Salbutamol use in relation to maintenance bronchodilator efficacy in COPD: a prospective subgroup analysis of the EMAX trial.

BACKGROUND: Short-acting ß2-agonist (SABA) bronchodilators help alleviate symptoms in chronic obstructive pulmonary disease (COPD) and may be a useful marker of symptom severity. This analysis investigated whether SABA use impacts treatment differences between maintenance dual- and mono-bronchodilators in patients with COPD. METHODS: The Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids 1:1:1 to once-daily umeclidinium/vilanterol 62.5/25 µg, once-daily umeclidinium 62.5 µg or twice-daily salmeterol 50 µg for 24 weeks. Pre-specified subgroup analyses stratified patients by median baseline SABA use (low, < 1.5 puffs/day; high, ≥1.5 puffs/day) to examine change from baseline in trough forced expiratory volume in 1 s (FEV1), change in symptoms (Transition Dyspnoea Index [TDI], Evaluating Respiratory Symptoms-COPD [E-RS]), daily SABA use and exacerbation risk. A post hoc analysis used fractional polynomial modelling with continuous transformations of baseline SABA use covariates. RESULTS: At baseline, patients in the high SABA use subgroup (mean: 3.91 puffs/day, n = 1212) had more severe airflow limitation, were more symptomatic and had worse health status versus patients in the low SABA use subgroup (0.39 puffs/day, n = 1206). Patients treated with umeclidinium/vilanterol versus umeclidinium demonstrated statistically significant improvements in trough FEV1 at Week 24 in both SABA subgroups (59-74 mL; p < 0.001); however, only low SABA users demonstrated significant improvements in TDI (high: 0.27 [p = 0.241]; low: 0.49 [p = 0.025]) and E-RS (high: 0.48 [p = 0.138]; low: 0.60 [p = 0.034]) scores. By contrast, significant reductions in mean SABA puffs/day with umeclidinium/vilanterol versus umeclidinium were observed only in high SABA users (high: - 0.56 [p < 0.001]; low: - 0.10 [p = 0.132]). Similar findings were observed when comparing umeclidinium/vilanterol and salmeterol. Fractional polynomial modelling showed baseline SABA use ≥4 puffs/day resulted in smaller incremental symptom improvements with umeclidinium/vilanterol versus umeclidinium compared with baseline SABA use < 4 puffs/day. CONCLUSIONS: In high SABA users, there may be a smaller difference in treatment response between dual- and mono-bronchodilator therapy; the reasons for this require further investigation. SABA use may be a confounding factor in bronchodilator trials and in high SABA users; changes in SABA use may be considered a robust symptom outcome. FUNDING: GlaxoSmithKline (study number 201749 [NCT03034915]).

Simple non-mydriatic retinal photography is feasible and demonstrates retinal microvascular dilation in Chronic Obstructive Pulmonary Disease (COPD).

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with an increased risk of myocardial infarction and stroke but it remains unclear how to identify microvascular changes in this population. OBJECTIVES: We hypothesized that simple non-mydriatic retinal photography is feasible and can be used to assess microvascular damage in COPD. METHODS: Novel Vascular Manifestations of COPD was a prospective study comparing smokers with and without COPD, matched for age. Non-mydriatic, retinal fundus photographs were assessed using semi-automated software. RESULTS: Retinal images from 24 COPD and 22 control participants were compared. Cases were of similar age to controls (65.2 vs. 63.1 years, p = 0.38), had significantly lower Forced Expiratory Volume in one second (FEV1) (53.4 vs 100.1% predicted; p < 0.001) and smoked more than controls (41.7 vs. 29.6 pack years; p = 0.04). COPD participants had wider mean arteriolar (155.6 ±15 uM vs. controls [142.2 ± 12 uM]; p = 0.002) and venular diameters (216.8 ±20.7 uM vs. [201.3± 19.1 uM]; p = 0.012). Differences in retinal vessel caliber were independent of confounders, odds ratios (OR) = 1.08 (95% confidence intervals [CI] = 1.02, 1.13; p = 0.007) and OR = 1.05 (CI = 1.01, 1.09; p = 0.011) per uM increase in arteriolar and venular diameter respectively. FEV1 remained significantly associated with retinal vessel dilatation r = -0.39 (p = 0.02). CONCLUSIONS: Non-mydriatic retinal imaging is easily facilitated. We found significant arteriole and venous dilation in COPD compared to age-matched smokers without COPD associated with lung function independent of standard cardiovascular risk factors. Retinal microvascular changes are known to be strongly associated with future vascular events and retinal photography offers potential to identify this risk. TRIAL REGISTRATION: clinicaltrials.gov NCT02060292.

