HbA1c variability is independently associated with progression of diabetic kidney disease in an urban multi-ethnic cohort of people with type 1 diabetes.

AIMS/HYPOTHESIS: The role of HbA1c variability in the progression of diabetic kidney disease is unclear, with most studies to date performed in White populations and limited data on its role in predicting advanced kidney outcomes. Our aim was to evaluate if long-term intra-individual HbA1c variability is a risk factor for kidney disease progression (defined as an eGFR decline of ≥50% from baseline with a final eGFR of <30 ml/min per 1.73 m2) in an ethnically heterogeneous cohort of people with type 1 diabetes with a preserved eGFR ≥45 ml/min per 1.73 m2 at baseline. METHODS: Electronic health record data from people attending outpatient clinics between 2004 and 2018 in two large university hospitals in London were collected. HbA1c variability was assessed using three distinct methods: (1) SD of HbA1c (SD-HbA1c); (2) visit-adjusted SD (adj-HbA1c): SD-HbA1c/√n/(n-1), where n is the number of HbA1c measurements per participant; and (3) CV (CV-HbA1c): SD-HbA1c/mean-HbA1c. All participants had six or more follow-up HbA1c measurements. The eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration equation and clinical/biochemical results from routine care were extracted from electronic health records. RESULTS: In total, 3466 participants (50% female, 78% White, 13% African Caribbean, 3% Asian and 6% of mixed heritage or self-reporting as 'other') were followed for a median (IQR) of 8.2 (4.2-11.6) years. Of this cohort, 249 (7%) showed kidney disease progression. Higher HbA1c variability was independently associated with a higher risk of kidney disease progression, with HRs (95% CIs) of 7.76 (4.54, 13.26), 2.62 (1.75, 3.94) and 5.46 (3.40, 8.79) (lowest vs highest HbA1c variability quartile) for methods 1-3, respectively. Increasing age, baseline HbA1c, systolic BP and urinary albumin/creatinine ratio were also associated with kidney disease progression (p<0.05 for all). African Caribbean ethnicity was associated with an increased risk of kidney disease progression (HR [95% CI] 1.47 [1.09, 1.98], 1.76 [1.32, 2.36] and 1.57 [1.17, 2.12] for methods 1-3, respectively) and this effect was independent of glycaemic variability and other traditional risk factors. CONCLUSIONS/INTERPRETATION: We observed an independent association between HbA1c variability, evaluated using three distinct methods, and significant kidney disease progression in a multi-ethnic type 1 diabetes cohort. Further studies are needed to elucidate the mechanisms that may explain our results and evaluate if HbA1c variability is a modifiable risk factor for preventing diabetic kidney disease progression.

Determinants of lipid clinic referral and attendance in a multi-ethnic adult population in south London: a cross-sectional study.

BACKGROUND: Primary dyslipidaemias, including familial hypercholesterolaemia, are underdiagnosed genetic disorders that substantially increase risk for premature coronary artery disease in adults. Early identification of primary dyslipidaemias via lipid clinic referral optimises patient management and enables cascade screening of relatives. Improving the identification of primary dyslipidaemias, and understanding disparities in ascertainment and management, is an NHS priority. We aimed to assess determinants of lipid clinic referral or attendance (LCR) in ethnically diverse adults. METHODS: We did a retrospective cross-sectional study using the Lambeth DataNet containing anonymised data from 41 general practitioner (GP) practices in south London. We looked at referral data for adult patients aged 18 years and older from Jan 1, 1995, until May 14, 2018. LCR was the main outcome. We used sequential multilevel logistic regression models adjusted for practice effects to estimate the odds of LCR assessed across six ethnic groups (reference group White) and patient-level factors (demographic, socioeconomic, lifestyle, comorbidities, total cholesterol [TC] >7·5mmol/L, statin prescription, and practice factors). The study was approved by NHS South East London Clinical Commissioning Group (CCG) and NHS Lambeth CCG. FINDINGS: 780 (0·23%) of 332 357 adult patients were coded as referred (n=538) or seen (n=252) in a lipid clinic. 164 487 (46·49%) were women (appendix). The fully adjusted model for odds of LCR showed the following significant associations for age (odds ratio [OR] 0·96, 95% CI 0·96-0·97, p<0·001); Black, African, Caribbean, or Black-British ethnicity (0·67, 0·53-0·84, p=0·001); ex-smoker status (1·29, 1·05-1·57, p=0·014); TC higher than 7·5 mmol/L (12·18, 9·60-15·45, p<0·001); statin prescription (14·01, 10·85-18·10, p<0·001); diabetes (0·72, 0·58-0·91, p=0·005); high-frequency GP attendance at seven or more GP consultations in the past year (1·49, 1·21-1·84, p<0·001); high GP-density (0·5-0·99 full-time equivalent GPs per 1000 patients; 2·70, 1·23-5·92, p=0·013). Sensitivity analyses for LCR restricted to familial hypercholesterolaemia-coded patients (n=581) found associations with TC higher than 7·5 mmol/L (4·26, 1·89-9·62, p<0·001), statin prescription (16·96, 2·19-131·36, p=0·007), and high GP-density (5·73, 1·27-25·93, p=0·023), with no significant associations with ethnicity. The relative contribution of GP practices to LCR was 6·32% of the total variance. There were no significant interactions between ethnicity and deprivation, age, or obesity. INTERPRETATION: While interpretation is limited by the accuracy and completeness of coded records, the study showed factors associated with a higher likelihood of LCR included individuals recorded as having TC higher than 7·5 mmol/L, statin prescription, ex-smoker status, high-frequency GP attendance, and registration at a GP practice with 0·5-0·99 GP density. Patients with increasing age; Black, African, Caribbean, or Black-British ethnicity patients; and patients with diabetes had lower odds of LCR. Finally, the difference in odds of LCR between Black and White patients highlights potential health inequalities. FUNDING: NHS Race & Health Observatory.

