Category: Nevin Manimala

JAMA Otolaryngol Head Neck Surg. 2024 Jul 11. doi: 10.1001/jamaoto.2024.1854. Online ahead of print.

ABSTRACT

IMPORTANCE: Olfactory impairment (OI) and frailty are prevalent conditions associated with aging, but studies investigating their association with each other have been discordant.

OBJECTIVE: To summarize current evidence surrounding the association between OI and frailty.

DATA SOURCES: PubMed, Embase, Cochrane Library, SCOPUS, and CINAHL from inception to November 28, 2023.

STUDY SELECTION: This study included observational studies investigating the association between objectively or subjectively assessed OI and objectively evaluated frailty among adults.

DATA EXTRACTION AND SYNTHESIS: Two independent authors extracted data into a structured template. Maximally adjusted estimates were pooled using a random-effects model, and statistical heterogeneity was evaluated using I2 values. Additional prespecified subgroup and sensitivity analyses were performed. This study used the Newcastle-Ottawa Scale for bias assessment and the Grading of Recommendations Assessment, Development and Evaluation framework for overall evidence quality evaluation.

MAIN OUTCOMES AND MEASURES: The primary outcome was the cross-sectional association between OI and frailty, for which the odds of frailty were compared between participants with and without OI. The secondary outcome was the cross-sectional association between frailty and OI, for which the odds of OI were compared between participants with and without frailty.

RESULTS: This study included 10 studies with 10 624 patients (52.9% female; mean [SD] age, 62.9 [9.6] years). The Newcastle-Ottawa Scale score of studies ranged from low to moderate. Grading of Recommendations Assessment, Development and Evaluation scores ranged from low to moderate. OI was associated with a 2.32-fold (odds ratio [OR], 2.32; 95% CI, 1.63-3.31; I2 = 0%) greater odds of frailty compared with individuals with healthy olfactory function. The odds of OI was progressively greater with categorical frailty status, with a 1.55-fold (OR, 1.55; 95% CI, 1.32-1.82; I2 = 0%), 2.28-fold (OR, 2.28; 95% CI, 1.96-2.65; I2 = 0%), and 4.67-fold (OR, 4.67; 95% CI, 2.77-7.86; I2 = 0%) increase in odds for individuals with prefrailty, frailty, and the most frailty, respectively, compared with robust individuals. The results demonstrated stability in subgroup analyses (geographical continent of study, objective vs subjective olfactory assessment) and sensitivity tests.

CONCLUSIONS AND RELEVANCE: The results of this systematic review and meta-analysis suggest that there is an association between OI and frailty, with an increase in the odds of OI with worsening categorical frailty status among individuals with prefrailty, frailty, and the most frailty. OI may be a potential biomarker for frailty. Future studies could delve into whether OI may be a modifiable risk factor for frailty.

PMID:38990553 | DOI:10.1001/jamaoto.2024.1854

Death Stud. 2024 Jul 11:1-9. doi: 10.1080/07481187.2024.2376823. Online ahead of print.

ABSTRACT

This article explores the concept of posttraumatic growth (PTG) in individuals bereaved by suicide. The present study employs an exploratory approach to examine secondary data from a national survey. A sample of 2369 (n = 2369) responses were examined. Various instruments were utilized to assess grief experiences, social support, and personal growth. Descriptive statistics, correlational analysis and a hierarchical regression model were used to examine the relationship between the variables in this study. Hierarchical regression analysis revealed six independent predictors of PTG: social and formal support, time since loss, grief experiences, gender and multiple losses. The study highlighted the potential for growth in the aftermath of suicide bereavement, emphasizing the critical role of social support and the importance of time in promoting PTG. Despite some limitations, the present findings provide novel insight into the underlying mechanisms of PTG in suicide-bereaved individuals.

PMID:38990548 | DOI:10.1080/07481187.2024.2376823

Odontology. 2024 Jul 11. doi: 10.1007/s10266-024-00966-6. Online ahead of print.