Chronic kidney disease, worsening renal function and outcomes in a heart failure community setting: A UK national study.

BACKGROUND: Routine heart failure (HF) monitoring and management is in the community but the natural course of worsening renal function (WRF) and its influence on HF prognosis is unknown. We investigated the influence of routinely monitored renal decline and related comorbidities on imminent hospitalisation and death in the HF community population. METHODS: A nested case-control study within an incident HF cohort (N = 50,114) with 12-years follow-up. WRF over 6-months before first hospitalisation and 12-months before death was defined by >20% reduction in estimated glomerular filtration rate (eGFR). Additive interactions between chronic kidney disease (CKD) and comorbidities were investigated. RESULTS: Prevalence of CKD (eGFR<60 ml/min/1.73m2) in the HF community was 63%, which was associated with an 11% increase in hospitalisation and 17% in mortality. Both risk associations were significantly worse in the presence of diabetes. Compared to HF patients with eGFR,60-89, there was no or minimal increase in risk for mild to moderate CKD (eGFR,30-59) for both outcomes. Adjusted risk estimates for hospitalisation were increased only for severe CKD(eGFR,15-29); Odds Ratio 1.49 (95%CI;1.36,1.62) and renal failure(eGFR,<15); 3.38(2.67,4.29). The relationship between eGFR and mortality was U-shaped; eGFR, ≥90; 1.32(1.17,1.48), eGFR,15-29; 1.68(1.58,1.79) and eGFR,<15; 3.04(2.71,3.41). WRF is common and associated with imminent hospitalisation (1.50;1.37,1.64) and mortality (1.92;1.79,2.06). CONCLUSIONS: In HF, the risk associated with CKD differs between the community and the acute HF setting. In the community setting, moderate CKD confers no risk but severe CKD, WRF or CKD with other comorbidities identifies patients at high risk of imminent hospitalisation and death.

Consumer segmentation and time interval between types of hospital admission: a clinical linkage database study.

Background: Healthcare policies target unplanned hospital admissions and 30-day re-admission as key measures of efficiency, but do not focus on factors that influence trajectories of different types of admissions in the same patient over time. Objectives: To investigate the influence of consumer segmentation and patient factors on the time intervals between different types of hospital admission. Research design, subjects and measures: A cohort design was applied to an anonymised linkage database for adults aged 40 years and over (N = 58 857). Measures included Mosaic segmentation, multimorbidity defined on six chronic condition registers and hospital admissions over a 27-month time period. Results: The shortest mean time intervals between two consecutive planned admissions were: 90 years and over (160 days (95% confidence interval (CI): 146-175)), Mosaic groups 'Twilight subsistence' (171 days (164-179)) or 'Welfare borderline' and 'Municipal dependency' (177 days (172-182)) compared to the reference Mosaic groups (186 days (180-193)), and multimorbidity count of four or more (137 days (130-145)). Mosaic group 'Twilight subsistence' (rate ratio (RR) 1.22 (95% CI: 1.08-1.36)) or 'Welfare borderline' and 'Municipal dependency' RR 1.20 (1.10-1.31) were significantly associated with higher rate to an unplanned admission following a planned event. However, associations between patient factors and unplanned admissions were diminished by adjustment for planned admissions. Conclusion: Specific consumer segmentation and patient factors were associated with shorter time intervals between different types of admissions. The findings support innovation in public health approaches to prevent by a focus on long-term trajectories of hospital admissions, which include planned activity.

Serum testosterone, testosterone replacement therapy and all-cause mortality in men with type 2 diabetes: retrospective consideration of the impact of PDE5 inhibitors and statins.

