Incidence of Strabismus Post-Plaque Brachytherapy in Patients With Uveal Melanoma.

PURPOSE: To determine the incidence and type of strabismus in patients with uveal melanoma treated with plaque brachytherapy. DESIGN: Multicenter, retrospective incidence estimation study. METHODS: A total of 438 eyes of 438 patients with uveal melanoma treated with plaque brachytherapy between October 2011 and May 2021. Intervention was Iodine 125, and Palladium 103 plaque brachytherapy. The variables reviewed included incidence of nonresolving strabismus post-plaque brachytherapy, type of strabismus developed, extraocular muscles operated, and modality of treatment received. RESULTS: A total of 438 patients underwent plaque brachytherapy treatment for uveal melanoma. Eleven patients developed strabismus post-plaque brachytherapy (2.5%, n = 11/438). Of these patients, 5 (1.1%, n = 5/438) developed strabismus immediately postoperation. Specifically, 2 patients (0.5%, n = 2/438) developed strabismus immediately postoperation due to slipped muscles, 2 patients (0.5%, n = 2/438) due to decompensated phorias, and 1 patient (0.5%, n = 1/438) due to a fibrotic muscle. Six patients (1.4%, n = 6/438) developed late-onset sensory strabismus. A total of 355 patients (81.1%, n = 355/438) had their extraocular muscles disinserted during surgery, with the lateral rectus being the most common, accounting for 45.4% (n = 161/355), followed by the superior rectus at 26.8% (n = 95/355). Strabismus surgery was the most common treatment modality, comprising 72.7% (n = 8/11) of patients. CONCLUSIONS: The incidence of strabismus after plaque brachytherapy treatment for uveal melanoma was low and primarily classified as late-onset sensory strabismus. Previous studies may underestimate the long-term incidence of strabismus after plaque brachytherapy by focusing primarily on strabismus present immediately postoperatively.

Risk of secondhand smoke exposure and severity of COVID-19 infection: multicenter case-control study.

Introduction: Exposure to secondhand smoke (SHS) is an established causal risk factor for cardiovascular disease (CVD) and chronic lung disease. Numerous studies have evaluated the role of tobacco in COVID-19 infection, severity, and mortality but missed the opportunity to assess the role of SHS. Therefore, this study was conducted to determine whether SHS is an independent risk factor for COVID-19 infection, severity, mortality, and other co-morbidities. Methodology: Multicentric case-control study was conducted across six states in India. Severe COVID-19 patients were chosen as our study cases, and mild and moderate COVID-19 as control were evaluated for exposure to SHS. The sample size was calculated using Epi-info version 7. A neighborhood-matching technique was utilized to address ecological variability and enhance comparability between cases and controls, considering age and sex as additional matching criteria. The binary logistic regression model was used to measure the association, and the results were presented using an adjusted odds ratio. The data were analyzed using SPSS version 24 (SPSS Inc., Chicago, IL, USA). Results: A total of 672 cases of severe COVID-19 and 681 controls of mild and moderate COVID-19 were recruited in this study. The adjusted odds ratio (AOR) for SHS exposure at home was 3.03 (CI 95%: 2.29-4.02) compared to mild/moderate COVID-19, while SHS exposure at the workplace had odds of 2.19 (CI 95%: 1.43-3.35). Other factors significantly related to the severity of COVID-19 were a history of COVID-19 vaccination before illness, body mass index (BMI), and attached kitchen at home. Discussion: The results of this study suggest that cumulative exposure to secondhand cigarette smoke is an independent risk factor for severe COVID-19 illness. More studies with the use of biomarkers and quantification of SHS exposure in the future are needed.

The Need to Set up a Biobank Dedicated to Lymphoid Malignancies: Experience of a Single Center (Laboratory of Clinical and Experimental Pathology, University Côte d'Azur, Nice, France).

