Showing papers by "Leicester General Hospital published in 2019"

Evaluating a New International Risk-Prediction Tool in IgA Nephropathy

Abstract: Importance Although IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, there is no validated tool to predict disease progression. This limits patient-specific risk stratification and treatment decisions, clinical trial recruitment, and biomarker validation. Objective To derive and externally validate a prediction model for disease progression in IgAN that can be applied at the time of kidney biopsy in multiple ethnic groups worldwide. Design, setting, and participants We derived and externally validated a prediction model using clinical and histologic risk factors that are readily available in clinical practice. Large, multi-ethnic cohorts of adults with biopsy-proven IgAN were included from Europe, North America, China, and Japan. Main outcomes and measures Cox proportional hazards models were used to analyze the risk of a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, and were evaluated using the R2D measure, Akaike information criterion (AIC), C statistic, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and calibration plots. Results The study included 3927 patients; mean age, 35.4 (interquartile range, 28.0-45.4) years; and 2173 (55.3%) were men. The following prediction models were created in a derivation cohort of 2781 patients: a clinical model that included eGFR, blood pressure, and proteinuria at biopsy; and 2 full models that also contained the MEST histologic score, age, medication use, and either racial/ethnic characteristics (white, Japanese, or Chinese) or no racial/ethnic characteristics, to allow application in other ethnic groups. Compared with the clinical model, the full models with and without race/ethnicity had better R2D (26.3% and 25.3%, respectively, vs 20.3%) and AIC (6338 and 6379, respectively, vs 6485), significant increases in C statistic from 0.78 to 0.82 and 0.81, respectively (ΔC, 0.04; 95% CI, 0.03-0.04 and ΔC, 0.03; 95% CI, 0.02-0.03, respectively), and significant improvement in reclassification as assessed by the NRI (0.18; 95% CI, 0.07-0.29 and 0.51; 95% CI, 0.39-0.62, respectively) and IDI (0.07; 95% CI, 0.06-0.08 and 0.06; 95% CI, 0.05-0.06, respectively). External validation was performed in a cohort of 1146 patients. For both full models, the C statistics (0.82; 95% CI, 0.81-0.83 with race/ethnicity; 0.81; 95% CI, 0.80-0.82 without race/ethnicity) and R2D (both 35.3%) were similar or better than in the validation cohort, with excellent calibration. Conclusions and relevance In this study, the 2 full prediction models were shown to be accurate and validated methods for predicting disease progression and patient risk stratification in IgAN in multi-ethnic cohorts, with additional applications to clinical trial design and biomarker research.

Physical activity, multimorbidity, and life expectancy: a UK Biobank longitudinal study.

Abstract: Multimorbidity is an emerging public health priority. Physical activity (PA) is recommended as one of the main lifestyle behaviours, yet the benefits of PA for people with multimorbidity are unclear. We assessed the benefits of PA on mortality and life expectancy in people with and without multimorbidity. Using the UK Biobank dataset, we extracted data on 36 chronic conditions and defined multimorbidity as (a) 2 or more conditions, (b) 2 or more conditions combined with self-reported overall health, and (c) 2 or more top-10 most common comorbidities. Leisure-time PA (LTPA) and total PA (TPA) were measured by questionnaire and categorised as low (< 600 metabolic equivalent (MET)-min/week), moderate (600 to < 3000 MET-min/week), and high (≥ 3000 MET-min/week), while objectively assessed PA was assessed by wrist-worn accelerometer and categorised as low (4 min/day), moderate (10 min/day), and high (22 min/day) walking at brisk pace. Survival models were applied to calculate adjusted hazard ratios (HRs) and predict life expectancy differences. 491,939 individuals (96,622 with 2 or more conditions) had a median follow-up of 7.0 (IQR 6.3–7.6) years. Compared to low LTPA, for participants with multimorbidity, HR for mortality was 0.75 (95% CI 0.70–0.80) and 0.65 (0.56–0.75) in moderate and high LTPA groups, respectively. This finding was consistent when using TPA measures. Using objective PA, HRs were 0.49 (0.29–0.80) and 0.29 (0.13–0.61) in the moderate and high PA groups, respectively. These findings were similar for participants without multimorbidity. In participants with multimorbidity, at the age of 45 years, moderate and high LTPA were associated with an average of 3.12 (95% CI 2.53, 3.71) and 3.55 (2.34, 4.77) additional life years, respectively, compared to low LTPA; in participants without multimorbidity, corresponding figures were 1.95 (1.59, 2.31) and 1.85 (1.19, 2.50). Similar results were found with TPA. For objective PA, moderate and high levels were associated with 3.60 (− 0.60, 7.79) and 5.32 (− 0.47, 11.11) life years gained compared to low PA for those with multimorbidity and 3.88 (1.79, 6.00) and 4.51 (2.15, 6.88) life years gained in those without. Results were consistent when using other definitions of multimorbidity. There was an inverse dose-response association between PA and mortality. A moderate exercise is associated with a longer life expectancy, also in individuals with multimorbidity.

