Glucocorticoid-induced hyperglycaemia in respiratory disease: a systematic review and meta-analysis.

The relative risk of glucocorticoid-induced hyperglycaemia is poorly quantified. We undertook a meta-analysis to estimate the association between glucocorticoid treatment and hyperglycaemia, overall and separately in individuals with and without diabetes and underlying respiratory disease. We searched electronic databases for clinical trials of adults randomized to either glucocorticoid treatment or placebo. Eight articles comprising 2121 participants were identified. We performed a random effects meta-analysis to determine relative risks for the associations between glucocorticoid use and both hyperglycaemia and starting hypoglycaemic therapy. In all individuals, the relative risk of hyperglycaemia comparing glucocorticoid treatment with placebo was 1.72 [95% confidence interval (CI) 1.50-2.04; p < .001]. The relative risks in individuals with and those without diabetes were 2.10 (95% CI 0.92-5.02; p = .079) and 1.50 (95% CI 0.79-2.86; p = .22), respectively. In all individuals, the relative risk of hyperglycaemia requiring initiation of hypoglycaemic therapy, comparing glucocorticoid treatment with placebo, was 1.73 (95% CI 1.40-2.14; p < .001). In conclusion, glucocorticoid therapy increases the risk of hyperglycaemia in all individuals with underlying respiratory disease but not when diabetic status is analysed separately.Medical Research Council (Grant ID: MC_UU_12015/1)This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/dom.1273

Lifestyle Advice Combined with Personalized Estimates of Genetic or Phenotypic Risk of Type 2 Diabetes, and Objectively Measured Physical Activity: A Randomized Controlled Trial

$\textbf{Background}$ Information about genetic and phenotypic risk of type 2 diabetes is now widely available and is being incorporated into disease prevention programs. Whether such information motivates behavior change or has adverse effects is uncertain. We examined the effect of communicating an estimate of genetic or phenotypic risk of type 2 diabetes in a parallel group, open, randomized controlled trial. $\textbf{Methods and Findings}$ We recruited 569 healthy middle-aged adults from the Fenland Study, an ongoing population-based, observational study in the east of England (Cambridgeshire, UK). We used a computer-generated random list to assign participants in blocks of six to receive either standard lifestyle advice alone (control group, $n$ = 190) or in combination with a genetic ($n$ = 189) or a phenotypic ($n$ = 190) risk estimate for type 2 diabetes (intervention groups). After 8 wk, we measured the primary outcome, objectively measured physical activity (kJ/kg/day), and also measured several secondary outcomes (including self-reported diet, self-reported weight, worry, anxiety, and perceived risk). The study was powered to detect a between-group difference of 4.1 kJ/kg/d at follow-up. 557 (98%) participants completed the trial. There were no significant intervention effects on physical activity (difference in adjusted mean change from baseline: genetic risk group versus control group 0.85 kJ/kg/d (95% CI −2.07 to 3.77, $p$ = 0.57); phenotypic risk group versus control group 1.32 (95% CI −1.61 to 4.25, $p$ = 0.38); and genetic risk group versus phenotypic risk group −0.47 (95% CI −3.40 to 2.46, $p$ = 0.75). No significant differences in self-reported diet, self-reported weight, worry, and anxiety were observed between trial groups. Estimates of perceived risk were significantly more accurate among those who received risk information than among those who did not. Key limitations include the recruitment of a sample that may not be representative of the UK population, use of self-reported secondary outcome measures, and a short follow-up period. $\textbf{Conclusions}$ In this study, we did not observe short-term changes in behavior associated with the communication of an estimate of genetic or phenotypic risk of type 2 diabetes. We also did not observe changes in worry or anxiety in the study population. Additional research is needed to investigate the conditions under which risk information might enhance preventive strategies. (Current Controlled Trials ISRCTN09650496; Date applied: April 4, 2011; Date assigned: June 10, 2011). $\textbf{Trial Registration}$ The trial is registered with Current Controlled Trials, ISRCTN09650496.This trial was conducted at the MRC Epidemiology Unit in Cambridge, UK. It was funded by the Medical Research Council (MC_U106179474), the Sixth Framework Programme (LSHM-CT-2006-037197), and the National Institute for Health Research (RP-PG- 0606-1259)

Change in cardio-protective medication and health-related quality of life after diagnosis of screen-detected diabetes: Results from the ADDITION-Cambridge cohort.

