Lindsay Govan

Does the prevention of complications explain the survival benefit of organized inpatient (stroke unit) care?: further analysis of a systematic review.

Background and Purpose— Systematic reviews have shown that organized inpatient (stroke unit) care reduces the risk of death after stroke. However, it is unclear how this is achieved. We tested whether stroke unit care could reduce deaths by preventing complications. Methods— We updated a collaborative systematic review of 31 controlled clinical trials (6936 participants) to include reported interventions and complications during early hospital care plus the certified cause of death during follow up. Each secondary analysis used data from between 7 and 17 studies (1652 to 3327 participants). Complications were grouped as physiological, neurological, cardiovascular, complications of immobility, and others. Bayesian hierarchical models were used to estimate odds ratios for features occurring in stroke units versus conventional care. Results— Based on the data of 17 trials (3327 participants), organized (stroke unit) care reduced case fatality during scheduled follow up (OR: 0.75; 95% credible intervals: 0.59 to 0.92), in particular deaths certified as attributable to complications of immobility (0.59; 0.41 to 0.86). Stroke unit care was associated with statistically significant increases in the reported use of oxygen (2.39; 1.39 to 4.66), measures to prevent aspiration (2.42; 1.36 to 4.36), and paracetamol (2.80; 1.14 to 4.83) plus a nonsignificant reduction in the use of urinary catheterization. Stroke units were associated with statistically significant reductions in stroke progression/recurrence (0.66; 0.46 to 0.95) and in some complications of immobility: chest infections (0.60; 0.42 to 0.87), other infections (0.56; 0.40 to 0.84), and pressure sores (0.44; 0.22 to 0.85). There were no significant differences in cardiovascular, physiological, or other complications. Conclusions— Organized inpatient (stroke unit) care appears to reduce the risk of death after stroke through the prevention and treatment of complications, in particular infections.

Categorizing Stroke Prognosis Using Different Stroke Scales

Background and Purpose— Stroke severity and dependency are often categorized to allow stratification for randomization or analysis. However, there is uncertainty whether the categorizations used for different stroke scales are equivalent. We investigated the amount of information retained by categorizing severity and dependency, and whether the currently used cut-offs are equivalent across different stroke scales. Methods— Stroke severity and dependency have been categorized as mild, moderate, or severe. We studied 2 acute stroke unit cohorts, measuring Scandinavian Stroke Scale (SSS), modified Rankin Scale (mRS), Barthel Index (BI), and modified National Institutes of Health Stroke Scale (mNIHSS). Receiver operating characteristic (ROC) curves were examined to determine the ability of full and categorized scales to predict death and dependency. A weighted kappa analysis assessed agreement between the categorized scales. Results— When scales are categorized, the area under the ROC curve is significantly reduced; however, the differences are small and may not be practically important. BI, mRS, and SSS all have excellent agreement with each other when categorized, whereas mNIHSS has substantial agreement with mRS and BI. Conclusions— Little predictive information is lost when stroke scales are categorized. There is substantial to almost perfect agreement among categorized scales. Therefore the use and categorization of a variety of stroke severity or dependency scales is acceptable in analyses.

A meta-analysis of the risk of boys with isolated cryptorchidism developing testicular cancer in later life

Background Significant variability exists for the relative risk (RR) of testicular malignancy in isolated cryptorchidism. Objective To perform a meta-analysis to clarify the true magnitude of this risk, allowing clinicians to better counsel patients and their families. Setting Secondary research conducted by undergraduate researchers, clinical academics and a clinical statistician. Design, data sources, and methods A search of the English literature was performed for studies relating to testicular cancer and cryptorchidism, published between 1 January 1980 and 31 December 2010, using Embase and Medline databases. 735 papers were identified and analysed by four authors independently in accordance with our inclusion and exclusion criteria. Studies reporting an association between cryptorchidism and subsequent development of testicular malignancy were included. Genetic syndromes or other conditions which predisposed to the development of cryptorchidism were excluded. Pooled estimates and 95% CIs for the RRs were calculated. Results Nine case–control studies and three cohort studies were selected. The case–control studies included 2281 cases and 4811 controls. Cohort studies included 2 177 941 boys, with a total of 345 boys developing testicular cancer (total length of follow-up was 58 270 679 person-years). The pooled RR was 2.90 (95% CI 2.21 to 3.82) with significant heterogeneity (p<0.00001; I2=89%). Conclusion Boys with isolated cryptorchidism are three times more likely to develop testicular cancer. The limitations of this study must be acknowledged, in particular, possible publication bias and the lack of high-quality evidence focusing on the risk of malignancy in boys with isolated cryptorchidism.

