Incidence, morbidity, mortality and disparities in dementia: A population linked electronic health records study of 4.3 million individuals.

INTRODUCTION: We report dementia incidence, comorbidities, reasons for health-care visits, mortality, causes of death, and examined dementia patterns by relative deprivation in the UK. METHOD: A longitudinal cohort analysis of linked electronic health records from 4.3 million people in the UK was conducted to investigate dementia incidence and mortality. Reasons for hospitalization and causes of death were compared in individuals with and without dementia. RESULTS: From 1998 to 2016 we observed 145,319 (3.1%) individuals with incident dementia. Repeated hospitalizations among senior adults for infection, unknown morbidity, and multiple primary care visits for chronic pain were observed prior to dementia diagnosis. Multiple long-term conditions are present in half of the individuals at the time of diagnosis. Individuals living in high deprivation areas had higher dementia incidence and high fatality. DISCUSSION: There is a considerable disparity of dementia that informs priorities of prevention and provision of patient care.

The health economic impact of cow's milk allergy in childhood: A retrospective cohort study.

BACKGROUND: Cow's milk allergy (CMA) is one of the most common food allergies among children. Whilst avoidance of cow's milk protein is the cornerstone of management, further treatment of symptoms including those affecting the gastrointestinal, skin and respiratory systems plus other allergic comorbidities, maybe required. This study aimed to quantify the wider economic impact of CMA and its management in the United Kingdom (UK). METHODS: We conducted a retrospective matched cohort study on children with CMA (diagnosis read code and/or hypoallergenic formula prescription for ≥3 months) examining healthcare data (medication prescriptions and healthcare professional contacts) from case records within The Health Improvement Network (A Cegedim Proprietary Database) in the UK. A comparative cost analysis was calculated based on healthcare tariff and unit costs in the UK. RESULTS: 6998 children (54% male; mean observation period 4.2 years) were included (n = 3499 with CMA, mean age at diagnosis 4.04 months; n = 3499 matched controls without CMA). Compared to those without CMA, medications were prescribed to significantly more children with CMA (p < 0.001) at a higher rate (p < 0.001). Children with CMA also required significantly more healthcare contacts (p < 0.001) at higher rate (p < 0.001) compared to those without CMA. CMA was associated with additional potential healthcare costs of £1381.53 per person per year. CONCLUSION: The findings of this large cohort study suggest that CMA and its associated co-morbidities presents a significant additional healthcare burden with economic impact due to higher prescribing of additional medications. Further research into management approaches that may impact these clinical and economic outcomes of CMA is warranted.

The clinical burden of cow's milk allergy in early childhood: A retrospective cohort study.

INTRODUCTION: Cow's milk allergy (CMA) is common in infants and children. Clinical presentations may vary, with a range of symptoms affecting the gastrointestinal (GI), skin and respiratory systems. Whilst the primary focus of research to date has been on the management of these symptoms, studies investigating the broader clinical burden of CMA are limited. METHODS: We performed a retrospective matched cohort study examining clinical data, including allergic symptoms and infections, extracted from case records within The Health Improvement Network database. A total of 6998 children (54% male) were included in the study, including 3499 with CMA (mean age at diagnosis 4.04 months) and 3499 matched controls without CMA, observed for a mean period of 4.2 years. RESULTS: GI, skin and respiratory symptoms affected significantly more children with CMA (p < .001), which recurred more often (p < .001), compared with children without CMA. More children with CMA had symptoms affecting multiple systems (p < .001). CMA was associated with a greater probability of these symptoms requiring hypoallergenic formula (HAF) prescription persisting over time (log-rank test p < .0001, unadjusted hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.76-0.85, p < .001), with a longer median duration of symptoms and HAF prescription compared with the duration of symptoms in those without CMA (3.48 vs. 2.96 years). GI, skin, respiratory and ear infections affected significantly more children with CMA than those without, increasing by 74% (p < .001), 20% (p < .001), 9% (p < .001), and 30% (p < .001) respectively. These infections also recurred more often among children with CMA, increasing by 62% for GI infections, 37% for skin and respiratory infections, and 44% for ear infections (p < .001). CONCLUSIONS: This real-world study provides evidence to suggest that CMA presents a significant clinical burden to children, which has implications for the healthcare system. Further research is warranted to understand the health economic impact of this, and the phenotypes, factors and management approaches which may affect clinical outcomes.

Atrial fibrillation epidemiology, disparity and healthcare contacts: a population-wide study of 5.6 million individuals.