AIMS: Establishing a balance between the benefits and harms of treatment is important among individuals with screen-detected diabetes, for whom the burden of treatment might be higher than the burden of the disease. We described the association between cardio-protective medication and health-related quality of life (HRQoL) among individuals with screen-detected diabetes. METHODS: 867 participants with screen-detected diabetes underwent clinical measurements at diagnosis, one and five years. General HRQoL (EQ5D) was measured at baseline, one- and five-years, and diabetes-specific HRQoL (ADDQoL-AWI) and health status (SF-36) at one and five years. Multivariable linear regression was used to quantify the association between change in HRQoL and change in cardio-protective medication. RESULTS: The median (IQR) number of prescribed cardio-protective agents was 2 (1 to 3) at diagnosis, 3 (2 to 4) at one year and 4 (3 to 5) at five years. Change in cardio-protective medication was not associated with change in HRQoL from diagnosis to one year. From one year to five years, change in cardio-protective agents was not associated with change in the SF-36 mental health score. One additional agent was associated with an increase in the SF-36 physical health score (2.1; 95%CI 0.4, 3.8) and an increase in the EQ-5D (0.05; 95%CI 0.02, 0.08). Conversely, one additional agent was associated with a decrease in the ADDQoL-AWI (-0.32; 95%CI -0.51, -0.13), compared to no change. CONCLUSIONS: We found little evidence that increases in the number of cardio-protective medications impacted negatively on HRQoL among individuals with screen-detected diabetes over five years.ADDITION-Cambridge was supported by the Wellcome Trust (grant reference No G061895) the Medical Research Council (grant reference no: G0001164), National Health Service R&D support funding (including the Primary Care Research and Diabetes Research Networks), and the National Institute for Health Research. We received an unrestricted grant from University of Aarhus, Denmark, to support the ADDITION-Cambridge trial. Bio-Rad provided equipment to undertake capillary glucose screening by HbA1c in general practice. The Primary Care Research Unit is supported by NIHR Research funds. SJG receives support from the Department of Health NIHR Programme Grant funding scheme (RP-PG-0606-1259). This article presents independent research funded by the NIHR under the Programme Grants for Applied Research programme (RP-PG-0606-1259]. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.diabres.2015.04.01

The association between a biomarker score for fruit and vegetable intake and incident type 2 diabetes: the EPIC-Norfolk study.

BACKGROUND/OBJECTIVES: Biomarkers for a mixed fruit and vegetable (FV) diet are needed to provide a better understanding of the association between FV intake and type 2 diabetes. We aimed to examine the prospective association between a composite score comprised of three biomarkers of FV intake in free-living populations and incident diabetes. SUBJECTS/METHODS: A total of 318 incident diabetes cases and 926 controls from the EPIC (European Prospective Investigation of Cancer)-Norfolk study aged 40-79 years at baseline (1993-1997), completed 7-day prospective food diary and had plasma vitamin C and carotenoid measures. A composite biomarker score (CB-score) comprising the sum of plasma vitamin C, beta-carotene and lutein was derived. Odds ratios (ORs) and 95% confidence intervals (CIs) for incident diabetes were estimated using multivariable logistic regression. RESULTS: A strong inverse association was found between the CB-score and incident diabetes. The ORs (95% CI) of diabetes comparing quartiles Q2, Q3 and Q4 of the CB-score with Q1 (reference category) were 0.70 (0.49, 1.00), 0.34 (0.23, 0.52) and 0.19 (0.12, 0.32), respectively, and 0.49 (0.40, 0.58) per s.d. change in CB-score in a model adjusted for demographic and lifestyle factors. The association was marginally attenuated after additionally adjusting for body mass index and waist circumference (0.60 (0.49 and 0.74) per s.d. change in CB-score). CONCLUSIONS: A combination of biomarkers representing the intake of a mixed FV diet was strongly inversely associated with incident diabetes. These findings provide further support for measuring dietary biomarkers in studies of diet-disease associations and highlight the importance of consuming FV for the prevention of diabetes.The EPIC Norfolk study is supported by programme grants from the Medical Research Council UK and Cancer Research UK. The sponsors did not participate in the design or conduct of this study; in the collection, management, analysis, or interpretation of data; in the writing of the manuscript; or in the preparation, review, approval, or decision to submit this manuscript for publication. We acknowledge support from the MRC Epidemiology Unit (MC_UU_12015/5).This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ejcn.2014.24