The GOAL study : a prospective examination of the impact of factor V Leiden and ABO(H) blood groups on haemorrhagic and thrombotic pregnancy outcomes

Factor V Leiden (FVL) and ABO(H) blood groups are the common influences on haemostasis and retrospective studies have linked FVL with pregnancy complications. However, only one sizeable prospective examination has taken place. As a result, neither the impact of FVL in unselected subjects, any interaction with ABO(H) in pregnancy, nor the utility of screening for FVL is defined. A prospective study of 4250 unselected pregnancies was carried out. A venous thromboembolism (VTE) rate of 1·23/1000 was observed, but no significant association between FVL and pre‐eclampsia, intra‐uterine growth restriction or pregnancy loss was seen. No influence of FVL and/or ABO(H) on ante‐natal bleeding or intra‐partum or postpartum haemorrhage was observed. However, FVL was associated with birth‐weights >90th centile [odds ratio (OR) 1·81; 95% confidence interval (CI95) 1·04–3·31] and neonatal death (OR 14·79; CI95 2·71–80·74). No association with ABO(H) alone, or any interaction between ABO(H) and FVL was observed. We neither confirmed the protective effect of FVL on pregnancy‐related blood loss reported in previous smaller studies, nor did we find the increased risk of some vascular complications reported in retrospective studies.

Inpatient costs for people with type 1 and type 2 diabetes in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group

Aims/hypothesisThe rising prevalence of diabetes worldwide has increased interest in the cost of diabetes. Inpatient costs for all people with diabetes in Scotland were investigated.MethodsThe Scottish Care Information—Diabetes Collaboration (SCI-DC), a real-time clinical information system of almost all diagnosed cases of diabetes in Scotland, UK, was linked to data on all hospital admissions for people with diabetes. Inpatient stay costs were estimated using the 2007–2008 Scottish National Tariff. The probability of hospital admission and total annual cost of admissions were estimated in relation to age, sex, type of diabetes, history of vascular admission, HbA1c, creatinine, body mass index and diabetes duration.ResultsIn Scotland during 2005–2007, 24,750 people with type 1 and 195,433 people with type 2 diabetes were identified, accounting for approximately 4.3% of the total Scottish population (5.1 million). The estimated total annual cost of admissions for all people diagnosed with type 1 and type 2 diabetes was £26 million and £275 million, respectively, approximately 12% of the total Scottish inpatient expenditure (£2.4 billion). Sex, increasing age, serum creatinine, previous vascular history and HbA1c (the latter differentially in type 1 and type 2) were all associated with likelihood and total annual cost of admission.Conclusions/interpretationDiabetes inpatient expenditure accounted for 12% of the total Scottish inpatient expenditure, whilst people with diabetes account for 4.3% of the population. Of the modifiable risk factors, HbA1c was the most important driver of cost in type 1 diabetes.

Derivation and validation of simple equations to predict total muscle mass from simple anthropometric and demographic data

