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"Holt, Richard I G"
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The Effectiveness of Pharmacological and Non-Pharmacological Interventions for Improving Glycaemic Control in Adults with Severe Mental Illness: A Systematic Review and Meta-Analysis
2017
People with severe mental illness (SMI) have reduced life expectancy compared with the general population, which can be explained partly by their increased risk of diabetes. We conducted a meta-analysis to determine the clinical effectiveness of pharmacological and non-pharmacological interventions for improving glycaemic control in people with SMI (PROSPERO registration: CRD42015015558). A systematic literature search was performed on 30/10/2015 to identify randomised controlled trials (RCTs) in adults with SMI, with or without a diagnosis of diabetes that measured fasting blood glucose or glycated haemoglobin (HbA1c). Screening and data extraction were carried out independently by two reviewers. We used random effects meta-analysis to estimate effectiveness, and subgroup analysis and univariate meta-regression to explore heterogeneity. The Cochrane Collaboration's tool was used to assess risk of bias. We found 54 eligible RCTs in 4,392 adults (40 pharmacological, 13 behavioural, one mixed intervention). Data for meta-analysis were available from 48 RCTs (n = 4052). Both pharmacological (mean difference (MD), -0.11mmol/L; 95% confidence interval (CI), [-0.19, -0.02], p = 0.02, n = 2536) and behavioural interventions (MD, -0.28mmol//L; 95% CI, [-0.43, -0.12], p<0.001, n = 956) were effective in lowering fasting glucose, but not HbA1c (pharmacological MD, -0.03%; 95% CI, [-0.12, 0.06], p = 0.52, n = 1515; behavioural MD, 0.18%; 95% CI, [-0.07, 0.42], p = 0.16, n = 140) compared with usual care or placebo. In subgroup analysis of pharmacological interventions, metformin and antipsychotic switching strategies improved HbA1c. Behavioural interventions of longer duration and those including repeated physical activity had greater effects on fasting glucose than those without these characteristics. Baseline levels of fasting glucose explained some of the heterogeneity in behavioural interventions but not in pharmacological interventions. Although the strength of the evidence is limited by inadequate trial design and reporting and significant heterogeneity, there is some evidence that behavioural interventions, antipsychotic switching, and metformin can lead to clinically important improvements in glycaemic measurements in adults with SMI.
Journal Article
Association Between Antipsychotic Medication Use and Diabetes
2019
Purpose of ReviewThe prevalence of diabetes is 2–3-fold higher in people with severe mental illness than the general population. There are concerns that antipsychotics increase the risk of diabetes. This review will examine the latest epidemiological studies linking antipsychotics and diabetes, as well as the mechanisms underlying the association and the clinical implications to minimise the impact of antipsychotics on metabolic health.Recent FindingsAlthough there is an increased risk of diabetes in people with first-episode psychosis, the prevalence increases rapidly after antipsychotics are started. Antipsychotics likely increase the risk of diabetes through weight gain and directly by adversely affecting insulin sensitivity and secretion.SummaryIt is important to implement measures to prevent diabetes, to screen for diabetes to ensure prompt diagnosis and to provide effective diabetes care. Further research is needed to understand how antipsychotics cause diabetes and to improve the clinical management of diabetes in people with severe mental illness.
Journal Article
Diabetes and infection: review of the epidemiology, mechanisms and principles of treatment
by
Luk, Andrea O. Y.
,
Ma, Ronald C. W.
,
Cockram, Clive S.
in
COVID-19
,
Diabetes
,
Diabetes mellitus
2024
An association between diabetes and infection has been recognised for many years, with infection being an important cause of death and morbidity in people with diabetes. The COVID-19 pandemic has re-kindled an interest in the complex relationship between diabetes and infection. Some infections occur almost exclusively in people with diabetes, often with high mortality rates without early diagnosis and treatment. However, more commonly, diabetes is a complicating factor in many infections. A reciprocal relationship occurs whereby certain infections and their treatments may also increase the risk of diabetes. People with diabetes have a 1.5- to 4-fold increased risk of infection. The risks are the most pronounced for kidney infection, osteomyelitis and foot infection, but are also increased for pneumonia, influenza, tuberculosis, skin infection and general sepsis. Outcomes from infection are worse in people with diabetes, with the most notable example being a twofold higher rate of death from COVID-19. Hyperglycaemia has deleterious effects on the immune response. Vascular insufficiency and neuropathy, together with altered skin, mucosal and gut microbial colonisation, contribute to the increased risk of infection. Vaccination is important in people with diabetes although the efficacy of certain immunisations may be compromised, particularly in the presence of hyperglycaemia. The principles of treatment largely follow those of the general population with certain notable exceptions.