Background: We aimed to evaluate atrial fibrillation occurrence, reasons for healthcare visits, mortality, causes of death and examined patterns by relative deprivation in the UK. Methods: To study the atrial fibrillation (AF) incidence, mortality and case-fatality, we implemented a prospective cohort study with the linked electronic health records of 5.6 million population in the United Kingdom Clinical Practice Research Datalink from 1998 to 2016. A matched case-control study was used to investigate causes of hospitalisation and death comparing individuals with and without incident AF. Results: During a median follow-up of 10.3 years, 199,433(3.6%) patients developed incident AF. Increased risk of hospitalisation for heart failure, cardiovascular conditions and infection was present among patients who later developed AF. Following an AF diagnosis, patients were frequently admitted to the hospital for heart failure, lower respiratory tract infection, chronic obstructive pulmonary disease and ischemic heart disease. One in 5 AF patients died during the first year after diagnosis, and the mortality increased to 42.7% at the fifth year. The excess deaths in AF cases compared to controls may result from cardiovascular diseases, infection and metabolic disorders. Individuals from areas with higher deprivation in socioeconomic and living status had both higher AF incidence and fatality. Interpretation: We observed an elevated risk of hospitalisation for cardiovascular or respiratory diseases among incident AF patients, and the considerable disparity in AF burden by socioeconomic deprivation informs priorities for prevention and provision of patient care. Funding: The study was supported by the GlaxoSmithKline, University College London Hospital and National Institute for Health Research. The funders did not have any role in study design, data collection, data analysis, interpretation, and writing of the report.

The Use of an Amino Acid Formula Containing Synbiotics in Infants with Cow's Milk Protein Allergy-Effect on Clinical Outcomes.

Cow's milk protein allergy (CMPA) is common and costly. Clinical trials of infants with CMPA have shown that the use of an amino acid formula containing pre- and probiotics (synbiotics) (AAF-Syn) may lead to significant reductions in infections, medication prescriptions and hospital admissions, compared to AAF without synbiotics. These effects have not yet been confirmed in real-world practice. This retrospective matched cohort study examined clinical and healthcare data from The Health Improvement Network database, from 148 infants with CMPA (54% male, mean age at diagnosis 4.69 months), prescribed either AAF-Syn (probiotic Bifidobacterium breve M16-V and prebiotics, including chicory-derived oligo-fructose and long-chain inulin) or AAF. AAF-Syn was associated with fewer symptoms (-37%, p < 0.001), infections (-35%, p < 0.001), medication prescriptions (-19%, p < 0.001) and healthcare contacts (-18%, p = 0.15) vs. AAF. Infants prescribed AAF-Syn had a significantly higher probability of achieving asymptomatic management without hypoallergenic formula (HAF) (adjusted HR 3.70, 95% CI 1.97-6.95, p < 0.001), with a shorter clinical course of symptoms (median time to asymptomatic management without HAF 1.35 years vs. 1.95 years). AAF-Syn was associated with potential cost-savings of £452.18 per infant over the clinical course of symptoms. These findings may be attributable to the effect of the specific synbiotic on the gut microbiome. Further research is warranted to explore this. This real-world study provides evidence consistent with clinical trials that AAF-Syn may produce clinical and healthcare benefits with potential economic impact.

Renin-angiotensin system inhibitors and susceptibility to COVID-19 in patients with hypertension: a propensity score-matched cohort study in primary care.

INTRODUCTION: Renin-angiotensin system (RAS) inhibitors have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This study investigated whether there is an association between their prescription and the incidence of COVID-19 and all-cause mortality. METHODS: We conducted a propensity-score matched cohort study comparing the incidence of COVID-19 among patients with hypertension prescribed angiotensin-converting enzyme I (ACE) inhibitors or angiotensin II type-1 receptor blockers (ARBs) to those treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 in each drug exposure group. We used Cox proportional hazards models to produce adjusted hazard ratios for COVID-19. We assessed all-cause mortality as a secondary outcome. RESULTS: The incidence rate of COVID-19 among users of ACE inhibitors and CCBs was 9.3 per 1000 person-years (83 of 18,895 users [0.44%]) and 9.5 per 1000 person-years (85 of 18,895 [0.45%]), respectively. The adjusted hazard ratio was 0.92 (95% CI 0.68 to 1.26). The incidence rate among users of ARBs was 15.8 per 1000 person-years (79 out of 10,623 users [0.74%]). The adjusted hazard ratio was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of RAS inhibitors and all-cause mortality. CONCLUSION: Use of ACE inhibitors was not associated with the risk of COVID-19 whereas use of ARBs was associated with a statistically non-significant increase compared to the use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality.

