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Nevin Manimala Statistics

Safety and Efficacy of B-Cell Depletion with Rituximab for the Treatment of Systemic Sclerosis Associated Pulmonary Arterial Hypertension: A Multi-center, Double-blind, Randomized, Placebo-controlled Trial

Am J Respir Crit Care Med. 2021 Mar 2. doi: 10.1164/rccm.202009-3481OC. Online ahead of print.

ABSTRACT

RATIONALE: Systemic sclerosis-pulmonary arterial hypertension (SSc-PAH) is one of the most prevalent and deadly forms of PAH. B cells may contribute to SSc pathogenesis.

OBJECTIVE: We investigated the safety and efficacy of B-cell depletion for SSc-PAH.

METHODS AND MEASUREMENTS: In an NIH-sponsored, multi-center, double-blinded, randomized, placebo-controlled, proof-of-concept trial, 57 SSc-PAH patients on stable-dose standard medical therapy received two infusions of 1000 mg of rituximab or placebo administered two weeks apart. The primary outcome measure was the change in six-minute walk distance (6MWD) at 24 weeks. Secondary endpoints included safety and invasive hemodynamics. We applied a machine learning approach to predict drug-responsiveness.

MAIN RESULTS: We randomized 57 subjects from 2010-2018. In the primary analysis, using data through week 24, the adjusted mean change in 6MWD at 24 weeks favored the treatment arm but did not reach statistical significance (23.6±11.1m vs. 0.5±9.7m, p=0.12). While a negative study, when data through week 48 were also considered, the estimated change in 6MWD at week 24 was 25.5±8.8m for rituximab and 0.4±7.4m for placebo (p=0.03). Rituximab treatment appeared to be safe and well tolerated. Low levels of rheumatoid factor (RF), IL-12, and IL-17 were sensitive and specific as favorable predictors of a rituximab response as measured by an improved 6MWD (ROC AUC 0.88-0.95).

CONCLUSIONS: B cell depletion therapy is a potentially effective and safe adjuvant treatment for SSc-PAH. Future studies in these patients can confirm whether the identified biomarkers predict rituximab-responsiveness. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT01086540.

PMID:33651671 | DOI:10.1164/rccm.202009-3481OC

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Nevin Manimala Statistics

Batch Coherence-Driven Network for Part-aware Person Re-Identification

IEEE Trans Image Process. 2021 Mar 2;PP. doi: 10.1109/TIP.2021.3060909. Online ahead of print.

ABSTRACT

Existing part-aware person re-identification methods typically employ two separate steps: namely, body part detection and part-level feature extraction. However, part detection introduces an additional computational cost and is inherently challenging for low-quality images. Accordingly, in this work, we propose a simple framework named Batch Coherence-Driven Network (BCD-Net) that bypasses body part detection during both the training and testing phases while still learning semantically aligned part features. Our key observation is that the statistics in a batch of images are stable, and therefore that batch-level constraints are robust. First, we introduce a batch coherence-guided channel attention (BCCA) module that highlights the relevant channels for each respective part from the output of a deep backbone model. We investigate channel-part correspondence using a batch of training images, then impose a novel batch-level supervision signal that helps BCCA to identify part-relevant channels. Second, the mean position of a body part is robust and consequently coherent between batches throughout the training process. Accordingly, we introduce a pair of regularization terms based on the semantic consistency between batches. The first term regularizes the high responses of BCD-Net for each part on one batch in order to constrain it within a predefined area, while the second encourages the aggregate of BCD-Net’s responses for all parts covering the entire human body. The above constraints guide BCD-Net to learn diverse, complementary, and semantically aligned part-level features. Extensive experimental results demonstrate that BCD-Net consistently achieves state-of-the-art performance on four large-scale ReID benchmarks.

PMID:33651691 | DOI:10.1109/TIP.2021.3060909

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Nevin Manimala Statistics

Examining Tweet Content and Engagement of Canadian Public Health Agencies and Decision-Makers during COVID-19: Mixed Methods Analysis

J Med Internet Res. 2021 Feb 17. doi: 10.2196/24883. Online ahead of print.

ABSTRACT

BACKGROUND: Effective communication during a health crisis can ease public concerns and promote the adoption of important risk-mitigating behaviors. Public health agencies and leaders have served as the primary communicators of information related to COVID-19 and a key part of their public outreach has taken place on social media platforms.

OBJECTIVE: This study examined the content and engagement of COVID-19 Tweets authored by Canadian public health agencies and decision-makers. We propose ways that public health accounts can adjust their Tweeting practices during public health crises to improve risk communication and maximize engagement.

METHODS: We retrieved data from Tweets by Canadian public health agencies and decision-makers from January 1st, 2020 to June 30th, 2020. The Twitter accounts were categorized as either a public health agency, regional/local health department, provincial health authority, medical health officer, or minister of health. We analyzed trends in COVID-19 Tweet engagement and conducted a content analysis on a stratified random sample of 485 Tweets to examine the message functions and risk communication strategies used by each account type.