Factors affecting the delivery of community-based salon interventions to prevent cardiovascular disease and breast cancer among ethnically diverse women in South London: a concept-mapping approach.

BACKGROUND: In the UK, women from ethnically diverse and socioeconomically deprived communities are at increased risk of underdiagnosis of cardiovascular disease (CVD) and breast cancer. Promoting CVD prevention and awareness of breast cancer screening via community salons and primary health care partnerships can improve uptake of screening services and early detection. METHODS: Concept mapping is a multistage mixed methods participatory approach comprised of six stages: preparation, brainstorming, structuring of statements, representing statements, interpretation and utilisation of maps using Group wisdom software. A target of 20 salons, excluding male-only salons were approached. Salons included Salons included hairdressing or hairdressing and beauty salons. Purposeful and convenience sampling (online and face to face) among UK salons (hair and beauty) was conducted. Participants were given a focus prompt "What would be some factors that can influence the ability of salons to deliver this service?" and required to generate statements, which were sorted into categories based on similarity and rated for importance and feasibility. Concept maps using multidimensional scaling and hierarchical cluster analyses were produced. FINDINGS: Of 35 participants invited, 25 (71%) consented and agreed to take part in concept mapping. Reported ages were 26-35 years (n=5, 20%), 36-45 years (n=12, 48%), 46-55 years (n=3, 12%), 56-65 years (n=5, 20%), and no age reported (n=10, 40%). Around 36% (n=9) of participants were from non-White ethnic groups, with 12% (n=3) being male and 88% (n=22) female. Seven clusters emerged. Salon staff capabilities and capacities and engaging in health conversations in community salons scored average bridging values of 0·09 and 0·2 respectively, indicating good cluster homogeneity (similar meaning statements were closely sorted). Facilitating health-care access with GP practices was rated highly important to effectively promote the intervention. Engaging in health conversations in community salons and salon incentives for participation were examples of factors that were highly feasible to address. The r correlation coefficient was 0·68 between importance and feasibility to address factors affecting community health interventions. INTERPRETATION: Salons are well positioned to support health promotion interventions. Actionable priorities were identified for a salon-GP surgery partnership to promote CVD prevention through lifestyle changes and health check uptake, raising breast cancer screening awareness and address issue of equity. FUNDING: National Institute of Health and Care Research (NIHR), Research for Patient Benefit (RfPB) Programme NIHR202769.

Protocol for the STEADY intervention for type 1 diabetes and disordered eating: Safe management of people with Type 1 diabetes and EAting Disorders studY.

This paper describes the protocol to test the feasibility of the Safe management of people with Type 1 diabetes and EAting Disorders studY (STEADY) intervention. STEADY is a novel complex intervention for people with type 1 diabetes and disordered eating (T1DE) of mild to moderate severity. The STEADY intervention integrates cognitive behavioural therapy (CBT) with diabetes education, and was developed using Experience-Based Co-Design. METHODS: The feasibility of STEADY will be tested using a randomised controlled feasibility trial. Forty adults with T1DE will be recruited and randomised into the STEADY intervention or treatment as usual control group. We will collect demographic, biomedical and psychometric data, routine glucose metrics and conduct the Structured Clinical Interview for DSM-5. Participants randomised to the STEADY intervention will receive 12 STEADY therapy sessions with a diabetes specialist nurse trained in CBT, delivered via videoconference and an optional smartphone app. The main outcome at 6 months will be the feasibility of STEADY (recruitment, dropout rates, feasibility of delivery). The secondary outcomes are biomedical (HbA1c and glucose time in range) and psychological (person-reported outcome measures in disordered eating, diabetes distress, depression and anxiety). A process evaluation will evaluate the fidelity, feasibility, acceptability and appropriateness of STEADY, and participant experiences. ETHICS AND DISSEMINATION: The protocol was approved by the East of England-Essex Research Ethics Committee (21/EE/0235). Study findings will be shared with study participants and disseminated through peer-reviewed publications and conference presentations.

Effect of active vitamin-D on left ventricular mass index: Results of a randomized controlled trial in type 2 diabetes and chronic kidney disease.

