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BACKGROUND: Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar, the choice of which second-line therapy to prescribe next is not clear from currently available evidence. The existence of frailty and comorbidities in older adults further increases the complexity of medical decision-making. As only a relatively small proportion of trials report results separately for older adults, the relative efficacy and safety of second-line therapies in older adults with type 2 diabetes mellitus are unknown and require further investigation. This individual participant data (IPD) network meta-analysis evaluates the relative efficacy and safety of second-line therapies on their own or in combination in older adults with type 2 diabetes mellitus. METHODS: All relevant published and unpublished trials will be identified. Studies published prior to 2015 will be identified from two previous comprehensive aggregate data network meta-analyses. Searches will be conducted in CENTRAL, MEDLINE, and EMBASE from 1st January 2015 onwards, and in clinicaltrials.gov from inception. Randomised controlled trials with at least 100 estimated older adults (≥ 65 years) receiving at least 24 weeks of intervention that assess the effects of glucose-lowering drugs on mortality, glycemia, vascular and other comorbidities outcomes, and quality of life will be eligible. The screening and data extraction process will be conducted independently by two researchers. The quality of studies will be assessed using the Cochrane risk of bias tool 2. Anonymised IPD of all eligible trials will be requested via clinical trial portals or by contacting the principal investigators or sponsors. Received data will be reanalysed where necessary to standardise outcome metrics. Network meta-analyses will be performed to determine the relative effectiveness of therapies. DISCUSSION: With the increasing number of older adults with type 2 diabetes worldwide, an IPD network meta-analysis using data from all eligible trials will provide new insights into the optimal choices of second-line antidiabetic drugs to improve patient management and reduce unnecessary adverse events and the subsequent risk of comorbidities in older adults. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021272686.
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Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Metaanálisis en Red , Revisiones Sistemáticas como Asunto , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Anciano , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Proyectos de InvestigaciónRESUMEN
BACKGROUND: Asthma remains a common cause of hospital admissions across the life course. We estimated the contribution of key risk factors to asthma-related hospital and intensive care unit (ICU) admissions in children, adolescents and adults. METHODS: This was a UK-based cohort study using linked primary care (Clinical Practice Research Datalink Aurum) and secondary care (Hospital Episode Statistics Admitted Patient Care) data. Patients were eligible if they were aged 5 years and older and had been diagnosed with asthma. This included 90 989 children aged 5-11 years, 114 927 adolescents aged 12-17 years and 1 179 410 adults aged 18 years or older. The primary outcome was asthma-related hospital admissions from 1 January 2017 to 31 December 2019. The secondary outcome was asthma-related ICU admissions. Incidence rate ratios adjusted for demographic and clinical risk factors were estimated using negative binomial models. Population attributable fraction (PAF) was estimated for modifiable risk factors. RESULTS: Younger age groups, females and those from ethnic minority and lower socioeconomic backgrounds had an increased risk of asthma-related hospital admissions. Increasing medication burden, including excessive use of short-acting bronchodilators, was also strongly associated with the primary outcome. Similar risk factors were observed for asthma-related ICU admissions. The key potentially modifiable or treatable risk factors were smoking in adolescents and adults (PAF 6.8%, 95% CI 0.9% to 12.3% and 4.3%, 95% CI 3.0% to 5.7%, respectively), and obesity (PAF 23.3%, 95% CI 20.5% to 26.1%), depression (11.1%, 95% CI 9.1% to 13.1%), gastro-oesophageal reflux disease (2.3%, 95% CI 1.2% to 3.4%), anxiety (2.0%, 95% CI 0.5% to 3.6%) and chronic rhinosinusitis (0.8%, 95% CI 0.3% to 1.3%) in adults. CONCLUSIONS: There are significant sociodemographic inequalities in the rates of asthma-related hospital and ICU admissions. Treating age-specific modifiable risk factors should be considered an integral part of asthma management, which could potentially reduce the rate of avoidable hospital admissions.