Several therapies to improve the management of lymphoma are currently being investigated, necessitating the development of new biomarkers. However, this requires high-quality and clinically annotated biological material. Therefore, we established a lymphoma biobank including all available biological material (tissue specimens and matched biological resources) along with associated clinical data for lymphoma patients diagnosed, according to the WHO classification, between 2005 and 2022 in the Laboratory of Clinical and Experimental Pathology, Nice, France. We retrospectively included selected cases in a new collection at the Côte d'Azur Biobank, which contains 2150 samples from 363 cases (351 patients). The male/female ratio was 1.3, and the median age at diagnosis was 58 years. The most common lymphoma types were classical Hodgkin lymphoma, diffuse large B-cell lymphoma, and extra-nodal marginal zone lymphoma of MALT tissue. The main sites of lymphoma were the mediastinum, lymph node, Waldeyer's ring, and lung. The Côte d'Azur Biobank is ISO 9001 and ISO 20387 certified and aims to provide high quality and diverse biological material to support translational research projects into lymphoma. The clinico-pathological data generated by this collection should aid the development of new biomarkers to enhance the survival of patients with lymphoid malignancies.

A First Look at Equity, Diversity, and Inclusion of Canadian Medical Physicists: Results From the 2021 COMP EDI Climate Survey.

PURPOSE: In 2021, the Canadian Organization of Medical Physicists (COMP) conducted its first equity, diversity, and inclusion Climate Survey. The membership's experiences of inclusion, belonging, professional opportunities, discrimination, microaggressions, racism, and harassment in their professional lives are presented. METHODS AND MATERIALS: The ethics-reviewed survey was distributed in English and French to full members of COMP. Participants responded to questions covering demographics and professional climate. Simple descriptive statistics were used to measure frequency of responses. Data pertaining to impressions on the climate within the profession were compared using nonparametric statistical tests. RESULTS: The survey was distributed to 649 eligible members; 243 (37%) responded, and 214 (33%) provided full response sets. From the full response sets, findings showed that in general, age, highest academic degree, and racial and ethnic distribution trends of medical physicists were comparable with previously collected data and/or the Canadian population. The experiences of respondents relating to harassment in the workplace and perception of climate are reported and provide a useful benchmark for future assessments of interventions or training programs. In the workplace, fewer women (58%) reported having professional opportunities compared with men (70%). The survey also found that 17% of respondents (most of whom were women) directly or indirectly experienced sexual harassment in the workplace within the past 5 years. Finding that 23% of survey respondents identified as having a disability is a valuable reminder that accommodations in the workplace are necessary for more than 1 in every 5 medical physicists working in clinics. CONCLUSIONS: This study provided insight into the diversity and experiences of medical physicists in Canada. The majority of respondents had positive perceptions about their professional environment. However, equity-lacking groups were identified, such as women, underrepresented minorities, Indigenous peoples, and people with visible and invisible disabilities.

Evaluation of a Hospitalized Pediatric COVID-19 Cohort from Indian National Clinical Registry of COVID-19.

OBJECTIVE: To evaluate the factors associated with mortality of a multicentric cohort of hospitalized COVID-19 patients, 0-18 y old, from 42 centers across India. METHODS: The National Clinical Registry for COVID-19 (NCRC) is an on-going prospective data collection platform enrolling COVID-19 patients diagnosed by real-time PCR or rapid antigen test. The data are collected in prestructured e-capture forms. The sociodemographic, clinical, laboratory, and hospital outcome data from 1st September 2020 to 20th February 2022 were analyzed. RESULTS: Of the 1244 enrolled hospitalized COVID-19 patients aged 0-18 y, 98 and 124 were infants and neonates, respectively. Only 68.6% children were symptomatic at admission, with fever being the most common symptom. Diarrhea, rash, and neurological symptoms were also noted. At least 1 comorbidity was present in 260 (21%) children. The in-hospital mortality rate was 6.2% (n = 67), the highest in infants (12.5%). Altered sensorium (aOR: 6.8, CI: 1.9, 24.6), WHO ordinal scale ≥ 4 at admission (aOR: 19.6, CI: 8.0, 47.8), and malignancy (aOR: 8.9, 95% CI: 2.4, 32.3) were associated with higher odds of death. Malnutrition did not affect the outcome. Mortality rates were similar across the three waves of the pandemic, though a significant shift towards the under-five group was observed in the third wave. CONCLUSION: This multicentric cohort of admitted Indian children showed that the COVID-19 was milder in children than adults, and the pattern was consistent across all waves of the pandemic.

Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type diffuse large B-cell lymphoma.