Premenopausal abnormal uterine bleeding and risk of endometrial cancer.

BACKGROUND: Endometrial biopsies are undertaken in premenopausal women with abnormal uterine bleeding but the risk of endometrial cancer or atypical hyperplasia is unclear. OBJECTIVES: To conduct a systematic literature review to establish the risk of endometrial cancer and atypical hyperplasia in premenopausal women with abnormal uterine bleeding. SEARCH STRATEGY: Search of PubMed, Embase and the Cochrane Library from database inception to August 2015. SELECTION CRITERIA: Studies reporting rates of endometrial cancer and/or atypical hyperplasia in women with premenopausal abnormal uterine bleeding. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two reviewers and cross-checked. For each outcome, the risk and a 95% CI were estimated using logistic regression with robust standard errors to account for clustering by study. MAIN RESULTS: Sixty-five articles contributed to the analysis. Risk of endometrial cancer was 0.33% (95% CI 0.23-0.48%, n = 29 059; 97 cases) and risk of endometrial cancer or atypical hyperplasia was 1.31% (95% CI 0.96-1.80, n = 15 772; 207 cases). Risk of endometrial cancer was lower in women with heavy menstrual bleeding (HMB) (0.11%, 95% CI 0.04-0.32%, n = 8352; 9 cases) compared with inter-menstrual bleeding (IMB) (0.52%, 95% CI 0.23-1.16%, n = 3109; 14 cases). Of five studies reporting the rate of atypical hyperplasia in women with HMB, none identified any cases. CONCLUSIONS: The risk of endometrial cancer or atypical hyperplasia in premenopausal women with abnormal uterine bleeding is low. Premenopausal women with abnormal uterine bleeding should first undergo conventional medical management. Where this fails, the presence of IMB and older age may be indicators for further investigation. Further research into the risks associated with age and the cumulative risk of co-morbidities is needed. TWEETABLE ABSTRACT: Contrary to practice, premenopausal women with heavy periods or inter-menstrual bleeding rarely require biopsy.The work was undertaken under the auspices of the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence which is funded by the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust

Bidirectional association between physical activity and muscular strength in older adults: Results from the UK Biobank study.

BACKGROUND: The relationship between physical activity and muscular strength has not been examined in detail among older adults. The objective of this study was to examine the associations between physical activity and hand grip strength among adults aged ≥ 60 years. METHODS: Using data from the UK Biobank study, we included 66 582 men and women with complete baseline data and 6599 with 4.5 years of follow-up data. We used multiple linear regression models to examine the cross-sectional, longitudinal and bidirectional associations between moderate-to-vigorous physical activity (MVPA) and grip strength, adjusting for potential confounding by age, sex, height, weight, health status, education level, smoking status, Townsend deprivation index and retirement status. RESULTS: In cross-sectional analyses, grip strength and MVPA were linearly and positively associated with each other. Longitudinally, baseline MVPA was not associated with grip strength at follow-up {difference between quintile [Q] 5 and Q1 = 0.40 [95% confidence interval (CI): -0.14, 0.94]kg}, whereas baseline grip strength was associated with MVPA at follow-up [Q5 vs Q1 = 7.15 (1.18, 13.12) min/day]. People who maintained/increased time spent in MVPA did not experience any benefit in grip strength [0.08 (-0.20, 0.37) kg] whereas those who increased their grip strength spent 3.69 (0.20, 7.17) min/day extra in MVPA. CONCLUSION: Promotion of strength-training activities may enable and maintain participation in regular physical activity among older adults.This work was supported by the Medical Research Council [Programme number: MC_UU_12015/4] and has been conducted using the UK Biobank Resource.This is the final version of the article. It first appeared from Oxford University Press via https://doi.org/10.1093/ije/dyw05