BACKGROUND: Low testosterone levels occur in over 40% of men with type 2 diabetes mellitus (T2DM) and have been associated with increased mortality. Testosterone replacement together with statins and phosphodiesterase 5 inhibitors (PDE5I) are widely used in men with T2DM. PURPOSE: To determine the impact of testosterone and testosterone replacement therapy (TRT) on mortality and assess the independence of this effect by adjusting statistical models for statin and PDE5I use. METHODS: We studied 857 men with T2DM screened from five primary care practices during April 2007-April 2009. Of the 857 men, 175/637 men with serum total testosterone ≤ 12 nmol/l or free testosterone (FT) ≤ 0.25 nmol/l received TU for a mean of 3.8 ± 1.2 (SD) years. PDE5I and statins were prescribed to 175/857 and 662/857 men respectively. All-cause mortality was the primary end-point. Cox regression models were used to compare survival in the three testosterone level/treatment groups, the analysis adjusted for age, statin and PDE5I use, BMI, blood pressure and lipids. RESULTS: Compared with the Low T/untreated group, mortality in the Normal T/untreated (HR: 0.62, CI: 0.41-0.94) or Low T/treated (HR: 0.38, CI: 0.16-0.90) groups was significantly reduced. PDE5I use was significantly associated with reduced mortality (HR: 0.21, CI: 0.066-0.68). After repeating the Cox regression in the 682 men not given a PDE5I, mortality in the Normal T/untreated and Low T/treated groups was significantly lower than that in the reference Low T/untreated group. Mortality in the PDE5I/treated was significantly reduced compared with the PDE5I/untreated group (OR: 0.06, CI: 0.009-0.47). CONCLUSIONS: Testosterone replacement therapy is independently associated with reduced mortality in men with T2DM. PDE5I use, included as a confounding factor, was associated with decreased mortality in all patients and, those not on TRT, suggesting independence of effect. The impact of PDE5I treatment on mortality (both HR and OR < 0.25) needs confirmation by independent studies.

Non-cardiovascular comorbidity, severity and prognosis in non-selected heart failure populations: A systematic review and meta-analysis.

BACKGROUND: Non-cardiovascular comorbidities are recognised as independent prognostic factors in selected heart failure (HF) populations, but the evidence on non-selected HF and how comorbid disease severity and change impacts on outcomes has not been synthesised. We identified primary HF comorbidity follow-up studies to compare the impact of non-cardiovascular comorbidity, severity and change on the outcomes of quality of life, all-cause hospital admissions and all-cause mortality. METHODS: Literature databases (Jan 1990-May 2013) were screened using validated strategies and quality appraisal (QUIPS tool). Adjusted hazard ratios for the main HF outcomes were combined using random effects meta-analysis and inclusion of comorbidity in prognostic models was described. RESULTS: There were 68 primary HF studies covering nine non-cardiovascular comorbidities. Most were on diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD) and renal dysfunction (RD) for the outcome of mortality (93%) and hospital admissions (16%), median follow-up of 4 years. The adjusted associations between HF comorbidity and mortality were DM (HR 1.34; 95% CI 1.2, 1.5), COPD (1.39; 1.2, 1.6) and RD (1.52; 1.3, 1.7). Comorbidity severity increased mortality from moderate to severe disease by an estimated 78%, 42% and 80% respectively. The risk of hospital admissions increased up to 50% for each disease. Few studies or prognostic models included comorbidity change. CONCLUSIONS: Non-cardiovascular comorbidity and severity significantly increases the prognostic risk of poor outcomes in non-selected HF populations but there is a major gap in investigating change in comorbid status over time. The evidence supports a step-change for the inclusion of comorbidity severity in new HF interventions to improve prognostic outcomes.

Maternal and child health after assisted vaginal delivery: five-year follow up of a randomised controlled study comparing forceps and ventouse.