Despite the effectiveness of immuno-chemotherapy, 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience relapse or refractory disease. Longitudinal studies have previously focused on the mutational landscape of relapse but fell short of providing a consistent relapse-specific genetic signature. In our study, we have focused attention on the changes in GEP accompanying DLBCL relapse using archival paired diagnostic/relapse specimens from 38 de novo patients with DLBCL. COO remained stable from diagnosis to relapse in 80% of patients, with only a single patient showing COO switching from activated B-cell-like (ABC) to germinal center B-cell-like (GCB). Analysis of the transcriptomic changes that occur following relapse suggest ABC and GCB relapses are mediated via different mechanisms. We developed a 30-gene discriminator for ABC-DLBCLs derived from relapse-associated genes that defined clinically distinct high- and low-risk subgroups in ABC-DLBCLs at diagnosis in datasets comprising both population-based and clinical trial cohorts. This signature also identified a population of <60-year-old patients with superior PFS and OS treated with ibrutinib-R-CHOP as part of the PHOENIX trial. Altogether this new signature adds to the existing toolkit of putative genetic predictors now available in DLBCL that can be readily assessed as part of prospective clinical trials.

Management of Uveal Melanoma: Updated Cancer Care Alberta Clinical Practice Guideline.

OBJECTIVE: The purpose of this guideline update is to reassess and update recommendations in the prior guideline from 2016 on the appropriate management of patients with uveal melanoma. METHODS: In 2021, a multidisciplinary working group from the Provincial Cutaneous Tumour Team, Cancer Care Alberta, Alberta Health Services was convened to update the guideline. A comprehensive review of new research evidence in PubMed as well as new clinical practice guidelines from prominent oncology groups informed the update. An enhancement in methodology included adding levels of evidence and strength of recommendations. The updated guideline was circulated to all members of the Provincial Cutaneous Tumour Team for review and endorsement. RESULTS: New and modified recommendations address provider training requirements, diagnostic imaging for the detection of metastases, neo-adjuvant pre-enucleation radiotherapy, intravitreal anti-vascular endothelial growth factor agents for radiation retinopathy, genetic prognostic testing, surveillance following definitive local therapy, and systemic therapy for patients with metastatic uveal melanoma. DISCUSSION: The recommendations represent evidence-based standards of care agreed to by a large multidisciplinary group of healthcare professionals.

Estimates of major non-communicable disease risk factors for India, 2010 & 2015: A summary of evidence.

Background & objectives: The National Monitoring Framework for the prevention and control of NCDs in India has set targets for reduction of risk factors relative to the measure recorded in 2010. Estimates for 2010 and 2015 were established using meta-analyses in the absence of a national risk factor survey till 2017. Methods: We searched national survey reports and also articles published in English from India between 2008 and 2017 in PubMed, Google Scholar and Cochrane review databases for specific risk factors among 18-69 yr Indians. Quality of studies was evaluated using Joanna-Briggs tool, but all studies were included in analyses. Estimates for each of the eight strata by age, gender and place of residence, respectively, were generated. MetaXL was used to calculate the pooled estimate for 2010 and 2015 using a random effects model. Strata-specific estimates were combined to arrive at national estimate using population weight of each stratum. The credibility of the estimates was determined using four parameters - average Briggs score; representativeness of the contributing studies and precision and stability of the estimates. Results: The estimates [95% confidence interval (CI)] for 2010 for different risk factors were as follows: current alcohol use, 15.7 per cent (13.2-18.2); current tobacco use, 27 per cent (21.4-32.6); household solid fuel use, 61.5 per cent (50.2-72.5); physical inactivity, 44.2 per cent (37.8-50.6); obesity, seven per cent (3.8-10.2) and raised blood pressure, 20.2 per cent (18.4-22.1). In 2015, compared to 2010, tobacco use showed a relative decline of 18 per cent, household solid fuel use of nine per cent and physical inactivity of 15 per cent. The estimates were stable for alcohol use, raised blood pressure and obesity between 2010 and 2015. All estimates varied between moderate and high degrees of credibility. Interpretation & conclusions: The estimates are consistent with other available estimates and with current national-level initiatives focused on tobacco control and improving access to clean fuel. These estimates can be used to monitor progress on non-communicable disease risk factor targets for India.

Non-Locatable Internal Opening in Anal Fistula Associated with Acute Abscess and Its Definitive Management by Garg Protocol.

Background: Definitive management of acute fistula-abscess (anal fistulas associated with acute abscess) is gaining popularity against the two-staged approach (early abscess drainage with deferred fistula management). However, locating an internal opening (IO) in acute fistula-abscess can be difficult. A recent protocol (Garg protocol) has been shown to be effective in managing anal fistulas with non-locatable IO. Purpose: To test the efficacy of the Garg protocol in managing acute fistula-abscess with non-locatable IO. Methods: Patients with acute fistula-abscess operated by a definitive procedure were included. A preoperative MRI was done in all patients. Patients in whom the IO was non-locatable after clinical, MRI, and intraoperative examination were managed by the three-step Garg protocol. Garg protocol: 1) Reassessment of MRI; 2) In non-horseshoe fistulas, the IO was assumed to be at the point where the fistula tract reached closest to the sphincter-complex; 3) In horseshoe fistulas, the IO was assumed to be located in the midline (anterior or posterior as per the horseshoe location). Low fistulas were treated by fistulotomy and high fistulas by a sphincter-sparing procedure. The long-term healing rate and change in continence (Vaizey scores) were evaluated. Results: A total of 201 patients with acute fistula-abscess were operated over six years, and 19 were lost to follow-up. A total of 182 patients (154-males) were followed up (median-37 months). The IO was locatable in 133/182 (73.1%) (control group) and was non-locatable in 49/182 (26.9%) (study group). The study group was managed as per the Garg protocol. The age, sex-ratio, and fistula parameters were comparable in both groups. The long-term healing rate was 112/133(84.2%) in the IO-locatable group and 43/49 (87.8%) in the IO-non-locatable group (p=0.64, not-significant). The objective continence scores did not change significantly after surgery in both groups. Conclusion: Acute fistula-abscess with non-locatable IO can be managed successfully by the Garg protocol without any risk of incontinence.

Efficacy of Kegel exercises in preventing incontinence after partial division of internal anal sphincter during anal fistula surgery.

BACKGROUND: The transanal opening of intersphincteric space (TROPIS) procedure, performed to treat complex anal fistulas, preserves the external anal sphincter (EAS) but involves partial incision of the internal anal sphincter (IAS). AIM: To ascertain the incidence of incontinence after the division of the IAS as is done in TROPIS and to evaluate whether regular Kegel exercises (KE) in the postoperative period can prevent incontinence due to IAS division. METHODS: Patients operated on for high complex fistulas and having no preoperative continence problem (score = 0) were included in the study. All patients were operated on by the TROPIS procedure and were recommended KE (pelvic contraction exercises) 50 times/day. KE were commenced on the 10th postoperative day and continued for 1 year. Incontinence was evaluated objectively (by modified Vaizey's scores) in the immediate postoperative period (Pre-KE group) and on long-term follow-up (Post-KE group). The incontinence scores in both groups were compared to evaluate the efficacy of KE. RESULTS: Of 102 anal fistula patients operated on between July 2018 and July 2020 were included in this study. There were 90 males, the mean age was 42.3 ± 12.8, and the median follow-up was 30 mo (18-42 mo). Three patients were lost to follow-up. There were 65 recurrent fistulas, 92 had multiple tracts, 42 had associated abscess, 46 had horseshoe fistula and 34 were supralevator fistulas. All were magnetic resonance imaging-documented high fistulas (> 1/3 EAS involved). Overall incontinence occurred in 31% patients (Pre-KE group) with urge and gas incontinence accounting for the majority of cases (28.3%). The mean incontinence scores in the Pre-KE group were 1.19 ± 1.96 (in 31 patients, solid = 0, liquid = 7, gas = 8, urge = 24) and in the Post-KE group were 0.26 ± 0.77 (in 13 patients, solid = 0, liquid = 2, gas = 3, urge = 10) (P = 0.00001, t-test). CONCLUSION: Division of the IAS led to incontinence, mainly urge incontinence, and also to a mild degree of gas and liquid incontinence. However, regular KE led to a significant reduction in incontinence (both in the number of affected patients and the severity of scores in these patients).

Mortality Associated with Ambient PM2.5 Exposure in India: Results from the Million Death Study.

