Kate Birnie

Childhood Socioeconomic Position and Objectively Measured Physical Capability Levels in Adulthood: A Systematic Review and Meta-Analysis

Background Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood. Methods and Findings Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations. Conclusions Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.

Age and gender differences in physical capability levels from mid-life onwards: the harmonisation and meta-analysis of data from eight UK cohort studies.

Using data from eight UK cohorts participating in the Healthy Ageing across the Life Course (HALCyon) research programme, with ages at physical capability assessment ranging from 50 to 90+ years, we harmonised data on objective measures of physical capability (i.e. grip strength, chair rising ability, walking speed, timed get up and go, and standing balance performance) and investigated the cross-sectional age and gender differences in these measures. Levels of physical capability were generally lower in study participants of older ages, and men performed better than women (for example, results from meta-analyses (N = 14,213 (5 studies)), found that men had 12.62 kg (11.34, 13.90) higher grip strength than women after adjustment for age and body size), although for walking speed, this gender difference was attenuated after adjustment for body size. There was also evidence that the gender difference in grip strength diminished with increasing age,whereas the gender difference in walking speed widened (p<0.01 for interactions between age and gender in both cases). This study highlights not only the presence of age and gender differences in objective measures of physical capability but provides a demonstration that harmonisation of data from several large cohort studies is possible. These harmonised data are now being used within HALCyon to understand the lifetime social and biological determinants of physical capability and its changes with age.

Predictive models for kidney disease: improving global outcomes (KDIGO) defined acute kidney injury in UK cardiac surgery.

IntroductionAcute kidney injury (AKI) risk prediction scores are an objective and transparent means to enable cohort enrichment in clinical trials or to risk stratify patients preoperatively. Existing scores are limited in that they have been designed to predict only severe, or non-consensus AKI definitions and not less severe stages of AKI, which also have prognostic significance. The aim of this study was to develop and validate novel risk scores that could identify all patients at risk of AKI.MethodsProspective routinely collected clinical data (n = 30,854) were obtained from 3 UK cardiac surgical centres (Bristol, Birmingham and Wolverhampton). AKI was defined as per the Kidney Disease: Improving Global Outcomes (KDIGO) Guidelines. The model was developed using the Bristol and Birmingham datasets, and externally validated using the Wolverhampton data. Model discrimination was estimated using the area under the ROC curve (AUC). Model calibration was assessed using the Hosmer–Lemeshow test and calibration plots. Diagnostic utility was also compared to existing scores.ResultsThe risk prediction score for any stage AKI (AUC = 0.74 (95% confidence intervals (CI) 0.72, 0.76)) demonstrated better discrimination compared to the Euroscore and the Cleveland Clinic Score, and equivalent discrimination to the Mehta and Ng scores. The any stage AKI score demonstrated better calibration than the four comparison scores. A stage 3 AKI risk prediction score also demonstrated good discrimination (AUC = 0.78 (95% CI 0.75, 0.80)) as did the four comparison risk scores, but stage 3 AKI scores were less well calibrated.ConclusionsThis is the first risk score that accurately identifies patients at risk of any stage AKI. This score will be useful in the perioperative management of high risk patients as well as in clinical trial design.

Systematic review and meta-analysis of the effect of intraoperative α2-adrenergic agonists on postoperative behaviour in children

Undergoing general anaesthesia is distressing for children, with up to two-thirds demonstrating abnormal behaviours after their procedure, such as emergence delirium (ED) and post-hospitalization behaviour change. The aim of this systematic review was to determine the effect of intraoperative i.v. α₂-adrenergic agonists on postoperative behaviour in children. We included published full-text reports of randomized controlled trials involving children who received i.v. clonidine or dexmedetomidine after induction of general anaesthesia, who were assessed for postoperative behavioural disturbance. After screening of references identified by the search strategy, a data collection form was developed and piloted. Data extraction was performed by one reviewer and checked by a second. Twelve randomized trials met the inclusion criteria. Ten studies (n=669) reported dichotomous data that were included in the pooled analysis of α₂-adrenergic agonists vs placebo. There was strong evidence that i.v. α₂-adrenergic agonists reduced postoperative ED (overall summary odds ratio 0.28, 95% confidence interval 0.19-0.40, P<0.001). No studies examined post-hospitalization negative behaviour changes. There was evidence that α₂-adrenergic agonists prolonged time in the recovery room. No adverse haemodynamic events were reported in any arm of any study. This meta-analysis provides evidence that intraoperative i.v. α₂-adrenergic agonists reduce the incidence of emergency delirium in children. The prolongation of time in recovery is unlikely to be clinically relevant. The absence of data regarding the effect on post-hospitalization behavioural changes provides an opportunity for future research.