Therapeutic inertia in type 2 diabetes: prevalence, causes, consequences and methods to overcome inertia.

Abstract: Early glycaemic control leads to better outcomes, including a reduction in long-term macrovascular and microvascular complications. Despite good-quality evidence, glycaemic control has been shown to be inadequate globally. Therapeutic inertia has been shown present in all stages of treatment intensification, from the first oral antihyperglycaemic drug (OAD), all the way to the initiation of insulin. The causes and possible solutions to the problem of therapeutic inertia are complex but can be understood better when viewed from the perspective of the providers [healthcare professionals (HCPs)], patients and healthcare systems. In this review, we will discuss the possible aetiologies, consequences and solutions of therapeutic inertia, drawing upon evidence from published literature on the subject of type 2 diabetes.

Causality between non-alcoholic fatty liver disease and risk of cardiovascular disease and type 2 diabetes: A meta-analysis with bias analysis.

Abstract: BACKGROUND & AIMS A causal association of non-alcoholic fatty liver disease (NAFLD) with cardiovascular disease (CVD) and type 2 diabetes (T2DM) remains unproved. We aimed to quantify the likelihood of causality examining the sensitivity of observational associations to possible confounding. METHODS Studies investigating longitudinal associations of NAFLD with CVD or T2DM were searched on 5 June 2018. Study-specific relative risks (RRs) were combined in random-effects meta-analyses and pooled estimates used in bias analyses. RESULTS Associations of NAFLD with CVD and T2DM were reported in 13 (258 743/18 383 participants/events) and 20 (240 251/12 891) studies respectively. Comparing patients with NAFLD to those without, the pooled RR was 1.48 (95% CI: 0.96, 2.29) for CVD and 2.17 (1.77, 2.65) for T2DM. In bias analyses, for an unmeasured confounder associated to both NAFLD and CVD with a RR of 1.25, the proportion of studies with a true (causal) effect of NAFLD on CVD surpassing a RR of 1.10 (ie, 10% increased risk of CVD in participants with NAFLD) was 0.67 (95% CI: 0.42, 0.92) while for 75% increase, it was 0.36 (0.11, 0.62). Corresponding figures for T2DM were 0.97 (0.91, 1.00) for a 10% increased risk of T2DM in participants with NAFLD to 0.70 (0.49, 0.92) for a 75% increase. CONCLUSIONS The results of this study are strongly suggestive for a causal relationship between NAFLD and T2DM, while the evidence for a causal link between NAFLD and CVD is less robust. Therapeutic strategies targeting NAFLD are likely to reduce the risk of developing T2DM.

Associations between social jetlag and mental health in young people: A systematic review.