BACKGROUND: Studies on the extent to which long-term exposure to ambient particulate matter (PM) with aerodynamic diameter ≤2.5µm (PM2.5) contributes to adult mortality in India are few, despite over 99% of Indians being exposed to levels that the World Health Organization (WHO) considers unsafe. OBJECTIVE: We conducted a retrospective cohort study within the Million Death Study (MDS) to provide the first-ever quantification of national mortality from exposure to PM2.5 in India from 1999 to 2014. METHODS: We calculated relative risks (RRs) by linking a total of ten 3-y intervals of satellite-based estimated PM2.5 exposure to deaths 3 to 5 y later in over 7,400 small villages or urban blocks covering a total population of 6.8 million. We applied using a model-based geostatistical model, adjusted for individual age, sex, and year of death; smoking prevalence, rural/urban residency, area-level female illiteracy, languages, and spatial clustering and unit-level variation. RESULTS: PM2.5 exposure levels increased from 1999 to 2014, particularly in central and eastern India. Among 212,573 deaths at ages 15-69 y, after spatial adjustment, we found a significant RR of 1.09 [95% credible interval (CI): 1.04, 1.14] for stroke deaths per 10-µg/m3 increase in PM2.5 exposure, but no significant excess for deaths from chronic respiratory disease and ischemic heart disease (IHD), all nonaccidental causes, and total mortality (after excluding stroke). Spatial adjustment attenuated the RRs for chronic respiratory disease and IHD but raised those for stroke. The RRs were consistent in various sensitivity analyses with spatial adjustment, including stratifying by levels of solid fuel exposure, by sex, and by age group, addition of climatic variables, and in supplementary case-control analyses using injury deaths as controls. DISCUSSION: Direct epidemiological measurements, despite inherent limitations, yielded associations between mortality and long-term PM2.5 inconsistent with those reported in earlier models used by the WHO to derive estimates of PM2.5 mortality in India. The modest RRs in our study are consistent with near or null mortality effects. They suggest suitable caution in estimating deaths from PM2.5 exposure based on MDS results and even more caution in extrapolating model-based associations of risk derived mostly from high-income countries to India. https://doi.org/10.1289/EHP9538.

Deep Learning using Pre-Brachytherapy MRI to Automatically Predict Applicator Induced Complex Uterine Deformation.

This novel deep-learning (DL) algorithm addresses the challenging task of predicting uterine shape and location when deformed from its natural anatomy by the presence of an intrauterine (tandem)/intravaginal (ring) applicator during brachytherapy (BT) treatment for locally advanced cervical cancer. Paired pelvic MRI datasets from 92 subjects, acquired without (pre-BT) and with (at-BT) applicators, were used. We propose a novel automated algorithm to segment the uterus in pre-BT MR images using a deep convolutional neural network (CNN) incorporated with autoencoders. The proposed neural net is based on a pre-trained CNN Inception V4 architecture. It predicts a compressed vector by applying a multi-layer autoencoder, which is then back-projected into the segmentation contour of the uterus. Following this, another transfer learning approach using a modified U-net model is employed to predict the at-BT uterus shape from pre-BT MRI. The complex and large deformations of the uterus are quantified using free form deformation method. The proposed algorithm yielded an average Dice Coefficient (DC) of 94.1±3.3 and an average Hausdorff Distance (HD) of 4.0±3.1 mm compared to the manually defined ground truth by expert clinicians. Further, the modified U-net prediction of the at-BT uterus resulted in a DC accuracy of 88.1±3.8 and HD of 5.8±3.6 mm. The mean uterine surface point-to-point displacement was 25.0 [10.0-62.5] mm from the pre-BT position. Our unique DL method can thus successfully predict tandem-deformed uterine shape and position from MR images taken before the BT implant procedure i.e. without the applicator in place. Clinical relevance-The proposed DL-based framework can be incorporated as an automatic prediction tool of uterine deformation due to applicator insertion for personalized BT treatments. It holds promise for more streamlined clinical/technical decision-making before BT applicator insertion resulting in improved dosimetric outcomes.

Assessment of Community Behavior and COVID-19 Transmission during Festivities in India: A Qualitative Synthesis through a Media Scanning Technique.

