Comorbid depression and risk of cardiac events and cardiac mortality in people with diabetes: A systematic review and meta-analysis

Objective: To examine the association of comorbid occurrence of diabetes and depression with risk of cardiovascular endpoints including cardiovascular mortality, coronary heart disease and stroke. Research Design and Methods: A systematic review and metaanalysis. We searched PUBMED/MEDLINE, Medscape, Cochrane Library, CINAHL, EMBASE and Scopus databases assessing cardiac events and mortality associated with depression in diabetes up until 1 December 2018. Pooled hazard ratios were calculated using random- effects models. Results: Nine studies met the inclusion criteria. The combined pooled hazard ratios showed a significant association of cardiac events in people with depression and type 2 diabetes, compared to those with type 2 diabetes alone. For cardiovascular mortality the pooled hazard ratio was 1.48 (95% CI: 1.185, 1.845), p=0.001, for coronary heart disease 1.37 (1.165, 1.605), p?0.001 and for stroke 1.33 (1.291, 1.369), p?0.001. Heterogeneity was high in the meta-analysis for stroke events (I-squared = 84.7%) but was lower for coronary heart disease and cardiovascular mortality (15% and 43.4% respectively). Meta-regression analyses showed that depression was not significantly associated with the study level covariates mean age, duration of diabetes, length of follow-up, BMI, sex and ethnicity (p?0.05 for all models). Only three studies were found that examined the association of depression in type 1 diabetes, there was a high degree of heterogeneity and data synthesis was not conducted for these studies. Conclusions: We have demonstrated a 47.9% increase in cardiovascular mortality, 36.8% increase in coronary heart disease and 32.9% increase in stroke in people with diabetes and comorbid depression. The presence of depression in a person with diabetes should trigger the consideration of evidence-based therapies for cardiovascular disease prevention irrespective of the baseline risk of cardiovascular disease or duration of diabetes

Areas of improvement in the medical care of SMA : evidence from a nationwide patient registry in Germany

Background Management and treatment of spinal muscular atrophy (SMA) has changed in recent years due to the introduction of novel transformative and potentially curative therapies resulting in the emergence of new disease phenotypes. Yet, little is known about the uptake and impact of these therapies in real-world clinical practice. The objective of this study was to describe current motor function, need of assistive devices, and therapeutic and sup‑ portive interventions provided by the healthcare system, as well as the socioeconomic situation of children and adults with diferent SMA phenotypes in Germany. We conducted a cross-sectional, observational study of German patients with genetically confrmed SMA identifed and recruited via a nationwide SMA patient registry (www.sma-register. de) within the TREAT-NMD network. Study data was recorded directly from patient-caregiver pairs through a study questionnaire administered online via a dedicated study website. Results The fnal study cohort consisted of 107 patients with SMA. Of these, 24 were children and 83 adults. In total, about 78% of all participants were taking medication for SMA (predominantly nusinersen and risdiplam). All children with SMA1 were able to sit and 27% of children with SMA2 were able to stand or walk. Impaired upper limb function, scoliosis and bulbar dysfunction were observed more frequently in patients with reduced lower limb performance. Physiotherapy, occupational therapy, and speech therapy, as well as the use of cough assists were less common than indicated by care guidelines. Family planning and educational and employment status appear to be related to motor skill impairment. Conclusions We show that the natural history of disease has changed in Germany following improvements in SMA care and the introduction of novel therapies. Yet, a non-trivial proportion of patients remain untreated. We also identi‑ fed considerable limitations in rehabilitation and respiratory care, as well as low labour-market participation among adults with SMA, calling for action to improve the current situation

Significance of lobular intraepithelial neoplasia at margins of breast conservation specimens: a report of 38 cases and literature review

