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Nevin Manimala Statistics

Designing a multi-epitopes subunit vaccine against human herpes virus 6A based on molecular dynamics and immune stimulation

Int J Biol Macromol. 2023 May 26:125068. doi: 10.1016/j.ijbiomac.2023.125068. Online ahead of print.

ABSTRACT

Human Herpesvirus 6A (HHV-6A) is a prevalent virus associated with various clinical manifestations, including neurological disorders, autoimmune diseases, and promotes tumor cell growth. HHV-6A is an enveloped, double-stranded DNA virus with a genome of approximately 160-170 kb containing a hundred open-reading frames. An immunoinformatics approach was applied to predict high immunogenic and non-allergenic CTL, HTL, and B cell epitopes and design a multi-epitope subunit vaccine based on HHV-6A glycoprotein B (gB), glycoprotein H (gH), and glycoprotein Q (gQ). The stability and correct folding of the modeled vaccines were confirmed through molecular dynamics simulation. Molecular docking found that the designed vaccines have a strong binding network with human TLR3, with Kd values of 1.5E-11 mol/L, 2.6E-12 mol/L, 6.5E-13 mol/L, and 7.1E-11 mol/L for gB-TLR3, gH-TLR3, gQ-TLR3, and the combined vaccine-TLR3, respectively. The codon adaptation index values of the vaccines were above 0.8, and their GC content was around 67 % (normal range 30-70 %), indicating their potential for high expression. Immune simulation analysis demonstrated robust immune responses against the vaccine, with approximately 650,000/ml combined IgG and IgM antibody titer. This study lays a strong foundation for developing a safe and effective vaccine against HHV-6A, with significant implications for treating associated conditions.

PMID:37245745 | DOI:10.1016/j.ijbiomac.2023.125068

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Overviews of reviews in the cardiovascular field underreported critical methodological and transparency characteristics: a methodological study based on the PRIOR statement

J Clin Epidemiol. 2023 May 26:S0895-4356(23)00130-0. doi: 10.1016/j.jclinepi.2023.05.018. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the epidemiology, reporting characteristics and adherence to the Preferred Reporting Items for Overviews of Reviews (PRIOR) statement of overviews of reviews (overviews) of interventions in the cardiovascular field.

STUDY DESIGN AND SETTING: MEDLINE, Scopus and the Cochrane Database of Systematic Reviews were searched from January 1, 2000 to October 15, 2020. Updated search was performed in MEDLINE, Epistemonikos and Google Scholar up to August 25, 2022. Overviews of interventions published in English and primarily considering populations, interventions and outcomes pertinent to the cardiovascular field were eligible. Study selection, data extraction and PRIOR adherence assessment were performed by two authors independently.

RESULTS: We analyzed 96 overviews. Almost half (43/96 [45%]) were published between 2020-2022 and contained a median of 15 systematic reviews (SR) (interquartile range 9-28). The commonest title terminology was “overview of (systematic) reviews” (38/96 [40%]). Methods for handling SR overlap were reported in 24/96 (25%), methods for assessing primary study overlap in 18/96 (19%), handling of discrepant data in 11/96 (11%) and methods for methodological quality or risk of bias assessment of the primary studies within SRs in 23/96 (24%). Authors included data sharing statements in 28/96 (29%), complete funding disclosure in 43/96 (45%), protocol registration in 43/96 (45%) and conflict of interest statement in 82/96 (85%) overviews.

CONCLUSION: Insufficient reporting was identified in methodological characteristics unique in overviews’ conduct and most transparency markers. Adoption of PRIOR from the research community could ameliorate overviews’ reporting.

PMID:37245702 | DOI:10.1016/j.jclinepi.2023.05.018

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Vital signs-based deterioration prediction model assumptions can lead to losses in prediction performance

J Clin Epidemiol. 2023 May 26:S0895-4356(23)00133-6. doi: 10.1016/j.jclinepi.2023.05.020. Online ahead of print.

ABSTRACT

OBJECTIVE: Vital signs-based models are complicated by repeated measures per patient and frequently missing data. This paper investigated impacts of common vital signs modelling assumptions during clinical deterioration prediction model development.