Graphical Abstract
Journal Article
The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)
by
Hans, DeVries J
,
Weinstock, Ruth S
,
Ludwig, Barbara
in
Best practice
,
Diabetes
,
Diabetes mellitus (insulin dependent)
2021
The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) convened a writing group to develop a consensus statement on the management of type 1 diabetes in adults. The writing group has considered the rapid development of new treatments and technologies and addressed the following topics: diagnosis, aims of management, schedule of care, diabetes self-management education and support, glucose monitoring, insulin therapy, hypoglycaemia, behavioural considerations, psychosocial care, diabetic ketoacidosis, pancreas and islet transplantation, adjunctive therapies, special populations, inpatient management and future perspectives. Although we discuss the schedule for follow-up examinations and testing, we have not included the evaluation and treatment of the chronic microvascular and macrovascular complications of diabetes as these are well-reviewed and discussed elsewhere. The writing group was aware of both national and international guidance on type 1 diabetes and did not seek to replicate this but rather aimed to highlight the major areas that healthcare professionals should consider when managing adults with type 1 diabetes. Though evidence-based where possible, the recommendations in the report represent the consensus opinion of the authors.
Journal Article
Liraglutide and the management of overweight and obesity in people with severe mental illness: qualitative sub-study
by
Whicher, Clare A.
,
Phiri, Peter
,
Holt, Richard I. G.
in
Antidiabetics
,
Body weight
,
Body weight loss
2022
Background
People with severe mental illness are two to three times more likely to be overweight or have obesity than the general population and this is associated with significant morbidity and premature mortality. Liraglutide 3 mg is a once daily injectable GLP-1 receptor agonist that is licensed for the treatment of obesity in the general population and has the potential to be used in people with severe mental illness.
Aims
To record the expectations and experiences of people with schizophrenia, schizoaffective disorders or first episode psychosis taking daily liraglutide 3 mg injections in a clinical trial for the treatment of obesity.
To seek the views of healthcare professionals about the feasibility of delivering the intervention in routine care.
Methods
Qualitative interviews were undertaken with a purposive sub-sample of people with schizophrenia, schizoaffective disorders or first episode psychosis with overweight or obesity who were treated with a daily injection of liraglutide 3 mg in a double-blinded, randomised controlled pilot study evaluating the use of liraglutide for the treatment of obesity. Interviews were also conducted with healthcare professionals.
Results
Seventeen patient participants were interviewed. Sixteen took part in the baseline interview, eight completed both baseline and follow-up interviews, and one took part in follow-up interview only. Mean interview duration was thirteen minutes (range 5-37 min). Despite reservations by some participants about the injections before the study, most of those who completed the trial reported no challenges in the timing of or administering the injections. Key themes included despondency regarding prior medication associated weight gain, quality of life impact of weight loss, practical aspects of participation including materials received and clinic attendance. Healthcare professionals reported challenges with recruitment, however, overall it was a positive experience for them and for participants.
Conclusion
Liraglutide appears to be an acceptable therapy for obesity in this population with limited side effects. The quality of life benefits realised by several intervention participants reinforce the biomedical benefits of achieved weight loss.
Journal Article
A core outcomes set for clinical trials of interventions for young adults with type 1 diabetes: an international, multi-perspective Delphi consensus study
2017
Background
Achieving consensus from a range of relevant stakeholders about an agreed set of core outcomes to be measured and reported as a minimum in clinical trials has the potential to enhance evidence synthesis and make findings more relevant and applicable. Intervention research to improve outcomes for young adults with type 1 diabetes (T1DM) is hampered by inconsistent use of outcome measures. This population frequently struggles to manage their condition and reports suboptimal clinical outcomes. Our aim was to conduct an international, e-Delphi consensus study to identify a core outcome set (COS) that key stakeholders (young adults with T1DM, diabetes health professionals, diabetes researchers and diabetes policy makers) consider as essential outcomes for future intervention research.
Methods
Using a list of 87 outcomes generated from a published systematic review, we administered two online surveys to a sample of international key stakeholders. Participants in the first survey (survey 1;
n
= 132) and the second survey (survey 2;
n
= 81) rated the importance of the outcomes. Survey 2 participants received information on total mean rating for each outcome and a reminder of their personal outcome ratings from Survey 1. Survey 2 results were discussed at a consensus meeting and participants (
n
= 12: three young adults with T1DM, four diabetes health professionals, four diabetes researchers and one diabetes policy maker) voted on outcomes. Final core outcomes were included provided that 70% of consensus group participants voted for their inclusion.