<p>Abstract</p> <p>Background</p> <p>Presence of lobular intraepithelial neoplasia (LIN) is not routinely reported as part of margin assessment in breast conservation therapy (BCT) as in ductal carcinoma in situ (DCIS). With new emerging evidence of LIN as possible precursor lesion, the hypothesis is that LIN at the margin may increase the risk of local recurrence with BCT. The aim is to determine whether there is an increase incidence of recurrence when LIN is found at surgical margins on BCT.</p> <p>Methods</p> <p>We retrospectively reviewed a total of 1,334 BCT at a single institution in a 10 year period. Inclusion criteria are positive margin with LIN from primary BCT containing invasive and/or in situ carcinoma with comparison to the negative control group who had similar diseases with negative margin for LIN.</p> <p>Results</p> <p>We identified 38 cases (2.8%) with LIN either lobular carcinoma in situ/atypical lobular hyperplasia (LCIS/ALH) at a margin on initial BCT with 36% recurrence rate. Of the 38 cases: 5 (13%) were lost to follow-up, 12 (32%) had no further procedures performed and 21 (55%) had re-excision. Out of 21 patients who had re-excisions, 12 (57%) had residual invasive carcinoma or DCIS, three (14%) had pleomorphic LCIS and 4 (19%) showed residual classic type LCIS. 71% had significant residual disease (local recurrence) and 29% had no residual disease. A negative control group consisted of 38 cases. We found two patients with bone or brain metastasis and one local recurrence. Clinical follow up periods range from 1 to 109 months.</p> <p>Conclusions</p> <p>LIN found at a margin on BCT showed a significant recurrent ipsilateral disease. Our study supports the view that LIN seen at the margin may play a role in recurrence.</p

A systematic review and meta-analysis to compare the prevalence of depression between people with and without Type 1 and Type 2 diabetes

Aims Diabetes can significantly impact quality of life and mental health. However, inconsistencies have been reported in the prevalence of depression in those with Type 1 and Type 2 diabetes, and those without. Systematic reviews also included studies without adequate control subjects. We update existing literature, by comparing depression prevalence between individuals with and without Type 1 and Type 2 diabetes. Methods A systematic review and meta-analysis. We searched MEDLINE, EMBASE and PSYCHINFO, from January 1985 to August 2021. Studies were excluded if they failed to have an adequate control group, specified type of diabetes, or reported depression prevalence by type of diabetes. Results 44 studies were selected for inclusion. The prevalence of depression was significantly higher in people with Type 1 (22% vs 13%, OR = 2.10 (95% CI: 1.23,3.52)), or Type 2 diabetes (19% vs 11%, OR = 1.76 (1.55,2.01)) compared to those without diabetes. There was no association between study effect size and mean age or gender. Findings did not significantly differ between methods of depression assessment. Prevalence of depression in people with diabetes was higher in studies carried out in specialist care (36%, OR = 3.14 (2.12,4.63)) compared to those in community or primary care (12%, OR= 1.51 (1.35,1.70) and in low- and middle-income countries (OR = 2.58 (1.91, 3.50) compared to countries with high income economies (OR= 1.59 (1.39, 1.82)). Conclusions Depression prevalence remains significant in those with type 1 and type 2 diabetes. Effective chronic disease management in people with diabetes is important, particularly screening and managing depression and diabetes distress in specialist care settings

Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and meta-analysis

Objective To estimate and compare progression rates to type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) and healthy controls.Design Systematic review and meta-analysis.Data sources Medline and Embase between January 2000 and December 2019, studies published in English and conducted on humans.Eligibility criteria for selecting studies Observational studies investigating progression to T2DM. Inclusion criteria were postpartum follow-up for at least 12 months, incident physician based diagnosis of diabetes, T2DM reported as a separate outcome rather than combined with impaired fasting glucose or impaired glucose tolerance, and studies with both a group of patients with GDM and a control group.Results This meta-analysis of 20 studies assessed a total of 1 332 373 individuals (67 956 women with GDM and 1 264 417 controls). Data were pooled by random effects meta-analysis models, and heterogeneity was assessed by use of the I2 statistic. The pooled relative risk for the incidence of T2DM between participants with GDM and controls was estimated. Reasons for heterogeneity between studies were investigated by prespecified subgroup and meta-regression analyses. Publication bias was assessed by funnel plots and, overall, studies were deemed to have a low risk of bias (P=0.58 and P=0.90). The overall relative risk for T2DM was almost 10 times higher in women with previous GDM than in healthy controls (9.51, 95% confidence interval 7.14 to 12.67, PConclusions Women with a history of GDM appear to have a nearly 10-fold higher risk of developing T2DM than those with a normoglycaemic pregnancy. The magnitude of this risk highlights the importance of intervening to prevent the onset of T2DM, particularly in the early years after pregnancy.</div

Ethnicity and prognosis following a cardiovascular event in people with and without type 2 diabetes: observational analysis in over 5 million subjects in England.