BACKGROUND: Active vitamin-D deficiency is a potential modifiable risk factor for increased ventricular mass. We explored the effects of active vitamin-D (calcitriol) treatment on left ventricular mass in patients with type-2 diabetes (T2D) and chronic kidney disease (CKD). METHODS: We performed a 48-week duration single center randomized double-blind parallel group trial examining the impact of calcitriol, 0.5 mcg once daily, as compared to placebo on a primary endpoint of change from baseline in left ventricular mass index (LVMI) measured by magnetic resonance imaging . Patients with T2D, CKD stage-3 and raised left ventricular mass on stable renin angiotensin aldosterone system blockade, who all had elevated intact parathyroid hormone were eligible. Secondary endpoints included interstitial myocardial fibrosis, assessed with cardiac magnetic resonance imaging. In total, 45 (male 73%) patients with T2D and stage-3 CKD were studied (calcitriol n = 19, placebo n = 26). RESULTS: Following 48-weeks calcitriol treatment, the median difference and the (95% CI) of LVMI between the 2 treatment arms was 1.84 (-1.28, 4.96), similar between the 2 groups studied. Intact parathyroid hormone fell only in the calcitriol group from 142 pg/mL (80-293) to 76 pg/mL (41-204)(median, interquartile range, P= .04). No significant differences were observed in interstitial myocardial fibrosis or other secondary endpoints. CONCLUSIONS: The study did not provide evidence that treatment with calcitriol as compared to placebo might improve LVMI in patients with T2D, mild left ventricular hypertrophy and stable CKD. Our data does not support the routine use of active vitamin-D for LVMI regression and cardiovascular protection in patients with T2D and stage-3 CKD.

Effect of calcitriol treatment on arterial stiffness in people with type 2 diabetes and stage 3 chronic kidney disease.

AIMS: Active vitamin D deficiency is associated with increased aortic-pulse wave velocity (Ao-PWV) in people with type 2 diabetes (T2DM) and chronic kidney disease (CKD). There are no randomised controlled trials investigating the effect of active vitamin D treatment on Ao-PWV in people with T2DM and CKD. METHODS: A 48-week duration single-centre randomised double-blind parallel-group trial examined the impact of oral 1,25 dihydroxyvitamin D (calcitriol 0.25 mcg OD) as compared to placebo on a primary endpoint of Ao-PWV. People with T2DM and stable stage 3 CKD with intact parathyroid hormone (iPTH) level >30 pg/mL were eligible. RESULTS: In total, 127 (70% male) people were randomised (calcitriol n = 64 or placebo n = 63). There was no change in Ao-PWV observed, mean ± standard deviation (SD), in the calcitriol group of 11.79 (±2.5) to 12.08 (3.0) m/s as compared to 10.90 (±2.4) to 11.39 (±2.6) m/s with placebo. The between-treatment group adjusted mean (95% confidence interval [(CI]] change was 0.23 (-0.58 to 1.05) m/s, P = .57. No effect of calcitriol was observed on central arterial pressures, albuminuria, serum calcium or phosphate levels. However, iPTH fell with calcitriol treatment (mean [95% CI] between-group difference of -27.8 (-42.3 to -13.2) pg/mL, P < .001. CONCLUSION: In T2DM and stage 3 CKD, calcitriol as compared to placebo does not improve Ao-PWV or other markers of arterial stiffness. Our study does not provide evidence for the use of active vitamin D for improving arterial stiffness in T2DM with stage 3 CKD.

The psychometric properties of PSYCHLOPS, an individualized patient-reported outcome measure of personal distress.

OBJECTIVE: Few studies report the psychometric properties of individualized patient-reported outcome measures (I-PROMs) combining traditional analysis and Item Response Theory (IRT). METHODS: Pre- and posttreatment PSYCHLOPS data derived from six clinical samples (n = 939) were analyzed for validity, reliability, and responsiveness; caseness cutoffs and reliable change index were calculated. Exploratory and confirmatory factor analyses were used to determine whether items represented a unidimensional construct; IRT examined item properties of this construct. RESULTS: Values for internal consistency, construct validity, convergent and discriminant validity, and structural validity were satisfactory. Responsiveness was high: Cohen's d, 1.48. Caseness cutoff and reliable clinical change scores were 6.41 and 4.63, respectively. IRT analysis confirmed that item scores possess strong properties in assessing the underlying trait measured by PSYCHLOPS. CONCLUSION: PSYCHLOPS met the criteria for norm-referenced measurement of patient psychological distress. PSYCHLOPS functioned as a measure of a single latent trait, which we describe as "personal distress."

Idiographic patient reported outcome measures (I-PROMs) for routine outcome monitoring in psychological therapies: Position paper.

Idiographic patient-reported outcome measures (I-PROMs) are a growing set of individualized tools for use in routine outcome monitoring (ROM) in psychological therapies. This paper presents a position statement on their conceptualization, use, and analysis, based on contemporary evidence and clinical practice. Four problem-based, and seven goal-based, I-PROMs, with some evidence of psychometric evaluation and use in psychotherapy, were identified. I-PROMs may be particularly valuable to the evaluation of psychological therapies because of their clinical utility and their alignment with a patient-centered approach. However, there are several challenges for I-PROMs: how to generate items in a robust manner, their measurement model, methods for establishing their reliability and validity, and the meaning of an aggregated I-PROM score. Based on the current state of the literature, we recommend that I-PROMs are used to complement nomothetic measures. Research recommendations are also made regarding the most appropriate methods for analyzing I-PROM data.

