Disability-adjusted life years (DALYs) due to the direct health impact of COVID-19 in India, 2020.

COVID-19 has affected all countries. Its containment represents a unique challenge for India due to a large population (> 1.38 billion) across a wide range of population densities. Assessment of the COVID-19 disease burden is required to put the disease impact into context and support future pandemic policy development. Here, we present the national-level burden of COVID-19 in India in 2020 that accounts for differences across urban and rural regions and across age groups. Input data were collected from official records or published literature. The proportion of excess COVID-19 deaths was estimated using the Institute for Health Metrics and Evaluation, Washington data. Disability-adjusted life years (DALY) due to COVID-19 were estimated in the Indian population in 2020, comprised of years of life lost (YLL) and years lived with disability (YLD). YLL was estimated by multiplying the number of deaths due to COVID-19 by the residual standard life expectancy at the age of death due to the disease. YLD was calculated as a product of the number of incident cases of COVID-19, disease duration and disability weight. Scenario analyses were conducted to account for excess deaths not recorded in the official data and for reported COVID-19 deaths. The direct impact of COVID-19 in 2020 in India was responsible for 14,100,422 (95% uncertainty interval [UI] 14,030,129-14,213,231) DALYs, consisting of 99.2% (95% UI 98.47-99.64%) YLLs and 0.80% (95% UI 0.36-1.53) YLDs. DALYs were higher in urban (56%; 95% UI 56-57%) than rural areas (44%; 95% UI 43.4-43.6) and in men (64%) than women (36%). In absolute terms, the highest DALYs occurred in the 51-60-year-old age group (28%) but the highest DALYs per 100,000 persons were estimated for the 71-80 years old age group (5481; 95% UI 5464-5500 years). There were 4,815,908 (95% UI 4,760,908-4,924,307) DALYs after considering reported COVID-19 deaths only. The DALY estimations have direct and immediate implications not only for public policy in India, but also internationally given that India represents one sixth of the world's population.

Meta-analysis and adjusted estimation of COVID-19 case fatality risk in India and its association with the underlying comorbidities.

Management of coronavirus disease 2019 (COVID-19) in India is a top government priority. However, there is a lack of COVID-19 adjusted case fatality risk (aCFR) estimates and information on states with high aCFR. Data on COVID-19 cases and deaths in the first pandemic wave and 17 state-specific geodemographic, socio-economic, health and comorbidity-related factors were collected. State-specific aCFRs were estimated, using a 13-day lag for fatality. To estimate country-level aCFR in the first wave, state estimates were meta-analysed based on inverse-variance weighting and aCFR as either a fixed- or random-effect. Multiple correspondence analyses, followed by univariable logistic regression, were conducted to understand the association between aCFR and geodemographic, health and social indicators. Based on health indicators, states likely to report a higher aCFR were identified. Using random- and fixed-effects models, cumulative aCFRs in the first pandemic wave on 27 July 2020 in India were 1.42% (95% CI 1.19%-1.70%) and 2.97% (95% CI 2.94%-3.00%), respectively. At the end of the first wave, as of 15 February 2021, a cumulative aCFR of 1.18% (95% CI 0.99%-1.41%) using random and 1.64% (95% CI 1.64%-1.65%) using fixed-effects models was estimated. Based on high heterogeneity among states, we inferred that the random-effects model likely provided more accurate estimates of the aCFR for India. The aCFR was grouped with the incidence of diabetes, hypertension, cardiovascular diseases and acute respiratory infections in the first and second dimensions of multiple correspondence analyses. Univariable logistic regression confirmed associations between the aCFR and the proportion of urban population, and between aCFR and the number of persons diagnosed with diabetes, hypertension, cardiovascular diseases and stroke per 10,000 population that had visited NCD (Non-communicable disease) clinics. Incidence of pneumonia was also associated with COVID-19 aCFR. Based on predictor variables, we categorised 10, 17 and one Indian state(s) expected to have a high, medium and low aCFR risk, respectively. The current study demonstrated the value of using meta-analysis to estimate aCFR. To decrease COVID-19 associated fatalities, states estimated to have a high aCFR must take steps to reduce co-morbidities.

Public health interventions slowed but did not halt the spread of COVID-19 in India.

The government of India implemented social distancing interventions to contain the COVID-19 epidemic. However, effects of these interventions on epidemic dynamics are yet to be understood. Rates of laboratory-confirmed COVID-19 infections per day and effective reproduction number (Rt ) were estimated for 7 periods (Pre-lockdown, Lockdown Phases 1 to 4 and Unlock 1-2) according to nationally implemented interventions with phased relaxation. Adoption of these interventions was estimated using Google mobility data. Estimates at the national level and for 12 Indian states most affected by COVID-19 are presented. Daily case rates ranged from 0.03 to 285.60/10 million people across 7 discrete periods in India. From 18 May to 31 July 2020, the NCT of Delhi had the highest case rate (999/10 million people/day), whereas Madhya Pradesh had the lowest (49/10 million/day). Average Rt was 1.99 (95% CI 1.93-2.06) and 1.39 (95% CI 1.38-1.40) for the entirety of India during the period from 22 March 2020 to 17 May 2020 and from 18 May 2020 to 31 July 2020, respectively. Median mobility in India decreased in all contact domains during the period from 22 March 2020 to 17 May 2020, with the lowest being 21% in retail/recreation, except home which increased to 129% compared to the 100% baseline value. Median mobility in the 'Grocery and Pharmacy' returned to levels observed before 22 March 2020 in Unlock 1 and 2, and the enhanced mobility in the Pharmacy sector needs to be investigated. The Indian government imposed strict contact mitigation, followed by a phased relaxation, which slowed the spread of COVID-19 epidemic progression in India. The identified daily COVID-19 case rates and Rt will aid national and state governments in formulating ongoing COVID-19 containment plans. Furthermore, these findings may inform COVID-19 public health policy in developing countries with similar settings to India.

Comparative assessment of growth media and incubation conditions for enhanced recovery and isolation of Acinetobacter baumannii from aquatic matrices.

Acinetobacter baumannii causes serious multidrug resistant nosocomial infections around the world. This comprehensive comparative study was designed to assess the effect of temperature (30, 37 and 42 °C), incubation (aerobic and microaerobic) condition and selective [CHROMagar Acinetobacter (CHR) and Leeds Acinetobacter Medium (LAM)] and non-selective [Modified Karmali Agar (MKA)] growth media on the enhanced recovery of A. baumannii from a variety of water (agricultural, recreational, raw drinking intake source, pre-chlorinated and post-chlorinated wastewater effluent) samples spiked with a known number of A. baumannii cells. After spiking each water type with a known number of cells in 10 mL volume, the sample was passed through a membrane filter (pore size 0.45 µm) and filters were placed on different selective media plates and subjected to incubate at various incubation conditions. The results reported in this study show that for all water types tested (except post-chlorinated wastewater effluent), LAM was the most effective selective growth medium in combination with variable temperature and incubation conditions for yielding high recovery rates of A. baumannii cells. Overall, A. baumannii showed that it has a high adaptive capacity to grow on selective and non-selective growth media at different temperature and incubation conditions. The data described in this study suggest that no single incubation condition and growth media would efficiently recover A. baumannii from all environmental water types tested. This data also indicate that selective growth media and incubation condition can significantly affect the recovery of A. baumannii. Differences in recovery of A. baumannii observed in this study which appeared to be dependent on the temperature and environmental characteristics of incubation as well as the sample type, suggest the need for caution when comparing recovery using different protocols.

Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke. METHODS: For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0-1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018. FINDINGS: Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups. INTERPRETATION: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo. FUNDING: Canadian Institutes for Health Research, Alberta Innovates, and NoNO.

Modeling and Staging of Osteoarthritis Progression Using Serial CT Imaging and Arthroscopy.

OBJECTIVE: The objective of this study was to describe in life methods by which osteoarthritis can be staged in order to time therapeutic interventions that are relevant to osteoarthritis (OA) clinical trials. METHODS: Twenty-two sheep underwent arthroscopic meniscal destabilization to induce OA. Serial computed tomography (CT) imaging and arthroscopy were used to monitor osteoarthritis progression at 3-month intervals over 9 months. Eleven sheep received 1 intra-articular injection of hyaluronate 3 months after OA induction and another group of 11 received saline. A linear mixed model was used to define the trajectory of shape change in the medial joint compartment. Ordinal logistic regression was used to investigate the association between morphological changes and sclerosis. RESULTS: Three months after meniscal destabilization there were early bipolar chondral lesions in the medial compartment of the knee, as well as osteophytes and bone remodeling. Superficial fissures and cartilage cracks progressed to discrete areas of cartilage thinning and fibrillation on the medial tibial plateau by 6 months that became cartilage erosions by nine months. A linear mixed effect model demonstrated significant change in medial compartment length and width with over time (P < 0.05) for both groups. A significant association between severity of sclerosis and medial compartment morphology was also observed. CONCLUSIONS: The induction of osteoarthritic lesions with meniscal release model can be followed using noninvasive and minimally invasive procedures allowing for real-time decisions about redosing therapies, or other changes such as extending trial timelines without sacrificing animals to conduct assessments.

Association of Levels of Specialized Care With Risk of Premature Mortality in Patients With Epilepsy.

Importance: Patients with epilepsy are at an elevated risk of premature mortality. Interventions to reduce this risk are crucial. Objective: To determine if the level of care (non-neurologist, neurologist, or comprehensive epilepsy program) is negatively associated with the risk of premature mortality. Design, Setting, and Participants: In this retrospective open cohort study, all adult patients 18 years or older who met the administrative case definition for incident epilepsy in linked databases (Alberta Health Services administrative health data and the Comprehensive Calgary Epilepsy Programme Registry [CEP]) inclusive of the years 2002 to 2016 were followed up until death or loss to follow-up. The final analyses were performed on May 1, 2019. Exposures: Evaluation by a non-neurologist, neurologist, or epileptologist. Main Outcomes and Measures: The outcome was all-cause mortality. We used extended Cox models treating exposure to a neurologist or the CEP as time-varying covariates. Age, sex, socioeconomic deprivation, disease severity, and comorbid burden at index date were modeled as fixed-time coefficients. Results: A total 23 653 incident cases were identified (annual incidence of 89 per 100 000); the mean age (SD) at index date was 50.8 (19.1) years and 12 158 (50.3%) were women. A total of 14 099 (60%) were not exposed to specialist neurological care, 9554 (40%) received care by a neurologist, and 2054 (9%) received care in the CEP. In total, 4098 deaths (71%) occurred in the nonspecialist setting, 1481 (26%) for those seen by a neurologist, and 176 (3%) for those receiving CEP care. The standardized mortality rate was 7.2% for the entire cohort, 9.4% for those receiving nonspecialist care, 5.6% for those seen by a neurologist, and 2.8% for those seen in the CEP. The hazard ratio (HR) of mortality was lower in those receiving neurologist (HR, 0.85; 95% CI, 0.77-0.93) and CEP (HR, 0.49; 95% CI, 0.38-0.62) care. In multivariable modeling, specialist care, the age at index, and disease severity were retained in the final model of the association between specialist care and mortality. Conclusions and Relevance: Exposure to specialist care is associated with incremental reductions in the hazard of premature mortality. Those referred to a comprehensive epilepsy program received the greatest benefit.

Correction: Age-specific global epidemiology of hydrocephalus: Systematic review, metanalysis and global birth surveillance.

[This corrects the article DOI: 10.1371/journal.pone.0204926.].

Assessment of a Bidirectional Association Between Major Depressive Disorder and Alopecia Areata.

Importance: Alopecia areata (AA) is an autoimmune disease characterized by hair loss that can impose a substantial psychological burden on patients, including major depressive disorder (MDD), yet many patients report mental health symptoms prior to the onset of AA. As such, there may be an association between MDD and AA that acts in both directions. Objective: To assess the bidirectional association between MDD and AA. Design, Setting, and Participants: This population-based retrospective cohort study included patients 10 to 90 years of age registered with The Health Improvement Network in general practices in the United Kingdom between January 1, 1986, and May 16, 2012. Statistical analysis was conducted from August 17, 2017, to April 23, 2018. To assess the risk of AA, the following 2 cohorts were defined: patients with an incident diagnosis of MDD (exposure) and a reference general population cohort. To assess the risk of MDD, the following 2 cohorts were defined: patients with an incident diagnosis of AA (exposure) and a reference general population cohort. Person-time was partitioned into unexposed and exposed time in the exposure cohorts. Main Outcomes and Measures: In the analysis of the risk of AA, development of incident AA during follow-up was considered the main outcome measure. In the analysis of the risk of MDD, development of incident MDD during follow-up was considered the primary outcome measure. Results: In the analysis of the risk of AA, 405 339 patients who developed MDD (263 916 women and 141 423 men; median age, 36.7 years [interquartile range, 26.6-50.5 years]) and 5 738 596 patients who did not develop MDD (2 912 201 women and 2 826 395 men; median age, 35.8 years [interquartile range, 25.3-52.6 years]) were followed up for 26 years. After adjustment for covariates, MDD was found to increase the risk of subsequently developing AA by 90% (hazard ratio, 1.90; 95% CI, 1.67-2.15; P < .001). Antidepressants demonstrated a protective effect on the risk of AA (hazard ratio, 0.57; 95% CI, 0.53-0.62; P < .001). In the analysis of the risk of MDD, 6861 patients who developed AA (3846 women and 3015 men; median age, 31.5 years [interquartile range, 18.2 years]) and 6 137 342 patients who did not develop AA (3 172 371 women and 2 964 971 men; median age, 35.9 years [interquartile range, 27.0 years]) were followed up for 26 years. After adjustment for covariates, AA was found to increase the risk of subsequently developing MDD by 34% (hazard ratio, 1.34; 95% CI, 1.23-1.46; P < .001). Conclusions and Relevance: These temporal analyses suggest that, while patients with AA are at risk for subsequently developing MDD, having MDD also appears to be a significant risk factor for development of AA, with antidepressant use confounding this risk.

Depression increases the risk of inflammatory bowel disease, which may be mitigated by the use of antidepressants in the treatment of depression.

OBJECTIVE: Depression is associated with IBD, but the effect of antidepressants on IBD has been sparsely studied. We assessed the impact of depression and antidepressant therapies on the development of IBD. DESIGN: The Health Improvement Network (THIN) was used to identify a cohort of patients with new-onset depression from 1986 to 2012. THIN patients who did not meet the defining criteria for depression were part of the referent group. The outcome was incident Crohn's disease (CD) or ulcerative colitis (UC). Cox proportional hazards modelling was performed to evaluate the rate of Crohn's disease or UC development among patients with an exposure of depression after controlling for age, sex, socioeconomic status, comorbid conditions, smoking, anxiety and antidepressant use including atypical antidepressants, mirtazapine, monoamine oxidase inhibitors (MAOI), serotonin norepinephrine reuptake inhibitors (SNRI), selective serotonin reuptake inhibitors (SSRI), serotonin modulators; and tricyclic antidepressants (TCA). RESULTS: We identified 403 665 (7.05%) patients with incident depression. Individuals with depression had a significantly greater risk of developing CD (adjusted HR=2.11, 95% CI 1.65 to 2.70) and UC (adjusted HR=2.23, 95% CI 1.92 to 2.60) after controlling for demographic and clinical covariates. SSRI and TCA were protective against CD, whereas mirtazapine, SNRI, SSRI, serotonin modulators and TCA were protective for UC. CONCLUSION: Patients with a history of depression were more likely to be diagnosed with IBD. In contrast, antidepressant treatments were selectively protective for Crohn's disease and UC. These results may impact counselling and management of depression and IBD.

A multimodal (FACILE) classification for optical diagnosis of inflammatory bowel disease associated neoplasia.

BACKGROUND: Characterization of colonic lesions in inflammatory bowel disease (IBD) remains challenging. We developed an endoscopic classification of visual characteristics to identify colitis-associated neoplasia using multimodal advanced endoscopic imaging (Frankfurt Advanced Chromoendoscopic IBD LEsions [FACILE] classification). METHODS: The study was conducted in three phases: 1) development - an expert panel defined endoscopic signs and predictors of dysplasia in IBD and, using multivariable logistic regression created the FACILE classification; 2) validation - using 60 IBD lesions from an image library, two assessments of diagnostic accuracy for neoplasia were performed and interobserver agreement between experts using FACILE was determined; 3) reproducibility - the reproducibility of the FACILE classification was tested in gastroenterologists, trainees, and junior doctors after completion of a training module. RESULTS: The experts initially selected criteria such as morphology, color, surface, vessel architecture, signs of inflammation, and lesion border. Multivariable logistic regression confirmed that nonpolypoid lesion, irregular vessel architecture, irregular surface pattern, and signs of inflammation within the lesion were predictors of dysplasia. Area under the curve of this logistic model using a bootstrapped estimate was 0.76 (0.73 - 0.78). The training module resulted in improved accuracy and kappa agreement in all nonexperts, though in trainees and junior doctors the kappa agreement was still moderate and poor, respectively. CONCLUSION: We developed, validated, and demonstrated reproducibility of a new endoscopic classification (FACILE) for the diagnosis of dysplasia in IBD using all imaging modalities. Flat shape, irregular surface and vascular patterns, and signs of inflammation predicted dysplasia. The diagnostic performance of all nonexpert participants improved after a training module.

Vitiligo and major depressive disorder: A bidirectional population-based cohort study.

BACKGROUND: Vitiligo patients often report their mental health has an effect on their skin. However, it is unknown as to whether a common mental disorder, such as major depressive disorder (MDD), can also precipitate the onset of vitiligo. OBJECTIVE: Evaluate a bidirectional relationship between MDD and vitiligo using The Health Improvement Network database. METHODS: Incident MDD and referent cohorts were followed until the development of vitiligo. Also, incident vitiligo and referent cohorts were followed until the development of MDD. Cox proportional hazards models were used, and numerous covariates were adjusted for. RESULTS: In adjusted models, MDD patients (n = 405,397) were at a 64% increased risk for vitiligo (hazard ratio 1.64, 95% confidence interval [CI] 1.43-1.87, P < .0001) compared with the referent cohort (n = 5,739,048). This risk was decreased in patients using antidepressants. Compared with the referent cohort (n = 6,137,696), patients with vitiligo (n = 7104) that were <30 years of age at diagnosis had a higher risk of developing MDD than patients ≥30 years of age (hazard ratio 1.31, 95% CI 1.14-1.50, P < .0001 vs 1.22, 95% CI 1.08-1.37, P = .001, respectively). LIMITATIONS: This study did not evaluate the severity of MDD or vitiligo on outcome development. CONCLUSION: These results highlight the burden of depression in patients with vitiligo and support the possible existence of pathophysiological connections between these 2 conditions.

Increasing Rates of Arthroplasty for Psoriatic Arthritis in the United Kingdom Between 1995 and 2010.

OBJECTIVE: Arthroplasty requirements among patients with psoriatic arthritis (PsA) are not well known. This information is important to clinical and policy stakeholders for health-system planning and may serve as a surrogate for estimation of the efficacy of disease-modifying therapy. METHODS: We utilized The Health Improvement Network (THIN), a large general practice medical records database in the UK, to assess rates of primary total arthroplasty among patients with PsA and the general population between the years 1995 and 2010. Linear regression was used to estimate arthroplasty rates for the 2 cohorts during the study period, and Poisson regression was used to determine age- and sex-adjusted incidence rate ratios (IRRs) between the PsA and general population cohorts. RESULTS: We identified 5,619 patients with incident PsA and 5,090,814 eligible patients from the general population between 1995 and 2010. In total, 187 primary total arthroplasties were documented in patients with PsA, and 80,163 primary total arthroplasties were documented in the general population. A trend of increasing arthroplasty rates was observed for both the PsA (R2 = 0.809; P < 0.0001) and general population (R2 = 0.890; P < 0.0001) cohorts during the study period. After adjustment for age and sex, patients with PsA had a first arthroplasty incidence rate that was twice that of the general population (IRR 2.01 [95% confidence interval 1.73-2.34]; P < 0.0001), notably beyond the year 2003 when biologic therapies were introduced. CONCLUSION: Both the general population and patients with PsA have experienced increasing rates of first arthroplasty from 1995 to 2010, although the overall incidence rate was significantly higher for those with PsA.

Age-specific global epidemiology of hydrocephalus: Systematic review, metanalysis and global birth surveillance.

BACKGROUND: Hydrocephalus is a debilitating disorder, affecting all age groups. Evaluation of its global epidemiology is required for healthcare planning and resource allocation. OBJECTIVES: To define age-specific global prevalence and incidence of hydrocephalus. METHODS: Population-based studies reporting prevalence of hydrocephalus were identified (MEDLINE, EMBASE, Cochrane, and Google Scholar (1985-2017)). Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Two authors reviewed abstracts, full text articles and abstracted data. Metanalysis and meta-regressions were used to assess associations between key variables. Heterogeneity and publication bias were assessed. Main outcome of interest was hydrocephalus prevalence among pediatric (≤ 18 years), adults (19-64 years), and elderly (≥ 65) patients. Annual hydrocephalus incidence stratified by country income level and folate fortification requirements were obtained (2003-2014) from the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). RESULTS: Of 2,460 abstracts, 52 met review eligibility criteria (aggregate population 171,558,651). Mean hydrocephalus prevalence was 85/100,000 [95% CI 62, 116]. The prevalence was 88/100,000 [95% CI 72, 107] in pediatrics; 11/100,000 [95% CI 5, 25] in adults; and 175/100,000 [95% CI 67, 458] in the elderly. The ICBDSR-based incidence of hydrocephalus diagnosed at birth remained stable over 11 years: 81/100,000 [95% CI 69, 96]. A significantly lower incidence was identified in high-income countries. CONCLUSION: This systematic review established age-specific global hydrocephalus prevalence. While high-income countries had a lower hydrocephalus incidence according to the ICBDSR registry, folate fortification status was not associated with incidence. Our findings may inform future healthcare resource allocation and study.

Depression as a risk factor for the development of rheumatoid arthritis: a population-based cohort study.

OBJECTIVES: Major depressive disorder (MDD) is associated with increased levels of systemic proinflammatory cytokines, including tumour necrosis factor alpha. As these cytokines are pathogenic in autoimmune diseases such as rheumatoid arthritis (RA), our aim was to explore on a population-level whether MDD increases the risk of developing RA. METHODS: A retrospective cohort study was conducted using The Health Improvement Network (THIN) database (from 1986 to 2012). Observation time was recorded for both the MDD and referent cohorts until patients developed RA or were censored. Cox proportional hazards models were used to determine the risk of developing RA among patients with MDD, accounting for age, sex, medical comorbidities, smoking, body mass index and antidepressant use. RESULTS: A cohort of 403 932 patients with MDD and a referent cohort of 5 339 399 patients without MDD were identified in THIN. Cox proportional hazards models revealed a 31% increased risk of developing RA among those with MDD in an unadjusted model (HR=1.31, 95% CI 1.25 to 1.36, p<0.0001). When adjusting for all covariates, the risk remained significantly increased among those with MDD (HR=1.38, 95% CI 1.31 to 1.46, p<0.0001). Antidepressant use demonstrated a confounding effect that was protective on the association between MDD and RA. CONCLUSION: MDD increased the risk of developing RA by 38%, and antidepressants may decrease this risk in these patients. Future research is necessary to confirm the underlying mechanism of MDD on the pathogenesis of RA.

Psoriasis and the risk of foot and ankle tendinopathy or enthesopathy in the absence of psoriatic arthritis: a population-based study.

OBJECTIVES: Imaging studies in patients with cutaneous psoriasis have demonstrated asymptomatic bone and tendon changes, commonly of the foot and ankle. We sought to determine if patients with cutaneous psoriasis have an increased risk of clinically significant foot and ankle tendinopathy or enthesopathy compared with the general population. METHODS: Patients with cutaneous psoriasis and a general population cohort were identified in The Health Improvement Network, a general practice medical records database from the UK. All patients with psoriatic arthritis were excluded. Cox proportional-hazards models (α=0.05) estimated the HR for development of foot and ankle tendinopathy or enthesopathy among patients with psoriasis, with adjustment for numerous covariates. RESULTS: In total, 78 630 patients with cutaneous psoriasis and 5 983 338 persons from the general population were identified. In an unadjusted model, patients with cutaneous psoriasis had a 25% increased risk of developing foot and ankle tendinopathy or enthesopathy compared with the general population (HR 1.25, 95% CI 1.20 to 1.30, p<0.0001). The HR remained unchanged and statistically significant after adjusting for covariates, and in sensitivity analyses. CONCLUSIONS: These data suggest that patients with psoriasis can have foot and ankle tendinopathy or enthesopathy without having psoriatic arthritis, presenting a diagnostic challenge to physicians. Further research is needed to elucidate mechanisms contributing to this increased risk.

Prescription trends and psychiatric symptoms following first receipt of one of seven common antiepileptic drugs in general practice.

We sought to examine the risk of psychiatric symptoms associated with a first prescription for specific antiepileptic drugs (AEDs) used in monotherapy in a general cohort of patients with epilepsy. We used The Health Improvement Network database (comprising the years 2000-2012) to identify incident patients with epilepsy. The index date was that on which they met the case definition for epilepsy, and analyses only included patients who remained on monotherapy or received no AED therapy following diagnosis to avoid confounding by polytherapy. Psychiatric symptoms were defined using mental health clinical or treatment (medical or therapeutic) code. We analyzed the AED of interest as a time-varying covariate in multivariate Cox proportional hazard regression models controlling for confounding factors. We identified 9595 patients with incident epilepsy, 7400 of whom (77%) received a first-recorded AED prescription. Prescriptions for newer generation AEDs (lamotrigine and levetiracetam) steadily increased (constituting over 30% of all AED prescriptions by 2012) while valproate use significantly declined in females (~40% in 2002 to just over 20% by 2012). A total of 2190 patients were first exposed to carbamazepine (29.3%) and 222 to lamotrigine (3%), both of which were associated with a lower hazard of any coded psychiatric symptom or disorder in multivariate analyses (hazard ratio [HR]: 0.84, 95% confidence interval [95% CI]: 0.73-0.97; p = 0.02 and HR: 0.83, 95% CI: 0.70-0.99; p = 0.03, respectively, for carbamazepine and lamotrigine). Carbamazepine was also associated with a lower hazard for depression (HR: 0.81; 95% CI: 0.69-0.96; p = 0.013) and anxiety (HR: 0.77; 95% CI: 0.63-0.95; p = 0.013) in secondary analyses. This study provides evidence that carbamazepine and lamotrigine are associated with lower hazards for psychiatric symptoms following a diagnosis of epilepsy. These estimates can be used in clinical settings, and the precision should improve with more contemporary data that include larger proportions of newer generation AEDs.

Development and validation of the SIMPLE endoscopic classification of diminutive and small colorectal polyps.

BACKGROUND: Prediction of histology of small polyps facilitates colonoscopic treatment. The aims of this study were: 1) to develop a simplified polyp classification, 2) to evaluate its performance in predicting polyp histology, and 3) to evaluate the reproducibility of the classification by trainees using multiplatform endoscopic systems. METHODS: In phase 1, a new simplified endoscopic classification for polyps - Simplified Identification Method for Polyp Labeling during Endoscopy (SIMPLE) - was created, using the new I-SCAN OE system (Pentax, Tokyo, Japan), by eight international experts. In phase 2, the accuracy, level of confidence, and interobserver agreement to predict polyp histology before and after training, and univariable/multivariable analysis of the endoscopic features, were performed. In phase 3, the reproducibility of SIMPLE by trainees using different endoscopy platforms was evaluated. RESULTS: Using the SIMPLE classification, the accuracy of experts in predicting polyps was 83 % (95 % confidence interval [CI] 77 % - 88 %) before and 94 % (95 %CI 89 % - 97 %) after training (P â€Š= 0.002). The sensitivity, specificity, positive predictive value, and negative predictive value after training were 97 %, 88 %, 95 %, and 91 %. The interobserver agreement of polyp diagnosis improved from 0.46 (95 %CI 0.30 - 0.64) before to 0.66 (95 %CI 0.48 - 0.82) after training. The trainees demonstrated that the SIMPLE classification is applicable across endoscopy platforms, with similar post-training accuracies for narrow-band imaging NBI classification (0.69; 95 %CI 0.64 - 0.73) and SIMPLE (0.71; 95 %CI 0.67 - 0.75). CONCLUSIONS: Using the I-SCAN OE system, the new SIMPLE classification demonstrated a high degree of accuracy for adenoma diagnosis, meeting the ASGE PIVI recommendations. We demonstrated that SIMPLE may be used with either I-SCAN OE or NBI.

Control of glycemia and blood pressure in British adults with diabetes mellitus and subsequent therapy choices: a comparison across health states.

BACKGROUND: To examine the intensity of glycemic and blood pressure control in British adults with diabetes mellitus and whether control levels or treatment deintensification rates differ across health states. METHODS: Retrospective cohort study using primary care electronic medical records (the United Kingdom Health Improvement Network Database) for adults with diabetes diagnosed at least 6 months before the index HbA1C and systolic blood pressure (SBP) measurements (to give their primary care physicians time to achieve treatment goals). We used prescribing records for 6 months pre/post the index measurements to determine who had therapy subsequently deintensified (based on "glycemic therapy score" and "antihypertensive therapy score" derived from number and dosage of medications). RESULTS: Of 292,170 individuals with diabetes, HbA1C < 6% or SBP < 120 mmHg after at least 6 months of management was less common in otherwise fit patients (15.0 and 12.7%) than in those who were mildly frail (16.6 and 13.2%) or moderately-severely frail (20.2 and 17.0%, both p < 0.0001). In the next 6 months, only 44.7% of those with HbA1C < 6% had glycemic therapy reduced (44.4% of fit, 47.1% of mildly frail, and 41.5% of moderate-severely frail patients) and 39.8% of those with SBP < 120 had their antihypertensives decreased (39.3% of fit, 43.0% of mildly frail, and 46.7% of moderate-severely frail patients). On the other hand, more individuals exhibited higher than recommended levels for HbA1C or SBP after the first 6 months of therapy (37.3, 33.4, and 31.3% of fit, mildly frail, and moderately-severely frail patients had HbA1C > 7.5% and 46.6, 51.4, and 48.5% had SBP > 140 mmHg). The proportions of patients with HbA1C or SBP out of recommended treatment ranges changed little 6 months later despite frequent (median 14 per year) primary care visits. CONCLUSIONS: Glycemic and hypertensive control exhibited statistically significant but small magnitude differences across frailty states. Medication deintensification was uncommon, even in frail patients below SBP and HbA1C targets. SBP levels were more likely to be outside recommended treatment ranges than glycemic levels. Trial registration As this study is a retrospective secondary analysis of electronic medical record data and not a health care intervention trial it was not registered.