In India during the first wave of COVID-19 infection, the authorities were concerned about the advent of the festive season, which could lead to a surge in cases of SARS-CoV-2 infection. The present study attempted to assess the socio-behavioral aspects of COVID-appropriate behavior (CAB) at individual and community levels, and their impact on the transmission of COVID-19 during festivities in India. Media scanning was conducted to qualitatively assess CAB by analyzing 284 news reports from across India; quantitative data on COVID-19 daily cases from March 2020 to December 2020 were used to determine the trends of the adjusted test positivity (ATP) ratio for six cities. Peaks in ATP were observed in Chandigarh, Delhi-NCR in North India during and after Dussehra and Deepavali, and in Mumbai, in the west, after Navratri. Additionally, a surge in ATP was observed in Trivandrum after Onam and in Chennai around Deepavali in the south; meanwhile, in the eastern city of Kolkata, cases increased following Durga Puja. The major challenges were adherence to CAB viz. social distancing, hygiene, and compliance with the mask mandate. Microlevel CAB indicated relatively higher laxity in maintaining hand hygiene in all cities. Observations from the current study indicate that innovative community-driven initiatives during festivals in each geographical zone are key to the large-scale implementation of disease prevention measures.

Brachytherapy workflow for locally advanced cervical cancer: A survey of Canadian Medical Physicists.

PURPOSE: To report on brachytherapy (BT) workflows for image-based treatments of locally advanced cervical cancer (CC) in Canada. METHODS: Medical Physicists in every Canadian cancer center were contacted and those with a CC-BT program were emailed a 44-item electronic questionnaire surveying workflow patterns including: fractionation schedules, prescription, equipment, imaging, and treatment delivery. RESULTS: Of 47 centers contacted, all 34 who performed CC-BT participated in the survey. Brachytherapy boost, following external beam treatments, was delivered using high-dose-rate (HDR); one center also used pulsed-dose-rate. Intracavitary and/or interstitial treatments were done in 47% centers for 25-80% of their patients. All centers used image-based planning: CT (32%), CT planned with MRI for contouring (47%), MRI (18%), or cone beam CT (3%). For those performing volume-based planning (74%), the contours commonly included Clinical Target Volume (CTV)-High Risk (HR), CTV-Intermediate Risk, rectum, sigmoid, and bladder. The most common HDR dose-fractionation schedule was 7 [4.6 - 10] Gy in 4 [3 - 6] fractions with radiobiological dose prescriptions performed in 62% centers. Medical physics contribution was significant during most activities along the BT treatment pathway in all centers, especially in planning (88%), second checks (68%), and during treatment delivery (88%). CONCLUSIONS: Compared to previous surveys, there is an increasing trend in the use of image-based volumetric planning, interstitial procedures, and radiobiological dose prescription. Cervical cancer brachytherapy in Canada is becoming more streamlined with the use of international practice guidelines. Involvement of medical physicists is vital to all stages of CC-BT, including program implementation, routine quality control, dosimetry, and treatment delivery.

Burden of cancers in India - estimates of cancer crude incidence, YLLs, YLDs and DALYs for 2021 and 2025 based on National Cancer Registry Program.

BACKGROUND: Cancer is the major cause of morbidity and mortality worldwide. The cancer burden varies within the regions of India posing great challenges in its prevention and control. The national burden assessment remains as a task which relies on statistical models in many developing countries, including India, due to cancer not being a notifiable disease. This study quantifies the cancer burden in India for 2016, adjusted mortality to incidence (AMI) ratio and projections for 2021 and 2025 from the National Cancer Registry Program (NCRP) and other publicly available data sources. METHODS: Primary data on cancer incidence and mortality between 2012 and 2016 from 28 Population Based Cancer Registries (PBCRs), all-cause mortality from Sample Registration Systems (SRS) 2012-16, lifetables and disability weight from World Health Organization (WHO), the population from Census of India and cancer prevalence using the WHO-DisMod-II tool were used for this study. The AMI ratio was estimated using the Markov Chain Monte Carlo method from longitudinal NCRP-PBCR data (2001-16). The burden was quantified at national and sub-national levels as crude incidence, mortality, Years of Life Lost (YLLs), Years Lived with Disability (YLDs) and Disability Adjusted Life Years (DALYs). The projections for the years 2021 and 2025 were done by the negative binomial regression model using STATA. RESULTS: The projected cancer burden in India for 2021 was 26.7 million DALYsAMI and expected to increase to 29.8 million in 2025. The highest burden was in the north (2408 DALYsAMI per 100,000) and northeastern (2177 DALYsAMI per 100,000) regions of the country and higher among males. More than 40% of the total cancer burden was contributed by the seven leading cancer sites - lung (10.6%), breast (10.5%), oesophagus (5.8%), mouth (5.7%), stomach (5.2%), liver (4.6%), and cervix uteri (4.3%). CONCLUSIONS: This study demonstrates the use of reliable data sources and DisMod-II tools that adhere to the international standard for assessment of national and sub-national cancer burden. A wide heterogeneity in leading cancer sites was observed within India by age and sex. The results also highlight the need to focus on non-leading sites of cancer by age and sex. These findings can guide policymakers to plan focused approaches towards monitoring efforts on cancer prevention and control. The study simplifies the methodology used for arriving at the burden estimates and thus, encourages researchers across the world to take up similar assessments with the available data.