RESULTS: We analyzed 32,737 Tweets authored by 111 Canadian public health Twitter accounts, of which 6,982 Tweets were about COVID-19. Medical health officers authored the largest percentage of COVID-related Tweets (35%) relative to total Tweets, and averaged the highest number of retweets per COVID-19 Tweet (60 retweets per Tweet). Public health agencies had the highest frequency of daily Tweets about COVID-19 throughout the study period. Compared to Tweets containing media and user-mentions, hashtags and URLs were used in Tweets more frequently by all account types, appearing in 69% and 68% of COVID-related Tweets, respectively. Tweets containing hashtags also received the highest average retweets (47 retweets per Tweet). Our content analysis revealed that of the three Tweet message functions analyzed (information, action, community), Tweets providing information constituted the largest share (42%); however, Tweets promoting actions from users received higher average retweets (55 retweets per Tweet). When examining Tweets that received one or more retweet (n=359), the difference between mean retweets across the message functions was statistically significant (P<.001). Risk communication strategies that we examined were not widely used by any account type, only appearing in 262 out of 485 Tweets. However, when these strategies were used, these Tweets received more retweets compared to Tweets that did not use any risk communication strategies (P<.001) (61 retweets versus 13 retweets on average).

CONCLUSIONS: Public health agencies and decision-makers ought to examine what messaging best meets the needs of their Twitter audiences to maximize shares of their communications. Public health accounts that do not currently employ risk communication strategies in their Tweets may be missing an important opportunity to engage with information users about the mitigation of health risks related to COVID-19.

PMID:33651705 | DOI:10.2196/24883

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Nevin Manimala Statistics

Socioeconomic inequalities in physical and cognitive functioning: cross-sectional evidence from 37 cohorts across 28 countries in the ATHLOS project

J Epidemiol Community Health. 2021 Mar 1:jech-2020-214714. doi: 10.1136/jech-2020-214714. Online ahead of print.

ABSTRACT

BACKGROUND: Physical and cognitive functioning in older age follows a socioeconomic gradient but it is unclear whether the strength of the association differs between populations. Using harmonised data from an international collaboration of cohort studies, we assessed socioeconomic inequalities in physical and cognitive functioning and explored if the extent of inequalities varied across countries based on their economic strength or wealth distribution.

METHODS: Harmonised data from 37 population-based cohorts in 28 countries were used, with an overall sample size of 126 765. Socioeconomic position of participants was indicated by education and household income. Physical functioning was assessed by self-reported mobility and activities of daily living; and cognitive functioning by memory and verbal fluency tests. Relative (RII) and slope (SII) index of inequality were calculated in each cohort, and their association with the source country’s Gross Domestic Product (GDP) and Gini-index was assessed with correlation and cross-level interaction in multilevel models.

RESULTS: RII and SII values indicated consistently higher risk of low physical and cognitive functioning in participants with lower education or income across cohorts. Regarding RII, there were weak but statistically significant correlations and interactions with GDP and Gini-index, suggesting larger inequalities in countries with lower Gini-index and higher GDP. For SII, no such correlations were observed.

CONCLUSION: This study confirms that socioeconomic inequalities in physical and cognitive functioning exist across different social contexts but the magnitude of these inequalities varies. Relative inequalities appear to be larger in higher-income countries but it remains to be seen whether such observation can be replicated.

PMID:33649052 | DOI:10.1136/jech-2020-214714

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Evaluating the health effect of a Social Housing programme, Minha Casa Minha Vida, using the 100 million Brazilian Cohort: a natural experiment study protocol

BMJ Open. 2021 Mar 1;11(3):e041722. doi: 10.1136/bmjopen-2020-041722.

ABSTRACT

INTRODUCTION: Social housing programmes have been shown to influence health, but their effects on cardiovascular mortality and incidence of infectious diseases, such as leprosy and tuberculosis, are unknown. We will use individual administrative data to evaluate the effect of the Brazilian housing programme Minha Casa Minha Vida (MCMV) on cardiovascular disease (CVD) mortality and incidence of leprosy and tuberculosis.

METHODS AND ANALYSIS: We will link the baseline of the 100 Million Brazilian Cohort (2001-2015), which includes information on socioeconomic and demographic variables, to the MCMV (2009-2015), CVD mortality (2007-2015), leprosy (2007-2015) and tuberculosis (2007-2015) registries. We will define our exposed population as individuals who signed the contract to receive a house from MCMV, and our non-exposed group will be comparable individuals within the cohort who have not signed a contract for a house at that time. We will estimate the effect of MCMV on health outcomes using different propensity score approaches to control for observed confounders. Follow-up time of individuals will begin at the date of exposure ascertainment and will end at the time a specific outcome occurs, date of death or end of follow-up (31 December 2015). In addition, we will conduct stratified analyses by the follow-up time, age group, race/ethnicity, gender and socioeconomic position.