Abstract: Adolescence and early adulthood (collectively categorized as "young people") is a transitional period associated with a number of key physiological, social and psychological changes. Sleep difficulties, notable in this age group, may adversely affect physical and mental health. Of interest is the impact of the natural shift in young people towards a more evening-type sleep pattern (chronotype), whilst social constraints encourage early waking to fit with school/work timings. This leads to a misalignment in sleep timing between weekdays and weekends, known as social jetlag, which may contribute to emerging mental health difficulties seen during this age group. A systematic literature review was undertaken to investigate the association between social jetlag and mental health outcomes. Systematic searching of electronic databases (The Cochrane Library; PsycINFO; CINAHL; Scopus; and PubMed), grey literature and review of reference lists identified seven studies which assessed associations between social jetlag and mental health outcomes in young people. Quality appraisal was completed using the Appraisal Tool for Cross-Sectional Studies. Findings appeared equivocal; however significant associations were revealed with social jetlag associated with clinical depression and seasonal depression, in female participants and high latitude regions. Quality of included studies was moderate (10-13 criteria met). A lack of homogeneity between study methodologies precluded the conduct of a meta-analysis. The ambiguous results found may result from confounding factors including non-comparable methods of measuring social jetlag and mental health both in this age group and the selected studies. Future research should address a lack of homogeneity through the development of an interdisciplinary core outcome set, and agreement on a standardized measure and calculation for social jetlag.

Test–retest reliability, validation, and “minimal detectable change” scores for frequently reported tests of objective physical function in patients with non-dialysis chronic kidney disease

Abstract: Physical function is an important outcome in chronic kidney disease (CKD). We aimed to establish the reliability, validity, and the “minimal detectable change” (MDC) of several common tests used in...

Lifestyle drift and the phenomenon of 'citizen shift' in contemporary UK health policy.

Abstract: Despite political change over the past 25 years in Britain there has been an unprecedented national policy focus on the social determinants of health and population-based approaches to prevent chronic disease. Yet, policy impacts have been modest, inequalities endure and behavioural approaches continue to shape strategies promoting healthy lifestyles. Critical public health scholarship has conceptualised this lack of progress as a problem of 'lifestyle drift' within policy whereby 'upstream' social contributors to health inequalities are reconfigured 'downstream' as a matter of individual behaviour change. While the lifestyle drift concept is now well established there has been little empirical investigation into the social processes through which it is realised as policies are (re)formulated and implementation is localised. Addressing this gap we present empirical findings from an ethnography conducted in a deprived English neighbourhood in order to explore: (i) the local context in the process of lifestyle drift and; (ii) the social relations that reproduce (in)equities in the design and delivery of lifestyle interventions. Analysis demonstrates how and why 'precarious partnerships' between local service providers were significant in the process of 'citizen shift' whereby government responsibility for addressing inequity was decollectivised.

Comparability of accelerometer signal aggregation metrics across placements and dominant wrist cut points for the assessment of physical activity in adults.

Abstract: Large epidemiological studies that use accelerometers for physical behavior and sleep assessment differ in the location of the accelerometer attachment and the signal aggregation metric chosen. This study aimed to assess the comparability of acceleration metrics between commonly-used body-attachment locations for 24 hours, waking and sleeping hours, and to test comparability of PA cut points between dominant and non-dominant wrist. Forty-five young adults (23 women, 18–41 years) were included and GT3X + accelerometers (ActiGraph, Pensacola, FL, USA) were placed on their right hip, dominant, and non-dominant wrist for 7 days. We derived Euclidean Norm Minus One g (ENMO), Low-pass filtered ENMO (LFENMO), Mean Amplitude Deviation (MAD) and ActiGraph activity counts over 5-second epochs from the raw accelerations. Metric values were compared using a correlation analysis, and by plotting the differences by time of the day. Cut points for the dominant wrist were derived using Lin’s concordance correlation coefficient optimization in a grid of possible thresholds, using the non-dominant wrist estimates as reference. They were cross-validated in a separate sample (N = 36, 10 women, 22–30 years). Shared variances between pairs of acceleration metrics varied across sites and metric pairs (range in r2: 0.19–0.97, all p < 0.01), suggesting that some sites and metrics are associated, and others are not. We observed higher metric values in dominant vs. non-dominant wrist, thus, we developed cut points for dominant wrist based on ENMO to classify sedentary time (<50 mg), light PA (50–110 mg), moderate PA (110–440 mg) and vigorous PA (≥440 mg). Our findings suggest differences between dominant and non-dominant wrist, and we proposed new cut points to attenuate these differences. ENMO and LFENMO were the most similar metrics, and they showed good comparability with MAD. However, counts were not comparable with ENMO, LFENMO and MAD.