Trends in COVID-19-related in-hospital mortality in women and men.

INTRODUCTION: Whether political, scientific and medical development in a country is associated with better clinical results according to gender in patients with COVID-19 has not yet been clearly elucidated. OBJECTIVE: To determine the trends of COVID-19-related in-hospital mortality in women and men from March 2020 to February 2022. METHODS: Clinical data of all patients with COVID-19 cared for at 21 Spanish hospitals were used, both of those who were discharged and of those who died during hospitalization. The association between hospital length of stay and mortality was analyzed with logistic regression models. RESULTS: Out of 7,974 patients that were included, 3,234 were women; 928 patients died. A significant decreasing trend in mortality was identified. When the analysis was carried out by gender, no significant mortality trend was found in women (OR = 0.96 [0.90-1.03], p = 0.239), while in men there was a significant decreasing trend identified (OR = 0.87 [0.82-0.92], p < 0.001). CONCLUSION: Health policies, together with clinical and preventive interventions, may explain these results. Response to treatment and behavioral differences may explain why mortality does not decrease for women.

INTRODUCCIÓN: Todavía no se comprende si el desarrollo político, científico y médico en un país se asocia a mejores resultados clínicos de los pacientes con COVID-19 según el sexo. OBJETIVO: Determinar las tendencias de mortalidad hospitalaria asociada a COVID-19 en mujeres y hombres entre marzo de 2020 y febrero de 2022. MÉTODOS: Se utilizaron los datos clínicos de todos los pacientes con COVID-19 atendidos en 21 hospitales españoles, tanto de quienes fueron dados de alta como de quienes fallecieron durante el ingreso. La asociación entre la fecha del ingreso y la mortalidad se analizó con modelos de regresión logística. RESULTADOS: Fueron incluidos 7974 pacientes, de los cuales 3234 fueron mujeres y 928 fallecieron. Se encontró una tendencia significativa y decreciente en la mortalidad según avanzaba la fecha del ingreso. Cuando el análisis se realizó por sexos, no se halló una tendencia significativa en las mujeres (RM = 0.96 [0.90-1.03], p = 0.239), pero sí en los hombres (RM = 0.87 [0.82-0.92], p < 0.001). CONCLUSIÓN: Las políticas de salud, junto con las intervenciones clínicas y preventivas, pueden dar cuenta de los resultados. Diferencias en la respuesta al tratamiento o en los comportamientos pueden explicar por qué la mortalidad no disminuye en las mujeres.

Azithromycin in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Azithromycin has been widely used in the management of COVID-19. However, the evidence on its actual effects remains disperse and difficult to apply in clinical settings. This systematic review and meta-analysis summarizes the available evidence to date on the beneficial and adverse effects of azithromycin in patients with COVID-19. METHODS: The PRISMA 2020 statement criteria were followed. Randomized controlled trials (RCTs) and observational studies comparing clinical outcomes of patients treated with and without azithromycin, indexed until 5 July 2021, were searched in PubMed, Embase, The Web of Science, Scopus, The Cochrane Central Register of Controlled Trials and MedRXivs. We used random-effects models to estimate pooled effect size from aggregate data. RESULTS: The initial search produced 4950 results. Finally, 16 studies, 5 RCTs and 11 with an observational design, with a total of 22 984 patients, were included. The meta-analysis showed no difference in mortality for those treated with or without azithromycin, in observational studies [OR: 0.90 (0.66-1.24)], RCTs [OR: 0.97 (0.87-1.08)] and also when both types of studies were pooled together [with an overall OR: 0.95 (0.79-1.13)]. Different individual studies also reported no significant difference for those treated with or without azithromycin in need for hospital admission or time to admission from ambulatory settings, clinical severity, need for intensive care, or adverse effects. CONCLUSIONS: The results presented in this systematic review do not support the use of azithromycin in the management of COVID-19. Future research on treatment for patients with COVID-19 may need to focus on other drugs.

Frailty and perioperative patient-reported disability in patients undergoing cardiac surgery: a pilot study.