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Asma , Hospitalización , Unidades de Cuidados Intensivos , Atención Primaria de Salud , Atención Secundaria de Salud , Humanos , Asma/epidemiología , Femenino , Masculino , Niño , Adolescente , Factores de Riesgo , Atención Secundaria de Salud/estadística & datos numéricos , Adulto , Preescolar , Reino Unido/epidemiología , Atención Primaria de Salud/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Adulto Joven , Unidades de Cuidados Intensivos/estadística & datos numéricos , Estudios de Cohortes , Persona de Mediana Edad , AncianoRESUMEN
OBJECTIVE: To determine whether the combined use of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors is associated with a decreased risk of major adverse cardiovascular events and serious renal events compared with either drug class alone among patients with type 2 diabetes, and to assess the effect of the combination on the individual components of major adverse cardiovascular events, heart failure, and all cause mortality. DESIGN: Population based cohort study using a prevalent new-user design, emulating a trial. SETTING: UK Clinical Practice Research Datalink linked to Hospital Episode Statistics Admitted Patient Care and Office for National Statistics databases. PARTICIPANTS: Two prevalent new-user cohorts were assembled between January 2013 and December 2020, with follow-up until the end of March 2021. The first cohort included 6696 patients who started GLP-1 receptor agonists and added on SGLT-2 inhibitors, and the second included 8942 patients who started SGLT-2 inhibitors and added on GLP-1 receptor agonists. Combination users were matched, in a 1:1 ratio, to patients prescribed the same background drug, duration of background drug, and time conditional propensity score. MAIN OUTCOME MEASURES: Cox proportional hazards models were fitted to estimate the hazard ratios and 95% confidence intervals of major adverse cardiovascular events and serious renal events, separately, comparing the GLP-1 receptor agonist-SGLT-2 inhibitor combination with the background drug, either GLP-1 receptor agonists or SGLT-2 inhibitors, depending on the cohort. Secondary outcomes included associations with the individual components of major adverse cardiovascular events (myocardial infarction, ischaemic stroke, cardiovascular mortality), heart failure, and all cause mortality. RESULTS: Compared with GLP-1 receptor agonists, the SGLT-2 inhibitor-GLP-1 receptor agonist combination was associated with a 30% lower risk of major adverse cardiovascular events (7.0 v 10.3 events per 1000 person years; hazard ratio 0.70, 95% confidence interval 0.49 to 0.99) and a 57% lower risk of serious renal events (2.0 v 4.6 events per 1000 person years; hazard ratio 0.43, 0.23 to 0.80). Compared with SGLT-2 inhibitors, the GLP-1 receptor agonist-SGLT-2 inhibitor combination was associated with a 29% lower risk of major adverse cardiovascular events (7.6 v 10.7 events per 1000 person years; hazard ratio 0.71, 0.52 to 0.98), whereas serious renal events generated a wide confidence interval (1.4 v 2.0 events per 1000 person years; hazard ratio 0.67, 0.32 to 1.41). Secondary outcomes generated similar results but with wider confidence intervals. CONCLUSIONS: In this cohort study, the GLP-1 receptor agonist-SGLT-2 inhibitor combination was associated with a lower risk of major adverse cardiovascular events and serious renal events compared with either drug class alone.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Agonistas Receptor de Péptidos Similares al Glucagón , Hipoglucemiantes , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Estudios de Cohortes , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Quimioterapia Combinada , Agonistas Receptor de Péptidos Similares al Glucagón/efectos adversos , Agonistas Receptor de Péptidos Similares al Glucagón/uso terapéutico , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Incidencia , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Clinical guidelines recommend that patients admitted to hospital for asthma attacks are reviewed in primary care following hospital discharge. AIM: To evaluate asthma management in primary care following a hospital admission for asthma and its associations with patient characteristics. DESIGN AND SETTING: A retrospective cohort study using English primary care data from the Clinical Practice Research Datalink Aurum database and linked Hospital Episode Statistics Admitted Patient Care data. METHOD: Patients with asthma aged ≥5 years who had at least one asthma-related hospital admission from 1 January 2017 to 31 December 2019 were included. The primary outcome was a composite of any of the following delivered in primary care within 28 days from hospital discharge: asthma review, asthma management plan, asthma medication prescriptions, demonstration of inhaler technique, or smoking cessation counselling. The association between patient characteristics and delivery of clinical care was assessed using logistic regression. RESULTS: The study included 17 457 patients. A total of 10 515 (60.2%) patients received the primary outcome within 28 days of hospital discharge. There were 2311 (13.2%) who received an asthma review, 1459 (8.4%) an asthma management plan, 9996 (57.3%) an asthma medication, 1500 (8.6%) a demonstration of inhaler technique, and 52 (1.2% of smokers) had smoking cessation counselling. Patients from Black ethnic minority groups received less of this care (27%-54% lower odds, depending on age). However, short-acting bronchodilator prescriptions in the previous year were associated with an increased likelihood of the primary outcome. CONCLUSION: A significant proportion of patients do not receive timely follow-up in primary care following asthma-related admissions to hospital, particularly among Black ethnic minority groups.