Association of lipoprotein (a) with coronary artery disease in a South Asian population: A case-control study.

INTRODUCTION: Coronary artery disease (CAD), the leading cause of mortality worldwide, is characterised by an earlier onset and more severe disease in South Asians as compared to Western populations. METHODS: This is an observational study on 928 individuals who attended three tertiary care centres in Kerala, India from 2014-to 2017. The demographic, anthropometric, behavioural factors and the lipoprotein (Lp(a)) and cholesterol values were compared between the two groups and across disease severity. The Chi-square test was used to compare the categorical variables and independent sample t-test for the continuous variables. Multivariable logistic regression was performed to investigate the association of demographic, clinical and behavioural factors with the disease. Odds ratios are presented with a 95% confidence interval. In individuals below 50 years, two logistic regression models were compared to investigate the improvement in modelling the association of the independent factors and Lp(a) with the occurrence of the disease. RESULTS: We included 682 patients in the diseased group and 246 patients treated for non-coronary conditions in the control group. Those in the control group were significantly younger than in the diseased group(p<0.002). Significantly more patients were diabetic, hypertensive, tobacco users and consumers of alcohol in the diseased group. Multivariable logistic regression on data from all age groups showed that age (OR = 2.55, 95% CI 1.51-4.33, p = 0.01), diabetes (OR = 3.71, 95% CI 2.42-5.70, p = 0.01), hypertension (OR = 3.03, 95% CI 2.12-4.34, p = 0.01) and tobacco use (OR = 5.44, 95% CI 3.39-8.75, p = 0.01) are significantly associated with the disease. Lp(a) (OR = 1.22, 95% CI 0.87-1.72) increased the odds of the disease by 22% but was not statistically significant. In individuals below 50 years, Lp(a) significantly increased the likelihood of CAD (OR = 3.52, 95% CI 1.63-7.57, p = 0.01). Those with diabetes were seven times more likely to be diseased (OR = 7.06, 95% CI 2.59-19.21, p = 0.01) and the tobacco users had six times the likelihood of disease occurrence (OR = 6.38, 95% CI 2.62-15.54, p = 0.01). The median Lp(a) values showed a statistically significant increasing trend with the extent/severity of the disease in those below 50 years. CONCLUSION: Age, diabetes, hypertension and tobacco use appear to be associated more with the occurrence of coronary artery disease in adults of all ages. Lipoprotein(a), cholesterol and BMI categories do not seem to be related to disease status in all ages. However, in individuals below 50 years, diabetes, tobacco use and lipoprotein (a) are significantly associated with the occurrence of the disease.

Uncertainties Associated with Clonogenic Assays using a Cs-137 Irradiator and Ir-192 Afterloader: A Comprehensive Compilation for Radiation Researchers.

Clonogenic assays are the gold standard for measuring cell clonogenic survival and enable quantification of a cell line's radiosensitivity through the calculation of the surviving fraction, the ratio of cell clusters (colonies) formed after radiation exposure compared to the number formed without exposure. Such studies regularly utilize Cs-137 irradiators. While uncertainties for specific procedural aspects have been described previously, a comprehensive review has not been completed. We therefore quantified uncertainties associated with clonogenic assays performed using a Cs-137 Shepherd irradiator, and a recently established brachytherapy afterloader in vitro radiation delivery apparatus (BAIRDA), through a series of experiments and a literature review. The clonogenic assay is subject to uncertainties that affect the determination of the surviving fraction (e.g., accuracy of the number of cells seeded, potential effects of hypothermia, and the threshold number of cells for a cluster to be identified as a colony). Furthermore, dose delivery uncertainties related to both the Cs-137 irradiator and BAIRDA were also quantified. The combined standard (k = 1) uncertainty was ± 6.0% in the surviving fraction for the Cs-137 irradiator (±6.3% for BAIRDA), up to ± 2.2% in the dose delivered by the Cs-137 irradiator, and up to ± 4.3% in the dose delivered by BAIRDA. The largest individual uncertainties were associated with the number of cells seeded on a plate (3.4%) and inter-observer variability in counting (4.1%), suggesting that effective reduction of uncertainties in the conduct of the clonogenic assay may provide the greatest relief on the uncertainty budget. Finally, measurable impact on experimental findings was assessed by applying this uncertainty to clonogenic assays of SW756 cells using either a Cs-137 irradiator or BAIRDA, introducing a maximum shift in the reported radiobiological parameters α/ß and T1/2 of 0.3 Gy and 0.4 h, respectively, while the 95% confidence interval increased by 0.5 Gy and decreased by 0.4 h, respectively. Though the overall impact on radiobiological parameter estimation was small, the individual uncertainties could have a significant influence in other applications of in vitro experiments in radiation biology. Hence, better understanding of the uncertainties associated with both clonogenic assays and the radiation source used can improve the accuracy of experimental analysis and reproducibility of the results.