ETHICS AND DISSEMINATION: The study was approved by the ethic committees from Instituto Gonçalo Muniz-Oswaldo Cruz Foundation and University of Glasgow Medical, Veterinary and Life Sciences College. Data analysis will be carried out using an anonymised dataset, accessed by researchers in a secure computational environment according to the Centre for Integration of Data and Health Knowledge procedures. Study findings will be published in high quality peer-reviewed research journals and will also be disseminated to policy makers through stakeholder events and policy briefs.

PMID:33649053 | DOI:10.1136/bmjopen-2020-041722

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Instruments Measuring Physical Function for Psoriatic Arthritis Endorsed at GRAPPA 2020 Annual Meeting: Updates of the GRAPPA-OMERACT Working Group

J Rheumatol. 2021 Mar 1:jrheum.201679. doi: 10.3899/jrheum.201679. Online ahead of print.

ABSTRACT

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Working Group provided updates at the 2020 GRAPPA annual meeting on its work toward developing a core outcome set for PsA. Working groups were set up for the 4 prioritized domains: enthesitis, fatigue, structural damage, and physical function. Two instruments for measurement of physical function were provisionally endorsed: (1) the Health Assessment Questionnaire-Disability Index and (2) the physical functioning domain in the Medical Outcomes Study 36-item Short Form survey.

PMID:33649070 | DOI:10.3899/jrheum.201679

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Nevin Manimala Statistics

Randomized Phase II Trial of Polyphenon E versus Placebo in Patients at High Risk of Recurrent Colonic Neoplasia

Cancer Prev Res (Phila). 2021 Mar 1:canprevres.0598.2020. doi: 10.1158/1940-6207.CAPR-20-0598. Online ahead of print.

ABSTRACT

Polyphenon E (Poly E) is a green tea polyphenol preparation whose most active component is epigallocatechin gallate (EGCG). We studied the cancer preventive efficacy and safety of Poly E in subjects with rectal aberrant crypt foci (ACF) which represent putative precursors of colorectal cancers. Eligible subjects had prior colorectal advanced adenomas or cancers, and had > 5 rectal ACF at a pre-registration chromoendoscopy. Subjects (N=39) were randomized to 6-months of oral Poly E (780 mg EGCG) daily or placebo. Baseline characteristics were similar by treatment arm (all P >0.41); 32 of 39 (82%) subjects completed 6-months of treatment. The primary endpoint was percent reduction in rectal ACF at chromoendoscopy comparing before and after treatment. Among 32 subjects (15 Poly E,17 placebo), percent change in rectal ACF number (baseline vs 6-month) did not differ significantly between study arms (3.7% difference of means; P =0.28); total ACF burden was also similar (-2.3% difference of means; P =0.83). Adenoma recurrence rates at 6-months were similar by arm (P >0.35). Total drug received did not differ significantly by study arm; 31 (79%) subjects received >70% of prescribed Poly E. Poly E was well tolerated and adverse events (AEs) did not differ significantly by arm. One subject on placebo had two grade 3 AEs; one subject had grade 2 hepatic transaminase elevations attributed to treatment. In conclusion, Poly E for 6 months did not significantly reduce rectal ACF number relative to placebo. Poly E was well tolerated and without significant toxicity at the dose studied.

PMID:33648940 | DOI:10.1158/1940-6207.CAPR-20-0598

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Nevin Manimala Statistics

Is being a ‘left-behind’ child associated with an increased risk of self-poisoning in adulthood? Findings from a case-control study in Sri Lanka

BMJ Glob Health. 2021 Mar;6(3):e003734. doi: 10.1136/bmjgh-2020-003734.

ABSTRACT

PURPOSE: The long-term consequences of parental emigration on offspring self-harm risk is unknown.

METHODS: We investigated the association between experiencing parental emigration in childhood with hospital presentations for self-poisoning in adulthood using a hospital case-control study. Cases were adult self-poisoning patients (≥18 year olds) admitted to the medical toxicology ward Teaching Hospital Peradeniya, Sri Lanka. Sex and age frequency matched controls were recruited from the outpatient department or nearby specialist clinics at the same hospital. Details of parental emigration were collected using a pre-piloted questionnaire. The relationship between parental emigration and self-poisoning in adulthood was estimated using logistic regression models.

RESULTS: 298 cases, and 500 hospital controls were interviewed for the study. We estimate that one in five adults experienced parental emmigration as children (95% CI 17% to 24%). We find limited evidence that children from households with emigrating parents were more likely to experience adverse childhood experiences than those with non-emigrating parents. We found no statistical evidence of an increased risk of self-poisoning in adulthood in individuals who experienced parental emigration (maternal or paternal) during childhood. There was no statistical evidence that the impact differed by the sex of the participant.