ABSTRACT

The purpose of the study was to investigate the influence of different tooth-colored substrates and restoration thicknesses on the final color of gingiva-colored resin-based composites (GCRBCs). Five different shades of GCRBCs [light pink (LP), dark pink (DP), orange (Or), brown (Br), and purple (P)] were used to prepare disc-shaped specimens with 2 different thicknesses: 1.0 mm, and 2.0 mm. GCRBC discs (n = 5) were placed over 3 different tooth-colored substrates (ND1, ND5, and ND9) and color parameters were assessed using a spectroradiometer. Color differences (∆E*_ab and ∆E₀₀) were calculated using CIELab and CIEDE2000 formulas and compared to 50:50% perceptibility (PT: ∆E*_ab = 1.7, ΔE₀₀ = 1.1) and acceptability (AT: ∆E*_ab = 3.7, ΔE₀₀ = 2.8) visual thresholds. Color variation data were statistically analyzed using two-way ANOVAs followed by Bonferroni’s post hoc tests (a = 05). The ∆E*_ab and ΔE₀₀ values of GCRBCs placed over ND9 substrates were significantly higher in the LP-1.0 mm and Or-1.0 mm groups that presented values above AT (p< .001).Regardless of the substrate color and GCRBC thickness applied, ∆E*_ab and ΔE₀₀ values below AT were recorded in the gingival color groups of P. Substrate color significantly affected the color differences in the gingival color groups of LP, DP, and Or with a restoration thickness of 1.0 mm (p < .05). Gingival color, restoration thickness, and substrate color influenced the color differences of GCRBCs. When the gingival color was a lighter gingival color, rather than dark purple, the masking ability was decreased, especially with a restoration thickness of 1.0 mm.

PMID:38990497 | DOI:10.1007/s10266-024-00966-6

Esophagus. 2024 Jul 11. doi: 10.1007/s10388-024-01072-w. Online ahead of print.

ABSTRACT

BACKGROUND: S-588410, a cancer peptide vaccine (CPV), comprises five HLA-A*24:02-restricted peptides from five cancer-testis antigens. In a phase 2 study, S-588410 was well-tolerated and exhibited antitumor efficacy in patients with urothelial cancer. Therefore, we aimed to evaluate the efficacy, immune response, and safety of S-588410 in patients with completely resected esophageal squamous cell carcinoma (ESCC).

METHODS: This phase 3 study involved patients with HLA-A*24:02-positive and lymph node metastasis-positive ESCC who received neoadjuvant therapy followed by curative resection. After randomization, patients were administered S-588410 and placebo (both emulsified with Montanide™ ISA 51VG) subcutaneously. The primary endpoint was relapse-free survival (RFS). The secondary endpoints were overall survival (OS), cytotoxic T-lymphocyte (CTL) induction, and safety. Statistical significance was tested using the one-sided weighted log-rank test with the Fleming-Harrington class of weights.

RESULTS: A total of 276 patients were randomized (N = 138/group). The median RFS was 84.3 and 84.1 weeks in the S-588410 and placebo groups, respectively (P = 0.8156), whereas the median OS was 236.3 weeks and not reached, respectively (P = 0.6533). CTL induction was observed in 132/134 (98.5%) patients who received S-588410 within 12 weeks. Injection site reactions (137/140 patients [97.9%]) were the most frequent treatment-emergent adverse events in the S-588410 group. Prolonged survival was observed in S-588410-treated patients with upper thoracic ESCC, grade 3 injection-site reactions, or high CTL intensity.

CONCLUSIONS: S-588410 induced immune response and had acceptable safety but failed to reach the primary endpoint. A high CTL induction rate and intensity may be critical for prolonging survival during future CPV development.

PMID:38990441 | DOI:10.1007/s10388-024-01072-w

Adv Ther. 2024 Jul 11. doi: 10.1007/s12325-024-02921-x. Online ahead of print.

ABSTRACT

INTRODUCTION: Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) combination therapy is a standard of care for advanced non-squamous non-small cell lung cancer (NSQ-NSCLC); however, the lack of safety data limits its clinical application in Japan.

METHODS: This study compared the safety of ABCP with that of bevacizumab, carboplatin, and paclitaxel (BCP) combination for the treatment of advanced NSQ-NSCLC in Japanese patients by evaluating the clinical background and incidence of adverse events (AEs) based on data extracted from the Diagnosis Procedure Combination (DPC) database. Incidence rates and restricted mean survival times (RMSTs) for up to 1 year were analyzed for 19 clinically important AEs. Covariates were adjusted using the inverse probability weighting method.

RESULTS: A search conducted using the International Statistical Classification of Diseases and Related Health Problems 10th Revision codes identified 350,987 patients, of whom 202 were included in the ABCP cohort and 232 in the BCP cohort. Among the 19 AEs, the incidence of skin disorder and febrile neutropenia (FN) was significantly higher in the ABCP cohort versus the BCP cohort. The adjusted incidence rate ratios were 2.65 [95% confidence interval (CI) 1.43-4.91] for skin disorder and 1.70 (95% CI 1.01-2.85) for FN. The adjusted RMST differences were – 64.2 days (95% CI – 93.0 to – 35.4 days) and – 46.0 days (95% CI – 73.5 to – 18.5 days) for skin disorder and FN, respectively. These results were comparable to those of other pivotal clinical trials.

CONCLUSIONS: The findings of this DPC database study highlight the safety of ABCP in Japanese clinical practice, and this methodology may facilitate more efficient research in real-world settings.

TRIAL REGISTRATION: UMIN Clinical Trials Registry ID UMIN000041507.