Quality over quantity? Association of skeletal muscle myosteatosis and myofibrosis on physical function in chronic kidney disease.

Abstract: Background Chronic kidney disease (CKD) is characterized by adverse changes in body composition, which are associated with poor clinical outcome and physical functioning. Whilst size is the key for muscle functioning, changes in muscle quality specifically increase in intramuscular fat infiltration (myosteatosis) and fibrosis (myofibrosis) may be important. We investigated the role of muscle quality and size on physical performance in non-dialysis CKD patients. Methods Ultrasound (US) images of the rectus femoris (RF) were obtained. Muscle quality was assessed using echo intensity (EI), and qualitatively using Heckmatt's visual rating scale. Muscle size was obtained from RF cross-sectional area (RF-CSA). Physical function was measured by the sit-to-stand-60s (STS-60) test, incremental (ISWT) and endurance shuttle walk tests, lower limb and handgrip strength, exercise capacity (VO2peak) and gait speed. Results A total of 61 patients (58.5 ± 14.9 years, 46% female, estimated glomerular filtration rate 31.1 ± 20.2 mL/min/1.73 m2) were recruited. Lower EI (i.e. higher muscle quality) was significantly associated with better physical performance [STS-60 (r = 0.363) and ISWT (r = 0.320)], and greater VO2peak (r = 0.439). The qualitative rating was closely associated with EI values, and significant differences in function were seen between the ratings. RF-CSA was a better predictor of performance than muscle quality. Conclusions In CKD, increased US-derived EI was negatively correlated with physical performance; however, muscle size remains the largest predictor of physical function. Therefore, in addition to the loss of muscle size, muscle quality should be considered an important factor that may contribute to deficits in mobility and function in CKD. Interventions such as exercise could improve both of these factors.

Aspirin has potential benefits for primary prevention of cardiovascular outcomes in diabetes: updated literature-based and individual participant data meta-analyses of randomized controlled trials.

Abstract: The clinical benefit of aspirin for the primary prevention of cardiovascular disease (CVD) in diabetes remains uncertain. To evaluate the efficacy and safety of aspirin for the primary prevention of cardiovascular outcomes and all-cause mortality events in people with diabetes, we conducted an updated meta-analysis of published randomised controlled trials (RCTs) and a pooled analysis of individual participant data (IPD) from three trials. Randomised controlled trials of aspirin compared with placebo (or no treatment) in participants with diabetes with no known CVD were identified from MEDLINE, Embase, Cochrane Library, and manual search of bibliographies to January 2019. Relative risks with 95% confidence intervals were used as the summary measures of associations. We included 12 RCTs based on 34,227 participants with a median treatment duration of 5.0 years. Comparing aspirin use with no aspirin, there was a significant reduction in risk of major adverse cardiovascular events (MACE)0.89 (0.83–0.95), with a number needed to treat (NNT)of 95 (95% CI 61 to 208) to prevent one MACE over 5 years average follow-up. Evidence was lacking of heterogeneity and publication bias among contributing trials for MACE. Aspirin use had no effect on other endpoints including all-cause mortality; however, there was a significant reduction in stroke for aspirin dosage ≤ 100 mg/day 0.75 (0.59–0.95). There were no significant effects of aspirin use on major bleeding and other bleeding events, though some of the estimates were imprecise. Pooled IPD from the three trials (2306 participants) showed no significant evidence of an effect of aspirin on any of the outcomes evaluated; however, aspirin reduced the risk of MACE in non-smokers 0.70 (0.51–0.96) with a NNT of 33 (95% CI 20 to 246) to prevent one MACE. Aspirin has potential benefits in cardiovascular primary prevention in diabetes. The use of low dose aspirin may need to be individualised and based on each individual’s baseline CVD and bleeding risk. Systematic review registration PROSPERO: CRD42019122326

Enhancing the value of accelerometer-assessed physical activity: meaningful visual comparisons of data-driven translational accelerometer metrics.