CONCLUSION: Adults who experienced parental emigration as children were no more likely to self-poison than adults with non-emigrating parents. Further research using longitudinal data are needed to understand whether any adverse outcomes observed in ‘left-behind’ children are a consequence of parental emigration or due to factors associated but predate the emigration. Prospective data are also important to investigate whether there are any lasting effects on children who experience parental emigration.

PMID:33648980 | DOI:10.1136/bmjgh-2020-003734

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Neoadjuvant chemotherapy in early-stage cervical cancer (<2 cm) before conization for fertility preservation: is there any advantage over upfront conization?

Int J Gynecol Cancer. 2021 Mar;31(3):379-386. doi: 10.1136/ijgc-2020-001751.

ABSTRACT

BACKGROUND: Neoadjuvant chemotherapy before fertility-sparing surgery is an accepted option for patients with cervical tumors between 2 cm and 4 cm. There is a paucity of data regarding its role in patients with tumors <2 cm. Our objective was to compare the oncological and obstetrical outcomes between patients who underwent neoadjuvant chemotherapy before cervical conization versus upfront cervical conization in patients with cervical cancer with tumors <2 cm.

METHODS: We conducted a systematic literature review and searched MEDLINE, EMBASE, and CINAHL (from 1995 to March 2020) using the terms: uterine cervix neoplasms, cervical cancer, fertility-sparing surgery, fertility preservation, conization, cone biopsy, and neoadjuvant chemotherapy. We included manuscripts with information on patients with tumor size <2 cm, lymph node status, follow-up, oncological and obstetrical outcome, and toxicity related to neoadjuvant chemotherapy. We excluded review articles or articles with duplicated patient information.

RESULTS: We identified 12 articles, including 579 patients. For final analysis, 261 patients met inclusion criteria. The most common histology was non-squamous cell carcinoma (62%). Median follow-up time was 63.5 (range 7-122) months for the neoadjuvant chemotherapy group and 48 (range 12-184) months for the upfront cervical conization group. There was no difference in either overall survival (neoadjuvant chemotherapy group 100% vs upfront cervical conization 99.7%, p=0.79) or disease-free survival (neoadjuvant chemotherapy 100% vs upfront cervical conization 98.9%, p=0.59) between the groups. Fertility preservation rate was 81.4% versus 99.1% (p<0.001) favoring upfront cervical conization. No statistically significant differences were seen in live birth rate or pregnancy loss. Also, we found that all neoadjuvant chemotherapy patients reported chemotherapy-related toxicity (30.7% grade 3 and 69.2% grade 1-2).

CONCLUSIONS: There was no difference in disease-free survival or overall survival between patients who underwent neoadjuvant chemotherapy followed by conization and upfront cervical conization. Patients who underwent upfront cervical conization had a higher fertility preservation rate.

PMID:33649005 | DOI:10.1136/ijgc-2020-001751

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Treatment delay in early-stage oral squamous cell carcinoma and its relation to survival

J Craniomaxillofac Surg. 2021 Feb 12:S1010-5182(21)00053-6. doi: 10.1016/j.jcms.2021.02.007. Online ahead of print.

ABSTRACT

The aim of this study was to investigate the impact of a prolonged treatment delay on survival in patients with primary oral squamous cell carcinoma. The investigators hypothesized that treatment delay affects survival, supposing a poor outcome in patients with prolonged treatment initiation. In addition, a critical treatment delay should be defined. Inclusion criteria were a histopathological diagnosis of primary squamous cell carcinoma of the oral cavity and a surgery-based treatment of the tumor. Patients with a history of previously diagnosed malignancies and patients with distant metastasis at the time of diagnosis were excluded from this protocol. Common clinical and histopathological data were assessed retrospectively. Treatment delay was analyzed for the interval between initial presentation and the date of surgery. A total of 484 patients could be included. Considering early-stage patients, the risk of death increases by 1.8% for each day that the treatment delay is prolonged if all other characteristics do not change (p = 0.0035). In patients with advanced disease, a prolonged treatment delay does not affect the risk of death (p = 0.9134). In terms of progression-free survival, treatment delay tends to be associated with a higher risk of recurrence in early-stage disease, but without being statistically significant (p = 0.0718). For patients with early-stage disease, a treatment delay of 20 days is critical regarding overall survival (p = 0.011). For patients with advanced-stage disease, no significant differences have been observed. As patients with early-stage oral squamous cell carcinoma profit from early treatment initiation, we suggest an acceptable maximum treatment delay of no more than 20 days in the surgical management of these patients.

PMID:33648813 | DOI:10.1016/j.jcms.2021.02.007