BACKGROUND Muscle mass reflects and influences health status. Its reliable estimation would be of value for epidemiology. OBJECTIVE The aim of the study was to derive and validate anthropometric prediction equations to quantify whole-body skeletal muscle mass (SM) in adults. DESIGN The derivation sample included 423 subjects (227 women) aged 18-81 y with a body mass index (BMI; in kg/m(2)) of 15.9-40.8. The validation sample included 197 subjects (105 women) aged 19-83 y with a BMI of 15.7-36.4. Both samples were of mixed ethnic/racial groups. All underwent whole-body magnetic resonance imaging to quantify SM (dependent variable for multiple regressions) and anthropometric variables (independent variables). RESULTS Two prediction equations with high practicality and optimal derivation correlations with SM were further investigated to assess agreement and bias by using Bland-Altman plots and validated in separate data sets. Including race as a variable increased R(2) by only 0.1% in men and by 8% in women. For men: SM (kg) = 39.5 + 0.665 body weight (BW; kg) - 0.185 waist circumference (cm) - 0.418 hip circumference (cm) - 0.08 age (y) (derivation: R(2) = 0.76, SEE = 2.7 kg; validation: R(2) = 0.79, SEE = 2.7 kg). Bland-Altman plots showed moderate agreement in both derivation and validation analyses. For women: SM (kg) = 2.89 + 0.255 BW (kg) - 0.175 hip circumference (cm) - 0.038 age (y) + 0.118 height (cm) (derivation: R(2) = 0.58, SEE = 2.2 kg; validation: R(2) = 0.59, SEE = 2.1 kg). Bland-Altman plots had a negative slope, indicating a tendency to overestimate SM among women with smaller muscle mass and to underestimate SM among those with larger muscle mass. CONCLUSIONS Anthropometry predicts SM better in men than in women. Equations that include hip circumference showed agreement between methods, with predictive power similar to that of BMI to predict fat mass, with the potential for applications in groups, as well as epidemiology and survey settings.

Achieved Levels of HbA1c and Likelihood of Hospital Admission in People With Type 1 Diabetes in the Scottish Population: A study from the Scottish Diabetes Research Network Epidemiology Group

OBJECTIVE People with type 1 diabetes have increased risk of hospital admission compared with those without diabetes. We hypothesized that HbA1c would be an important indicator of risk of hospital admission. RESEARCH DESIGN AND METHODS The Scottish Care Information–Diabetes Collaboration, a dynamic national register of diagnosed cases of diabetes in Scotland, was linked to national data on admissions. We identified 24,750 people with type 1 diabetes during January 2005 to December 2007. We assessed the relationship between deciles of mean HbA1c and hospital admissions in people with type 1 diabetes adjusting for patient characteristics. RESULTS There were 3,229 hospital admissions. Of the admissions, 8.1% of people had mean HbA1c <7.0% (53 mmol/mol) and 16.3% had HbA1c <7.5% (58 mmol/mol). The lowest odds of admission were associated with HbA1c 7.7–8.7% (61–72 mmol/mol). When compared with this decile, a J-shaped relationship existed between HbA1c and admission. The highest HbA1c decile (10.8–18.4%/95–178 mmol/mol) showed significantly higher odds ratio (95% CI) for any admission (2.80, 2.51–3.12); the lowest HbA1c decile (4.4–7.1%/25–54 mmol/mol) showed an increase in odds of admission of 1.29 (1.10–1.51). The highest HbA1c decile experienced significantly higher odds of diabetes-related (3.31, 2.94–3.72) and diabetes ketoacidosis admissions (10.18, 7.96–13.01). CONCLUSIONS People with type 1 diabetes with highest and lowest mean HbA1c values were associated with increased odds of admission. People with high HbA1c (>10.8%/95 mmol/mol) were at particularly high risk. There is the need to develop effective interventions to reduce this risk.

Multimodal Secondary Prevention Behavioral Interventions for TIA and Stroke: A Systematic Review and Meta-Analysis

Background Guidelines recommend implementation of multimodal interventions to help prevent recurrent TIA/stroke. We undertook a systematic review to assess the effectiveness of behavioral secondary prevention interventions. Strategy Searches were conducted in 14 databases, including MEDLINE (1980-January 2014). We included randomized controlled trials (RCTs) testing multimodal interventions against usual care/modified usual care. All review processes were conducted in accordance with Cochrane guidelines. Results Twenty-three papers reporting 20 RCTs (6,373 participants) of a range of multimodal behavioral interventions were included. Methodological quality was generally low. Meta-analyses were possible for physiological, lifestyle, psychosocial and mortality/recurrence outcomes. Note: all reported confidence intervals are 95%. Systolic blood pressure was reduced by 4.21 mmHg (mean) (−6.24 to −2.18, P = 0.01 I2 = 58%, 1,407 participants); diastolic blood pressure by 2.03 mmHg (mean) (−3.19 to −0.87, P = 0.004, I2 = 52%, 1,407 participants). No significant changes were found for HDL, LDL, total cholesterol, fasting blood glucose, high sensitivity-CR, BMI, weight or waist:hip ratio, although there was a significant reduction in waist circumference (−6.69 cm, −11.44 to −1.93, P = 0.006, I2 = 0%, 96 participants). There was no significant difference in smoking continuance, or improved fruit and vegetable consumption. There was a significant difference in compliance with antithrombotic medication (OR 1.45, 1.21 to 1.75, P<0.0001, I2 = 0%, 2,792 participants) and with statins (OR 2.53, 2.15 to 2.97, P< 0.00001, I2 = 0%, 2,636 participants); however, there was no significant difference in compliance with antihypertensives. There was a significant reduction in anxiety (−1.20, −1.77 to −0.63, P<0.0001, I2 = 85%, 143 participants). Although there was no significant difference in odds of death or recurrent TIA/stroke, there was a significant reduction in the odds of cardiac events (OR 0.38, 0.16 to 0.88, P = 0.02, I2 = 0%, 4,053 participants). Conclusions There are benefits to be derived from multimodal secondary prevention interventions. However, the findings are complex and should be interpreted with caution. Further, high quality trials providing comprehensive detail of interventions and outcomes, are required. Review Registration PROSPERO CRD42012002538.

Controlling ecological bias in evidence synthesis of trials reporting on collapsed and overlapping covariate categories

Meta-analysis of randomized controlled trials based on aggregated data is vulnerable to ecological bias if trial results are pooled over covariates that influence the outcome variable, even when the covariate does not modify the treatment effect, or is not associated with the treatment. This paper shows how, when trial results are aggregated over different levels of covariates, the within-study covariate distribution, and the effects of both covariates and treatments can be simultaneously estimated, and ecological bias reduced. Bayesian Markov chain Monte Carlo methods are used. The method is applied to a mixed treatment comparison evidence synthesis of six alternative approaches to post-stroke inpatient care. Results are compared with a model using only the stratified covariate data available, where each stratum is treated as a separate trial, and a model using fully aggregated data, where no covariate data are used.

The effect of deprivation and HbA1c on admission to hospital for diabetic ketoacidosis in type 1 diabetes

Aims/hypothesisDiabetic ketoacidosis is a potentially life-threatening complication of diabetes and has a strong relationship with HbA1c. We examined how socioeconomic group affects the likelihood of admission to hospital for diabetic ketoacidosis.MethodsThe Scottish Care Information – Diabetes Collaboration (SCI-DC), a dynamic national register of all cases of diagnosed diabetes in Scotland, was linked to national data on hospital admissions. We identified 24,750 people with type 1 diabetes between January 2005 and December 2007. We assessed the relationship between HbA1c and quintiles of deprivation with hospital admissions for diabetic ketoacidosis in people with type 1 diabetes adjusting for patient characteristics.ResultsWe identified 23,479 people with type 1 diabetes who had complete recording of covariates. Deprivation had a substantial effect on odds of admission to hospital for diabetic ketoacidosis (OR 4.51, 95% CI 3.73, 5.46 in the most deprived quintile compared with the least deprived). This effect persisted after the inclusion of HbA1c and other risk factors (OR 2.81, 95% CI 2.32, 3.39). Men had a reduced risk of admission to hospital for diabetic ketoacidosis (OR 0.71, 95% CI 0.63, 0.79) and those with a history of smoking had increased odds of admission to hospital for diabetic ketoacidosis by a factor of 1.55 (95% CI 1.36, 1.78).Conclusions/interpretationWomen, smokers, those with high HbA1c and those living in more deprived areas have an increased risk of admission to hospital for diabetic ketoacidosis. The effect of deprivation was present even after inclusion of other risk factors. This work highlights that those in poorer areas of the community with high HbA1c represent a group who might be usefully supported to try to reduce hospital admissions.