Abstract: The lack of consensus on meaningful and interpretable physical activity outcomes from accelerometer data hampers comparison across studies. Cut-point analyses are simple to apply and easy to interpret but can lead to results that are not comparable. We propose that the optimal accelerometer metrics for data analysis are not the same as the optimal metrics for translation. Ideally, analytical metrics are precise continuous variables that cover the intensity spectrum, while translational metrics facilitate meaningful, public-health messages and can be described in terms of activities (e.g. brisk walking) or intensity (e.g. moderate-to-vigorous physical activity). Two analytical metrics that capture the volume and intensity of the 24-h activity profile are average acceleration (volume) and intensity gradient (intensity distribution). These allow investigation of independent, additive and interactive associations of volume and intensity of activity with health; however, they are not immediately interpretable. The MX metrics, the acceleration above which the most active X minutes are accumulated, are translational metrics that can be interpreted in terms of indicative activities. Using a range of MX metrics illustrates the intensity gradient and average acceleration (i.e. 24-h activity profile). The M120, M60, M30, M15 and M5 illustrate the most active accumulated minutes of the day, the M1/3DAY the most active accumulated 8 h of the day. We demonstrate how radar plots of MX metrics can be used to interpret and translate results from between- and within-group comparisons, provide information on meeting guidelines, assess individual activity profiles relative to percentiles and compare activity profiles between domains and/or time periods.

Reproducibility of the Oxford classification of immunoglobulin A nephropathy, impact of biopsy scoring on treatment allocation and clinical relevance of disagreements: evidence from the VALidation of IGA study cohort.

Abstract: Background The VALidation of IGA (VALIGA) study investigated the utility of the Oxford Classification of immunoglobulin A nephropathy (IgAN) in 1147 patients from 13 European countries. Methods. Biopsies were scored by local pathologists followed by central review in Oxford. We had two distinct objectives: to assess how closely pathology findings were associated with the decision to give corticosteroid/immunosuppressive (CS/IS) treatments, and to determine the impact of differences in MEST-C scoring between central and local pathologists on the clinical value of the Oxford Classification. We tested for each lesion the associations between the type of agreement (local and central pathologists scoring absent, local present and central absent, local absent and central present, both scoring present) with the initial clinical assessment, as well as long-term outcomes in those patients who did not receive CS/IS. Results All glomerular lesions (M, E, C and S) assessed by local pathologists were independently associated with the decision to administer CS/IS therapy, while the severity of tubulointerstitial lesions was not. Reproducibility between local and central pathologists was moderate for S (segmental sclerosis) and T (tubular atrophy/interstitial fibrosis), and poor for M (mesangial hypercellularity), E (endocapillary hypercellularity) and C (crescents). Local pathologists found statistically more of each lesion, except for the S lesion, which was more frequent with central review. Disagreements were more likely to occur when the proportion of glomeruli affected was low. The M lesion, assessed by central pathologists, correlated better with the severity of the disease at presentation and discriminated better with outcomes. In contrast, the E lesion, evaluated by local pathologists, correlated better with the clinical presentation and outcomes when compared with central review. Both C and S lesions, when discordant between local and central pathologists, had a clinical phenotype intermediate to double absent lesions (milder disease) and double present (more severe). Conclusion We conclude that differences in the scoring of MEST-C criteria between local pathologists and a central reviewer have a significant impact on the prognostic value of the Oxford Classification. Since the decision to offer immunosuppressive therapy in this cohort was intimately associated with the MEST-C score, this study indicates a need for a more detailed guidance for pathologists in the scoring of IgAN biopsies.

