Real-World Estimates of Adrenal Insufficiency-Related Adverse Events in Children With Congenital Adrenal Hyperplasia.

BACKGROUND: Although congenital adrenal hyperplasia (CAH) is known to be associated with adrenal crises (AC), its association with patient- or clinician-reported sick day episodes (SDE) is less clear. METHODS: Data on children with classic 21-hydroxylase deficiency CAH from 34 centers in 18 countries, of which 7 were Low or Middle Income Countries (LMIC) and 11 were High Income (HIC), were collected from the International CAH Registry and analyzed to examine the clinical factors associated with SDE and AC. RESULTS: A total of 518 children-with a median of 11 children (range 1, 53) per center-had 5388 visits evaluated over a total of 2300 patient-years. The median number of AC and SDE per patient-year per center was 0 (0, 3) and 0.4 (0.0, 13.3), respectively. Of the 1544 SDE, an AC was reported in 62 (4%), with no fatalities. Infectious illness was the most frequent precipitating event, reported in 1105 (72%) and 29 (47%) of SDE and AC, respectively. On comparing cases from LMIC and HIC, the median SDE per patient-year was 0.75 (0, 13.3) vs 0.11 (0, 12.0) (P < 0.001), respectively, and the median AC per patient-year was 0 (0, 2.2) vs 0 (0, 3.0) (P = 0.43), respectively. CONCLUSIONS: The real-world data that are collected within the I-CAH Registry show wide variability in the reported occurrence of adrenal insufficiency-related adverse events. As these data become increasingly used as a clinical benchmark in CAH care, there is a need for further research to improve and standardize the definition of SDE.

Evidence synthesis for constructing directed acyclic graphs (ESC-DAGs): a novel and systematic method for building directed acyclic graphs.

BACKGROUND: Directed acyclic graphs (DAGs) are popular tools for identifying appropriate adjustment strategies for epidemiological analysis. However, a lack of direction on how to build them is problematic. As a solution, we propose using a combination of evidence synthesis strategies and causal inference principles to integrate the DAG-building exercise within the review stages of research projects. We demonstrate this idea by introducing a novel protocol: 'Evidence Synthesis for Constructing Directed Acyclic Graphs' (ESC-DAGs)'. METHODS: ESC-DAGs operates on empirical studies identified by a literature search, ideally a novel systematic review or review of systematic reviews. It involves three key stages: (i) the conclusions of each study are 'mapped' into a DAG; (ii) the causal structures in these DAGs are systematically assessed using several causal inference principles and are corrected accordingly; (iii) the resulting DAGs are then synthesised into one or more 'integrated DAGs'. This demonstration article didactically applies ESC-DAGs to the literature on parental influences on offspring alcohol use during adolescence. CONCLUSIONS: ESC-DAGs is a practical, systematic and transparent approach for developing DAGs from background knowledge. These DAGs can then direct primary data analysis and DAG-based sensitivity analysis. ESC-DAGs has a modular design to allow researchers who are experienced DAG users to both use and improve upon the approach. It is also accessible to researchers with limited experience of DAGs or evidence synthesis.

Effects of Vildagliptin on Ventricular Function in Patients With Type 2 Diabetes Mellitus and Heart Failure: A Randomized Placebo-Controlled Trial.

