUSIONS: CBT-based GSH is feasible to implement and efficacious. Further evaluation is indicated. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that CBT-based GSH therapy improves self-reported general health, as measured by the CGI, in patients with functional neurologic symptoms.

Is microbiological analysis of donor cornea transport culture media necessary?

PURPOSE: To investigate microbial contamination of the transport medium. Examination of corneoscleral rims is not included in this series. METHODS: Transport media of 63 consecutive grafts done at Tennent Institute of Ophthalmology, Glasgow, were collected for microbial examination. RESULTS: None of the culture plates showed any growth after prolonged culture, and microscopy was negative in 100% of cases. CONCLUSIONS: Routine culture of transport media may not be necessary.

Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis.

CONTEXT: Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction. OBJECTIVE: To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction. DATA SOURCES: Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies. STUDY SELECTION: Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality. DATA EXTRACTION: Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease. RESULTS: Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women. CONCLUSION: Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

Microbial contamination of preservative free eye drops in multiple application containers.

BACKGROUND/AIMS: The majority of eye drops used in the United Kingdom contain preservatives and are bottled in plastic containers. Preservative free drops are used to avoid ocular irritation and allergies in certain individuals. The aim of this study was to investigate the incidence of microbial contamination of preservative free drops dispensed from multiusage containers. METHODS: Eye drop bottles were collected from patients attending the Tennent Institute of Ophthalmology outpatient and inpatient departments. The bottles were collected on day 3 (for inpatients) and day 7 (for outpatients) of use. The drops were inoculated onto different culture plates (chocolate agar, blood agar, fungal culture media, and enriched media) and the resulting microbial growth was identified using standard microbial identification techniques. RESULTS: 95 eye drop bottles were collected, containing a variety of 10 different eye drops. Significant bacterial growth was found in eight bottles. In total, seven different types of organism were identified from the eye drops. The organisms identified were Staphylococcus aureus, coagulase negative staphylococcus, Bacillus spp, Serattia spp, Klebsiella oxytoca, Enterobacter cloacae, and alpha streptococcus. Staph aureus was the commonest microbial organism. CONCLUSION: Preservative free eye drops in multiple application containers are at risk of contamination by potentially pathogenic micro-organisms.

Linezolid penetration into osteo-articular tissues.

Penetration of linezolid into osteo-articular tissue and fluid was studied in 10 patients undergoing primary total knee replacement. Linezolid 600 mg 12 hourly was given orally over the 48 h before operation and intravenously 1 h before induction of anaesthesia. Mean concentrations of linezolid at 90 min after the final dose, in serum, synovial fluid, synovium, muscle and cancellous bone, assayed by HPLC, were at least twice the MIC(90) for staphylococci and streptococci. The concentrations obtained indicate good penetration of this antibiotic and support its use in the management of multidrug-resistant Gram-positive bone, joint and deep-seated soft-tissue infections.

Candida glabrata infection after total hip arthroplasty.

Only two incidents of periprosthetic infection due to Candida glabrata have been reported in the literature. We report successful treatment of a total hip replacement infected with this rare organism by a two-stage revision and synergistic combination antifungal therapy with Amphotericin B and 5-Flucytosine.

Balance in cluster randomized trials.

This paper explores the role of balancing covariates between treatment groups in the design of cluster randomized trials. General expressions are obtained for two criteria to evaluate designs for parallel group studies with two treatments. The first is the variance of the estimated treatment effect and the second is the extent to which the estimated treatment effect is changed by adjusting for covariates. It is argued that the second of these is more important for cluster randomized trials. Methods of obtaining balanced designs from covariates which are available at the start of a study are proposed. An imbalance measure is used to compare the extent to which designs balance important covariates between the arms of a trial. Several approaches to selecting a well balanced design are possible. A method that randomly selects one member from the class of designs with acceptable bias will allow randomization inference as well as model-based inference. The methods are illustrated with data from a trial of school-based sex education.

Methicillin-resistant Staphylococcus epidermidis in infection of hip arthroplasties.

We investigated the incidence of cephalosporin-resistant bacteria in infected hip arthroplasties. Of 740 patients having hip replacement or related procedures performed over three years, 30 had positive bacteriological cultures from tissue removed at the time of surgery. In 18 of the 30 cultures Staphylococcus epidermidis was grown and 12 of these were methicillin-resistant. A prospective study of skin swabs taken from 100 consecutive patients at the time of admission for THR showed methicillin-resistant Staphylococcus epidermidis in 25. This cephalosporin-resistant organism was shown to be the commonest proven cause of infection, and its presence as a skin commensal raises important questions about current antibiotic prophylaxis for joint replacement.

Fatal rhinocerebral mucormycosis in newly diagnosed diabetic.

A 48-year-old male developed fever and sore throat while in Spain and was admitted to hospital, dehydrated, ketotic, pyrexial, and with a blood glucose of 35 mmol/l. Despite treatment with intravenous fluids, insulin, cephalosporin, potassium and bicarbonate he returned to Britain 7 days later, underhydrated and acidotic, though euglycaemic. His face was discoloured, there was painless nasal and maxillary swelling, oral candidiasis, and he went on to develop ophthalmoplegia and sudden blindness. Staphylococcus albus and mycelial fungus were isolated, the latter was identified as Mucor hiemalis, but despite treatment with amphotericin B co-ordinated with radical maxillary-facial surgery he died 31 days after the initial symptoms. Rhinocerebral mucormycosis is a recognized complication of ketoacidosis which is rarely reported in the UK. The organism invades arteries aggressively, therefore radical therapy must be started early to prevent the high mortality.