BACKGROUND: Preoperative frailty may predispose patients to poorer outcomes in cardiac surgery; however, there are limited data concerning how preoperative frailty predicts patient-centred outcomes, such as patient-reported disability. Our objective was to evaluate the association between preoperative frailty and postoperative disability. METHODS: Patients were prospectively evaluated using the Comprehensive Assessment of Frailty score, separating patients into frail and non-frail cohorts. Disability levels were quantified using the WHO Disability Assessment Schedule (WHODAS) 2.0 in percentage of the maximum disability score, with disability defined as a value ≥25%. RESULTS: Frail patients had increased median [inter-quartile range] disability scores of 31 [16-45]% preoperatively, 29 [9-54]% at 1 month, and 15 [3-31]% at 3 months postoperatively, compared with disability scores in non-frail patients of 10 [5-17]%, 17 [6-29]%, and 2.1 [0-12.0]%, respectively. Preoperative frailty was associated with a reduced likelihood of patients being free of disability and alive at 3 months; adjusted odds ratio 0.51 (for age, European System for Cardiac Operative Risk Evaluation II, and WHODAS 2.0: 12-Part Questionnaire score); P=0.045. The trajectory of disability scores, assessed in percentage change from the preoperative baseline, showed non-frail patients had increased disability burden at 1 month, whereas frail patients had reduced disability burden (+4.2% vs -2.1%; P=0.04). Although the disability burden decreased for both groups at 3 months, this was most marked for frail patients (-6.3% vs -10.4%; P=0.02). CONCLUSIONS: Disability burden in frail patients improves continuously postoperatively, whereas in non-frail patients, it worsens at 1 month before improving at 3 months postoperatively. This positive trajectory of patient-centred outcomes in frail patients should be considered in preoperative decision-making.

The effect of intravenous iron supplementation on exercise capacity in iron-deficient but not anaemic patients with chronic kidney disease: study design and baseline data for a multicentre prospective double-blind randomised controlled trial.

BACKGROUND: Many people living with chronic kidney disease (CKD) are iron deficient, even though they may not be anaemic. The Iron and Muscle study aims to evaluate whether iron supplementation reduces symptoms of fatigue, improves muscle metabolism, and leads to enhanced exercise capacity and physical function. We report here the trial design and baseline characteristics. METHODS: This is a prospective, double-blind multicentre randomised controlled trial (RCT) including 75 non-dialysis stage 3-4 CKD patients with iron deficiency but without anaemia. Patients were randomly (1:1) assigned to either: i) intravenous iron therapy, or ii) placebo, with concurrent recruitment of eight CKD non-iron deficient participants and six healthy volunteers. The primary outcome of the study is the six-minute walk test (6MWT) distance between baseline and four-weeks. An additional exercise training programme for patients in both groups was initiated and completed between 4 and 12 weeks, to determine the effect of iron repletion compared to placebo treatment in the context of patients undertaking an exercise programme. Additional secondary outcomes include fatigue, physical function, muscle strength, muscle metabolism, quality of life, resting blood pressure, clinical chemistry, safety and harms associated with the iron therapy intervention and the exercise training intervention, and hospitalisations. All outcomes were conducted at baseline, 4, and 12 weeks, with a nested qualitative study, to investigate the experience of living with iron deficiency and intervention acceptability. The cohort have been recruited and baseline assessments undertaken. RESULTS: Seventy-five individuals were recruited. 44% of the randomised cohort were male, the mean (SD) age was 58 (14) years, and 56% were White. Body mass index was 31 (7) kg/m2; serum ferritin was 59 (45) µg/L, transferrin saturation was 22 (10) %, and haemoglobin was 125 (12) g/L at randomisation for the whole group. Estimated glomerular filtration rate was 35 (12) mL/min/1.73 m2 and the baseline 6MWT distance was 429 (174) m. CONCLUSION: The results from this study will address a substantial knowledge gap in the effects of intravenous iron therapy, and offer potential clinical treatment options, to improve exercise capacity, physical function, fatigue, and muscle metabolism, for non-dialysis patients with CKD who are iron-deficient but not anaemic. It will also offer insight into the potential novel effects of an 8-week exercise training programme. TRIAL REGISTRATION: EudraCT: 2018-000,144-25 Registered 28/01/2019.

Do changes in outcomes following primary and revision hip replacement differ and relate to markers of socioeconomic status? A 1-year population-based cohort study.

BACKGROUND AND PURPOSE: There is little evidence on improvement after revision total hip replacement (THR). Moreover, improvements may be associated with socioeconomic status (SES). We investigated whether changes in Harris Hip Score (HHS) differ among patients undergoing primary and revision THR, and their association with markers of SES. PATIENTS AND METHODS: We conducted a populationbased cohort study on 16,932 patients undergoing primary and/or revision THR from 1995 to 2018 due to hip osteoarthritis. The patients were identified in the Danish Hip Arthroplasty Registry. Outcome was defined as mean change in HHS (0-100) from baseline to 1-year follow-up, and its association with SES markers (education, cohabiting, and wealth) was analyzed using multiple linear regression adjusting for sex, age, comorbidities, and baseline HHS. RESULTS: At 1-year follow-up, HHS improved clinically relevant for patients undergoing both primary THR: mean 43 (95% CI 43-43) and revision THR: mean 31 (CI 29-33); however, the increase was 12 points (CI 10-14) higher for primary THR. For primary THR, improvements were 0.9 points (CI 0.4-1.5) higher for patients with high educational level compared with low educational level, 0.4 points (CI 0.0-0.8) higher for patients cohabiting compared with living alone, and 2.6 points higher (CI 2.1-3.0) for patients with high wealth compared with low wealth. INTERPRETATION: Patients undergoing primary THR achieve higher improvements on HHS than patients undergoing revision THR, and the improvements are negatively related to markers of low SES. Health professionals should be aware of these characteristics and be able to identify patients who may benefit from extra rehabilitation to improve outcomes after THR to ensure equality in health.

