Category: Nevin Manimala

Stat Methods Med Res. 2021 Jul 7:9622802211008945. doi: 10.1177/09622802211008945. Online ahead of print.

ABSTRACT

Mammographic screening and prophylactic surgery such as risk-reducing salpingo oophorectomy can potentially reduce breast cancer risks among mutation carriers of BRCA families. The evaluation of these interventions is usually complicated by the fact that their effects on breast cancer may change over time and by the presence of competing risks. We introduce a correlated competing risks model to model breast and ovarian cancer risks within BRCA1 families that accounts for time-varying covariates. Different parametric forms for the effects of time-varying covariates are proposed for more flexibility and a correlated gamma frailty model is specified to account for the correlated competing events.We also introduce a new ascertainment correction approach that accounts for the selection of families through probands affected with either breast or ovarian cancer, or unaffected. Our simulation studies demonstrate the good performances of our proposed approach in terms of bias and precision of the estimators of model parameters and cause-specific penetrances over different levels of familial correlations. We applied our new approach to 498 BRCA1 mutation carrier families recruited through the Breast Cancer Family Registry. Our results demonstrate the importance of the functional form of the time-varying covariate effect when assessing the role of risk-reducing salpingo oophorectomy on breast cancer. In particular, under the best fitting time-varying covariate model, the overall effect of risk-reducing salpingo oophorectomy on breast cancer risk was statistically significant in women with BRCA1 mutation.

PMID:34232831 | DOI:10.1177/09622802211008945

Stat Methods Med Res. 2021 Jul 7:9622802211009259. doi: 10.1177/09622802211009259. Online ahead of print.

ABSTRACT

Cox’s proportional hazards model is the most commonly used model for regression analysis of failure time data and some methods have been developed for its variable selection under different situations. In this paper, we consider a general type of failure time data, case K interval-censored data, that include all of other types discussed as special cases, and propose a unified penalized variable selection procedure. In addition to its generality, another significant feature of the proposed approach is that unlike all of the existing variable selection methods for failure time data, the proposed approach allows dependent censoring, which can occur quite often and could lead to biased or misleading conclusions if not taken into account. For the implementation, a coordinate descent algorithm is developed and the oracle property of the proposed method is established. The numerical studies indicate that the proposed approach works well for practical situations and it is applied to a set of real data arising from Alzheimer’s Disease Neuroimaging Initiative study that motivated this study.

PMID:34232833 | DOI:10.1177/09622802211009259

Stat Methods Med Res. 2021 Jul 7:9622802211025992. doi: 10.1177/09622802211025992. Online ahead of print.

ABSTRACT

By combining data across multiple studies, researchers increase sample size, statistical power, and precision for pooled analyses of biomarker-disease associations. However, researchers must adjust for between-study variability in biomarker measurements. Previous research often treats the biomarker measurements from a reference laboratory as a gold standard, even though those measurements are certainly not equal to their true values. This paper addresses measurement error and bias arising from both the reference and study-specific laboratories. We develop two calibration methods, the exact calibration method and approximate calibration method, for pooling biomarker data drawn from nested or matched case-control studies, where the calibration subset is obtained by randomly selecting controls from each contributing study. Simulation studies are conducted to evaluate the empirical performance of the proposed methods. We apply the proposed methods to a pooling project of nested case-control studies to evaluate the association between circulating 25-hydroxyvitamin D (25(OH)D) and colorectal cancer risk.

PMID:34232834 | DOI:10.1177/09622802211025992

Ocul Immunol Inflamm. 2021 Jul 7:1-6. doi: 10.1080/09273948.2021.1934036. Online ahead of print.

ABSTRACT

Purpose: To compare an analog visual scale in grading anterior chamber cells (ACC) to a modified Standardization of Uveitis Nomenclature (SUN) ACC scale.Method: A graphical representation of anterior chamber cells as a reference and a test set was created and shown to two groups of experienced uveitis experts. Group 1 was given the analog scale in written format, while group two was given the reference images for comparison. Each test subject was asked to provide the best approximation for each grade.Results: Eleven graders participated in phase 1. Correct grading occurred in 87.4% of cases. Discrepancies were seen at all grades. Only 3 of 11 graders were able to achieve a perfect score. Seven graders participated in phase 2. Agreement was 95.2% with 4/7 graders achieving a perfect score. Discrepancies were seen at higher grades only.Conclusions: ACC grading is improved by a visual grading scale, and interobserver variability is reduced.

PMID:34232824 | DOI:10.1080/09273948.2021.1934036

Prehosp Emerg Care. 2021 Jul 7:1-9. doi: 10.1080/10903127.2021.1951407. Online ahead of print.