OBJECTIVE: To undertake a five year follow up of a cohort of women and children delivered by forceps or vacuum extractor in a randomised controlled study. DESIGN: Follow up of a randomised controlled trial. SETTING: District general hospital in the West Midlands. POPULATION: Follow up questionnaires were sent to 306 of the 313 women originally recruited at the North Staffordshire Hospital to a randomised controlled study comparing forceps and vacuum extractor for assisted delivery. Two hundred and twenty-eight women responded (74.5%) and all were included in the study; forceps (n = 115) and vacuum extractor (n = 113). MAIN OUTCOME MEASURES: Bowel and urinary dysfunction, child vision assessment, and child development. RESULTS: Maternal adverse symptoms at long term follow up were relatively common. Urinary incontinence of various severity was reported by 47%, bowel habit urgency was reported by 44% (98/225), and loss of bowel control 'sometimes' or 'frequently' by 20% of women (46/226). No significant differences between instruments were found in terms of either bowel or urinary dysfunction. Overall, 13% (20/158) of children were noted to have visual problems. There was no significant difference in visual function between the two groups: ventouse 11/86 (12.8%), compared with forceps 9/72 (12.5%); odds ratio 0.97, 95% CI 0.38-2.50. Of the 20 children with visual problems, a family history was known in 18, and 17/18 (94%) had a positive family history for visual problems. No significant differences in child development were found between the two groups. CONCLUSIONS: There is no evidence to suggest that at five years after delivery use of the ventouse or forceps has specific maternal or child benefits or side effects.

Extrafine beclomethasone/formoterol in severe COPD patients with history of exacerbations.

The FORWARD study is a randomised, double-blind trial that compares the efficacy and safety of 48 weeks treatment with extrafine beclomethasone dipropionate/formoterol fumarate (BDP/FOR), 100/6 µg pMDI, 2 inhalations BID, vs. FOR 12 µg pMDI, 1 inhalation BID, in severe COPD patients with a history of exacerbations. Co-primary endpoints were exacerbation rate over 48 weeks and pre-dose morning FEV(1) at 12 weeks. The ITT population included 1186 patients (69% males, mean age 64 years) with severe airflow limitation (mean post-bronchodilator FEV(1) 42% predicted). Salbutamol as rescue therapy, theophylline and tiotropium (if stable regimen prior to screening) were allowed. Compared to FOR, BDP/FOR: (1) reduced the exacerbation rate (rate ratio: 0.72 [95% confidence interval 0.62-0.84], p < 0.001); (2) improved pre-dose morning FEV(1) (mean difference: 0.069 L [0.043-0.095] p < 0.001); (3) prolonged the time to first exacerbation; (4) improved the SGRQ total score. The percentage of patients with adverse events was similar (52.1% with BDP/FOR and 49.2% with FOR). Pneumonia incidence was low, slightly higher with BDP/FOR (3.8%) than with FOR (1.8%). No difference for laboratory values, ECG or vital signs. Extrafine BDP/FOR significantly reduces the exacerbation rate and improves lung function of patients with severe COPD and history of exacerbations as compared to FOR alone.

The role of regional anaesthesia in the surgical management of vulval malignancy.

Abstract Surgical excision is the management of choice in vulval cancer however, the patient population are typically elderly and comorbid, for whom general anaesthesia (GA) carries considerable risk. The outcome of 107 procedures were reviewed in order investigate the postoperative complication rates associated with general and regional anaesthesia for the surgical management of vulval cancer. GA was used in 78 (72.9%) cases; 27 (22.9%) had a regional anaesthetic (spinal/epidural/ileoinguinal) and two women had a GA following a failed spinal anaesthetic. Women having a regional anaesthetic were significantly older (p = 0.0198), had a higher ACE (p = 0.0001) and ASA score (p < 0.0001) than those having a GA. There was an association between GA and grade II+ complications, compared with regional techniques (odds ratio, OR 2.72) but this was not significant due to the small number of events. Regional anaesthetic techniques are safe, well-tolerated alternatives to GA for the surgical management of vulval cancer, especially in an elderly and comorbid population.

Measuring respiratory symptoms in clinical trials of COPD: reliability and validity of a daily diary.