Socio-economic disadvantage from childhood to adulthood and locomotor function in old age: a lifecourse analysis of the Boyd Orr and Caerphilly prospective studies

Background Socio-economic influences over a lifetime impact on health and may contribute to poor physical functioning in old age. Methods The authors examined the impact of both childhood and adulthood socio-economic factors on locomotor function at 63–86 years (measured with the get up and go timed walk and flamingo balance test) in the UK-based Boyd Orr (n=405) and Caerphilly (n=1196) prospective cohorts. Results There was a marked reduction in walking speed and balance time with increasing age. Each year of age was associated with a 1.7% slower walk time and a 14% increased odds of poor balance. Participants who moved from a low socio-economic position in childhood to a high socio-economic position in adulthood had 3% slower walking times (95% CI −2% to 8%) than people with a high socio-economic position in both periods. Participants who moved from a high socio-economic position in childhood to a low adulthood socio-economic position had 5% slower walking times (95% CI −2% to 12%). Participants with a low socio-economic position in both periods had 10% slower walking times (95% CI 5% to 16%; p for trend <0.001). In Boyd Orr, low socio-economic position in childhood was associated with poor balance in old age (OR per worsening category=1.26; 95% CI 1.01 to 1.57; p=0.043), as was socio-economic position in adulthood (OR=1.71; 95% CI 1.20 to 2.45; p=0.003). Similar associations were not observed in Caerphilly. Conclusion Accumulating socio-economic disadvantage from childhood to adulthood is associated with slower walking time in old age, with mixed results for balance ability.

Injection Drug Use and Hepatitis C as Risk Factors for Mortality in HIV-Infected Individuals: The Antiretroviral Therapy Cohort Collaboration

Background:HIV-infected individuals with a history of transmission through injection drug use (IDU) have poorer survival than other risk groups. The extent to which higher rates of hepatitis C (HCV) infection in IDU explain survival differences is unclear. Methods:Adults who started antiretroviral therapy between 2000 and 2009 in 16 European and North American cohorts with >70% complete data on HCV status were followed for 3 years. We estimated unadjusted and adjusted (for age, sex, baseline CD4 count and HIV-1 RNA, AIDS diagnosis before antiretroviral therapy, and stratified by cohort) mortality hazard ratios for IDU (versus non-IDU) and for HCV-infected (versus HCV uninfected). Results:Of 32,703 patients, 3374 (10%) were IDU; 4630 (14%) were HCV+; 1116 (3.4%) died. Mortality was higher in IDU compared with non-IDU [adjusted HR 2.71; 95% confidence interval (CI): 2.32 to 3.16] and in HCV+ compared with HCV− (adjusted HR 2.65; 95% CI: 2.31 to 3.04). The effect of IDU was substantially attenuated (adjusted HR 1.57; 95% CI: 1.27 to 1.94) after adjustment for HCV, while attenuation of the effect of HCV was less substantial (adjusted HR 2.04; 95% CI: 1.68 to 2.47) after adjustment for IDU. Both IDU and HCV were strongly associated with liver-related mortality (adjusted HR 10.89; 95% CI: 6.47 to 18.3 for IDU and adjusted HR 14.0; 95% CI: 8.05 to 24.5 for HCV) with greater attenuation of the effect of IDU (adjusted HR 2.43; 95% CI: 1.24 to 4.78) than for HCV (adjusted HR 7.97; 95% CI: 3.83 to 16.6). Rates of CNS, respiratory and violent deaths remained elevated in IDU after adjustment for HCV. Conclusions:A substantial proportion of the excess mortality in HIV-infected IDU is explained by HCV coinfection. These findings underscore the potential impact on mortality of new treatments for HCV in HIV-infected people.

Improving the Diagnosis and Treatment of Urinary Tract Infection in Young Children in Primary Care: Results from the DUTY Prospective Diagnostic Cohort Study

PURPOSE Up to 50% of urinary tract infections (UTIs) in young children are missed in primary care. Urine culture is essential for diagnosis, but urine collection is often difficult. Our aim was to derive and internally validate a 2-step clinical rule using (1) symptoms and signs to select children for urine collection; and (2) symptoms, signs, and dipstick testing to guide antibiotic treatment. METHODS We recruited acutely unwell children aged under 5 years from 233 primary care sites across England and Wales. Index tests were parent-reported symptoms, clinician-reported signs, urine dipstick results, and clinician opinion of UTI likelihood (clinical diagnosis before dipstick and culture). The reference standard was microbiologically confirmed UTI cultured from a clean-catch urine sample. We calculated sensitivity, specificity, and area under the receiver operator characteristic (AUROC) curve of coefficient-based (graded severity) and points-based (dichotomized) symptom/sign logistic regression models, and we then internally validated the AUROC using bootstrapping. RESULTS Three thousand thirty-six children provided urine samples, and culture results were available for 2,740 (90%). Of these results, 60 (2.2%) were positive: the clinical diagnosis was 46.6% sensitive, with an AUROC of 0.77. Previous UTI, increasing pain/crying on passing urine, increasingly smelly urine, absence of severe cough, increasing clinician impression of severe illness, abdominal tenderness on examination, and normal findings on ear examination were associated with UTI. The validated coefficient- and points-based model AUROCs were 0.87 and 0.86, respectively, increasing to 0.90 and 0.90, respectively, by adding dipstick nitrites, leukocytes, and blood. CONCLUSIONS A clinical rule based on symptoms and signs is superior to clinician diagnosis and performs well for identifying young children for noninvasive urine sampling. Dipstick results add further diagnostic value for empiric antibiotic treatment.