STUDY DESIGN AND SETTING: Electronic medical record data from five Australian hospitals (1 January 2019 to 31 December 2020) were used. Summary statistics for each observation’s prior vital signs were created. Missing data patterns were investigated using boosted decision trees, then imputed with common methods. Two example models predicting in-hospital mortality were developed: logistic regression and XGBoost. Model discrimination and calibration were assessed using the C-statistic and nonparametric calibration plots.

RESULTS: The data contained 5,620,641 observations from 342,149 admissions. Missing vitals were associated with observation frequency, vital sign variability, and patient consciousness. Summary statistics improved discrimination slightly for logistic regression and markedly for XGBoost. Imputation method led to notable differences in model discrimination and calibration. Model calibration was generally poor.

CONCLUSION: Summary statistics and imputation methods can improve model discrimination and reduce bias during model development but it is questionable whether these differences are clinically significant. Researchers should consider why data are missing during model development and how this may impact clinical utility.

PMID:37245699 | DOI:10.1016/j.jclinepi.2023.05.020

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The impact of providing material benefits to improve access to food on clinical parameters, dietary intake, and household food insecurity in people with diabetes: a systematic review with narrative synthesis

Adv Nutr. 2023 May 26:S2161-8313(23)00317-4. doi: 10.1016/j.advnut.2023.05.012. Online ahead of print.

ABSTRACT

The high cost of healthy foods makes maintaining a healthy dietary pattern challenging, particularly amongst people with diabetes who are experiencing food insecurity. The objectives of this study were to: 1) review evidence on the impact of providing material benefits (e.g., food coupons/vouchers, free food, or financial subsidies/incentives) to improve access to food on clinical parameters, dietary intake, and household food insecurity in people with diabetes, and 2) review relevant economic evidence. Six databases were searched from inception to March 2023 for longitudinal studies with quantitative outcomes. Twenty-one studies were included in the primary review and two in the economic analysis. Risk of bias was high in 20 studies and moderate in one study. The number of RCTs and non-randomized studies reporting statistically significant improvement, alongside GRADE certainty of evidence was: A1C: 1/6 and 4/12 (very low), systolic blood pressure: 0/3 and 1/8 (very low), diastolic blood pressure: 0/3 and 1/7 (very low), BMI: 0/5 and 2/8 (very low), body weight: 0/0 and 1/3 (very low), hypoglycemia: 1/2 and 1/2 (very low), daily intake of fruits and vegetables: 1/1 and 1/3 (very low), daily intake of whole grains: 0/0 and 0/2 (very low), overall diet quality: 2/2 and 1/1 (low), and household food insecurity: 2/3 and 0/0 (very low). The two studies included in the economic analysis showed no difference in Medicare spending from Supplemental Nutrition Assistance Program participation and cost-savings from medically tailored meals in an economic simulation. Overall, providing material benefits to improve access to food for people with diabetes may improve household food insecurity, fruit and vegetable intake, and overall diet quality but effects on clinical parameters and whole grain intake are unclear. The certainty of evidence was very low to low by GRADE. PROSPERO REGISTRATION NUMBER: CRD42021212951.

PMID:37245685 | DOI:10.1016/j.advnut.2023.05.012

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Medical Knowledge Acquisition during a Pandemic: Pediatric Subspecialty In-Training Examination and Board Certification Exam Passing Rate

Acad Pediatr. 2023 May 26:S1876-2859(23)00162-6. doi: 10.1016/j.acap.2023.05.013. Online ahead of print.

ABSTRACT

OBJECTIVE: The COVID-19 pandemic resulted in training programs restructuring their curricula. Fellowship programs are required to monitor each fellow’s training progress through a combination of formal evaluations, competency tracking, and measures of knowledge acquisition. The American Board of Pediatrics administers Subspecialty In-Training Examinations to pediatric fellowship trainees annually and board certification exams at the completion of fellowship. The objective of this study was to compare SITE scores and certification exam passing rates before and during the pandemic.

METHODS: In this retrospective observational study, we collected summative data on SITE scores and certification exam passing rates for all pediatric subspecialties from 2018 to 2022. Trends over time were assessed using ANOVA analysis to test for trends across years within one group and t-test analysis to compare groups before and during the pandemic.