BACKGROUND: Although respiratory symptoms are characteristic features of COPD, there is no standardised method for quantifying their severity in stable disease. OBJECTIVE: To evaluate the EXACT-Respiratory Symptom (E-RS) measure, a daily diary comprising 11 of the 14 items in the Exacerbations of Chronic Pulmonary Disease Tool (EXACT). METHODS: Qualitative: patient focus group and interviews to address content validity. Quantitative: secondary data analyses to test reliability and validity. RESULTS: Qualitative: n=84; mean (SD) age 65 (10) years, FEV1 1.2(0.4) L; 44% male. Subject descriptions of their respiratory symptoms were consistent with E-RS content and structure. Quantitative: n=188; mean (SD) age 66 (10) years, FEV1 1.2(0.5) L; 50% male. Factor analysis (FA) showed 3 subscales: RS-Breathlessness, RS-Cough & Sputum, and RS-Chest Symptoms; second-order FA supported a general factor and total score. Reliability (total and subscales): 0.88, 0.86, 0.73, 0.81; 2-day test-retest ICC: 0.90, 0.86, 0.87, 0.82, respectively. VALIDITY: Total scores correlated significantly (p < 0.0001) with SGRQ Total (r=0.75), Symptoms (r=0.66), Activity (r=0.57), Impact (r=0.70) scores; subscale correlations were also significant (r=0.26, p < 0.05 (RS-Chest Symptoms with Activity) to r=0.69, p < 0.0001 (RS-Cough & Sputum with Symptoms). RS-Breathlessness correlated with rescue medication use (r=0.32, p < 0.0001), clinician-reported mMRC (r=0.33, p < 0.0001), and FEV1% predicted (r=-0.17, p < 0.05). E-RS scores differentiated groups based on chronic bronchitis diagnosis (p < 0.01-0.001), smoking status (p < 0.05-0.001), and rescue medication use (p < 0.05-0.0001). CONCLUSIONS: Results suggest the RS-Total is a reliable and valid instrument for evaluating respiratory symptom severity in stable COPD. Further study of sensitivity to change is warranted.

Seasonality and determinants of moderate and severe COPD exacerbations in the TORCH study.

We investigated the impact of season relative to other determinants of chronic obstructive pulmonary disease (COPD) exacerbation frequency in a long-term international study of patients with forced expiratory volume in 1 s (FEV(1)) <60% predicted. COPD exacerbations were defined by worsening symptoms requiring systemic corticosteroids and/or antibiotics (moderate) or hospital admission (severe). Seasonality effect was calculated as the proportion of patients experiencing an exacerbation each month. Exacerbations in the northern and southern regions showed an almost two-fold increase in the winter months. No seasonal pattern occurred in the tropics. Overall, 38% of exacerbations were treated with antibiotics only, 19% with systemic corticosteroids only and 43% with both, while 20% required hospital admission irrespective of the season. Exacerbation frequency was associated with older age, lower body mass index, lower FEV(1) % pred and history of prior exacerbations. Females and patients with worse baseline breathlessness, assessed using the Medical Research Council (MRC) dyspnoea scale, exacerbated more often (rate ratio (RR) for male versus female 0.7, 95% CI 0.7-0.8 (p<0.001); RR for MRC dyspnoea score 3 versus 1 and 2 combined 1.1, 95% CI 1.1-1.2 (p<0.001)). The effect of season was independent of these risk factors. COPD exacerbations and hospitalisations were more frequent in winter.

Properties of the COPD assessment test in a cross-sectional European study.

A short, easy-to-use health status questionnaire is needed in the multidimensional assessment of chronic obstructive pulmonary disease (COPD) in routine practice. The performance of the eight-item COPD assessment test (CAT) was analysed in 1,817 patients from primary care in seven European countries. The CAT has a scoring range of 0-40 (high score representing poor health status). Mean CAT scores indicated significant health status impairment that was related to severity of airway obstruction, but within each Global Initiative for Obstructive Lung Disease stage (I to IV) there was a wide range of scores (I: 16.2 ± 8.8; II: 16.3 ± 7.9; III: 19.3 ± 8.2; and IV: 22.3 ± 8.7; I versus II, p = 0.88; II versus III, p<0.0001; III versus IV, p = 0.0001). CAT scores showed relatively little variability across countries (within ± 12% of the mean across all countries). Scores were significantly better in patients who were stable (17.2 ± 8.3) versus those suffering an exacerbation (21.3 ± 8.4) (p<0.0001); and in patients with no (17.3 ± 8.1) or one or two (16.6 ± 8.2) versus three or more (19.7 ± 8.5) comorbidities (p<0.0001 for both). The CAT distinguished between classes of other impairment measures and was strongly correlated with the St George's Respiratory Questionnaire (r = 0.8, p<0.0001). The CAT is a simple and easy-to-use questionnaire that distinguishes between patients of different degrees of COPD severity and appears to behave the same way across countries.