Evaluation of an intervention to reduce tidal volumes in ventilated ICU patients

BACKGROUND There is considerable evidence that the use of tidal volumes <6 ml kg(-1) predicted body weight (PBW) reduces mortality in mechanically ventilated patients. We evaluated the effectiveness of using a large screen displaying delivered tidal volume in ml kg(-1) (PBW) for reducing tidal volumes. METHODS We assessed the intervention in two 6-month periods. A qualitative study was undertaken after the intervention period to examine staff interaction with the intervention. The study was conducted in a mixed medical and surgical intensive care unit at University Hospitals Bristol, UK. Consecutive patients requiring controlled mechanical ventilation for more than 1 h were included. Alerts were triggered when tidal volume breached predetermined targets and these alerts were visible to ICU clinicians in real time. RESULTS A total of 199 patients with 7640 h of data were observed during the control time period and 249 patients with 10 656 h of data were observed in the intervention period. Time spent with tidal volumes <6 ml kg(-1) PBW increased from 17.5 to 28.6% of the period of controlled mechanical ventilation. Time spent with a tidal volume <8 ml kg(-1) PBW increased from 60.6 to 73.9%. The screens were acceptable to staff and stimulated an increase in attendance of clinicians at the bedside to adjust ventilators. CONCLUSIONS Changing the format of data and displaying it with real-time alerts reduced delivered tidal volumes. Configuring information in a format more likely to result in desired outcomes has the potential to improve the translation of evidence into practice.

Associations of insulin and insulin-like growth factors with physical performance in old age in the Boyd Orr and Caerphilly studies.

Objective Insulin and the insulin-like growth factor (IGF) system regulate growth and are involved in determining muscle mass, strength and body composition. We hypothesised that IGF-I and IGF-II are associated with improved, and insulin with worse, physical performance in old age. Methods Physical performance was measured using the get-up and go timed walk and flamingo balance test at 63–86 years. We examined prospective associations of insulin, IGF-I, IGF-II and IGFBP-3 with physical performance in the UK-based Caerphilly Prospective Study (CaPS; n = 739 men); and cross-sectional insulin, IGF-I, IGF-II, IGFBP-2 and IGFBP-3 in the Boyd Orr cohort (n = 182 men, 223 women). Results In confounder-adjusted models, there was some evidence in CaPS that a standard deviation (SD) increase in IGF-I was associated with 1.5% faster get-up and go test times (95% CI: −0.2%, 3.2%; p = 0.08), but little association with poor balance, 19 years later. Coefficients in Boyd Orr were in the same direction as CaPS, but consistent with chance. Higher levels of insulin were weakly associated with worse physical performance (CaPS and Boyd Orr combined: get-up and go time = 1.3% slower per SD log-transformed insulin; 95% CI: 0.0%, 2.7%; p = 0.07; OR poor balance 1.13; 95% CI; 0.98, 1.29; p = 0.08), although associations were attenuated after controlling for body mass index (BMI) and co-morbidities. In Boyd Orr, a one SD increase in IGFBP-2 was associated with 2.6% slower get-up and go times (95% CI: 0.4%, 4.8% slower; p = 0.02), but this was only seen when controlling for BMI and co-morbidities. There was no consistent evidence of associations of IGF-II, or IGFBP-3 with physical performance. Conclusions There was some evidence that high IGF-I and low insulin levels in middle-age were associated with improved physical performance in old age, but estimates were imprecise. Larger cohorts are required to confirm or refute the findings.

Erythropoiesis-stimulating agent dosing, haemoglobin and ferritin levels in UK haemodialysis patients 2005-13.

ABSTRACT Background: Erythropoiesis-stimulating agents (ESAs) with intravenous iron supplementation are the main treatment for anaemia in patients with chronic kidney disease. Although observational studies suggest better outcomes for patients who achieve higher haemoglobin (Hb) levels, randomized controlled trials comparing higher and lower Hb targets have led to safety concerns over higher targets and to changes in treatment guidelines. Methods: Quarterly data from 2005 to 2013 were obtained on 28 936 haemodialysis patients from the UK Renal Registry. We examined trends in ESA use and average dose, Hb and ferritin values over time and Hb according to the UK Renal Association guideline range. Results: The average ESA dose declined over time, with sharper decreases of epoetin seen towards the end of 2006 and from 2009. Average Hb for patients on ESAs was 114.1 g/L [95% confidence interval (CI) 113.7, 114.6] in the first quarter of 2005, which decreased to 109.6 g/L (95% CI 109.3, 109.9) by the end of 2013. Average serum ferritin was 353 µg/L (95% CI 345, 360) at the start of 2005, increasing to 386 µg/L (95% CI 380, 392) in the final quarter of 2013. The percentage of patients with Hb in the range of 100–120 g/L increased from 46.1 at the start of 2005 to 57.6 at the end of 2013. Conclusions: Anaemia management patterns for haemodialysis patients changed in the UK between 2005 and 2013. These patterns most likely reflect clinician response to emerging trial evidence and practice guidelines. Registries play an important role in continued observation of anaemia management and will monitor further changes as new evidence on optimal care emerges.