ABSTRACT

Background: Research networks need access to EMS data to conduct pilot studies and determine feasibility of prospective studies. Combining data across EMS agencies is complicated and costly. Leveraging the National EMS Information System (NEMSIS) to extract select agencies’ data may be an efficient and cost-effective method of providing network-level data.Objective: Describe the process of creating a Pediatric Emergency Care Applied Research Network (PECARN) specific NEMSIS data set and determine if these data were nationally representative.Methods: We established data use agreements (DUAs) with EMS agencies participating in PECARN to allow for agency identification through NEMSIS. Using 2019 NEMSIS version 3.4.0 data for EMS events with patients 18 years old and younger, we compared PECARN NEMSIS data to national NEMSIS data. Analyzed variables were selected for their ability to characterize events. No statistical analyses were utilized due to the large sample, instead, differences of ±5% were deemed clinically meaningful.Results: DUAs were established for 19 EMS agencies, creating a PECARN data set with 305,188 EMS activations of which 17,478 (5.7%) were pediatric. Of the pediatric activations, 17,140 (98.1%) were initiated through 9-1-1 and 9,487 (55.4%) resulted in transport by the documenting agency. The national data included 36,288,405 EMS activations of which 2,152,849 (5.9%) were pediatric. Of the pediatric activations 1,704,141 (79.2%) were initiated through 9-1-1 and 1,055,504 (61.9%) were transported by the documenting agency. Age and gender distributions were similar between the two groups, but the PECARN-specific data under-represents Black and Latinx patients. Comparison of EMS provider primary impressions revealed that three of the five most common were similar with injury being the most prevalent for both data sets along with mental/behavioral health and seizure.Conclusion: We demonstrated that NEMSIS can be leveraged to create network specific data sets. The PECARN’s EMS data were similar to the national data, though racial/ethnic minorities and some primary impressions may be under-represented. Additionally, more EMS activations in PECARN study areas originated through 9-1-1 and were treated and transported by the documenting agency. This is likely related to the type of participating agencies, their ALS response level, and the diversity of the communities they serve.

PMID:34232828 | DOI:10.1080/10903127.2021.1951407

J Ocul Pharmacol Ther. 2021 Jul 7. doi: 10.1089/jop.2021.0033. Online ahead of print.

ABSTRACT

Purpose: To determine the effect of discontinuing chronic topical immune modulating (IM) treatment on Schirmer tear test (STT) values in dogs with dry eye disease (DED). Methods: Serial measurements of STTs from 14 dogs (16 eyes) previously diagnosed with DED were obtained before and after discontinuation of topical IM agents. Dogs with moderate to severe DED that had been well controlled with a topical IM treatment were included. After initial assessment topical IM treatment was discontinued, but topical lubricant was continued, and STT values were obtained sequentially. A mixed-effects regression model was used to evaluate the effects of age, gender, breed, clinical score, frequency of treatment, baseline STT value, and drug type on final STT values after IM withdrawal. P < 0.05 was considered statistically significant. Results: During the follow-up period after the IM treatment had been discontinued (136 ± 29 days), 50% of the eyes (n = 8) exhibited STT values that never decreased to <10 mm/min. In the other 50% (n = 8), STT values decreased from 15.9 ± 4.7 mm/min to 6.1 ± 0.9 mm/min. In this group, the time it took to decrease the STT to <10 mm/min was 21.1 ± 9.5 days. Severe clinical signs of DED and low baseline STT pre-IM treatment significantly affected STT post-IM treatment withdrawal (P < 0.05). Conclusions: The duration that a residual effect of topical IM treatment persists needs to be taken into consideration when studies are designed utilizing dogs with previous IM treatment for DED.

PMID:34232790 | DOI:10.1089/jop.2021.0033

Rev Med Inst Mex Seguro Soc. 2021 Jun 14;59(2):127-132.

ABSTRACT

BACKGROUND: Infections increase morbidity and mortality in patients with autoimmune disorders; however, this association has not been established in rheumatic diseases and SARS-CoV-2 infection.

OBJECTIVE: To describe the clinical characteristics and mortality of patients with rheumatic diseases and severe COVID-19.

MATERIAL AND METHODS: Observational and descriptive case series in patients with rheumatic diseases and severe SARS-CoV-2 infection, confirmed by PCR or pulmonary tomography, hospitalized in Mexico City from March to August 2020.

RESULTS: 15 patients with a mean age of 57 years (SD ± 11) were included, 66.6% were women, and 80% had a positive PCR test. The time from onset of symptoms to hospitalization, on average, was 7.2 days (SD ± 2.1). 46.6% died. Patients who died had a lower mean platelet level compared to survivors. The inflammatory reactants were higher in the deceased. There were no statistically significant differences in mortality for the variables related to rheumatic disease.

CONCLUSIONS: The differences in mortality of patients with severe COVID-19 in this series of cases seem to be related to the infection and not to the rheumatic disease.

PMID:34231984

J Drugs Dermatol. 2021 Jul 1;20(7):767-770. doi: 10.36849/JDD.5732.

ABSTRACT

BACKGROUND: Dermatology is among the least racially/ethnically diverse medical specialties in the US Dermatology Interest Groups (DIGs). DIGs may play a critical role in addressing these disparities by facilitating early exposure and mentorship, both associated with higher rates of medical students pursuing specific fields.

OBJECTIVE: This study sought to characterize the activities, goals, and challenges of DIGs in medical schools nationwide.