RESULTS: Data were obtained from 14 pediatric subspecialties. Comparing pre-pandemic to pandemic scores, Infectious Diseases, Cardiology, and Critical Care Medicine saw statistically significant decreases in SITE scores. Conversely, Child Abuse Pediatrics and Emergency Medicine (PEM) saw increases in SITE scores. PEM saw a statistically significant increase in certification exam passing rates, while Gastroenterology and Pulmonology saw decreases in exam passing rates.

CONCLUSION: The COVID-19 pandemic resulted in restructuring didactics and clinical care based on the needs of the hospital. There were also societal changes affecting patients and trainees. Subspecialty programs with declining scores and certification exam passing rates may need to assess their educational and clinical programs and adapt to the needs of trainees’ learning edges.

WHAT’S NEW: This retrospective observational study is the first to look at summative pediatric subspecialty in-training exam scores and board certification passing rates for first-time test takers, specifically analyzing differences in pre-pandemic and pandemic scores. Program directors can follow trends to consider if adaptions need to be made to their curriculum.

PMID:37245666 | DOI:10.1016/j.acap.2023.05.013

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Pregnancy intention and preconception contraceptive behaviors and substandard prenatal care in France

J Gynecol Obstet Hum Reprod. 2023 May 26:102608. doi: 10.1016/j.jogoh.2023.102608. Online ahead of print.

ABSTRACT

OBJECTIVE: Evaluate the association between a combined measure of time-based pregnancy intention and preconception contraceptive behavior and suboptimal prenatal care.

POPULATION AND METHOD: women delivering a live birth in all maternity units during one week in March 2016 were interviewed in the postpartum ward (N=13132). Multinomial logistic regression models were used to assess the association between the indicator of pregnancy intention and substandard prenatal care (late initiation of care and less than the recommended number of prenatal visits (<60% recommended)).

RESULTS: 83.6% of women had timed pregnancies, 4.7% had mistimed pregnancies but discontinued contraception to conceive, 8.0% had mistimed pregnancies without discontinuing contraception to conceive and 3.7% had unwanted pregnancies. Women with timed pregnancies or mistimed pregnancies despite discontinuing contraception to conceive were more socially advantaged than those who had an unwanted pregnancy or a mistimed pregnancy without discontinuing contraception to conceive. 3.3% of women had a substandard number of prenatal visits and 2.5% had delayed prenatal care initiation. The adjusted odds ratios (aOR) of substandard prenatal visits were high among women with unwanted pregnancies (aOR=2.78; 95% confidence interval [1.91-4.05]) and women with mistimed pregnancies who had not discontinued contraception to conceive (aOR=1.69; [1.21-2.35]) compared to women with timed pregnancies. No difference was observed for women with mistimed pregnancies who discontinued contraception to conceive (aOR=1.22; [0.70-2.12]).

CONCLUSION: Using routinely collected information on preconception contraception allows a more nuanced assessment of pregnancy intentions that can help caregivers identify women at greater risk of substandard prenatal care.

PMID:37245644 | DOI:10.1016/j.jogoh.2023.102608

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Discordance between remnant cholesterol and low-density lipoprotein cholesterol predicts arterial stiffness progression

Hellenic J Cardiol. 2023 May 26:S1109-9666(23)00101-X. doi: 10.1016/j.hjc.2023.05.008. Online ahead of print.

ABSTRACT

BACKGROUND: Cross-sectional studies have shown that remnant cholesterol (RC) was associated with arterial stiffness. The present study evaluated the association of RC and the discordance between RC and low-density lipoprotein cholesterol (LDL-C) with arterial stiffness progression.

METHODS: Data were derived from the Kailuan study. RC was calculated as total cholesterol – high-density lipoprotein cholesterol – LDL-C. Discordant RC with LDL-C were defined by residuals, cutoff points and median values. Arterial stiffness progression was assessed by the brachial-ankle pulse wave velocity (baPWV) change, baPWV change rate, and increase/persistently high baPWV. Multivariable linear regression models and logistic regression models were used to explore the association of RC and discordant RC versus LDL-C with the arterial stiffness progression.

