Inpatient glycemic variability and long-term mortality in hospitalized patients with type 2 diabetes

Aims/Hypothesis: To determine the association between inpatient glycemic variability and long-term mortality in patients with type 2 diabetes mellitus. Methods: Capillary blood glucose (CBG) of inpatients from 8 hospitals was analysed. 28,353 admissions identified were matched for age, duration of diabetes and admission and median and interquartile range of CBG. 6 year mortality was investigated for (i) those with CBG IQR in the top half of all IQR measurements (matched for all except IQR), vs those in the lower half and (ii) those with the lowest quartile median glucose (matched for all except median). Results: 1. Glycemic variability 3165 matched pairs were analysed. Mortality was greater in those with IQR in upper 50% (≥ 50.9 mg/dl) over follow-up from day 90 post-discharge to a maximum of 6 years (p<0.01, HR 1.17). 2. Median glucose 2.3755 matched pairs were analysed. Mortality was lower in those with a median glucose in upper 50% (≥ 148.5 mg/dl) over follow-up from day 90 post-discharge to a maximum of 6 years (p < 0.01, HR 0.87). Conclusion: Higher inpatient glycemic variability is associated with increased mortality on long-term follow up. When matched by IQR, we have demonstrated higher median CBG is associated with lower long-term mortality. CBG variability may increase cardiovascular morbidity by increasing exposure to hypoglycaemia or to variability per se. In hospitalized patients with diabetes, glycemic variability should be minimised and when greater CBG variability is unavoidable, a less stringent CBG target considered

Recent developments in adjunct therapies for type 1 diabetes

Introduction: There have been many recent advances in the treatment of type 1 diabetes (T1D) including in insulin formulations, continuous glucose monitoring (CGM) technology and automated insulin delivery. However, long-term optimal glycemic control is still only achieved in a minority. Areas covered: Adjunct therapy – the use of therapeutic agents other than insulin – is one strategy aimed at improving outcomes. An ideal adjunct agent would improve glycemic control, reduce weight (or weight gain), reduce insulin requirement and prevent complications (e.g. cardiorenal) without increasing hypoglycemia. The amylin analogue pramlintide has been licensed in the USA, while the sodium glucose co-transporter-2 inhibitor (SGLT2i) dapagliflozin, was briefly (2019 − 2021) licensed for type 1 diabetes in Europe and the UK. However, other agents from the type 2 diabetes (T2D) arena including metformin, other SGLT2is, glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-IV (DPP-4) inhibitors have been investigated. Expert opinion: As evidence emerges for cardiorenal protection by SGLT2is and GLP-1RAs in T2D, it has become increasingly important to know whether people with T1D can also benefit. Here, we review recent trials of adjunct agents in T1D and discuss the efficacy and safety of these agents (alone and in combination) in an era in which continuous glucose monitoring is becoming standard of care

A quantitative approach for measuring the reservoir of latent HIV-1 proviruses.

A stable latent reservoir for HIV-1 in resting CD4+ T cells is the principal barrier to a cure1-3. Curative strategies that target the reservoir are being tested4,5 and require accurate, scalable reservoir assays. The reservoir was defined with quantitative viral outgrowth assays for cells that release infectious virus after one round of T cell activation1. However, these quantitative outgrowth assays and newer assays for cells that produce viral RNA after activation6 may underestimate the reservoir size because one round of activation does not induce all proviruses7. Many studies rely on simple assays based on polymerase chain reaction to detect proviral DNA regardless of transcriptional status, but the clinical relevance of these assays is unclear, as the vast majority of proviruses are defective7-9. Here we describe a more accurate method of measuring the HIV-1 reservoir that separately quantifies intact and defective proviruses. We show that the dynamics of cells that carry intact and defective proviruses are different in vitro and in vivo. These findings have implications for targeting the intact proviruses that are a barrier to curing HIV infection

Metformin and carotid intima-media thickness in never-smokers with type 1 diabetes: the REMOVAL trial

Aim: To determine whether metformin's effects on carotid artery intima‐media thickness (cIMT) in type 1 diabetes differ according to smoking status. Methods: Regression model effect estimates for the effect of metformin versus placebo (double‐blind) on carotid IMT were calculated as a subgroup analysis of the REMOVAL trial. Results: In 428 randomized participants (227 never‐smokers, 201 ever‐smokers), averaged mean carotid IMT progression (per year) was reduced by metformin versus placebo in never‐smokers (−0.012 mm, 95% CI −0.021 to −0.002; p = .0137) but not in ever‐smokers (0.003 mm, 95% CI −0.008 to 0.014; p = .5767); and similarly in non‐current smokers (−0.008 mm, 95% CI −0.015 to −0.00001; p = .0497) but not in current smokers (0.013 mm, 95% CI −0.007 to 0.032; p = .1887). Three‐way interaction terms (treatment*time*smoking status) were significant for never versus ever smoking (p = .0373, prespecified) and non‐current versus current smoking (p = .0496, exploratory). Averaged maximal carotid IMT progression (per year) was reduced by metformin versus placebo in never‐smokers (−0.020 mm, 95% CI −0.034 to −0.006; p = .0067) but not in ever‐smokers (−0.006 mm, 95% CI −0.020 to 0.008; p = .4067), although this analysis was not supported by a significant three‐way interaction term. Conclusions: This subgroup analysis of the REMOVAL trial provides additional support for a potentially wider role of adjunct metformin therapy in cardiovascular risk management in type 1 diabetes, particularly for individuals who have never smoked cigarettes