The impact of pharmacological and lifestyle interventions on body weight in people with type 1 diabetes: A systematic review and meta-analysis.

AIM: To systematically review the effects of pharmacological and lifestyle interventions on body weight as a secondary outcome in people with type 1 diabetes. METHODS: The Ovid Medline, Embase and Cochrane Library databases were searched for relevant pharmacological (glucagon-like peptide-1 [GLP-1] receptor agonist, sodium-glucose co-transporter-2 [SGLT-2] inhibitor, dipeptidyl peptidase-4 [DPP-4] inhibitor and metformin) and lifestyle intervention studies (diet and exercise) for adults with type 1 diabetes reporting body weight change and HbA1c published from January 2000 to May 2020. Meta-analyses were performed for 16 randomized controlled trials (RCTs). RESULTS: Thirty-three RCTs (n = 9344 participants), 26 pharmacological (on average 43.9 years, 83.1 kg, HbA1c 8.1%; 55.8% male) and seven lifestyle-based interventions (on average 37.0 years, 85.0 kg, HbA1c 8.1%; 84.6% male), were analysed. The GLP-1 receptor agonist liraglutide 0.6 mg (mean difference [MD]: -2.22 kg [95% CI: -2.55 to -1.90]), 1.2 mg (MD: -3.74 kg [95% CI: -4.16 to -3.33]) and 1.8 mg (MD: -4.85 kg [95% CI: -5.29 to -4.41]), and the SGLT-2 inhibitors empagliflozin 2.5 mg (MD: -1.47 kg [95% CI: -2.23 to -0.71]), 10 mg (MD: -2.77 kg [95% CI: -3.24 to -2.31]) and 25 mg (MD: -3.06 kg [95% CI: -3.57 to -2.55]) and sotagliflozin 200 mg (MD: -2.40 kg [95% CI: -2.87 to -1.94]) and 400 mg (MD: -3.23 [95% CI: -3.73 to -2.72]) were associated with significant reductions in body weight. No significant effect on body weight was found for DPP-4 inhibitors, other GLP-1-receptor agonists, metformin, or for lifestyle interventions (i.e. exercise and diet). CONCLUSIONS: In people with type 1 diabetes, several adjuvant pharmacological interventions showed weight reduction as a secondary outcome. Future studies in overweight people with type 1 diabetes are needed to establish whether the lifestyle and pharmacological interventions reviewed here have potential as components of complex interventions aimed at body weight reduction as a primary outcome.

Risk stratification of patients undergoing transvenous lead extraction with the ELECTRa Registry Outcome Score (EROS): an ESC EHRA EORP European lead extraction ConTRolled ELECTRa registry analysis.

AIMS: Transvenous lead extraction is associated with a significant risk of complications and identifying patients at highest risk pre-procedurally will enable interventions to be planned accordingly. We developed the ELECTRa Registry Outcome Score (EROS) and applied it to the ELECTRa registry to determine if it could appropriately risk-stratify patients. METHODS AND RESULTS: EROS was devised to risk-stratify patients into low risk (EROS 1), intermediate risk (EROS 2), and high risk (EROS 3). This was applied to the ESC EORP European Lead Extraction ConTRolled ELECTRa registry; 57.5% EROS 1, 31.8% EROS 2, and 10.7% EROS 3. Patients with EROS 3 or 2 were significantly more likely to require powered sheaths and a femoral approach to complete procedures. Patients with EROS 3 were more likely to suffer procedure-related major complications including deaths (5.1 vs. 1.3%; P < 0.0001), both intra-procedural (3.5 vs. 0.8%; P = 0.0001) and post-procedural (1.6 vs. 0.5%; P = 0.0192). They were more likely to suffer post-procedural deaths (0.8 vs. 0.2%; P 0.0449), cardiac avulsion or tear (3.8 vs. 0.5%; P < 0.0001), and cardiovascular lesions requiring pericardiocentesis, chest tube, or surgical repair (4.6 vs. 1.0%; P < 0.0001). EROS 3 was associated with procedure-related major complications including deaths [odds ratio (OR) 3.333, 95% confidence interval (CI) 1.879-5.914; P < 0.0001] and all-cause in-hospital major complications including deaths (OR 2.339, 95% CI 1.439-3.803; P = 0.0006). CONCLUSION: EROS successfully identified patients who were at increased risk of significant procedural complications that require urgent surgical intervention.

Discharge after hip fracture surgery by mobilisation timing: secondary analysis of the UK National Hip Fracture Database.