AIMS To quantify ethnic differences in the risk of all-cause mortality and cardiovascular disease (CVD) events following a first CVD event in people with and without type 2 diabetes. METHODS We identified 5,349,271 subjects with a first CVD between 1 January 2002 and 31 May 2020 in the UK; CVD included aortic aneurism, cerebrovascular accident, heart failure, myocardial infarction, peripheral vascular disease, and other cardiovascular diseases. We estimated adjusted hazard ratios (HRs) for type 2 diabetes and ethnicity of three outcomes: fatal and nonfatal second CVD event (different phenotype compared to the first) and all-cause mortality. RESULTS Relative to White, HRs indicated lower rates in all ethnicities and for all outcomes in both men (from 0.64 to 0.79 for all-cause death; 0.78 to 0.79 for CVD-related death; and 0.85 to 0.98 for a second CVD event) and women (0.69 to 0.77; 0.77 to 0.83; 0.83 to 0.95, respectively). Irrespective of ethnicity and sex, type 2 diabetes increased rates of all outcomes by around a third. CONCLUSIONS Prognosis following a CVD event was consistently worse in subjects with type 2 diabetes while varied across ethnicities, suggesting the implementation of different strategies for the secondary prevention of CVD in different ethnic groups

Variations in documentation of atrial fibrillation predicted by population and service level characteristics in primary health care in England

Identifying features associated with atrial fibrillation (AF) documentation could inform screening. This study used published data to describe differences in documented and estimated AF prevalence in general practices, and explored predictors of variations in AF prevalence.Cross-sectional study of 7318 general practices in England. Descriptive and inferential statistics were undertaken. Multiple linear regression was used to model the difference between estimated AF and documented AF, adjusted for population, practice and practice performance variables.Documented AF prevalence was lower than estimated (- 0.55% 95% confidence intervals, -1.89, 2.99). The proportion of variability accounted for in the final regression model was 0.25. Factors positively associated with AF documentation (increase in difference between estimated and documented), were patients 65-74 years, 75 years +, Black or South Asian ethnicity, diabetes mellitus and practices in East and Midlands of England. Eight variables (female patients, deprivation score, heart failure and peripheral artery disease, total patients per practice, full-time GPs and nurses; and location in South of England) were negatively associated with AF documentation (reduction in difference).Variations in AF documentation were predicted by several practice and population characteristics. Screening could target these sources of variation to decrease variation and improve AF documentation.</p

Consultation rates in people with type 2 diabetes with and without vascular complications: a retrospective analysis of 141,328 adults in England

Objective: To assess trends in primary and specialist care consultation rates and average length of consultation by cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), or cardiometabolic multimorbidity exposure status.  Methods: Observational, retrospective cohort study used linked Clinical Practice Research Datalink primary care data from 01/01/2000 to 31/12/2018 to assess consultation rates in 141,328 adults with newly diagnosed T2DM, with or without CVD. Patients who entered the study with either a diagnosis of T2DM or CVD and later developed the second condition during the study are classified as the cardiometabolic multimorbidity group. Face to face primary and specialist care consultations, with either a nurse or general practitioner, were assessed over time in subjects with T2DM, CVD, or cardiometabolic multimorbidity. Changes in the average length of consultation in each group were investigated.  Results: 696,255 (mean 4.9 years [95% CI, 2.02–7.66]) person years of follow up time, there were 10,221,798 primary and specialist care consultations. The crude rate of primary and specialist care consultations in patients with cardiometabolic multimorbidity (N = 11,881) was 18.5 (95% CI, 18.47–18.55) per person years, 13.5 (13.50, 13.52) in patients with T2DM only (N = 83,094) and 13.2 (13.18, 13.21) in those with CVD (N = 57,974). Patients with cardiometabolic multimorbidity had 28% (IRR 1.28; 95% CI: 1.27, 1.31) more consultations than those with only T2DM. Patients with cardiometabolic multimorbidity had primary care consultation rates decrease by 50.1% compared to a 45.0% decrease in consultations for those with T2DM from 2000 to 2018. Specialist care consultation rates in both groups increased from 2003 to 2018 by 33.3% and 54.4% in patients with cardiometabolic multimorbidity and T2DM, respectively. For patients with T2DM the average consultation duration increased by 36.0%, in patients with CVD it increased by 74.3%, and in those with cardiometabolic multimorbidity it increased by 37.3%.  Conclusions: Annual primary care consultation rates for individuals with T2DM, CVD, or cardiometabolic multimorbidity have fallen since 2000, while specialist care consultations and average consultation length have both increased. Individuals with cardiometabolic multimorbidity have significantly more consultations than individuals with T2DM or CVD alone. Service redesign of health care delivery needs to be considered for people with cardiometabolic multimorbidity to reduce the burden and health care costs.</p