OBJECTIVES: This study sought to examine the safety of the dipeptidyl peptidase-4 inhibitor, vildagliptin, in patients with heart failure and reduced ejection fraction. BACKGROUND: Many patients with type 2 diabetes mellitus have heart failure and it is important to know about the safety of new treatments for diabetes in these individuals. METHODS: Patients 18 to 85 years of age with type 2 diabetes and heart failure (New York Heart Association functional class I to III and left ventricular ejection fraction [LVEF] <0.40) were randomized to 52 weeks treatment with vildagliptin 50 mg twice daily (50 mg once daily if treated with a sulfonylurea) or matching placebo. The primary endpoint was between-treatment change from baseline in echocardiographic LVEF using a noninferiority margin of -3.5%. RESULTS: A total of 254 patients were randomly assigned to vildagliptin (n = 128) or placebo (n = 126). Baseline LVEF was 30.6 ± 6.8% in the vildagliptin group and 29.6 ± 7.7% in the placebo group. The adjusted mean change in LVEF was 4.95 ± 1.25% in vildagliptin treated patients and 4.33 ± 1.23% in placebo treated patients, a difference of 0.62 (95% confidence interval [CI]: -2.21 to 3.44; p = 0.667). This difference met the predefined noninferiority margin of -3.5%. Left ventricular end-diastolic and end-systolic volumes increased more in the vildagliptin group by 17.1 ml (95% CI: 4.6 to 29.5 ml; p = 0.007) and 9.4 ml (95% CI: -0.49 to 19.4 ml; p = 0.062), respectively. Decrease in hemoglobin A1c from baseline to 16 weeks, the main secondary endpoint, was greater in the vildagliptin group: -0.62% (95% CI: -0.93 to -0.30%; p < 0.001; -6.8 mmol/mol; 95% CI: -10.2 to -3.3 mmol/mol). CONCLUSIONS: Compared with placebo, vildagliptin had no major effect on LVEF but did lead to an increase in left ventricular volumes, the cause and clinical significance of which is unknown. More evidence is needed regarding the safety of dipeptidyl peptidase-4 inhibitors in patients with heart failure and left ventricular systolic dysfunction. (Effect of Vildagliptin on Left Ventricular Function in Patients With Type 2 Diabetes and Congestive Heart Failure; NCT00894868).

Cost-effectiveness Analysis in R Using a Multi-state Modeling Survival Analysis Framework: A Tutorial.

This tutorial provides a step-by-step guide to performing cost-effectiveness analysis using a multi-state modeling approach. Alongside the tutorial, we provide easy-to-use functions in the statistics package R. We argue that this multi-state modeling approach using a package such as R has advantages over approaches where models are built in a spreadsheet package. In particular, using a syntax-based approach means there is a written record of what was done and the calculations are transparent. Reproducing the analysis is straightforward as the syntax just needs to be run again. The approach can be thought of as an alternative way to build a Markov decision-analytic model, which also has the option to use a state-arrival extended approach. In the state-arrival extended multi-state model, a covariate that represents patients' history is included, allowing the Markov property to be tested. We illustrate the building of multi-state survival models, making predictions from the models and assessing fits. We then proceed to perform a cost-effectiveness analysis, including deterministic and probabilistic sensitivity analyses. Finally, we show how to create 2 common methods of visualizing the results-namely, cost-effectiveness planes and cost-effectiveness acceptability curves. The analysis is implemented entirely within R. It is based on adaptions to functions in the existing R package mstate to accommodate parametric multi-state modeling that facilitates extrapolation of survival curves.

Estimation of Survival Probabilities for Use in Cost-effectiveness Analyses: A Comparison of a Multi-state Modeling Survival Analysis Approach with Partitioned Survival and Markov Decision-Analytic Modeling.

Modeling of clinical-effectiveness in a cost-effectiveness analysis typically involves some form of partitioned survival or Markov decision-analytic modeling. The health states progression-free, progression and death and the transitions between them are frequently of interest. With partitioned survival, progression is not modeled directly as a state; instead, time in that state is derived from the difference in area between the overall survival and the progression-free survival curves. With Markov decision-analytic modeling, a priori assumptions are often made with regard to the transitions rather than using the individual patient data directly to model them. This article compares a multi-state modeling survival regression approach to these two common methods. As a case study, we use a trial comparing rituximab in combination with fludarabine and cyclophosphamide v. fludarabine and cyclophosphamide alone for the first-line treatment of chronic lymphocytic leukemia. We calculated mean Life Years and QALYs that involved extrapolation of survival outcomes in the trial. We adapted an existing multi-state modeling approach to incorporate parametric distributions for transition hazards, to allow extrapolation. The comparison showed that, due to the different assumptions used in the different approaches, a discrepancy in results was evident. The partitioned survival and Markov decision-analytic modeling deemed the treatment cost-effective with ICERs of just over £16,000 and £13,000, respectively. However, the results with the multi-state modeling were less conclusive, with an ICER of just over £29,000. This work has illustrated that it is imperative to check whether assumptions are realistic, as different model choices can influence clinical and cost-effectiveness results.