OBJECTIVE: To determine whether mobilisation timing was associated with the cumulative incidence of hospital discharge by 30 days after hip fracture surgery, accounting for potential confounders and the competing risk of in-hospital death. METHOD: We examined data for 135,105 patients 60 years or older who underwent surgery for nonpathological first hip fracture between 1 January 2014 and 31 December 2016 in any hospital in England or Wales. We tested whether the cumulative incidences of discharge differed between those mobilised early (within 36 h of surgery) and those mobilised late, accounting for potential confounders and the competing risk of in-hospital death. RESULTS: A total of 106,722 (79%) of patients first mobilised early. The average rate of discharge was 39.2 (95% CI 38.9-39.5) per 1,000 patient days, varying from 43.1 (95% CI 42.8-43.5) among those who mobilised early to 27.0 (95% CI 26.6-27.5) among those who mobilised late, accounting for the competing risk of death. By 30-day postoperatively, the crude and adjusted odds ratios of discharge were 2.36 (95% CI 2.29-2.43) and 2.08 (95% CI 2.00-2.16), respectively, among those who first mobilised early compared with those who mobilised late, accounting for the competing risk of death. CONCLUSION: Early mobilisation led to a 2-fold increase in the adjusted odds of discharge by 30-day postoperatively. We recommend inclusion of mobilisation within 36 h of surgery as a new UK Best Practice Tariff to help reduce delays to mobilisation currently experienced by one-fifth of patients surgically treated for hip fracture.

Orthopaedic physiotherapists' perceptions of mechanisms for observed variation in the implementation of physiotherapy practices in the early postoperative phase after hip fracture: a UK qualitative study.

OBJECTIVE: to explore physiotherapists' perceptions of mechanisms to explain observed variation in early postoperative practice after hip fracture surgery demonstrated in a national audit. METHODS: a qualitative semi-structured interview study of 21 physiotherapists working on orthopaedic wards at seven hospitals with different durations of physiotherapy during a recent audit. Thematic analysis of interviews drawing on Normalisation Process Theory to aid interpretation of findings. RESULTS: four themes were identified: achieving protocolised and personalised care; patient and carer engagement; multidisciplinary team engagement across the care continuum and strategies for service improvement. Most expressed variation from protocol was legitimate when driven by what is deemed clinically appropriate for a given patient. This tailored approach was deemed essential to optimise patient and carer engagement. Participants reported inconsistent degrees of engagement from the multidisciplinary team attributing this to competing workload priorities, interpreting 'postoperative physiotherapy' as a single professional activity rather than a care delivery approach, plus lack of integration between hospital and community care. All participants recognised changes needed at both structural and process levels to improve their services. CONCLUSION: physiotherapists highlighted an inherent conflict between their intention to deliver protocolised care and allowing for an individual patient-tailored approach. This conflict has implications for how audit results should be interpreted, how future clinical guidelines are written and how physiotherapists are trained. Physiotherapists also described additional factors explaining variation in practice, which may be addressed through increased engagement of the multidisciplinary team and resources for additional staffing and advanced clinical roles.

Discharge after hip fracture surgery in relation to mobilisation timing by patient characteristics: linked secondary analysis of the UK National Hip Fracture Database.

BACKGROUND: Early mobilisation leads to a two-fold increase in the adjusted odds of discharge by 30-days compared to late mobilisation. Whether this association varies by patient characteristics identified as reasons for delayed mobilisation is unknown. METHODS: Audit data was linked to hospitalisation records for 133,319 patients 60 years or older surgically treated for hip fracture in England or Wales between 2014 and 2016. Adjusted proportional odds regression models tested whether the cumulative incidences of discharge differed between those mobilised early and those mobilised late for subgroups defined by dementia, delirium, hypotension, prefracture ambulation, and prefracture residence, accounting for the competing risk of death. RESULTS: Overall, 34,253 patients presented with dementia, 9818 with delirium, and 10,123 with hypotension. Prefracture, 100,983 were ambulant outdoors, 30,834 were ambulant indoors only, 107,144 were admitted from home, and 23,588 from residential care. 1502 had incomplete data for ambulation and 2587 for prefracture residence. 10, 8, 8, 12, and 12% fewer patients with dementia, delirium, hypotension, ambulant indoors only prefracture, or admitted from residential care mobilised early when compared to those who presented without dementia, delirium, hypotension, with outdoor ambulation prefracture, or admitted from home. The adjusted odds ratios of discharge by 30-days postoperatively among those who mobilised early compared with those who mobilised late were 1.71 (95% CI 1.62-1.81) for those with dementia, 2.06 (95% CI 1.98-2.15) without dementia, 1.56 (95% CI 1.41-1.73) with delirium, 2.00 (95% CI 1.93-2.07) without delirium, 1.83 (95% CI, 1.66-2.02) with hypotension, 1.95 (95% CI, 1.89-2.02) without hypotension, 2.00 (95% CI 1.92-2.08) with outdoor ambulation prefracture, 1.80 (95% CI 1.70-1.91) with indoor ambulation only prefracture, 2.30 (95% CI 2.19-2.41) admitted from home, and 1.64 (95% CI 1.51-1.77) admitted from residential care, accounting for the competing risk of death. CONCLUSION: Irrespective of dementia, delirium, hypotension, prefracture ambulation or residence, early compared to late mobilisation increased the likelihood of hospital discharge by 30-days postoperatively. However, fewer patients with dementia, delirium, or hypotension, poorer prefracture ambulation, or from residential care mobilised early. There is a need reduce this care gap by ensuring sufficient resource to enable all patients to benefit from early mobilisation.

Evaluation of a novel approach to recognising community-acquired paediatric sepsis at ED triage by combining an electronic screening algorithm with clinician assessment.

