A previous study suggests an association between poor medication adherence and excess mortality in chronic disease. The purpose of this study was to assess the association between medication ...adherence and risk of cardiovascular disease (CVD), all-cause mortality, and hospitalization in type 2 diabetes.
We conducted an electronic search on many electronic databases from inception to 27 April 2016. We selected randomized controlled trials and case-control and cohort studies reporting on CVD, all-cause mortality, or hospitalization outcomes by adherence in adults with type 2 diabetes. Two reviewers independently screened for eligible studies and extracted outcome data. Pooled relative risks (RRs) were calculated using a random-effects meta-analysis; risk of bias in each of the included studies was assessed using the GRADE approach.
Eight observational studies were included (
= 318,125). The mean rate of poor adherence was 37.8% (95% CI 37.6-38.0). Adjusted estimates were provided by five studies only. The RRs of good (≥80%) versus poor adherence to medication were 0.72 (95% CI 0.62-0.82,
= 0%, three studies) for all-cause mortality and 0.90 (0.87-0.94,
= 63%, seven studies) for hospitalization. No evidence of small study bias was observed. Only one study reported CVD outcomes by adherence.
We identified no trials reporting on outcomes by adherence, suggesting a systematic failure to include this information. Pooled estimates from available observational studies suggest that good medication adherence is associated with reduced risk of all-cause mortality and hospitalization in people with type 2 diabetes, although bias cannot be excluded as an explanation for these findings.
Early glycaemic control leads to better outcomes, including a reduction in long-term macrovascular and microvascular complications. Despite good-quality evidence, glycaemic control has been shown to ...be inadequate globally. Therapeutic inertia has been shown present in all stages of treatment intensification, from the first oral antihyperglycaemic drug (OAD), all the way to the initiation of insulin. The causes and possible solutions to the problem of therapeutic inertia are complex but can be understood better when viewed from the perspective of the providers healthcare professionals (HCPs), patients and healthcare systems. In this review, we will discuss the possible aetiologies, consequences and solutions of therapeutic inertia, drawing upon evidence from published literature on the subject of type 2 diabetes.
Highlights • Timely achievement of glycaemic control is key to optimising clinical outcomes. • Clinical inertia is most pronounced at the intensification with insulin stage. • The NICE guidelines on ...type 2 diabetes do not explicitly address clinical inertia. • Barriers to treatment intensification span patient, clinician and system levels. • Clinical inertia can be tackled with increased education on therapeutic options.
Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. We undertook a self-controlled ...case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,752) or BNT162b2 (n = 12,134,782), and after a SARS-CoV-2-positive test (n = 2,005,280). There was an increased risk of Guillain-Barré syndrome (incidence rate ratio (IRR), 2.90; 95% confidence interval (CI): 2.15-3.92 at 15-21 days after vaccination) and Bell's palsy (IRR, 1.29; 95% CI: 1.08-1.56 at 15-21 days) with ChAdOx1nCoV-19. There was an increased risk of hemorrhagic stroke (IRR, 1.38; 95% CI: 1.12-1.71 at 15-21 days) with BNT162b2. An independent Scottish cohort provided further support for the association between ChAdOx1nCoV and Guillain-Barré syndrome (IRR, 2.32; 95% CI: 1.08-5.02 at 1-28 days). There was a substantially higher risk of all neurological outcomes in the 28 days after a positive SARS-CoV-2 test including Guillain-Barré syndrome (IRR, 5.25; 95% CI: 3.00-9.18). Overall, we estimated 38 excess cases of Guillain-Barré syndrome per 10 million people receiving ChAdOx1nCoV-19 and 145 excess cases per 10 million people after a positive SARS-CoV-2 test. In summary, although we find an increased risk of neurological complications in those who received COVID-19 vaccines, the risk of these complications is greater following a positive SARS-CoV-2 test.
Poor glycaemic control in type 2 diabetes (T2D) is a global problem despite the availability of numerous glucose‐lowering therapies and clear guidelines for T2D management. Tackling clinical or ...therapeutic inertia, where the person with diabetes and/or their healthcare providers do not intensify treatment regimens despite this being appropriate, is key to improving patients’ long‐term outcomes. This gap between best practice and current level of care is most pronounced when considering insulin regimens, with studies showing that insulin initiation/intensification is frequently and inappropriately delayed for several years. Patient‐ and physician‐related factors both contribute to this resistance at the stages of insulin initiation, titration and intensification, impeding achievement of optimal glycaemic control. The present review evaluates the evidence and reasons for this delay, together with available methods for facilitation of insulin initiation or intensification.