RESULTS: A total of 10,507 participants were enrolled in this study, with the mean age of 50.8±11.8 years, 60.9% (6,396) of male. Multivariable regression analyses showed that, each 1mmol/L increase in the RC level was associated with a 12.80 cm/s increase in baPWV change, a 3.08 cm/s/year increase in the baPWV change rate, and 13% (95% CI, 1.05-1.21) of increase in the risk for increase in /persistently high baPWV. Discordant high RC was associated with a 13.65 cm/s increase in baPWV change and 19% (95% CI, 1.06-1.33) of increase in the risk for increase in /persistently high baPWV compared to those with concordant group.

CONCLUSION: Discordantly high RC with LDL-C was associated with an increased risk of arterial stiffness progression. The findings demonstrated that RC may be an important marker of future coronary artery disease risk.

PMID:37245643 | DOI:10.1016/j.hjc.2023.05.008

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Quantifying Success After Reverse Total Shoulder Arthroplasty: the Minimal Clinically Important Percentage of Maximal Possible Improvement

J Shoulder Elbow Surg. 2023 May 26:S1058-2746(23)00388-9. doi: 10.1016/j.jse.2023.04.011. Online ahead of print.

ABSTRACT

INTRODUCTION: In high functioning patients, the ceiling effect associated with many patient-reported outcome measures (PROMs) limits the ability to appropriately stratify success. The percent maximal possible improvement (%MPI) was introduced as another evaluation tool, with a proposed threshold of success at 30%. It remains unclear if this threshold correlates with perceived patient success following shoulder arthroplasty. The purpose of this study was to compare the proportion of patients that achieved the minimal clinically important difference (MCID) and %MPI for different outcome scores and to define the %MPI thresholds associated with patient satisfaction following primary reverse shoulder arthroplasty (rTSA).

METHODS: A retrospective review was performed of an international shoulder arthroplasty database between 2003 and 2020. All primary rTSAs performed using a single implant system with minimum 2-year follow-up were reviewed. Pre- and postoperative outcome scores were evaluated for all patients to determine the raw improvement and %MPI. The proportion of patients achieving the MCID and 30% MPI were determined for each outcome score. Thresholds for the minimal clinically important %MPI (MCI-%MPI) were calculated using an anchor-based method for each outcome score and stratified by age and sex.

RESULTS: 2,573 shoulders with a mean follow-up of 47 months were included. Outcome scores with known ceiling effects (SST, SPADI, UCLA) had higher rates of patients achieving the 30% MPI, but not the previously reported MCID. Inversely, outcome scores without significant ceiling effects (Constant and SAS scores) had higher rates of patients achieving the MCID, but not the 30% MPI. The MCI-%MPI differed among outcome scores and mean values were as follows: 33% for the SST, 27% for the Constant score, 35% for the ASES score, 43% for the UCLA score, 34% for the SPADI score, and 30% for the SAS score. The MCI-%MPI increased with greater age for SPADI (p<0.04) and SAS (p<0.01) scores, meaning that patients with higher thresholds required a greater fraction of the possible improvement for a given score to be satisfied, but did not reach statistical significance for other scores. Females had a greater MCI-%MPI for the SAS and ASES scores and a lower MCI-MPI% for the SPADI score.

CONCLUSION: The %MPI offers a simple method to quickly assess improvements across patient outcome scores. However, the %MPI that represents patient improvement after surgery is not uniformly the previously established 30% threshold. Surgeons should utilize score-specific estimates of the MCI-%MPI to gauge success when evaluating patients undergoing primary rTSA.

LEVEL OF EVIDENCE: Basic Science Study; Validation of Outcome Instruments.

PMID:37245623 | DOI:10.1016/j.jse.2023.04.011

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Longitudinal Changes in Shoulder Arthroplasty Stratified by Age Groups, Types of Surgical Facilities, and Geographical Regions in Korea from 2010 to 2020

J Shoulder Elbow Surg. 2023 May 26:S1058-2746(23)00385-3. doi: 10.1016/j.jse.2023.04.008. Online ahead of print.