Scottish Keep Well health check programme: an interrupted time series analysis.

BACKGROUND: Effective interventions are available to reduce cardiovascular risk. Recently, health check programmes have been implemented to target those at high risk of cardiovascular disease (CVD), but there is much debate whether these are likely to be effective at population level. This paper evaluates the impact of wave 1 of Keep Well, a Scottish health check programme, on cardiovascular outcomes. METHODS: Interrupted time series analyses were employed, comparing trends in outcomes in participating and non-participating practices before and after the introduction of health checks. Health outcomes are defined as CVD mortality, incident hospitalisations and prescribing of cardiovascular drugs. RESULTS: After accounting for secular trends and seasonal variation, coronary heart disease mortality and hospitalisations changed by 0.4% (95% CI -5.2% to 6.3%) and -1.1% (-3.4% to 1.3%) in Keep Well practices and by -0.3% (-2.7% to 2.2%) and -0.1% (-1.8% to 1.7%) in non-Keep Well practices, respectively, following the intervention. Adjusted changes in prescribing in Keep Well and non-Keep Well practices were 0.4% (-10.4% to 12.5%) and -1.5% (-9.4% to 7.2%) for statins; -2.5% (-12.3% to 8.4%) and -1.6% (-7.1% to 4.3%) for antihypertensive drugs; and -0.9% (-6.5% to 5.0%) and -2.4% (-10.1% to 6.0%) for antiplatelet drugs. CONCLUSIONS: Any impact of the Keep Well health check intervention on CVD outcomes and prescribing in Scotland was very small. Findings do not support the use of the screening approach used by current health check programmes to address CVD. We used an interrupted time series method, but evaluation methods based on randomisation are feasible and preferable and would have allowed more reliable conclusions. These should be considered more often by policymakers at an early stage in programme design when there is uncertainty regarding programme effectiveness.

Characterization of subgroups of heart failure patients with preserved ejection fraction with possible implications for prognosis and treatment response.

BACKGROUND: Patients with heart failure and preserved ejection fraction (HFpEF) have a poor prognosis, and no therapies have been proven to improve outcomes. It has been proposed that heart failure, including HFpEF, represents overlapping syndromes that may have different prognoses. We present an exploratory study of patients enrolled in the Irbesartan in Heart Failure with Preserved Ejection Fraction Study (I-PRESERVE) using latent class analysis (LCA) with validation using the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved study to identify HFpEF subgroups. METHODS AND RESULTS: In total, 4113 HFpEF patients randomized to irbesartan or placebo were characterized according to 11 clinical features. The HFpEF subgroups were identified using LCA. Event-free survival and effect of irbesartan on the composite of all-cause mortality and cardiovascular hospitalization were determined for each subgroup. Subgroup definitions were applied to 3203 patients enrolled in CHARM-Preserved to validate observations regarding prognosis and treatment response. Six subgroups were identified with significant differences in event-free survival (P < 0.001). Clinical profiles and prognoses of the six subgroups were similar in CHARM-Preserved. The two subgroups with the worst event-free survival in both studies were characterized by a high prevalence of obesity, hyperlipidaemia, diabetes mellitus, anaemia, and renal insufficiency (Subgroup C) and by female predominance, advanced age, lower body mass index, and high rates of atrial fibrillation, valvular disease, renal insufficiency, and anaemia (Subgroup F). CONCLUSION: Using a data-driven approach, we identified HFpEF subgroups with significantly different prognoses. Further development of this approach for characterizing HFpEF subgroups is warranted.