PMID:38990434 | DOI:10.1007/s12325-024-02921-x

Arch Osteoporos. 2024 Jul 11;19(1):59. doi: 10.1007/s11657-024-01417-z.

ABSTRACT

The SPAH study is a population-based prospective cohort of Brazilian community-dwelling elderlies with higher fracture risk than observed in the studies used to construct the Brazilian FRAX model. In this study, the FRAX tool was a good fracture predictor within this high-risk elderly cohort, especially when calculated without bone density.

PURPOSE: To determine the performances of FRAX and age-dependent intervention thresholds according to National Osteoporosis Guideline Group (NOGG) guidelines with and without bone mineral density (BMD) regarding fracture prediction in community-dwelling elderly Brazilians.

METHODS: Seven hundred and five older adults (447 women; 258 men) were followed for 4.3 ± 0.8 years. FRAX risk for hip and major osteoporotic fractures with and without BMD was calculated at baseline. The bivariate analysis investigated the associations between the absolute probability of fracture (FRAX), as well as the age-dependent intervention thresholds (NOGG), and the incidence of vertebral fracture (VF), non-vertebral fracture (NVF), and major osteoporotic fractures (MOF), segregated by sex. Age-adjusted Poisson’s multiple regression and ROC curves were constructed to determine FRAX and NOGG’s accuracies as fracture predictors.

RESULTS: Fractures occurred in 22% of women and 15% of men. FRAX with and without BMD was higher in women with all types of fractures (p < 0.001). Only NOGG risk classification without BMD was associated with NVF (p = 0.047) and MOF (p = 0.024). FRAX was associated with NVF in the multiple regression, regardless of BMD. ROC curves of FRAX with and without BMD had AUCs of 0.74, 0.64, and 0.61 for NVF, VF, and MOF, respectively. The most accurate risk cutoffs for FRAX were 8% for MOF and 3% for hip fractures. No statistically significant associations were found in men.

CONCLUSION: FRAX predicted NVF more accurately than VF or MOF in elderlies, regardless of BMD. These results reiterate that FRAX may be used without BMD, even considering that Brazilian elderlies have known higher fracture risk.

PMID:38990403 | DOI:10.1007/s11657-024-01417-z

Mov Disord Clin Pract. 2024 Jul 11. doi: 10.1002/mdc3.14160. Online ahead of print.

ABSTRACT

BACKGROUND: Although performance rating scales, spiral drawing, water pouring, and accelerometry are commonly used to assess tremor severity, the extent to which their results correlate with impairment in activities of daily living (ADL) remains unclear.

OBJECTIVE: The aim was to identify the most effective predictors of ADL in essential tremor (ET).

METHODS: Forty ET patients were examined using The Essential Tremor Rating Assessment Scale (TETRAS), spiral drawing, volume of water spilled, and accelerometric tremor power. Root-mean-square error, R², and F-test were calculated for models predicting TETRAS ADL subscore.

RESULTS: TETRAS Performance Subscale explained the variability in TETRAS ADL with an R² value of 0.686. Models incorporating spiral rating and accelerometric tremor power (R² = 0.731) and water spillage volume (R² = 0.756) were not statistically superior.

CONCLUSIONS: TETRAS performance subscore predicted nearly 70% ADL impairment in ET patients. Incorporating the spiral rating, accelerometric tremor power, and water pouring test did not enhance ADL estimation.

PMID:38989643 | DOI:10.1002/mdc3.14160

Coron Artery Dis. 2024 Jul 8. doi: 10.1097/MCA.0000000000001402. Online ahead of print.

ABSTRACT

BACKGROUND: In myocardial infarction with nonobstructive coronary arteries (MINOCA), there are limited patient-level data on outcomes by sex and race.

OBJECTIVE: The aim of this study was to assess baseline demographics and 3-year outcomes by sex and race for MINOCA patients.

METHODS: Patients admitted to a single center with acute myocardial infarction (MI) between 1 January 2012 and 31 December 2018, were identified by chart and angiographic review. The primary outcome was nonfatal MI with secondary outcomes including nonfatal cerebrovascular accident (CVA), chest pain readmission, and repeat coronary angiography.