Mortality and morbidity in Cushing's disease over 50 years in Stoke-on-Trent, UK: audit and meta-analysis of literature.

CONTEXT: Pituitary ACTH-dependent Cushing's disease (CD) is uncommon, and there are very limited data on long-term mortality. OBJECTIVE: The aim was to summarize what is known about mortality in ACTH-dependent CD, to report on our own data, and to provide a meta-analysis of six other reports that addressed mortality of CD. DESIGN AND METHODS: Vital status of 60 CD patients was recorded as of December 31, 2009, and the standardized mortality ratio (SMR) was calculated and compared with the general population of England and Wales, United Kingdom. A meta-analysis of SMRs from seven studies (including ours) was performed for overall mortality in CD. Where reported (four studies), a similar meta-analysis was performed for those patients whose hypercortisolism was in remission after treatment compared to those patients from the same center with persistent disease. RESULTS: 1. From Stoke-on-Trent, 51 of 60 patients were female, median age at diagnosis was in the range of 36-46 yr, and median follow-up was 15 yr. There were 13 deaths, nine due to cardiovascular disease. Overall SMR for the whole cohort was 4.8 (95% confidence interval, 2.8-8.3) (P < 0001). SMR for vascular disease was 13.8 (7.2-36.5) (P < 0001). For persistent disease (n = 6), SMR was 16 (6.7-38.4) vs. remission (n = 54) SMR of 3.3 (1.7-6.7); after adjustment for age and sex, relative risk of death for persistent disease was 10.7 (2.3-48.6) (P = 0.002). Hypertension and diabetes mellitus were associated with significantly worse survival. 2. Using a random effects model meta-analysis revealed an overall (remission plus persistent disease) SMR of 2.2 (1.45-3.41) (P < 0.001). Pooled SMR was 1.2 (0.45-3.2) (P = not significant) for patients in remission and 5.5 (2.7-11.3) (P = 0.001) for patients with persistent disease. Persistence of disease, older age at diagnosis, and presence of hypertension and diabetes are the main determinants of mortality. CONCLUSIONS: Overall mortality in CD is double that of the general population. However, patients with CD in remission fare much better than those with persistence of hypercortisolism, and they appear not to have an increased mortality rate. Hypertension and diabetes mellitus are risk factors for worse outcome. Because diagnosis and treatment of patients are at a young age, much longer follow-up of patients in remission is required before one can be confident that their mortality outcome is no different from that of the general population, especially because cardiovascular risk factors may persist after successful biochemical control of the disease.

Health-related quality of life in patients by COPD severity within primary care in Europe.

Pan-European data on health-related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD) are lacking. This cross-sectional epidemiological study evaluated health status in 1817 COPD patients from an 'all-comers' primary care population in seven European countries (87% stable disease; 13% with current exacerbation) using: St George's Respiratory Questionnaire-COPD specific (SGRQ-C), the short form health survey (SF-12) and the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scale. Mean total score for SGRQ was 44.7 ± 19.4 showing marked impairment of HRQL. Scores differed little between countries (range 39.2-50.1). Impairment was associated with the severity of airway obstruction, but within each GOLD stage the variation (SD) was wide [Stage I: 38.5 ± 19.3 (n = 223); Stage II: 40.4 ± 18.1 (n = 868); Stage III: 50.2 ± 18.6 (n = 551); Stage IV: 58.6 ± 17.7 (n = 144)]. Patients suffering an exacerbation had a worse SGRQ score (54.9 ± 19.3) than those with stable disease (43.3 ± 19.0). The presence of ≥3 co-morbidities (CM) was also associated with a significantly worse score (49.9 ± 19.1) vs. 1-2 CM (42.1 ± 19.1) or no CM (42.3 ± 18.6). Findings with the SF-12 and FACIT-F results were consistent with those from the SGRQ-C. This large observational primary care study shows that health status is significantly impaired in COPD patients of all severities, even in those with mild airway obstruction. Within each GOLD stage of severity there is considerable heterogeneity in HRQL impairment among patients. (Study number: 111749).

Predicting dysglycaemia in patients under investigation for acute coronary syndrome.

AIMS: To examine methods for the identification of previously undetected dysglycaemia [diabetes and impaired glucose tolerance (IGT)] in patients investigated for possible acute coronary syndrome. Specifically, we wished to examine whether the recently advocated use of glycosylated haemoglobin (HbA1c) would enhance detection rates for diabetes in these patients. METHODS: Patients (n = 200) investigated for possible acute coronary syndrome and not previously known to have diabetes were recruited and anthropometric data collected. Random plasma glucose concentrations followed by oral glucose tolerance tests, HbA1c, fasting lipids, high sensitivity C-reactive protein and homeostatic modular assessment-insulin resistance were obtained during admission. Following discharge, the fasting plasma glucose (FPG) was repeated to determine the importance of sequential fasting levels. The accuracy of individual tests, combinations and sequential testing was assessed using receiver operating characteristic curves. A predictive index (PI) was generated using stepwise logistic regression models. RESULTS: The prevalence of diabetes and IGT were 21 and 32%, respectively. FPG >6.0 mmol/l and HbA1c ≥ 6.0% had specificities of 94.9% and 93.6% but sensitivities of only 31.7 and 39.0%, respectively. Combination and sequential testing provided little additional benefit. Use of a PI comprising FPG, HbA1c and age provided the best overall performance (75.6% sensitivity, 77.1% specificity, negative predictive value 92.4%). CONCLUSION: Our data confirm the high prevalence of dysglycaemia in this cohort. The commonly advocated screening tools have significant limitations if used in isolation, combination or sequentially. Our approach using a PI offers improved performance partly as it uses continuous data rather than arbitrary cut-off values.

Sensitivity to change of the cutaneous electrical perceptual threshold test in longitudinal monitoring of spinal cord injury.

STUDY DESIGN: Prospective longitudinal experimental study. OBJECTIVES: The aim of this study was to assess the sensitivity to change of the electrical perceptual threshold (EPT) test during the longitudinal monitoring of neurological changes in patients with incomplete spinal cord injury (SCI). SETTING: National Spinal Injuries Centre, Stoke Mandeville Hospital, Buckinghamshire Hospitals NHS Trust, Buckinghamshire, UK. METHODS: Perceptual threshold to 3 Hz cutaneous electrical stimulation was measured in 11 patients with incomplete SCI at selected American Spinal Injuries Association (ASIA) sensory key points on four occasions. The first three measurements were performed within a 5-day period (baseline) and the fourth measurement (follow-up) at least 9 months later. The results were tested for statistical significance and the effect sizes were calculated. RESULTS: There were no significant differences between the EPT results of the three baseline assessments. When the mean baseline and follow-up EPT results were compared, there were no significant differences in EPT values above the sensory level of lesion, but a significant difference (reduction in threshold values) was found at and below the level of SCI, with medium and large effect sizes, respectively. CONCLUSION: The EPT test showed good sensitivity to change in dermatomes at and directly below the sensory level of the SCI. This makes it a potentially useful quantitative sensory instrument for detecting changes in sensory function during longitudinal monitoring of patients with SCI.

Cognitive function in COPD.

In order to characterise the overall clinical picture of chronic obstructive pulmonary disease (COPD) a better understanding of all relevant comorbidities is required. It is increasingly recognised that COPD is a multi-component disease, but little attention has been paid to its effects on cognitive function. Cognitive dysfunction is associated with increased mortality and disability; however, it remains poorly understood in COPD. This review examines mechanisms of injury and dysfunction to the brain and considers the methods used to evaluate cognition, and assembles evidence concerning the nature and level of cognitive impairment in COPD. Our main findings are: 1) there may be a pattern of cognitive dysfunction specific to COPD; 2) cognitive function is only mildly impaired in patients without hypoxaemia; 3) the incidence of cognitive dysfunction is higher in hypoxaemia; 4) hypoxaemia, hypercapnia, smoking and comorbidities (such as vascular disease) are unlikely to account for all of the cognitive dysfunction seen in COPD; 5) there is weak or no association between cognitive function and mood, fatigue or health status; 6) cognitive dysfunction may be associated with increased mortality and disability; and 7) there is limited evidence for a significant effect of treatment on cognitive function.

Enhancement of the efficacy of a carbamate nematicide against the potato cyst nematode, Globodera pallida, through mycorrhization in commercial potato fields.