Consensus statement from the International Consensus Meeting on the Role of Decompressive Craniectomy in the Management of Traumatic Brain Injury

Abstract: Background: Two randomised trials assessing the effectiveness of decompressive craniectomy (DC) following traumatic brain injury (TBI) were published in recent years: DECRA in 2011 and RESCUEicp in 2016. As the results have generated debate amongst clinicians and researchers working in the field of TBI worldwide, it was felt necessary to provide general guidance on the use of DC following TBI and identify areas of ongoing uncertainty via a consensus-based approach. Methods: The International Consensus Meeting on the Role of Decompressive Craniectomy in the Management of Traumatic Brain Injury took place in Cambridge, UK, on the 28th and 29th September 2017. The meeting was jointly organised by the World Federation of Neurosurgical Societies (WFNS), AO/Global Neuro and the NIHR Global Health Research Group on Neurotrauma. Discussions and voting were organised around six pre-specified themes: (1) primary DC for mass lesions, (2) secondary DC for intracranial hypertension, (3) peri-operative care, (4) surgical technique, (5) cranial reconstruction and (6) DC in low- and middle-income countries. Results: The invited participants discussed existing published evidence and proposed consensus statements. Statements required an agreement threshold of more than 70% by blinded voting for approval. Conclusions: In this manuscript, we present the final consensus-based recommendations. We have also identified areas of uncertainty, where further research is required, including the role of primary DC, the role of hinge craniotomy and the optimal timing and material for skull reconstruction

Results of the ASCEND study: time to abandon aspirin for the primary prevention of cardiovascular disease in people with diabetes

No abstract available

Education and training interventions for physiotherapists working in dementia care: a scoping review

Objectives: Physiotherapy plays a key role in many aspects of dementia care, most notably in maintaining mobility. However, there is a lack of dementia care training at undergraduate and postgraduate level, and more importantly, a paucity of evidence as to what constitutes effective dementia education and training for physiotherapists. The aim of this scoping review was to explore and map the evidence, both quantitative and qualitative, relating to education and training for physiotherapists. Design: This scoping review followed the Joanna Briggs Institute methodology for scoping reviews. A chronological narrative synthesis of the data outlined how the results relate to the objectives of this study. Setting: All studies, both quantitative and qualitative on dementia education and training conducted in any setting, including acute, community care, residential or any educational setting in any geographical area were included. Participants: Studies that included dementia education and training for both qualified and student physiotherapists were considered. Results: A total of 11 papers were included in this review. The principal learning outcomes evaluated were knowledge, confidence, and attitudes. Immediate post- intervention scores showed an improvement in all three outcomes. The Kirkpatrick four level model was used to evaluate the level of outcome achieved. Most educational interventions reached Kirkpatrick level 2, which evaluates learning. A multi-modal approach, with active participation and direct patient involvement seems to enhance learning. Conclusions: Allowing for the heterogeneity of intervention design and evaluation, some common components of educational interventions were identified that led to positive outcomes. This review highlights the need for more robust studies in this area. Further research is needed to develop bespoke dementia curricula specific to physiotherapy

Hypoglycemia and Clinical Outcomes in Hospitalized Patients With Diabetes:Does Association With Adverse Outcomes Remain When Number of Glucose Tests Performed Is Accounted For?

Background: Hypoglycemia is associated with increased length of stay in hospital patients, but previous studies have not considered the confounding effect of increased hypoglycemia detection associated with increased capillary blood glucose (CBG) measurement in prolonged admissions. We aimed to determine the effect of recorded hypoglycemia on length of stay of hospital inpatients (LOS) when this mathematical association is subtracted. Methods: CBG data were analyzed for inpatients within our health board area (01/2009-01/2015). A simulated CBG data set was generated for each patient with an identical sampling frequency to the measured CBG data set. The mathematical component of increased LOS was determined using the simulated data set. Subtraction of this confounding mathematical association was used to provide measurement of the true clinical association between recorded hypoglycemia (CBG < 4 mmol [< 72mg/dl]) and LOS. Results: A total of 196 962 admissions of 52 475 individuals with known diabetes were analyzed. 68 809 admissions of 29 551 individuals had >4 CBG measurements made and were included in analysis. After subtraction of the mathematical association of increased sample number, the clinical effect of recorded hypoglycemia is reduced—but persists—compared to previous studies. 1-2 days with recorded hypoglycemia has a relatively minor effect on LOS. LOS increases rapidly if there are ≥3 days with recorded hypoglycemia, with an increase of 0.75 days LOS per additional day with hypoglycemia. Conclusions: This technique increases accuracy of economic modeling of the impact of hypoglycemia on health care systems. This could assist study of the impact of hypoglycemia on other outcomes by factoring for bias of increased sample numbers

Self-Implemented HIV Testing: Perspectives on Improving Dissemination Among Urban African American Youths

We examined the potential for increasing the reach of HIV testing to African American youths through the dissemination of oral-HIV testing. From 2012 through 2013 we examined the perceptions of alternatives to pharmacy dissemination of SITs in African American youths (5 focus groups) and service providers (4 focus groups), and conducted an ethnographic study of pharmacies (n = 10). Participants perceived significant advantages to delivering SITs through community health and services for adolescents (e.g., increased confidentiality, reduced stigma) over pharmacy dissemination. Given proper attention to fit, SIT dissemination could be facilitated through distribution by health and social service sites, and by improving elements of pharmacy dissemination