METHODS: A 15-question survey was distributed electronically to 92 DIG leaders enrolled in four-year accredited allopathic/osteopathic medical schools nationwide. Data collected included DIG leaders&rsquo; demographic information, medical training stage, DIG size/age, number/type of DIG activities hosted, presence of faculty/resident mentors, and goals/challenges.

RESULTS: There were 48 total and 46 complete responses (52% response rate). Most DIG leaders were female (81%), white (63%), and from allopathic medical schools of roughly equal geographic distribution. Over three-quarters of DIGs had affiliated dermatology departments and residencies. Most had faculty advisors; few had resident mentors. Presence of an affiliated dermatology department was associated with statistically significant increase in mentoring opportunities (P=0.034), significantly increased odds of having dedicated faculty mentors (OR=6.10, 95%CI 1.11&ndash;33.56), and non-significantly increased odds of having dedicated resident mentors (OR=2.96, 95%CI 0.33&ndash;26.79). DIG leaders self-identified early dermatology exposure, aiding in the match, relationship-building, and community engagement as main objectives and mismatches in opportunities, time, funding, and interest as main challenges.

CONCLUSIONS: DIGs provide valuable opportunities to medical students exploring the field and may play a role in reducing future dermatology workforce disparities. Dermatology departments, residencies, and medical schools should support their aims and reduce structural barriers to success. J Drugs Dermatol. 2021;20(7):767-770. doi:10.36849/JDD.5732.

PMID:34231994 | DOI:10.36849/JDD.5732

J Drugs Dermatol. 2021 Jul 1;20(7):744. doi: 10.36849/JDD.735.

ABSTRACT

BACKGROUND: Few studies have examined topical psoriasis therapies in patients with skin of color. Fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) was investigated in two phase 3, multicenter, double-blind, vehicle-controlled trials (NCT02462070; NCT02462122). This post hoc analysis evaluated HP/TAZ in subgroups of non-White and White participants, including Hispanic/Latino participants, from these trials.

METHODS: Adult participants were randomized (2:1) to receive HP/TAZ or vehicle lotion once daily for 8 weeks. Data were pooled and analyzed in non-mutually exclusive subgroups of self-identified non-White or White and Hispanic/Latino participants. Efficacy assessments included treatment success (&ge;2-grade improvement from baseline in investigator&rsquo;s global assessment [IGA] and score of clear/almost clear), reduction from baseline in affected body surface area (BSA), and reduction in mean IGA &times; BSA. Safety was evaluated via treatment-emergent adverse events (TEAEs).

RESULTS: Of 418 participants, 60 and 358 self-identified as non-White and White, respectively; 115 of 418 participants self-identified as Hispanic/Latino. At week 8, a higher percentage of HP/TAZ-treated participants achieved treatment success vs vehicle (non-White, 34.4% vs 19.0%; White, 41.8% vs 8.7%; Hispanic/Latino, 39.3% vs 9.3%); rates for White and Hispanic/Latino participants were statistically significant. Compared with vehicle, HP/TAZ-treated participants in each subgroup experienced numerically greater reductions in affected BSA and IGA &times; BSA at week 8. The most common TEAEs were contact dermatitis, pruritus, nasopharyngitis, and application-site pain; discontinuations due to TEAEs were few.

CONCLUSIONS: HP/TAZ reduced disease severity in non-White, White, and Hispanic/Latino participants with psoriasis, with good tolerability and safety over 8 weeks of treatment. J Drugs Dermatol. 2021;20(7):735-744. doi:10.36849/JDD.6158.

PMID:34232005 | DOI:10.36849/JDD.735

Rev Med Inst Mex Seguro Soc. 2021 Jun 14;59(2):110-118.

ABSTRACT

BACKGROUND: Occupational accidents represent an important problem that affects workers, families, society, industry, social security institutions and the nation as a whole, which affects directly the global economy.

OBJECTIVE: To assess the direct costs of occupational accidents at the Baja California Local Office of the Instituto Mexicano del Seguro Social (IMSS -Mexican Institute for Social Security-) in 2017.

MATERIAL AND METHODS: Cross-sectional descriptive study; the information was obtained from IMSS 2017 Statistical Memory and Baja California Local Office database. We analyzed 26,657 cases of work-related accidents and diseases. Years of potential productive life lost were calculated with the years of potential productive life lost indicator and the accumulated years of potential productive life lost indicator.

RESULTS: 97,901 certificates of temporary incapacity for work were issued in Baja California with a total amount of 150,284,001 Mexican pesos. 1593 permanent disabilities were granted with an average monthly amount of 3830 pesos and a total of 8982 accumulated years of potential productive life lost. 38 death certificates by work-related risks were issued and accounted for a total of 1048 years of potential productive life lost and 182 491 pesos for funeral expenses.

CONCLUSIONS: Direct costs of occupational accidents and diseases in the Baja California Local Office of IMSS have an impact on economic growth. Concerted efforts are needed to achieve a progressive reduction of work-related fatalities, accidents and diseases.

PMID:34231982