Two experiments were conducted over 2 years in commercial potato fields in Shropshire, UK, to evaluate the compatibility of the nematicide aldicarb with commercial inocula of arbuscular mycorrhizal fungi (AMF) in the control of the potato cyst nematode Globodera pallida. The AMF used were Vaminoc (mixed-AMF inoculum), Glomus intraradices (BioRize BB-E) and G. mosseae (isolate BEG 12). In the absence of AMF, the in-soil hatch of G. pallida increased 30% (P < 0.01) from wk-2 to wk-4 after planting. Inoculation of physiologically-aged potato (cv. Golden Wonder) tubers with AMF eliminated this delay in G. pallida hatch by stimulating a mean increase of 32% (P < 0.01) in hatch within 2 wk after planting. In the aldicarb-treated plots in Experiment 1, G. pallida multiplication rate was 38% lower (P < 0.05) in roots of AMF-inoculated than noninoculated plants, but in Experiment 2, this effect was slightly lower (P = 0.07). In these plots, the single AMF inocula showed also a weak trend (P = 0.10) towards greater tuber yields relative to their noninoculated counterparts. Mycorrhization therefore appears to enhance the efficacy of carbamate nematicides against G. pallida and consequently more research is proposed to validate these findings and fully explore the potential of this model.

Implementing the national invasive cervical cancer audit: correlation between local and regional classification.

OBJECTIVE: To determine the accuracy of information recorded regionally and locally on the screening classification of cervical cancer cases using the national invasive cervical cancer audit categories. METHODS: Comparison of the audit categorization of all cervical cancer cases diagnosed at the University Hospital of North Staffordshire (UHNS) between January 2003 and December 2006 with the classification assigned by the West Midlands Cervical Screening Quality Assurance Reference Centre (WMQARC). RESULTS: Eighty-seven cases of cervical cancer were diagnosed during the three-year study period. There was agreement between the UHNS and WMQARC classification of cases in 52 cases (59.7%), moderate agreement κ = 0.51 (95% CI 0.39-0.63). The greatest disparity was seen in the classification of lapsed attenders, with nine of the 26 cases categorized as 'lapsed' by the UHNS being assigned to the 'lost to follow-up' category by WMQARC. Three cases were deemed unclassifiable by WMQARC using the national classification since the women were over the age of 70 years but had previously been enrolled in the screening programme, and currently there is no national category for these women. CONCLUSIONS: Accurate and consistent classification of invasive cervical cancer cases is essential in order to obtain useful information on the efficiency of the national screening programme at a local, regional and national level. The use of a national algorithm would provide reassurance that all data used in the national evaluation of the NHS Cervical Screening Programme are consistent, meaning that robust conclusions could then be drawn from the data.

Is treatment with ICS and LABA cost-effective for COPD? Multinational economic analysis of the TORCH study.

The TOwards a Revolution in COPD Health (TORCH) study was a 3-yr multicentre trial of 6,112 patients randomised to salmeterol (Salm), fluticasone propionate (FP), a Salm/FP combination (SFC) or placebo (P). Here the cost-effectiveness of treatments evaluated in the TORCH study is assessed. For four regions, 3-yr all-cause hospitalisation, medication and outpatient care costs were calculated. The sample was restricted to the 21 countries (n = 4,237) in which European quality of life five-dimension (EQ-5D) data were collected in order to estimate the number of quality-adjusted life years (QALYs). Regression models were fitted to survival, study medication cost, other medication cost and EQ-5D data in order to estimate total cost, number of QALYs and cost per QALY, adjusted for missing data and region. SFC had a trial-wide estimate of cost per QALY of 43,600 US dollars (USD) compared with P (95% confidence interval 21,400-123,500 USD). Estimates for Salm versus P (197,000 USD) and FP versus P (78,000 USD) were less favourable. The US estimates were greater than those from other regions; for SFC versus P, the cost per QALY was 77,100 (46,200-241,700) USD compared to 24,200 (15,200-56,100) USD in Western Europe. Compared with P, SFC has a lower incremental cost-effectiveness ratio than either FP or Salm used alone, and is, therefore, preferred to these monotherapies on the grounds of cost-effectiveness.