OBJECTIVE: We report the utilisation and impact of a novel triage-based electronic screening tool (eST) combined with clinical assessment to recognise sepsis in paediatric ED. METHODS: An electronic sepsis screening tool was implemented in the paediatric EDs of two large UK secondary care hospitals between June 2018 and January 2019. Patients eligible for screening were children < 16 years of ages excluding those with minor injuries or who were brought directly to resuscitation. Subsequently, a retrospective evaluation was performed to determine the performance of the tool alone and in combination with clinical assessment after triage, to identify septic patients, using sensitivity, specificity, positive, negative predictive values (PPV and NPV) and likelihood ratios. RESULTS: 19 912 children were triaged during the study period, of whom 90 (0.45%) were classified as having sepsis. 99% of all eligible patients were screened. The eST alerted for 2651 (13.3%) patients. After immediate physician assessment, 151 were treated for sepsis in the ED, of whom 70 had a final diagnosis of sepsis. Eight patients who were not thought to be septic returned with sepsis within 24 hours. The eST showed a sensitivity of 86.7% (95% CI 77.5% to 92.6%), specificity 87.0% (95% CI 86.5% to 87.5%), PPV 2.94% (95% CI 2.35% to 3.68%), NPV 99.9% (95% CI 99.8% to 99.9%) which improved with combined clinical assessment to a sensitivity of 90.0% (95% CI 81.4% to 95.0%), specificity 99.4 (95% CI 99.3% to 99.5%), PPV 42.0 (95% CI 35.0% to 49.3%) and NPV 99.9% (95% CI 99.9% to 99.9%). CONCLUSION: Utilisation of a novel triage-based eST allowed sepsis screening in over 99% of eligible patients. The screening tool showed good accuracy to recognise sepsis at triage in the ED, which was augmented further by combining it with clinician assessment. The screening tool requires further refinement through multicentre evaluation to avoid missing sepsis cases.

Effect of Iron Isomaltoside on Skeletal Muscle Energetics in Patients With Chronic Heart Failure and Iron Deficiency.

BACKGROUND: Iron repletion augments exercise capacity in chronic heart failure (HF), but there is a lack of mechanistic data explaining how iron could augment exercise performance despite minimal changes in hemoglobin (Hb). Besides Hb, iron is an obligate component of mitochondrial enzymes that generate cellular energy in the form of adenosine triphosphate and phosphocreatine (PCr). Dynamic phosphorus magnetic resonance spectroscopy is a noninvasive tool that quantifies in vivo muscle energetics by measuring the kinetics of PCr recovery after exertion. We tested the hypothesis that intravenous iron repletion in chronic HF enhances skeletal muscle energetics as reflected by shorter PCr recovery half-times (PCr t1/2) on phosphorus magnetic resonance spectroscopy. METHODS: We enrolled 40 patients (50% anemic) with chronic HF, New York Heart Association class ≥II, left ventricular ejection fraction ≤45%, and iron deficiency (ferritin<100 µg/L or 100-300 µg/L with transferrin saturation <20%). Subjects underwent stratified (anemic versus nonanemic) randomization (1:1) to a single, double-blinded, total dose infusion of iron isomaltoside or saline placebo with end points reassessed early at 2 weeks posttreatment to minimize confounding from exercise adaptation. The primary end point was PCr t1/2 at 2 weeks. Secondary end points included ADP recovery half-time (ADP t1/2; energetic marker), iron status, symptoms, Hb, exercise capacity, and safety. RESULTS: In the total population, treatment groups were similar at baseline. At 2 weeks, iron isomaltoside improved PCr t1/2 (adjusted difference, -6.8 s; 95% CI, 11.5 to -2.1; P=0.006), ADP t1/2 (-5.3 s; 95% CI, -9.7 to -0.9; P=0.02), ferritin (304 ng/mL; 95% CI, 217-391; P<0.0001), transferrin saturation (6.8%; 95% CI, 2.7-10.8; P=0.002), New York Heart Association class (-0.23; 95% CI, -0.46 to -0.01; P=0.04), resting respiratory rate (-0.7 breaths/min; 95% CI, -1.2 to -0.2; P=0.009), and postexercise Borg dyspnea score (-2.0; 95% CI, -3.7 to -0.3; P=0.04), but not Hb (2.4 g/L; 95% CI, -3.5 to 8.4; P=0.41). Adverse events were similar between groups. In subgroup analyses, iron isomaltoside improved PCr t1/2 in anemic (-8.4 s; 95% CI, -16.7 to -0.2; P=0.04) and nonanemic (-5.2 s; 95% CI, -10.6 to 0.2; P=0.06) cohorts. CONCLUSIONS: In patients with chronic HF and iron deficiency, a total repletion dose of iron isomaltoside given at a single sitting is well tolerated and associated with faster skeletal muscle PCr t1/2 at 2 weeks, implying better mitochondrial function. Augmented skeletal muscle energetics might therefore be an important mechanism via which iron repletion confers benefits in chronic HF despite minimal Hb changes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005592-13/GB . Unique identifier: EudraCT 2012-005592-13.