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Asma , Hospitalización , Atención Primaria de Salud , Humanos , Asma/tratamiento farmacológico , Estudios Retrospectivos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adolescente , Niño , Anciano , Antiasmáticos/uso terapéutico , Alta del Paciente , Adulto Joven , Preescolar , Cese del Hábito de FumarRESUMEN
[This corrects the article DOI: 10.1016/j.eclinm.2022.101762.].
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BACKGROUND: Post-viral syndromes (PVS), including Long COVID, are symptoms sustained from weeks to years following an acute viral infection. Non-pharmacological treatments for these symptoms are poorly understood. This review summarises the evidence for the effectiveness of non-pharmacological treatments for PVS. METHODS: We conducted a systematic review to evaluate the effectiveness of non-pharmacological interventions for PVS, as compared to either standard care, alternative non-pharmacological therapy, or placebo. The outcomes of interest were changes in symptoms, exercise capacity, quality of life (including mental health and wellbeing), and work capability. We searched five databases (Embase, MEDLINE, PsycINFO, CINAHL, MedRxiv) for randomised controlled trials (RCTs) published between 1 January 2001 to 29 October 2021. The relevant outcome data were extracted, the study quality was appraised using the Cochrane risk-of-bias tool, and the findings were synthesised narratively. FINDINGS: Overall, five studies of five different interventions (Pilates, music therapy, telerehabilitation, resistance exercise, neuromodulation) met the inclusion criteria. Aside from music-based intervention, all other selected interventions demonstrated some support in the management of PVS in some patients. INTERPRETATION: In this study, we observed a lack of robust evidence evaluating the non-pharmacological treatments for PVS, including Long COVID. Considering the prevalence of prolonged symptoms following acute viral infections, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological treatments for patients with PVS. REGISTRATION: The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.
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COVID-19 , Virosis , Humanos , Síndrome Post Agudo de COVID-19 , Salud MentalRESUMEN
Background: The aim of this study was to systematically synthesise the global evidence on the prevalence of persistent symptoms in a general post COVID-19 population. Methods: A systematic literature search was conducted using multiple electronic databases (MEDLINE and The Cochrane Library, Scopus, CINAHL, and medRxiv) until January 2022. Studies with at least 100 people with confirmed or self-reported COVID-19 symptoms at ≥28 days following infection onset were included. Patient-reported outcome measures and clinical investigations were both assessed. Results were analysed descriptively, and meta-analyses were conducted to derive prevalence estimates. This study was pre-registered (PROSPERO-ID: CRD42021238247). Findings: 194 studies totalling 735,006 participants were included, with five studies conducted in those <18 years of age. Most studies were conducted in Europe (n = 106) or Asia (n = 49), and the time to follow-up ranged from ≥28 days to 387 days. 122 studies reported data on hospitalised patients, 18 on non-hospitalised, and 54 on hospitalised and non-hospitalised combined (mixed). On average, at least 45% of COVID-19 survivors, regardless of hospitalisation status, went on to experience at least one unresolved symptom (mean follow-up 126 days). Fatigue was frequently reported across hospitalised (28.4%; 95% CI 24.7%-32.5%), non-hospitalised (34.8%; 95% CI 17.6%-57.2%), and mixed (25.2%; 95% CI 17.7%-34.6%) cohorts. Amongst the hospitalised cohort, abnormal CT patterns/x-rays were frequently reported (45.3%; 95% CI 35.3%-55.7%), alongside ground glass opacification (41.1%; 95% CI 25.7%-58.5%), and impaired diffusion capacity for carbon monoxide (31.7%; 95% CI 25.8%-3.2%). Interpretation: Our work shows that 45% of COVID-19 survivors, regardless of hospitalisation status, were experiencing a range of unresolved symptoms at â¼ 4 months. Current understanding is limited by heterogeneous study design, follow-up durations, and measurement methods. Definition of subtypes of Long Covid is unclear, subsequently hampering effective treatment/management strategies. Funding: No funding.