Although myocarditis and pericarditis were not observed as adverse events in coronavirus disease 2019 (COVID-19) vaccine trials, there have been numerous reports of suspected cases following ...vaccination in the general population. We undertook a self-controlled case series study of people aged 16 or older vaccinated for COVID-19 in England between 1 December 2020 and 24 August 2021 to investigate hospital admission or death from myocarditis, pericarditis and cardiac arrhythmias in the 1-28 days following adenovirus (ChAdOx1, n = 20,615,911) or messenger RNA-based (BNT162b2, n = 16,993,389; mRNA-1273, n = 1,006,191) vaccines or a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (n = 3,028,867). We found increased risks of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines and the first and second doses of the mRNA-1273 vaccine over the 1-28 days postvaccination period, and after a SARS-CoV-2 positive test. We estimated an extra two (95% confidence interval (CI) 0, 3), one (95% CI 0, 2) and six (95% CI 2, 8) myocarditis events per 1 million people vaccinated with ChAdOx1, BNT162b2 and mRNA-1273, respectively, in the 28 days following a first dose and an extra ten (95% CI 7, 11) myocarditis events per 1 million vaccinated in the 28 days after a second dose of mRNA-1273. This compares with an extra 40 (95% CI 38, 41) myocarditis events per 1 million patients in the 28 days following a SARS-CoV-2 positive test. We also observed increased risks of pericarditis and cardiac arrhythmias following a positive SARS-CoV-2 test. Similar associations were not observed with any of the COVID-19 vaccines, apart from an increased risk of arrhythmia following a second dose of mRNA-1273. Subgroup analyses by age showed the increased risk of myocarditis associated with the two mRNA vaccines was present only in those younger than 40.
Multimorbidity is an emerging public health priority. Physical activity (PA) is recommended as one of the main lifestyle behaviours, yet the benefits of PA for people with multimorbidity are unclear. ...We assessed the benefits of PA on mortality and life expectancy in people with and without multimorbidity.
Using the UK Biobank dataset, we extracted data on 36 chronic conditions and defined multimorbidity as (a) 2 or more conditions, (b) 2 or more conditions combined with self-reported overall health, and (c) 2 or more top-10 most common comorbidities. Leisure-time PA (LTPA) and total PA (TPA) were measured by questionnaire and categorised as low (< 600 metabolic equivalent (MET)-min/week), moderate (600 to < 3000 MET-min/week), and high (≥ 3000 MET-min/week), while objectively assessed PA was assessed by wrist-worn accelerometer and categorised as low (4 min/day), moderate (10 min/day), and high (22 min/day) walking at brisk pace. Survival models were applied to calculate adjusted hazard ratios (HRs) and predict life expectancy differences.
491,939 individuals (96,622 with 2 or more conditions) had a median follow-up of 7.0 (IQR 6.3-7.6) years. Compared to low LTPA, for participants with multimorbidity, HR for mortality was 0.75 (95% CI 0.70-0.80) and 0.65 (0.56-0.75) in moderate and high LTPA groups, respectively. This finding was consistent when using TPA measures. Using objective PA, HRs were 0.49 (0.29-0.80) and 0.29 (0.13-0.61) in the moderate and high PA groups, respectively. These findings were similar for participants without multimorbidity. In participants with multimorbidity, at the age of 45 years, moderate and high LTPA were associated with an average of 3.12 (95% CI 2.53, 3.71) and 3.55 (2.34, 4.77) additional life years, respectively, compared to low LTPA; in participants without multimorbidity, corresponding figures were 1.95 (1.59, 2.31) and 1.85 (1.19, 2.50). Similar results were found with TPA. For objective PA, moderate and high levels were associated with 3.60 (- 0.60, 7.79) and 5.32 (- 0.47, 11.11) life years gained compared to low PA for those with multimorbidity and 3.88 (1.79, 6.00) and 4.51 (2.15, 6.88) life years gained in those without. Results were consistent when using other definitions of multimorbidity.
There was an inverse dose-response association between PA and mortality. A moderate exercise is associated with a longer life expectancy, also in individuals with multimorbidity.
Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at ...intermediate risk and with lower blood pressure is unclear.
In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years.
The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group. The first coprimary outcome occurred in 260 participants (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio, 0.93; 95% confidence interval CI, 0.79 to 1.10; P=0.40); the second coprimary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P=0.51). In one of the three prespecified hypothesis-based subgroups, participants in the subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were in the active-treatment group had significantly lower rates of the first and second coprimary outcomes than those in the placebo group; effects were neutral in the middle and lower thirds (P=0.02 and P=0.009, respectively, for trend in the two outcomes).
Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).
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