Association of Metformin with Susceptibility to COVID-19 in People with Type 2 Diabetes.

OBJECTIVE: Diabetes has emerged as an important risk factor for mortality from COVID-19. Metformin, the most commonly prescribed glucose-lowering agent, has been proposed to influence susceptibility to and outcomes of COVID-19 via multiple mechanisms. We investigated whether, in patients with diabetes, metformin is associated with susceptibility to COVID-19 and its outcomes. RESEARCH DESIGN AND METHODS: We performed a propensity score-matched cohort study with active comparators using a large UK primary care dataset. Adults with type 2 diabetes patients and a current prescription for metformin and other glucose-lowering agents (MF+) were compared to those with a current prescription for glucose-lowering agents that did not include metformin (MF-). Outcomes were confirmed COVID-19, suspected/confirmed COVID-19, and associated mortality. A negative control outcome analysis (back pain) was also performed. RESULTS: There were 29 558 and 10 271 patients in the MF+ and MF- groups, respectively, who met the inclusion criteria. In the propensity score-matched analysis, the adjusted hazard ratios for suspected/confirmed COVID-19, confirmed COVID-19, and COVID-19-related mortality were 0.85 (95% CI 0.67, 1.08), 0.80 (95% CI 0.49, 1.30), and 0.87 (95% CI 0.34, 2.20) respectively. The negative outcome control analysis did not suggest unobserved confounding. CONCLUSION: Current prescription of metformin was not associated with the risk of COVID-19 or COVID-19-related mortality. It is safe to continue prescribing metformin to improve glycemic control in patients with.

Sodium-glucose co-transporter-2 inhibitors and susceptibility to COVID-19: A population-based retrospective cohort study.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors are widely prescribed in people with type 2 diabetes. We aimed to investigate whether SGLT2 inhibitor prescription is associated with COVID-19, when compared with an active comparator. We performed a propensity-score-matched cohort study with active comparators and a negative control outcome in a large UK-based primary care dataset. Participants prescribed SGLT2 inhibitors (n = 9948) and a comparator group prescribed dipeptidyl peptidase-4 (DPP-4) inhibitors (n = 14 917) were followed up from January 30 to July 27, 2020. The primary outcome was confirmed or clinically suspected COVID-19. The incidence rate of COVID-19 was 19.7/1000 person-years among users of SGLT2 inhibitors and 24.7/1000 person-years among propensity-score-matched users of DPP-4 inhibitors. The adjusted hazard ratio was 0.92 (95% confidence interval 0.66 to 1.29), and there was no evidence of residual confounding in the negative control analysis. We did not observe an increased risk of COVID-19 in primary care amongst those prescribed SGLT2 inhibitors compared to DPP-4 inhibitors, suggesting that clinicians may safely use these agents in the everyday care of people with type 2 diabetes during the COVID-19 pandemic.

Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID-19.

OBJECTIVE: To identify whether active use of nonsteroidal antiinflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed coronavirus disease 2019 (COVID-19) compared to the use of other common analgesics. METHODS: We performed a propensity score-matched cohort study with active comparators, using a large UK primary care data set. The cohort consisted of adult patients age ≥18 years with osteoarthritis (OA) who were followed up from January 30 to July 31, 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine). A total of 13,202 patients prescribed NSAIDs were identified, compared to 12,457 patients prescribed the comparator drugs. The primary outcome measure was the documentation of suspected or confirmed COVID-19, and the secondary outcome measure was all-cause mortality. RESULTS: During follow-up, the incidence rates of suspected/confirmed COVID-19 were 15.4 and 19.9 per 1,000 person-years in the NSAID-exposed group and comparator group, respectively. Adjusted hazard ratios for suspected or confirmed COVID-19 among the unmatched and propensity score-matched OA cohorts, using data from clinical consultations in primary care settings, were 0.82 (95% confidence interval [95% CI] 0.62-1.10) and 0.79 (95% CI 0.57-1.11), respectively, and adjusted hazard ratios for the risk of all-cause mortality were 0.97 (95% CI 0.75-1.27) and 0.85 (95% CI 0.61-1.20), respectively. There was no effect modification by age or sex. CONCLUSION: No increase in the risk of suspected or confirmed COVID-19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic.