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.

The Lung Immune Prognostic Index Discriminates Survival Outcomes in Patients with Solid Tumors Treated with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICI) have revolutionized the treatment landscape of several solid tumor types. However, as patient outcomes are heterogeneous, clinical tools to aid in prognostication are needed. The Lung Immune Prognostic Index (LIPI) correlates with outcomes in patients with non-small cell lung cancer (NSCLC) treated with ICI, but its applicability beyond NSCLC is poorly defined. We sought to determine whether LIPI is associated with overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in a pooled, real-world, retrospective cohort of patients with solid tumors treated with ICI. Of the total pooled cohort (N = 578), 47.2%, 38.2% and 14.5% of patients were stratified into good, intermediate and poor LIPI group, respectively. Median OS were 22.8 (95% CI 17.4-29.5), 7.8 (95% CI 6.6-9.6), and 2.5 months (95% CI 1.4-3.4) (p < 0.0001). Median PFS were 9.9 (95% CI 7.2-11.5), 3.6 (95% CI 2.7-4.3), and 1.4 months (95% CI 1.2-2.2) (p < 0.0001). ORR was also associated with LIPI group (p < 0.001). Intermediate and poor LIPI were independently prognostic of OS compared to good LIPI, with hazard ratios (HR) of 1.8 (95% CI 1.4-2.3, p < 0.001) and 3.6 (95% CI 2.5-5.1, p < 0.001), respectively. These data are the first to suggest that in a real-world setting, the prognostic value of LIPI may be tumor agnostic.

Effect of a Commercially Available Footwear Insole on Biomechanical Variables Associated With Common Running Injuries.

OBJECTIVE: To determine whether Dr. Scholl's Active Series (DSAS) footwear insoles alter biomechanical variables associated with running injuries. DESIGN: Randomized, controlled experiment. SETTING: Sport medicine and biomechanics gait analysis laboratory. PARTICIPANTS: Fifteen healthy adults. INTERVENTIONS: The control condition was the participant's own athletic footwear. The experimental condition was the participant's own athletic footwear plus a DSAS insole. Participants completed running gait analysis trials with each condition. MAIN OUTCOME MEASURES: Peak vertical loading rates (VLRs), peak ankle eversion velocities (AEVs), peak ankle eversion angles (AEAs), and knee abduction angular impulses (KAAIs) were calculated and compared between the control and DSAS conditions because these variables have been associated with plantar fasciitis (VLRs), tibial stress syndrome (AEVs, AEAs), and patellofemoral pain syndrome (KAAIs). RESULTS: Dr. Scholl's Active Series insoles reduced VLRs across participants by 16% (P < 0.001) but had no consistent influence on AEVs, AEAs, or KAAIs. Participant-specific responses showed that most runners either experienced AEA and KAAI reductions or no change with the DSAS insole, whereas AEVs commonly increased with the DSAS insole. CONCLUSIONS: Dr. Scholl's Active Series insoles demonstrate efficacy in reducing VLRs, which are associated with plantar fasciitis. Biomechanical changes to variables associated with tibial stress syndrome (AEVs, AEAs) and patellofemoral pain syndrome (KAAIs) were inconsistent.

A Review of Perforator Flaps for Burn Scar Contractures of Joints.

OBJECTIVE: Perforator flaps are one possible surgical treatment for burn scar contractures; however, a review of evidence on this topic is lacking. METHODS: MEDLINE was searched for articles related to perforator flaps for burn contractures. Following title and abstract screen, full texts were searched to identify articles describing perforator flaps for burn scar joint contractures. Data were extracted and summarized descriptively. Only articles that contained ≥10 patients with burn scar contracture were considered. RESULTS: Two hundred forty-eight articles were identified, of which 17 met criteria for review. Of these, 16 were low-quality case series, while 1 was an open randomized controlled trial. In total, perforator flaps were performed on 339 patients (age range: 3-75 years), with the most common contracture locations being cervical (n = 218) and knee (n = 41). Nine of the 17 articles described a rehabilitation strategy. In general, functional outcomes were excellent, with the majority of patients experiencing return of normal joint range of motion and no recontracture. Compared to full-thickness skin grafts, perforator flaps showed greater improvements in joint range of motion. Cosmetically, perforator flaps were shown to have good color match with surrounding tissue, good contour around anatomical landmarks, and improved overall patient appearance. The most common complications were marginal flap necrosis (n = 26 patients) and venous congestion (n = 17 patients). CONCLUSIONS: Preliminary evidence from low-quality case series and 1 high-quality trial suggests perforator flaps may be successful for resurfacing released burn scar contractures; however, there is a need for additional trials comparing perforator flaps to other approaches.

OBJECTIF: Les lambeaux perforateurs font partie des traitements chirurgicaux des contractures des cicatrices de brûlure, mais il n'y a pas d'analyse des données probantes sur le sujet. MÉTHODOLOGIE: Les chercheurs ont effectué une recherche dans MEDLINE pour extraire les articles liés aux lambeaux perforateurs pour les contractures causées par des brûlures. Après un filtrage en fonction des titres et des résumés, ils ont fouillé les textes intégraux et retenu les articles décrivant les lambeaux perforateurs pour corriger les contractures causées par des cicatrices de brûlure. Ils ont extrait les données et procédé à un résumé descriptif. Ils n'ont évalué que les articles portant sur au moins dix patients ayant des contractures causées par des cicatrices de brûlure. RÉSULTATS: Les chercheurs ont extrait 248 articles, dont 17 respectaient les critères d'analyse. De ce nombre, 16 étaient des séries de cas de faible qualité et un, un essai aléatoire et contrôlé ouvert. Au total, 339 patients (de trois à 75 ans) ont reçu des lambeaux perforateurs, et les contractures étaient surtout situées dans la région du cou (n = 218) et du genou (n = 41). Neuf des 17 articles décrivaient une stratégie de réadaptation. En général, les résultats fonctionnels étaient excellents, car la majorité des patients retrouvaient une amplitude de mouvements normale et n'avaient plus de contractures. Par rapport aux greffes cutanées pleine épaisseur, les lambeaux perforateurs assuraient une plus grande amélioration de l'amplitude du mouvement articulaire. Sur le plan esthétique, les lambeaux perforateurs assuraient un bel appariement de couleur par rapport aux tissus avoisinants, un beau contour des repères anatomiques et une amélioration globale de l'apparence. Les principales complications étaient une nécrose du lambeau marginal (n = 26 patients) et une congestion veineuse (n = 17 patients). CONCLUSIONS: D'après les données probantes préliminaires de séries de cas de faible qualité et d'un essai de haute qualité, les lambeaux perforateurs peuvent être utiles pour le resurfaçage de contractures causées par des cicatrices de brûlure. D'autres études devront être réalisées pour comparer les lambeaux perforateurs à d'autres approches.

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.

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.

Effects of medical scribes on physician productivity in a Canadian emergency department: a pilot study.

BACKGROUND: Emergency department efficiency is a priority across Canada. In the United States, scribes may increase the number of patients seen per hour per physician; however, Canadian data are lacking. We sought to implement scribes in a Canadian emergency department with the hypothesis that scribes would increase the number of patients seen per hour per physician. METHODS: We conducted a 4-month quality improvement pilot study in a community emergency department in Ottawa, Ontario. Data collection began January 2015 after scribe training. Physicians received shifts with and without a scribe for a period of 4 months. Across the study, the mean number of patients seen per hour was determined for each physician during shifts with and without a scribe. We compared mean (± standard deviation [SD]) number of patients seen per hour based on presence or absence of a scribe by 2-tailed paired-samples t test. RESULTS: Eleven scribes participated and ranged in age from 18 to 23 years. Twenty-two full- or part-time emergency physicians were followed. We documented 463 physician-hours without use of a scribe and 693.75 physician-hours with use of a scribe. Across all 22 physicians, 18 (81.8%) saw more patients per hour with use of a scribe. Overall, the number of patients seen per hour per physician was significantly greater (+12.9%) during shifts with a scribe (mean [± SD] 2.81 [± 0.78]) than during shifts without a scribe (mean [± SD] 2.49 [± 0.60]; p = 0.006). INTERPRETATION: In this pilot study, the use of scribes resulted in an increased number of patients seen per hour per physician. Because this was a small study at a single centre, further research on the effects of scribes in Canada is warranted.

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.

Foot structure and knee joint kinetics during walking with and without wedged footwear insoles.

The relationship between static foot structure characteristics and knee joint biomechanics during walking, or the biomechanical response to wedged insoles are currently unknown. In this study, 3D foot scanning, dual X-ray absorptiometry and gait analysis methods were used to determine structural parameters of the foot and assess their relation to knee joint loading and biomechanical response to wedged insoles in 30 patients with knee osteoarthritis. In multiple linear regression models, foot fat content, height of the medial longitudinal arch and static hind foot angle were not associated with the magnitude of the knee adduction moment (R2 = 0.24, p = 0.060), knee adduction angular impulse (R2 = 0.21, p = 0.099) or 3D resultant knee moment (R2 = 0.23, p = 0.073) during gait. Furthermore, these foot structure parameters were not associated with the patients' biomechanical response to medial or lateral wedge footwear insoles (all p < 0.01). These findings suggest that static foot structure is not associated with gait mechanics at the knee, and that static foot structure alone cannot be utilized to predict an individual's biomechanical response to wedged footwear insoles in patients with knee osteoarthritis.

Depression Is Associated with an Increased Risk of Psoriatic Arthritis among Patients with Psoriasis: A Population-Based Study.

The factors that contribute to the development of psoriatic arthritis (PsA) among patients with psoriasis are not well known; however, systemic inflammation is believed to be important. On the basis of recent laboratory work demonstrating that major depressive disorder (MDD) is associated with increased systemic inflammation, we hypothesized that patients with psoriasis who develop MDD are at increased risk of subsequently developing PsA. We utilized The Health Improvement Network, a primary care medical records database, to identify 73,447 individuals with psoriasis. Patients were followed up to 25 years until the development of the primary outcome of PsA or the censor date. The exposure of interest was the development of MDD. Cox proportional-hazards models showed that patients with psoriasis who developed MDD were at significantly increased risk of subsequently developing PsA compared with patients who did not develop MDD, even after accounting for numerous covariates (hazard ratio 1.37, 95% confidence interval 1.05-1.80, P = 0.021). This result was maintained through numerous sensitivity analyses. These data support the hypothesis that MDD increases the risk of developing PsA among patients with psoriasis, suggesting a need for heightened prevention and management of MDD in patients with psoriasis.

Biomechanics in dermatology: Recent advances and future directions.

Biomechanics is increasingly being recognized as an important research area in dermatology. To highlight only a few examples, biomechanics has contributed to the development of novel topical therapies for aesthetic and medical purposes, enhanced our understanding of the pathogenesis of plantar melanoma, and provided insight into the epidemiology of psoriatic disease. This article summarizes the findings from recent studies to demonstrate the important role that biomechanics may have in dermatologic disease and therapy and places these biomechanical findings in a clinical context for the practicing physician. In addition, areas for future biomechanics research and development in dermatology are discussed.