Fatigue as a predictor of outcome in patients with heart failure: analysis of CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure).

OBJECTIVES: The purpose of this study was to examine the relationship between fatigue and clinical outcomes, using dyspnea as a comparator, in patients with left ventricular ejection fraction (LVEF) ≤35% enrolled in the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study. BACKGROUND: Although fatigue is a common symptom in heart failure (HF), little is known about its association with prognosis. METHODS: At baseline in CORONA, fatigue "during the past few days" was measured using a 5-point exertion scale (0 = none, 1 = heavy exertion, 2 = moderate exertion, 3 = slight exertion, 4 = rest); a 4-point scale was used for dyspnea (1 to 4 as for fatigue). Patients were grouped into 3 categories: a fatigue score 0 to 1 (n = 535), fatigue score 2 (n = 1,632), and fatigue score 3 to 4 (n = 1,663); and a dyspnea score of 1 (n = 292), dyspnea score of 2 (n = 1,695), and dyspnea score of 3 to 4 (n = 1,843). The association between fatigue and dyspnea and the composite outcome of cardiovascular (CV) death or HF hospital stay and each component separately was examined using Kaplan-Meier analysis and Cox proportional-hazard models. We also examined all-cause mortality. RESULTS: In univariate analyses, symptom severity was associated with a higher risk of CV death or HF hospital stay (fatigue: group 3, 49% [n = 810], vs. group 1, 30% [n = 160]; dyspnea: group 3, 50% [n = 918], vs. group 1, 28% [n = 82]) and all-cause mortality (fatigue: group 3, 38% [n = 623], vs. group 1, 24% [n = 130]; dyspnea: group 3, 38% [n = 697], vs. group 1, 23% [n = 66], log-rank p < 0.0001 for all). After adjusting for other prognostic variables, including LVEF, New York Heart Association class, and N-terminal pro-B-type natriuretic peptide level, worse fatigue remained associated with higher risk of HF hospital stay but not mortality (worse dyspnea remained associated with a higher risk of both). An increase in fatigue (or dyspnea) between baseline and 6 months was also associated with worse outcomes. CONCLUSIONS: In HF, greater fatigue is associated with worse clinical outcomes. Closer attention should be paid to this symptom in clinical practice, with more done to standardize its measurement and understand its origins, with a view to improving treatment.

Time trends in 30 day case-fatality following hospitalisation for asthma in adults in Scotland: a retrospective cohort study from 1981 to 2009.

BACKGROUND: The risk of case-fatality following hospitalisation for asthma has not been well characterised. We describe trends in 30 day case-fatality following hospitalisation for asthma in adults in Scotland from 1981 to 2009. METHODS: Using the Scottish Morbidity Record Scheme (SMR01) with all asthma hospitalisations for adults (≥18 years) with ICD9 493 and ICD10 J45-J46 in the principal diagnostic position at discharge (1981-2009). These data were linked to mortality data from the General Register Office for Scotland (GROS), with asthma case-fatality defined as death within 30 days of asthma admission (in or out of hospital). Logistic regression was used to explore the impact of age, sex, previous asthma admission (in the 12 months prior to hospitalisation), socioeconomic deprivation, year of admission and co-morbidity on 30-day case-fatality. RESULTS: There were a total of 116,457 asthma hospitalisations; a total of 1000 (0.9%) hospitalisations resulted in a post-admission death (within 30 days of admission). Odds ratios for unadjusted and adjusted case-fatality showed a decreased risk of case-fatality from the mid-1990s onwards when compared to case-fatality in 1981. Advancing age and co-morbid diagnoses of respiratory failure, cancer, renal failure, cor pulmonale, coronary heart disease and respiratory infection were associated with increased likelihood of death. CONCLUSIONS: 30 day case-fatality has declined over the last three decades, comparable to case-fatality reported in other parts of the U.K. This decline may be in part due to improved guidelines, protocols and disease management for asthma over the last 30 years. The likelihood of death 30 days following an asthma admission increased with age group and was associated with respiratory failure, renal failure and cancer.

Angina and intermittent claudication in 7403 participants of the 2003 Scottish Health Survey: impact on general and mental health, quality of life and five-year mortality.

BACKGROUND: Angina and intermittent claudication impair function and mobility and reduce health-related quality of life. Both symptoms have similar etiology, yet the physical and psychological impacts of these symptoms are rarely studied in community-based cohorts or in individuals with isolated symptoms. METHODS: The 2003 Scottish Health Survey was a cross-sectional survey which enrolled a random sample of individuals aged 16-95 years living in Scotland. The Rose Angina Questionnaire, the Edinburgh Claudication Questionnaire, the Short Form-12 (SF-12) and the General Health Questionnaire were completed. Self-assessed general health was reported. Survey results were linked to national death records and mortality at five years was calculated. Subjects with isolated angina or intermittent claudication and neither symptom were compared (22 participants with both symptoms were excluded); 7403 participants (aged ≥ 16 years) were included. RESULTS: Participants with angina (n=205; 60 ± 15 years; 45% male) rated their general health worse and were more likely to have a potential mental-health problem than those with intermittent claudication (n=173; 61 ± 15 years; 41% male). Mean (standard deviation) physical and mental component scores on the SF-12 were higher for participants with intermittent claudication relative to those with angina (physical component score: 42.3 (10.6) vs. 35.0 (11.7), p<0.001; mental component score: 52.3 (8.5) vs. 46.5 (11.7), p=0.001). There was an observed absolute difference in five-year mortality of 4.8% (angina 12.3%, 95% CI 8.5-17.6; intermittent claudication 7.5%, 95% CI 4.4-12.6) although not statistically significant (p=0.16). CONCLUSIONS: Both intermittent claudication and angina adversely impact general and mental health and survival, even in a relatively young, community-based cohort.

Trends in incidence and in short term survival following a subarachnoid haemorrhage in Scotland, 1986-2005: a retrospective cohort study.

BACKGROUND: To examine age and sex specific incidence and 30 day case fatality for subarachnoid haemorrhage (SAH) in Scotland over a 20 year period. METHODS: A retrospective cohort study using routine hospital discharge data linked to death records. RESULTS: Between 1986 and 2005, 12,056 individuals experienced an incident SAH. Of these 10,113 (84%) survived to reach hospital. Overall age-standardised incidence rates were greater in women than men and remained relatively stable over the study period. In 2005, incidence in women was 12.8 (95% CI 11.5 to 14.2) and in men 7.9 (95% CI 6.9 to 9.1). 30 day case fatality in individuals hospitalised with SAH declined substantially, falling from 30.0% in men and 33.9% in women in 1986-1990 to 24.5% in men and 29.1% in women in 2001-2005. For both men and women, the largest reductions were observed in those aged between 40 to 59 years. After adjustment for age, socio-economic status and co-morbidity, the odds of death at 30 days in 2005 compared to odds of death in 1986 was 0.64 (0.54 to 0.76), p < 0.001 for those below 70 years, and 1.14 (0.83 to 1.56), p = 0.4 in those 70 years and above. CONCLUSIONS: Incidence rates for SAH remained stable between 1986 and 2005 suggesting that a better understanding of SAH risk factors and their reduction is needed. 30 day case fatality rates have declined substantially, particularly in middle-age. However, they remain high and it is important to ensure that this is not due to under-diagnosis or under-treatment.

Estimating the impact of stroke unit care in a whole population: an epidemiological study using routine data.

BACKGROUND AND PURPOSE: Randomised trials indicate that organised inpatient (stroke unit) care has an important impact on patient outcomes with an absolute risk difference (ARD) of 3% for survival and 5% for returning home. However, it is unclear what impact this complex intervention actually has in routine practice. A comprehensive national dataset was used to study the impact of stroke unit implementation. METHODS: The Scottish linked discharge database was used to identify all patients admitted to hospital with an incident stroke. Analyses compared case fatality and discharge home (adjusted for age, sex, deprivation and comorbidity) for hospitals with or without a stroke unit during four consecutive study periods: 1986-1990, 1991-1995, 1996-2000 and 2001-2005. RESULTS: During the study period, the percentage of admissions to hospitals that had a stroke unit increased from 0% to 87%, the 6 month case fatality decreased from 45% to 29% and discharges home increased from 46% to 59%. Adjusted ORs (95% CI) for case fatality (stroke unit versus no unit) in each study period were as follows: not calculable (no units before 1991), 0.83 (0.78-0.89), 0.90 (0.86-0.94) and 0.87 (0.82-0.91). These equate to an ARD of 3.0% over the whole study period. Equivalent data for discharge home indicated an increased odds of discharge home: not calculable, 1.23 (1.15-1.31), 1.15 (1.10-1.21) and 1.17 (1.11-1.23) with an overall ARD of 5%. CONCLUSIONS: These results indicate a positive impact of a policy of stroke unit care on case fatality and discharge home. The estimated impact, after adjusting for case mix, appears very similar to that calculated using clinical trial data.

Improved survival with bisoprolol in patients with heart failure and renal impairment: an analysis of the cardiac insufficiency bisoprolol study II (CIBIS-II) trial.

AIMS: Information on the effectiveness of beta-blockade in patients with heart failure (HF) and concomitant renal impairment is scarce and beta-blockers are underutilized in these patients. METHODS AND RESULTS: The Cockcroft-Gault formula normalized for body surface-area was used to estimate renal function (eGFR(BSA)) in 2622 patients with HF, left ventricular ejection fraction < or =35%, New York Heart Association class III/IV and serum creatinine <300 micromol/L (3.4 mg/dL) in the second Cardiac Insufficiency Bisoprolol Study II. Patients were divided into four sub-groups according to baseline eGFR(BSA) (<45, 45-60, 60-75 and > or =75 mL/min per 1.73 m(2)). Cox proportional-hazards models adjusted for pre-specified confounders were used to assess the effect of bisoprolol and potential heterogeneity of effect across the eGFR(BSA) sub-groups. Older age, female-sex, diabetes and ischaemic-aetiology were more common in those with reduced eGFR(BSA). The hazard associated with bisoprolol use for all-cause mortality, the composite of all-cause mortality or HF-hospitalization and HF-hospitalization alone was consistently <1.0 across eGFR(BSA) categories with no treatment by renal-function interaction (P = 0.81, P = 0.66, P = 0.71, respectively). The rate of bisoprolol discontinuation was higher in patients with eGFR(BSA) < 45 mL/min per 1.73 m(2). Nevertheless the absolute benefit of bisoprolol was greater for patients with chronic kidney disease compared with those without. CONCLUSION: The beneficial effects of bisoprolol on mortality and hospitalization for worsening heart-failure were not modified by baseline eGFR(BSA). Renal impairment should not prevent the use of bisoprolol in patients with HF.

Treatment of type 2 diabetes and outcomes in patients with heart failure: a nested case-control study from the U.K. General Practice Research Database.

OBJECTIVE: Diabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with metformin than other antidiabetic agents. We designed this study to determine whether this association reflects a beneficial effect of metformin or a harmful effect of other agents. RESEARCH DESIGN AND METHODS: We performed a case-control study nested within the U.K. General Practice Research Database cohort in which diagnoses were assigned by each patient's primary care physician. Case subjects were patients 35 years or older, newly diagnosed with both heart failure and diabetes after January 1988, and who died prior to October 2007. Control subjects were matched to case subjects based on age, sex, clinic site, calendar year, and duration of follow-up. Analyses were adjusted for comorbidities, A1C, renal function, and BMI. RESULTS: The duration of concurrent diabetes and heart failure was 2.8 years (SD 2.6) in our 1,633 case subjects and 1,633 control subjects (mean age 78 years, 53% male). Compared with patients who were not exposed to antidiabetic drugs, the current use of metformin monotherapy (adjusted odds ratio 0.65 [0.48-0.87]) or metformin with or without other agents (0.72 [0.59-0.90]) was associated with lower mortality; however, use of other antidiabetic drugs or insulin was not associated with all-cause mortality. Conversely, the use of ACE inhibitors/angiotensin receptor blockers (0.55 [0.45-0.68]) and beta-blockers (0.76 [0.61-0.95]) were associated with reduced mortality. CONCLUSIONS: Our results confirm the benefits of trial-proven anti-failure therapies in patients with diabetes and support the use of metformin-based strategies to lower glucose.

Mathematical coupling may account for the association between baseline severity and minimally important difference values.

OBJECTIVE: To generate anchor-based values for the "minimally important difference" (MID) for a number of commonly used patient-reported outcome (PRO) measures and to examine whether these values could be applied across the continuum of preoperative patient severity. STUDY DESIGN AND SETTING: Six prospective cohort studies of patients undergoing elective surgery at hospitals in England and Wales. Patients completed questionnaires about their health and health-related quality of life before and after surgery. MID values were calculated using the mean change score for a reference group of patients who reported they were "a little better" after surgery minus the mean change score for those who said they were "about the same." Pearson's correlation was used to examine the association between baseline severity and change scores in the reference group. Baseline severity was expressed in two ways: first in terms of preoperative scores and second in terms of the average of pre- and postoperative scores (Oldham's method). RESULTS: Of the 10 PRO measures examined, eight demonstrated a moderate or high positive association between preoperative scores and MID values. Only two measures demonstrated such an association when Oldham's measure of baseline severity was used. CONCLUSION: In general, there is little association between baseline severity and MID values. However, a moderate association persists for some measures, and it is recommended that researchers continue to test for this relationship when generating anchor-based MID values from change scores.

Age- and sex-specific trends in fatal incidence and hospitalized incidence of stroke in Scotland, 1986 to 2005.

BACKGROUND: Temporal trends in stroke incidence are unclear. We aimed to examine age- and sex-specific temporal trends in incidence of fatal and nonfatal hospitalized stroke in Scotland from 1986 to 2005. METHODS AND RESULTS: Mean age at the time of first stroke was 70.8 (SD, 12.9) years in men and 76.4 (12.9) years in women. Between 1986 and 2005, rates fell in men from 235 (95% CI, 229 to 242) to 149 (144 to 154) and in women from 299 (292 to 306) to 182 (177 to 188). Poisson modeling showed that temporal trends were influenced by age with declines in incidence of hospitalized stroke starting later in younger than older age groups. In both men and women aged under 55 years, the overall incidence rate of stroke was significantly higher in 2005 than in 1986. CONCLUSIONS: We report in a whole country that the overall incidence of stroke declined steadily and substantially between 1986 and 2005, with a relative reduction in the risk of stroke of 31% in men and 42% in women. Reductions in rates of both hospitalized and nonhospitalized fatal stroke contributed to this overall decline. The increase in incident stroke rates in young people is of concern.

The impact of serum potassium concentration on mortality after liver transplantation: a cohort multicenter study.

BACKGROUND: Potassium plays a key role in human metabolism in both health and disease. The impact of recipient serum potassium concentration [K] on mortality after liver transplantation has not been described previously. METHODS: We assessed the effect of recipient [K] on the survival of adult first single-organ liver transplant recipients in the United Kingdom and Ireland between March 1, 1994, and February 28, 2007 (n=5942), adjusting for recipient, donor, and graft characteristics. RESULTS: The overall risk-adjusted mortality significantly varied by [K], being higher among hyperkalemic ([K]>5.0 mmol/L) recipients (n=424, hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.01-1.88) and those with [K] of 4.5-5.0 mmol/L (n=1154, HR 1.47, 95% CI 1.13-1.91), compared with hypokalemic ([K]<3.5 mmol/L) recipients (n=360). However, the excess mortality was confined to the first posttransplant year among hyperkalemic recipients (HR 1.61, 95% CI 1.10-2.35) with no significant difference thereafter (HR 1.03, 95% CI 0.62-1.73). This was also true for recipients with [K] of 4.5 to 5.0 mmol/L (< or =1 year: HR 1.70, 95% CI 1.22-2.38; >1 year: HR 1.09, 95% CI 0.71-1.66). In contrast, those with [K] of 3.5 to 3.9 mmol/L (n=1518) and [K] of 4.0-4.4 mmol/L (n=2091) had similar risk-adjusted mortality at the above time points. When [K] was used as a continuous variable in the multivariable analysis, a mmol increase in [K] was associated with an increased adjusted risk of mortality of 27% (95% CI 12%-44%) at 1 year and 19% (95% CI 7%-31%) at 5 years. CONCLUSION: Recipient [K] is an independent predictor of death after liver transplantation. This finding could be of clinical utility in the management, risk stratification, selection, and prioritization of appropriate candidates for transplantation among patients with end-stage liver disease.

Sex differences in incidence, mortality, and survival in individuals with stroke in Scotland, 1986 to 2005.

BACKGROUND AND PURPOSE: The aim of this study was to examine the effect of sex across different age groups and over time for stroke incidence, 30-day case-fatality, and mortality. METHODS: All first hospitalizations for stroke in Scotland (1986 to 2005) were identified using linked morbidity and mortality data. Age-specific rate ratios (RRs) for comparing women with men for both incidence and mortality were modeled with adjustment for study year and socioeconomic deprivation. Logistic regression was used to model 30-day case-fatality. RESULTS: Women had a lower incidence of first hospitalization than men and size of effect varied with age (55 to 64 years, RR=0.65, 95% CI 0.63 to 0.66; >or=85 years, RR=0.94, 95% CI 0.91 to 0.96). Women aged 55 to 84 years had lower mortality than men and again size of effect varied with age (65 to 74 years, RR=0.79, 95% CI 0.76 to 0.81); 75 to 84 years, RR=0.94, 95% CI 0.92 to 0.95). Conversely, women aged >or=85 years had 15% higher stroke mortality than men (RR=1.15, 95% CI 1.12 to 1.18). Adjusted risk of death within 30 days was significantly higher in women than men, and this difference increased over the 20-year period in all age groups (adjusted OR in 55 to 64 year olds 1.23, 95% CI 1.14 to 1.33 in 1986 and 1.51, 95% CI 1.39 to 1.63 in 2005). CONCLUSIONS: We observed lower rates of incidence and mortality in younger women than men. However, higher numbers of older women in the population mean that the absolute burden of stroke is greater in women. Short-term case-fatality is greater in women of all ages and, worryingly, these differences have increased from 1986 to 2005.

Diathermy power settings as a risk factor for hemorrhage after tonsillectomy.

OBJECTIVE: To investigate bipolar diathermy power settings as a risk factor for postoperative hemorrhage following tonsillectomy. STUDY DESIGN AND SETTING: A prospective cohort study was undertaken between July 2003 and September 2004 in National Health Service (NHS) and independent hospitals in England and Northern Ireland. Data were collected on patient characteristics, tonsillectomy technique, and postoperative hemorrhage within 28 days of surgery. RESULTS: Among the 9572 patients who had a tonsillectomy performed with bipolar diathermy dissection and hemostasis, the overall rate of hemorrhage was 4.6 percent and the risk of hemorrhage was not associated with the diathermy power setting. Among the 8465 patients who had tonsillectomy with cold steel dissection and bipolar diathermy hemostasis, the rate of hemorrhage increased from 1.8% in patients with the lowest power settings (6 to 8 watts) to 3.7% in those with settings above 18 watts (P value for trend = 0.005). CONCLUSION: In tonsillectomies using cold steel dissection and bipolar diathermy for hemostasis, the risk of postoperative hemorrhage becomes greater as diathermy power increases.