Improving the effectiveness of cancer multidisciplinary team meetings: analysis of a national survey of MDT members’ opinions about streamlining patient discussions

Abstract: Background Cancer is diagnosed and managed by multidisciplinary teams (MDTs) in the UK and worldwide, these teams meet regularly in MDT meetings (MDMs) to discuss individual patient treatment options. Rising cancer incidence and increasing case complexity have increased pressure on MDMs. Streamlining discussions has been suggested as a way to enhance efficiency and to ensure high-quality discussion of complex cases. Methods Secondary analysis of quantitative and qualitative data from a national survey of 1220 MDT members regarding their views about streamlining MDM discussions. Results The majority of participants agreed that streamlining discussions may be beneficial although variable interpretations of ‘streamlining’ were apparent. Agreement levels varied significantly by tumour type and occupational group. The main reason for opposing streamlining were concerns about the possible impact on the quality and safety of patient care. Participants suggested a range of alternative approaches for improving efficiency in MDMs in addition to the use of treatment protocols and pre-MDT meetings. Conclusions This work complements previous analyses in supporting the development of tumour-specific guidance for streamlining MDM discussions considering a range of approaches. The information provided about the variation in opinions between MDT for different tumour types will inform the development of these guidelines. The evidence for variation in opinions between those in different occupational groups and the reasons underlying these opinions will facilitate their implementation. The impact of any changes in MDM practices on the quality and safety of patient care requires evaluation.

Average acceleration and intensity gradient of primary school children and associations with indicators of health and well-being.

Abstract: Average acceleration (AvAcc) and intensity gradient (IG) have been proposed as standardised metrics describing physical activity (PA) volume and intensity, respectively. We examined hypothesised be...

Activity Intensity, Volume, and Norms: Utility and Interpretation of Accelerometer Metrics

Abstract: PURPOSE: The physical activity profile can be described from accelerometer data using two population-independent metrics: average acceleration (ACC, volume) and intensity gradient (IG, intensity). This article aims 1) to demonstrate how these metrics can be used to investigate the relative contributions of volume and intensity of physical activity for a range of health markers across data sets and 2) to illustrate the future potential of the metrics for generation of age and sex-specific percentile norms. METHODS: Secondary data analyses were conducted on five diverse data sets using wrist-worn accelerometers (ActiGraph/GENEActiv/Axivity): children (n = 145), adolescent girls (n = 1669), office workers (n = 114), premenopausal (n = 1218) and postmenopausal (n = 1316) women, and adults with type 2 diabetes (n = 475). Open-source software (GGIR) was used to generate ACC and IG. Health markers were (a) zBMI (children), (b) ut (adolescent girls and adults), (c) bone health (pre- and postmenopausal women), and (d) physical function (adults with type 2 diabetes). RESULTS: Multiple regression analyses showed that IG, but not ACC, was independently associated with zBMI/ut in children and adolescents. In adults, associations were stronger and the effects of ACC and IG were additive. For bone health and physical function, interactions showed associations were strongest if IG was high, largely irrespective of ACC. Exemplar illustrative percentile "norms" showed the expected age-related decline in physical activity, with greater drops in IG across age than ACC. CONCLUSION: The ACC and the IG accelerometer metrics facilitate the investigation of whether volume and intensity of physical activity have independent, additive, or interactive effects on health markers. In future studies, the adoption of data-driven metrics would facilitate the generation of age- and sex-specific norms that would be beneficial to researchers.

Longitudinal Trends in Quality of Life and Physical Function in Frail Older Dialysis Patients: A Comparison of Assisted Peritoneal Dialysis and In-Center Hemodialysis

Abstract: BackgroundIn-center hemodialysis (HD) has been the standard treatment for older dialysis patients, but reports suggest an associated decline in physical and cognitive function. Cross-sectional data...

Meta-analysis of the influence of lifestyle changes for preoperative weight loss on surgical outcomes