Disability Weights Estimates From India in 2018: Measurements From Community Members From Two Distinct States of India.

Background: India is undergoing a rapid demographic and epidemiologic transition. Thus demanding prioritization of diseases based on burden estimation is befitting our cultural diversity. Disability weights (DWs) by Global burden of disease (GBD) studies may not be representative. Hence, a study was conducted to estimate state-specific disability weights to capture the community health perceptions that included urban-rural settings as well as different socio-economic and literacy levels. Methods: A total of 2,055 community members (participants) from two distinct states of India, Odisha and Telangana, were interviewed to assign disability weights to the selected 14 health states based on the state burden and relevance. Each health state was described to the participants using pictorial representations of the health states and valuated using visual analog scale and card sort methods. Results: We noted that DWs in Odisha ranged from 0.32 (0.30-0.34) for upper limb fracture due to road traffic accident (least severe) to 0.90 (0.88-0.93) for breast cancer (most severe) among the 14 health states. While, in Telangana, diarrhea was considered least severe [DW = 0.22 (0.19-0.24)] and breast cancer remained most severe [DW = 0.85 (0.83-0.88)] as in Odisha. Marked difference in the DWs for other health states was also seen. Further, on comparison of community weights with GBD weights using Spearman correlation, we observed a low correlation (ρ = 0.104). Conclusion: Our study provides community-based findings that show how participants valued noncommunicable diseases higher than short-term ailments or infectious diseases. Additionally, the low correlation between GBD also suggests the need for local disability weights rather than universal acceptance. We therefore recommend that decisions in policy-making, especially for resource allocation and priority setting, need to be based not only on expert opinion but also include community in accordance with high scientific standards.

A Novel MRI and Clinical-Based Scoring System to Assess Post-Surgery Healing and to Predict Long-Term Healing in Cryptoglandular Anal Fistulas.

BACKGROUND: Anal fistulas cause great uncertainty and anxiety in patients and surgeons alike. This is largely because of the inability to accurately confirm postoperative fistula healing, especially long-term healing. There is no scoring system available that can objectively assess cryptoglandular anal fistulas for postoperative healing and can also accurately predict long-term healing. METHODS: Several parameters that could indicate anal fistula healing were assessed. Out of these, six parameters (four MRI-based and two clinical) were finalized, and a weighted score was given to each parameter. A novel scoring system (NSS) was developed. A minimum possible score (zero) indicated complete healing whereas the maximum weighted score (n = 20) indicated confirmed non-healing. Scoring was done with postoperative MRI (at least 3 months post-surgery), then compared with the actual healing status, and subsequently correlated with the final long-term clinical outcome. RESULTS: The NSS was validated in 183 operated cryptoglandular fistula-in-ano patients over a 3-year period in whom 283 MRIs (preoperative plus postoperative) were performed. The postoperative follow-up was 12-48 months (median-30 months). The NSS was found to have a very high positive predictive value (98.2%) and moderately high negative predictive value (83.7%) for long-term fistula healing. Additionally, its sensitivity and specificity in predicting healing were 93.9% and 94.7%, respectively. CONCLUSION: Thus, this new scoring system is highly accurate and would be a useful tool for surgeons and radiologists managing anal fistulas. By objectivizing the assessment of postoperative healing, it can both ease and streamline management. Moreover, reliable prediction of recurrence-free long-term healing will greatly allay the apprehensions associated with this dreaded disease.