Results
Eight core outcomes were agreed for inclusion in the final COS: measures of diabetes-related stress; diabetes-related quality of life; number of severe hypoglycaemic events; self-management behaviour; number of instances of diabetic ketoacidosis (DKA); objectively measured glycated haemoglobin (HbA
1C
); level of clinic engagement; and perceived level of control over diabetes.
Conclusions
This study is the first to identify a COS for inclusion in future intervention trials to improve outcomes for young adults with T1DM. Use of this COS will improve the quality of future research and increase opportunities for evidence synthesis. Future research is necessary to identify the most robust outcome measure instruments.
Journal Article
Diabetes and Depression
by
de Groot, Mary
,
Golden, Sherita Hill
,
Holt, Richard I. G.
in
Antidepressive Agents - therapeutic use
,
Comorbidity
,
Depression - epidemiology
2014
Diabetes and depression occur together approximately twice as frequently as would be predicted by chance alone. Comorbid diabetes and depression are a major clinical challenge as the outcomes of both conditions are worsened by the other. Although the psychological burden of diabetes may contribute to depression, this explanation does not fully explain the relationship between these 2 conditions. Both conditions may be driven by shared underlying biological and behavioral mechanisms, such as hypothalamic-pituitary-adrenal axis activation, inflammation, sleep disturbance, inactive lifestyle, poor dietary habits, and environmental and cultural risk factors. Depression is frequently missed in people with diabetes despite effective screening tools being available. Both psychological interventions and antidepressants are effective in treating depressive symptoms in people with diabetes but have mixed effects on glycemic control. Clear care pathways involving a multidisciplinary team are needed to obtain optimal medical and psychiatric outcomes for people with comorbid diabetes and depression.
Journal Article
STructured lifestyle education for people WIth SchizophrEnia (STEPWISE): mixed methods process evaluation of a group-based lifestyle education programme to support weight loss in people with schizophrenia
by
Barnard-Kelly, Katharine D.
,
Holt, Richard I. G.
,
Gossage-Worrall, Rebecca
in
Adolescent
,
Adult
,
Analysis
2019
Background
STEPWISE is a theory-informed self-management education programme that was co-produced with service users, healthcare professionals and interventionists to support weight loss for people with schizophrenia. We report the process evaluation to inform understanding about the intervention and its effectiveness in a randomised controlled trial (RCT) that evaluated its efficacy.
Methods
Following the UK Medical Research Council (MRC) Guidelines for developing and evaluating complex interventions, we explored implementation quality. We considered causal mechanisms, unanticipated consequences and contextual factors associated with variation in actual and intended outcomes, and integrated treatment fidelity, using the programme theory and a pipeline logic model.
We followed a modified version of Linnan and Steckler’s framework and single case design. Qualitative data from semi-structured telephone interviews with service-users (
n
= 24), healthcare professionals delivering the intervention (
n
= 20) and interventionists (
n
= 7) were triangulated with quantitative process and RCT outcome data and with observations by interventionists, to examine convergence within logic model components.
Results
Training and course materials were available although lacked co-ordination in some trusts. Healthcare professionals gained knowledge and some contemplated changing their practice to reflect the (facilitative) ‘style’ of delivery. They were often responsible for administrative activities increasing the burden of delivery. Healthcare professionals recognised the need to address antipsychotic-induced weight gain and reported potential value from the intervention (subject to the RCT results). However, some doubted senior management commitment and sustainability post-trial.
Service-users found the intervention highly acceptable, especially being in a group of people with similar experiences. Service-users perceived weight loss and lifestyle benefits; however, session attendance varied with 23% (
n
= 47) attending all group-sessions and 17% (
n
= 36) attending none. Service-users who lost weight wanted closer monitoring and many healthcare professionals wanted to monitor outcomes (e.g. weight) but it was outside the intervention design. No clinical or cost benefit was demonstrated from the intermediate outcomes (RCT) and any changes in RCT outcomes were not due to the intervention.
Conclusions
This process evaluation provides a greater understanding of why STEPWISE was unsuccessful in promoting weight loss during the clinical trial. Further research is required to evaluate whether different levels of contact and objective monitoring can support people with schizophrenia to lose weight.
Trial registration
ISRCTN,
ISRCTN19447796
. Registered 20 March 2014.
Journal Article