Abstract: BACKGROUND: The aim was to investigate whether preoperative weight loss results in improved clinical outcomes in surgical patients with clinically significant obesity. METHODS: This was a systematic review and aggregate data meta-analysis of RCTs and cohort studies. PubMed, MEDLINE, Embase and CINAHL Plus databases were searched from inception to February 2018. Eligibility criteria were: studies assessing the effect of weight loss interventions (low-energy diets with or without an exercise component) on clinical outcomes in patients undergoing any surgical procedure. Data on 30-day or all-cause in-hospital mortality were extracted and synthesized in meta-analyses. Postoperative thromboembolic complications, duration of surgery, infection and duration of hospital stay were also assessed. RESULTS: A total of 6060 patients in four RCTs and 12 cohort studies, all from European and North American centres, were identified. Most were in the field of bariatric surgery and all had some methodological limitations. The pooled effect estimate suggested that preoperative weight loss programmes were effective, leading to significant weight reduction compared with controls: mean difference -7·42 (95 per cent c.i. -10·09 to -4·74) kg (P < 0·001). Preoperative weight loss interventions were not associated with a reduction in perioperative mortality (odds ratio 1·41, 95 per cent c.i. 0·24 to 8·40; I2 = 0 per cent, P = 0·66) but the event rate was low. The weight loss groups had shorter hospital stay (by 27 per cent). No differences were found for morbidity. CONCLUSION: This limited preoperative weight loss has advantages but may not alter the postoperative morbidity or mortality risk.

Cardiovascular efficacy and safety of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: a systematic review and network meta-analysis.

Abstract: AIMS To compare the cardiovascular efficacy and safety of sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adults with Type 2 diabetes. METHODS Electronic databases were searched from inception to 22 October 2018 for randomized controlled trials designed to assess the cardiovascular efficacy of SGLT2 inhibitors or GLP-1RAs with regard to a three-point composite measure of major adverse cardiovascular events (non-fatal stroke, non-fatal myocardial infarction and cardiovascular mortality). Cardiovascular and safety data were synthesized using Bayesian network meta-analyses. RESULTS Eight trials, including 60 082 participants, were deemed eligible for the network meta-analysis. Both SGLT2 inhibitors [hazard ratio 0.86 (95% credible interval 0.74, 1.01]) and GLP-1RAs [hazard ratio 0.88 (95% credible interval 0.78, 0.98)] reduced the three-point composite measure compared to placebo, with no evidence of differences between them [GLP-1RAs vs SGLT2 inhibitors: hazard ratio 1.02 (95% credible interval 0.83, 1.23)]. SGLT2 inhibitors reduced risk of hospital admission for heart failure compared to placebo [hazard ratio 0.67 (95% credible interval 0.53, 0.85)] and GLP-1RAs [hazard ratio 0.71 (95% credible interval 0.53, 0.93)]. No differences were found between the two drug classes in non-fatal stroke, non-fatal myocardial infarction, cardiovascular mortality, all-cause mortality or safety outcomes. CONCLUSIONS SGLT2 inhibitors and GLP-1RAs reduced the three-point major adverse cardiovascular event risk compared to placebo, with no differences between them. Compared with GLP-1RAs and placebo, SGLT2 inhibitors led to a larger reduction in hospital admission for heart failure risk.

Quality of life with conservative care compared with assisted peritoneal dialysis and haemodialysis.

Abstract: Background There is little information about quality of life (QoL) for patients with end-stage kidney disease (ESKD) choosing conservative kidney management (CKM) The Frail and Elderly Patients on Dialysis (FEPOD) study demonstrated that frailty was associated with poorer QoL outcomes with little difference between dialysis modalities [assisted peritoneal dialysis (aPD) or haemodialysis (HD)] We therefore extended the FEPOD study to include CKM patients with estimated glomerular filtration rate ≤10 mL/min/173 m2 (ie individuals with ESKD otherwise likely to be managed with dialysis) Methods CKM patients were propensity matched to HD and aPD patients by age, gender, ethnicity, diabetes status and index of deprivation QoL outcomes measured were Short Form-12 (SF12), Hospital Anxiety and Depression Scale depression score, symptom score, Illness Intrusiveness Rating Scale (IIRS) and Renal Treatment Satisfaction Questionnaire Frailty was assessed using the Clinical Frailty Scale Generalized linear modelling was used to assess the impact of treatment modality on QoL outcomes, adjusting for baseline characteristics Results In total, 84 (28 CKM, 28 HD and 28 PD) patients were included Median age for the cohort was 82 (79-88) years Compared with CKM, aPD was associated with higher SF12 physical component score (PCS) [Exp B (95% confidence interval) = 120 (100-145), P < 005] and lower symptom score [Exp B = 062 (043-090), P = 001]; depression score was lower in HD compared with CKM [Exp B = 070 (052-092), P = 001] Worsening frailty was associated with higher depression scores [Exp B = 259 (145-462), P < 001], IIRS [Exp B = 120 (112-128), P < 001] and lower SF12 PCS [Exp B = 087 (083-093), P < 001] Conclusion Treatment by dialysis, both with aPD and HD, improved some QoL measures Overall, aPD was equal to or slightly better than the other modalities in this elderly population However, as in the primary FEPOD study, frailty was associated with worse QoL measures irrespective of CKD modality These findings highlight the need for an individualized approach to the management of ESKD in older people