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INTRODUCTION: Asthma is the most common chronic respiratory disease in children and adults. Asthma results in significant disease-related morbidity, healthcare costs and, in some cases, death. Despite efforts through implementation of national guidelines to improve asthma care, the UK has one of the highest asthma-related morbidity and mortality rates in the western world. New approaches are necessary to prevent asthma attacks in children and adults. The objectives of this study are to assess the association between demographic and clinical factors and asthma-related hospital admissions in children and adults, describe the epidemiology of asthma phenotypes among hospital attenders, and externally validate existing asthma risk prediction models. METHODS AND ANALYSIS: This is a retrospective cohort study of children and adults with asthma. Data will be extracted from the Clinical Practice Research Datalink (CPRD) Aurum database, which holds anonymised primary care data for over 13 million actively registered patients and covers approximately 19% of the UK population. The primary outcome will be asthma-related hospital admissions. The secondary outcomes will be prescriptions of short courses of oral corticosteroids (as a surrogate measure for asthma exacerbations), a composite outcome measure including hospital admissions and prescriptions of short courses of oral corticosteroids and delivery of asthma care management following hospital discharge. The primary analysis will use a Poisson regression model to assess the association between demographic and clinical risk factors and the primary and secondary outcomes. Latent class analysis will be used to identify distinct subgroups, which will further our knowledge on potential phenotypes of asthma among patients at high risk of asthma-related hospital admissions. A Concordance statistic (C-statistic) and logistic regression model will also be used to externally validate existing risk prediction models for asthma-related hospitalisations to allow for the optimal model to be identified and evaluated provide evidence for potential use of the optimal performing risk prediction model in primary care. ETHICS AND DISSEMINATION: This study was approved by the CPRD Independent Scientific Advisory Committee (reference number: 21_000512). Findings from this study will be published in a peer-reviewed journal and disseminated at national and international conferences.
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Asma , Atención Secundaria de Salud , Corticoesteroides/uso terapéutico , Asma/tratamiento farmacológico , Asma/epidemiología , Hospitalización , Humanos , Estudios Retrospectivos , Reino Unido/epidemiologíaRESUMEN
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.
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COVID-19 , Adulto , COVID-19/complicaciones , COVID-19/epidemiología , Estudios de Cohortes , Etnicidad , Femenino , Humanos , Masculino , Grupos Minoritarios , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2 , Síndrome Post Agudo de COVID-19RESUMEN
INTRODUCTION: Individuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4-12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies. METHODS AND ANALYSIS: A cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink, and invited by their general practitioners to participate on a digital platform (Atom5). Individuals will report symptoms, quality of life, work capability and patient-reported outcome measures. Data will be collected monthly for 1 year.Statistical clustering methods will be used to identify distinct Long COVID-19 symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear substudy which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy.We will review existing evidence on interventions for postviral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulative evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation.Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers. TRIAL REGISTRATION NUMBER: 1567490.
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COVID-19 , COVID-19/complicaciones , COVID-19/terapia , Prueba de COVID-19 , Humanos , Medición de Resultados Informados por el Paciente , Calidad de Vida , Síndrome , Síndrome Post Agudo de COVID-19RESUMEN
INTRODUCTION: Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as 'post COVID-19 syndrome', 'post-COVID condition' or more commonly 'Long COVID'. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments. AIMS: This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies. METHODS AND ANALYSIS: Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported. ETHICS AND DISSEMINATION: This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups. PROSPERO REGISTRATION NUMBER: The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).
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COVID-19 , Sesgo , COVID-19/complicaciones , COVID-19/terapia , Humanos , Metaanálisis como Asunto , Proyectos de Investigación , SARS-CoV-2 , Síndrome , Revisiones Sistemáticas como Asunto , Síndrome Post Agudo de COVID-19RESUMEN
OBJECTIVES: To investigate barriers to accessing a hospital-based personal health record (PHR) system. DESIGN: Retrospective cross-sectional study. SETTING: This study was conducted in a large secondary and tertiary acute care trust in Birmingham, UK. PARTICIPANTS: Data were collected from 28 637 patients who attended liver medicine, diabetes, renal medicine or endocrinology specialist outpatient clinics from 1 June 2017 to 31 May 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was sign up to and activation of the PHR. The secondary outcomes were the use of the PHR, defined as the number of logons and frequency of access of specific PHR functions. RESULTS: 8070 patients (28.2%) were signed up to the PHR and 4286 patients (53.1% of those signed up) went on to activate their PHR account. Patients aged 75 years and older were significantly less likely to be signed up (adjusted OR, aOR 0.40, 95% CI 0.36 to 0.44) or to activate (aOR 0.39, 0.32 to 0.47) their PHR than patients aged 35-54. Patients who did not need an interpreter were more likely to be signed up (aOR 1.63, 95% CI 1.33 to 1.99) and to activate (aOR 3.16, 95% CI 1.96 to 5.09) their PHR. Patients living in the least deprived areas were more than twice as likely to be signed up (aOR 2.31, 95% CI 2.04 to 2.63), and were three times more likely to activate their PHR (aOR 2.99, 95% CI 2.40 to 3.71), than those in the most deprived. CONCLUSION: Socioeconomic deprivation, older age and non-English language were significant barriers to accessing a hospital-based PHR. Strategies are needed to account for these factors to ensure that PHRs do not widen health inequalities.