RESULTS: During the study period, 304 patients were admitted with MINOCA. The cohort was predominantly female (66.4%), and women were significantly older (64.6 vs. 59.2). One-sixth of the total population were Black patients, and nearly half of Black patients (47.2%) were male. Prior CVA (19.7%) and comorbid anxiety, depression, or post-traumatic stress disorder (41.1%) were common. Rates of nonfatal MI were 6.3% without difference by sex or race. For secondary outcomes, rates of CVA were 1.7%, chest pain readmission was 22.4%, and repeat angiography was 8.9%. Men were significantly more likely to have repeat angiography (13.7 vs. 6.4%), and Black patients were more likely to be readmitted for angina (34.0 vs. 19.1%). Over one-quarter of patients underwent repeat stress testing, with 8.9% ultimately undergoing repeat angiograms and low numbers (0.7%) undergoing revascularization. Men were more likely to be referred for a repeat angiogram (13.7 vs. 6.4%, P = 0.035). In multivariate analysis, Black race [odds ratio (OR), 2.31; 95% confidence interval (CI), 1.06-5.03] was associated with an increased risk of readmission for angina, while female sex was associated with decreased odds of repeat angiography (OR, 0.36; 95% CI, 0.14-0.90) and current smoking was associated with increased odds of repeat angiography (OR, 4.07; 95% CI, 1.02-16.29)] along with hyperlipidemia (OR, 4.65; 95% CI, 1.22-17.7).

CONCLUSION: White women presented more frequently with MINOCA than White men, however, Black men are equally as affected as Black women. Rates of nonfatal MI were low without statistical differences by sex or race.

PMID:38989611 | DOI:10.1097/MCA.0000000000001402

Int Wound J. 2024 Jul;21(7):e14963. doi: 10.1111/iwj.14963.

ABSTRACT

Diabetic foot ulcer is the most common complication causing lots of admissions among diabetic patients. Understanding patients’ level of foot self-care knowledge, practice and associated factors is important for planning interventions to control and prevent diabetic foot complications. This study aimed to assess the level of knowledge and practice of foot self-care among diabetic patients attending diabetic clinics in The Gambia. Two hundred and seventeen patients attending diabetic clinics in two public hospitals were selected using a successive sampling technique. Data were collected using a validated interviewer-administered questionnaire. Descriptive statistics were used to summarize the demographic and clinical data. Multivariate logistic regression was used to identify factors associated with foot self-care knowledge and practice. The findings showed a poor level of foot self-care knowledge (n = 114; 52.5%) and practice (n = 149; 68.7%). Patients’ educational level was statistically significantly association with diabetic foot self-care knowledge (p = 0.02). Diabetic foot ulcer history (aOR = 0.23, 95% CI: 0.08-0.63; p < 0.001), diabetic hospitalization (aOR = 2.41, 95% CI: 1.23-4.75, p = 0.01) and diabetic foot care education (aOR = 2.65, 95% CI: 1.39-5.06, p < 0.001) were statistically significantly associated with foot self-care practice. The poor diabetic foot self-care knowledge and practice among these patients emphasize the need for a diabetic health education program in these clinics.

PMID:38989596 | DOI:10.1111/iwj.14963

Arterioscler Thromb Vasc Biol. 2024 Jul 11. doi: 10.1161/ATVBAHA.124.321085. Online ahead of print.

ABSTRACT

BACKGROUND: Evidence suggests that COVID-19 predisposes to cardiovascular diseases (CVDs). While monocytes/macrophages play a central role in the immunopathogenesis of atherosclerosis, less is known about their immunopathogenic mechanisms that lead to CVDs during COVID-19. Natural killer (NK) cells, which play an intermediary role during pathologies like atherosclerosis, are dysregulated during COVID-19. Here, we sought to investigate altered immune cells and their associations with CVD risk during severe COVID-19.

METHODS: We measured plasma biomarkers of CVDs and determined phenotypes of circulating immune subsets using spectral flow cytometry. We compared these between patients with severe COVID-19 (severe, n=31), those who recovered from severe COVID-19 (recovered, n=29), and SARS-CoV-2-uninfected controls (controls, n=17). In vivo observations were supported using in vitro assays to highlight possible mechanistic links between dysregulated immune subsets and biomarkers during and after COVID-19. We performed multidimensional analyses of published single-cell transcriptome data of monocytes and NK cells during severe COVID-19 to substantiate in vivo findings.

RESULTS: During severe COVID-19, we observed alterations in cardiometabolic biomarkers including oxidized-low-density lipoprotein, which showed decreased levels in severe and recovered groups. Severe patients exhibited dysregulated monocyte subsets, including increased frequencies of proinflammatory intermediate monocytes (also observed in the recovered) and decreased nonclassical monocytes. All identified NK-cell subsets in the severe COVID-19 group displayed increased expression of activation and tissue-resident markers, such as CD69. We observed significant correlations between altered immune subsets and plasma oxidized-low-density lipoprotein levels. In vitro assays revealed increased uptake of oxidized-low-density lipoprotein into monocyte-derived macrophages in the presence of NK cells activated by plasma of patients with severe COVID-19. Transcriptome analyses confirmed enriched proinflammatory responses and lipid dysregulation associated with epigenetic modifications in monocytes and NK cells during severe COVID-19.

CONCLUSIONS: Our study provides new insights into the involvement of monocytes and NK cells in the increased CVD risk observed during and after COVID-19.

PMID:38989579 | DOI:10.1161/ATVBAHA.124.321085