The Duke treadmill score with bicycle ergometer: Exercise capacity is the most important predictor of cardiovascular mortality.

Abstract: BackgroundThe Duke treadmill score, a widely used treadmill testing tool, is a weighted index combining exercise time or capacity, maximum ST-segment deviation and exercise-induced angina. No previ...

Therapeutic Inertia and the Legacy of Dysglycemia on the Microvascular and Macrovascular Complications of Diabetes

Abstract: Type 2 diabetes is characterized by a continuous decline in β‐cell function with the resultant progressive loss of glycemic control over time (1). The hyperglycemic burden is associated with longer-term microvascular and macrovascular complications. Early diagnosis and intensive glycemic control has conclusively demonstrated a reduction in microvascular complications (2,3) and possibly macrovascular complications over a long period of observation (4), the so-called legacy effect (5). Even though there have been improvements in survival from cardiovascular disease in the general population, people with type 2 diabetes remain at increased risk of cardiovascular mortality compared with matched population control subjects (6). A very high proportion of patients fail to reach the recommended glycemic targets for a considerable period of time after the diagnosis of diabetes (7–9), thus leading to the complications. Guidelines for the treatment of patients with type 2 diabetes suggest that tight glycemic control (defined as glycated hemoglobin [HbA1c] <7.0% [53 mmol/mol]) should be maintained from diagnosis through active titration of combinations of antihyperglycemic medications and lifestyle modification, as appropriate (10). Modeling studies suggest that when this is done through an individualized approach, it leads to reduced costs and increased quality of life (11). Besides patient-level characteristics such as multimorbidity and poor adherence to treatment recommendations, clinical inertia has been suggested as one key reason for not achieving glucose targets. The term “clinical inertia” in most instances has been used in relation to failure to advance therapy when appropriate to do so (12). However, the definition of therapeutic inertia is now also accepted to reflect the failure to de-intensify treatment when appropriate to do so (12). A number of studies have shown that therapeutic inertia is associated with worse microvascular and macrovascular outcomes. In a cohort study of 105,477 patients, mean HbA1c …

Can activity monitors predict outcomes in patients with heart failure? A systematic review

Abstract: Actigraphy is increasingly incorporated into clinical practice to monitor intervention effectiveness and patient health in congestive heart failure (CHF). We explored the prognostic impact of actigraphy-quantified physical activity (AQPA) on CHF outcomes. PubMed and Medline databases were systematically searched for cross-sectional studies, cohort studies or randomised controlled trials from January 2007 to December 2017. We included studies that used validated actigraphs to predict outcomes in adult HF patients. Study selection and data extraction were performed by two independent reviewers. A total of 17 studies (15 cohort, 1 cross-sectional, 1 randomised controlled trial) were included, reporting on 2,759 CHF patients (22-89 years, 27.7% female). Overall, AQPA showed a strong inverse relationship with mortality and predictive utility when combined with established risk scores, and prognostic roles in morbidity, predicting cognitive function, New York Heart Association functional class and intercurrent events (e.g. hospitalisation), but weak relationships with health-related quality of life scores. Studies lacked consensus regarding device choice, time points and thresholds of PA measurement, which rendered quantitative comparisons between studies difficult. AQPA has a strong prognostic role in CHF. Multiple sampling time points would allow calculation of AQPA changes for incorporation into risk models. Consensus is needed regarding device choice and AQPA thresholds, while data management strategies are required to fully utilise generated data. Big data and machine learning strategies will potentially yield better predictive value of AQPA in CHF patients.