ABSTRACT

BACKGROUND: Shoulder arthroplasty, including hemiarthroplasty, reverse and anatomical total shoulder arthroplasty, improves quality of life by reducing shoulder pain and restoring function in patients not only with irreparable rotator cuff tears and/or cuff tear arthropathy but also with osteoarthritis posttraumatic arthritis, proximal humeral fractures, etc. Given the rapid developments in artificial joints and improvements in postoperative outcomes, the number of shoulder arthroplasty surgeries is increasing worldwide. Therefore, we investigated changes in trends over time in Korea.

METHODS: We analyzed the longitudinal changes in the incidence of shoulder arthroplasty including anatomic and reverse total shoulder arthroplasty, hemiarthroplasty, and shoulder revision arthroplasty by changes in the Korean age profile, surgical facilities, and geographical regions using the Korean Health Insurance Review and Assessment Service (HIRA) database from 2010-2020. Data were also collected from the National Health Insurance Service (NHIS) and the Korean Statistical Information Service (KOSIS).

RESULTS: From 2010-2020, the total shoulder arthroplasty rate per 1,000,000 person-years increased from 10.571 to 101.372 (time trend = 1.252; 95% CI 1.233-1.271, p < 0.001). The shoulder hemiarthroplasty rate per 1,000,000 person-years decreased from 6.414 to 3.685 (time trend = 0.933; 95% CI 0.907-0.960, p < 0.001). The shoulder revision arthroplasty rate per 1,000,000 person-years increased from 0.792 to 2.315; the increase was significant (time trend = 1.133; 95% CI 1.101-1.166, p < 0.001).

DISCUSSION: Overall, total shoulder arthroplasty and shoulder revision arthroplasty are increasing and shoulder hemiarthroplasty is decreasing. For both total shoulder arthroplasty and shoulder revision arthroplasty, steep increases are evident in the numbers of patients in their 70s and older than 80 years. The shoulder hemiarthroplasty trend is decreasing regardless of differences in age groups, surgical facilities, and geographical regions. Shoulder revision arthroplasty is preferentially performed in Seoul.

PMID:37245622 | DOI:10.1016/j.jse.2023.04.008

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Operative Management of Rotator Cuff Tears: Identifying Disparities in Access on a National Level

J Shoulder Elbow Surg. 2023 May 26:S1058-2746(23)00384-1. doi: 10.1016/j.jse.2023.04.007. Online ahead of print.

ABSTRACT

BACKGROUND: The purpose of this study was to identify nationwide disparities in the rates of operative management of rotator cuff tears based on race, ethnicity, insurance type, and socioeconomic status.

METHODS: Patients diagnosed with a full or partial rotator cuff tear from 2006-2014 were identified in the Healthcare Cost and Utilization Project’s National Inpatient Sample database using International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes. Bivariate analysis using chi-square tests and adjusted, multivariable logistic regression models were used to evaluate differences in the rates of operative versus non-operative management for rotator cuff tears.

RESULTS: This study included 46,167 patients. When compared with white patients, adjusted analysis showed that minority race and ethnicity were associated with lower rates of operative management for Black [adjusted odds ratio (AOR): 0.31, 95% confidence interval (CI): 0.29-0.33; p < 0.001], Hispanic [AOR: 0.49, 95% CI: 0.45-0.52; p < 0.001], Asian or Pacific Islander [AOR: 0.72, 95% CI: 0.61-0.84; p < 0.001], and Native American patients [AOR: 0.65, 95% CI: 0.50-0.86; p = 0.002]. In comparison to privately insured patients, our analysis also found that self-payers [AOR: 0.08, 95% CI: 0.07-0.10; p < 0.001], Medicare beneficiaries [AOR: 0.76, 95% CI: 0.72-0.81; p < 0.001], and Medicaid beneficiaries [AOR: 0.33, 95% CI: 0.30-0.36; p < 0.001] had lower odds of receiving surgical intervention. Additionally, relative to those in the bottom income quartile, patients in all other quartiles experienced nominally higher rates of operative repair; these differences were statistically significant for the second quartile [AOR: 1.09, 95% CI: 1.03-1.16; p = 0.004].

CONCLUSION: There are significant nationwide disparities in the likelihood of receiving operative management for rotator cuff tear patients of differing race/ethnicity, payer status, and socioeconomic status. Further investigation is needed to fully understand and address causes of these discrepancies to optimize care pathways.

PMID:37245619 | DOI:10.1016/j.jse.2023.04.007