Effect of delay in treatment intensification in people with type 2 diabetes and suboptimal glycaemia after basal insulin initiation: A real‐world observational study

Aim Despite global recommendations for type 2 diabetes mellitus treatment to maintain optimal glycaemic targets, a significant proportion of people remain in suboptimal glycaemic control. Our objective was to investigate the impact of intensification delay after basal insulin (BI) initiation on long-term complications in people with suboptimal glycaemia. Materials and Methods We conducted a retrospective cohort study in individuals with type 2 diabetes mellitus initiated on BI. Those with suboptimal glycaemia (glycated haemoglobin ≥7% or ≥53 mmol/mol) within 12 months of BI initiation were divided into early (treatment intensified within 5 years), or late (≥5 years) intensification groups. We estimated the age-stratified risks of micro- and macrovascular complications among these groups compared with those with optimal glycaemia (glycated haemoglobin Results Of the 13 916 people with suboptimal glycaemia, 52.5% (n = 7304) did not receive any treatment intensification. In those aged Conclusions Those who had late intensification were at an increased risk of cardiovascular death if they were ≥65 years and an increased risk of macrovascular complications if they were <65 years. These findings highlight the critical need for earlier intensification of treatment and adopting personalized treatment strategies to improve patient outcomes.</p

Effect of more versus less intensive blood pressure control on cardiovascular, renal and mortality outcomes in people with type 2 diabetes A systematic review and meta-analysis

Background and Aims Currently, there is uncertainty as to whether blood pressure control in patients with type 2 diabetes should be treated to standard recommended levels or more intensively. Methods Medline, EMBASE, CENTRAL, and Clinicaltrials.gov were searched between January 1, 2000 and April 20th, 2023. Outcomes considered were all-cause mortality, stroke, heart failure, cardiovascular disease, albuminuria, coronary heart disease, and renal outcomes. Random-effects meta-analyses estimated pooled relative risks and mean differences. Results Nine trials enrolling 11,005 participants with type 2 diabetes were included. The pooled mean difference between the intensive and standard treatment groups at follow-up were −7.98 mmHg (95% CI: 12.19 to −3.76) in systolic blood pressure, and −5.08 mmHg (−7.00 to −3.17) in diastolic blood pressure; although between study heterogeneity was high for both meta-analyses (I2>85%). Intensive blood pressure lowering resulted in a reduction in risk of stroke (risk ratio 0.64; 0.52 to 0.79), and macro-albuminuria (0.77; 0.63 to 0.93). More intensive blood pressure control did not result in a statistically significant reduction in risk of all-cause mortality, heart failure, cardiovascular death, cardiovascular events, renal outcomes, and micro-albuminuria; although the direction of estimated effect was beneficial for all outcomes. Conclusions The use of intensive compared with standard blood pressure targets resulted in a significant reduction in blood pressure, stroke, and macro-albuminuria in patients with type 2 diabetes. The post-treatment blood pressure level in the intensive group was 125/73 mmHg, suggesting the current recommendations of 130/80 mmHg blood pressure or lower if tolerated, could be reduced further.</p