Cancer-related pain in head and neck cancer survivors: longitudinal findings from the Head and Neck 5000 clinical cohort

\ua9 The Author(s) 2024.Purpose: Reports suggest pain is common in head and neck cancer (HNC). However, past studies are limited by small sample sizes and design and measurement heterogeneity. Using data from the Head and Neck 5000 longitudinal cohort, we investigated pain over a year post-diagnosis. We assessed: temporal trends; compared pain across HNC treatments, stages, sites and by HPV status; and identified subgroups of patients at increased risk of pain. Methods: Sociodemographic and clinical data and patient-reported pain (measured by EORTC QLQ-C30 and QLQ-H&amp;N35) were collected at baseline (pre-treatment), 4- and 12- months. Using mixed effects multivariable regression, we investigated time trends and identified associations between (i) clinically-important general pain and (ii) HN-specific pain and clinical, socio-economic, and demographic variables. Results: 2,870 patients were included. At baseline, 40.9% had clinically-important general pain, rising to 47.6% at 4-months and declining to 35.5% at 12-months. HN-specific pain followed a similar pattern (mean score (sd): baseline 26.4 (25.10); 4-months. 28.9 (26.55); 12-months, 17.2 (19.83)). Across time, general and HN-specific pain levels were increased in: younger patients, smokers, and those with depression and comorbidities at baseline, and more advanced, oral cavity and HPV negative cancers. Conclusions: There is high prevalence of general pain in people living with HNC. We identified subgroups more often reporting general and HN-specific pain towards whom interventions could be targeted. Implications for cancer survivors: Greater emphasis should be placed on identifying and treating pain in HNC. Systematic pain screening could help identify those who could benefit from an early pain management plan

A two-step method for variable selection in the analysis of a case-cohort study.

Background: Accurate detection and estimation of true exposure-outcome associations is important in aetiological analysis; when there are multiple potential exposure variables of interest, methods for detecting the subset of variables most likely to have true associations with the outcome of interest are required. Case-cohort studies often collect data on a large number of variables which have not been measured in the entire cohort (e.g. panels of biomarkers). There is a lack of guidance on methods for variable selection in case-cohort studies. Methods: We describe and explore the application of three variable selection methods to data from a case-cohort study. These are: (i) selecting variables based on their level of significance in univariable (i.e. one-at-a-time) Prentice-weighted Cox regression models; (ii) stepwise selection applied to Prentice-weighted Cox regression; and (iii) a two-step method which applies a Bayesian variable selection algorithm to obtain posterior probabilities of selection for each variable using multivariable logistic regression followed by effect estimation using Prentice-weighted Cox regression. Results: Across nine different simulation scenarios, the two-step method demonstrated higher sensitivity and lower false discovery rate than the one-at-a-time and stepwise methods. In an application of the methods to data from the EPIC-InterAct case-cohort study, the two-step method identified an additional two fatty acids as being associated with incident type 2 diabetes, compared with the one-at-a-time and stepwise methods. Conclusions: The two-step method enables more powerful and accurate detection of exposure-outcome associations in case-cohort studies. An R package is available to enable researchers to apply this method.P.J.N. and S.R. were supported by the Medical Research Council [www.mrc.ac.uk] (Unit Programme number MC_UP_0801/1). P.J.N. also acknowledges partial support from the NIHR Cambridge Biomedical Research Centre. S.S. and S.C. were supported by the Medical Research Council [www.mrc.ac.uk] (Unit Programme number MC_U105260558). S.J.S. was supported by the Medical Research Council [www.mrc.ac.uk] (Unit Programme number MC_UU_12015/1). Funding for the EPIC-InterAct project was provided by the EU FP6 programme (grant number LSHM_CT_2006_037197)

Correction: External validation of risk prediction models for incident colorectal cancer using UK Biobank.

An amendment to this paper has been published and can be accessed via a link at the top of the paper