Tag: nevin manimala

JAMA Netw Open. 2024 Nov 4;7(11):e2444756. doi: 10.1001/jamanetworkopen.2024.44756.

ABSTRACT

IMPORTANCE: Respiratory syncytial virus (RSV) infection can cause severe illness in adults. However, there is considerable uncertainty in the burden of RSV-associated hospitalizations among adults prior to RSV vaccine introduction.

OBJECTIVE: To describe the demographic characteristics of adults hospitalized with laboratory-confirmed RSV and to estimate annual rates and numbers of RSV-associated hospitalizations, intensive care unit (ICU) admissions, and in-hospital deaths.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the RSV Hospitalization Surveillance Network (RSV-NET), a population-based surveillance platform that captures RSV-associated hospitalizations in 58 counties in 12 states, covering approximately 8% of the US population. The study period spanned 7 surveillance seasons from 2016-2017 through 2022-2023. Included cases from RSV-NET were nonpregnant hospitalized adults aged 18 years or older residing in the surveillance catchment area and with a positive RSV test result.

EXPOSURE: Laboratory-confirmed RSV-associated hospitalization, defined as a positive RSV test result within 14 days before or during hospitalization.

MAIN OUTCOMES AND MEASURES: Hospitalization rates per 100 000 adult population, stratified by age group. After adjusting for test sensitivity and undertesting for RSV in adults hospitalized with acute respiratory illnesses, rates were extrapolated to the US population to estimate annual numbers of RSV-associated hospitalizations. Clinical outcome data were used to estimate RSV-associated ICU admissions and in-hospital deaths.

RESULTS: From the 2016 to 2017 through the 2022 to 2023 RSV seasons, there were 16 575 RSV-associated hospitalizations in adults (median [IQR] age, 70 [58-81] years; 9641 females [58.2%]). Excluding the 2020 to 2021 and the 2021 to 2022 seasons, when the COVID-19 pandemic affected RSV circulation, hospitalization rates ranged from 48.9 (95% CI, 33.4-91.5) per 100 000 adults in 2016 to 2017 to 76.2 (95% CI, 55.2-122.7) per 100 000 adults in 2017 to 2018. Rates were lowest among adults aged 18 to 49 years (8.6 [95% CI, 5.7-16.8] per 100 000 adults in 2016-2017 to 13.1 [95% CI, 11.0-16.1] per 100 000 adults in 2022-2023) and highest among adults 75 years or older (244.7 [95% CI, 207.9-297.3] per 100 000 adults in 2022-2023 to 411.4 [95% CI, 292.1-695.4] per 100 000 adults in 2017-2018). Annual hospitalization estimates ranged from 123 000 (95% CI, 84 000-230 000) in 2016 to 2017 to 193 000 (95% CI, 140 000-311 000) in 2017 to 2018. Annual ICU admission estimates ranged from 24 400 (95% CI, 16 700-44 800) to 34 900 (95% CI, 25 500-55 600) for the same seasons. Estimated annual in-hospital deaths ranged from 4680 (95% CI, 3570-6820) in 2018 to 2019 to 8620 (95% CI, 6220-14 090) in 2017 to 2018. Adults 75 years or older accounted for 45.6% (range, 43.1%-48.8%) of all RSV-associated hospitalizations, 38.6% (range, 36.7%-41.0%) of all ICU admissions, and 58.7% (range, 51.9%-67.1%) of all in-hospital deaths.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of adults hospitalized with RSV before the 2023 introduction of RSV vaccines, RSV was associated with substantial burden of hospitalizations, ICU admissions, and in-hospital deaths in adults, with the highest rates occurring in adults 75 years or older. Increasing RSV vaccination of older adults has the potential to reduce associated hospitalizations and severe clinical outcomes.

PMID:39535791 | DOI:10.1001/jamanetworkopen.2024.44756

JAMA. 2024 Nov 13. doi: 10.1001/jama.2024.19585. Online ahead of print.

ABSTRACT

IMPORTANCE: Pediatric patients with cancer commonly experience severely bothersome symptoms. The effectiveness of routine symptom screening with symptom feedback and symptom management care pathways is unknown.

OBJECTIVE: To determine whether thrice-weekly symptom screening with symptom feedback and management care pathways, compared with usual care, improves overall self-reported symptom scores measured by the Symptom Screening in Pediatrics Tool (SSPedi) in pediatric patients with cancer.

DESIGN, SETTING, AND PARTICIPANTS: This cluster randomized trial enrolled participants between July 2021 and August 2023 from 20 pediatric cancer centers in the US. Patients newly diagnosed with cancer aged 8 to 18 years receiving any cancer treatment were included. Twenty sites were randomized to provide symptom screening (n = 10) vs usual care (n = 10); 221 participants were enrolled at intervention sites and 224 participants at control sites. The date of final follow-up was October 18, 2023.

INTERVENTION: Symptom screening included providing thrice-weekly symptom screening prompts to participants, email alerts to the health care team, and locally adapted symptom management care pathway implementation.

MAIN OUTCOMES AND MEASURES: The primary outcome was self-reported total SSPedi score at week 8 (range, 0-60; higher scores indicate more bothersome). Secondary outcomes were Patient-Reported Outcomes Measurement Information System Fatigue score (mean [SD] score, 50 [10]; higher scores indicate more fatigue), Pediatric Quality of Life 3.0 Acute Cancer Module scores (range, 0-100; higher scores indicate better health), symptom documentation and interventions at week 8, and unplanned health care encounters.

RESULTS: A total of 445 participants (median [range] age, 14.8 [8.1-18.9] years; 58.9% males) were enrolled. The mean (SD) 8-week SSPedi score was 7.9 (7.2) in the symptom screening group vs 11.4 (8.7) in the usual care group. Symptom screening was associated with significantly better 8-week total SSPedi scores (adjusted mean difference, -3.8 [95% CI, -6.4 to -1.2]) and less bothersome individual symptoms, with 12 of 15 symptoms being statistically significantly reduced. There was no difference in fatigue or quality of life. The mean (SD) number of emergency department visits was 0.77 (1.12) in the symptom screening group and 0.45 (0.81) in the usual care group. There were significantly more emergency department visits in the symptom screening group (rate ratio, 1.72 [95% CI, 1.03-2.87]).

CONCLUSIONS: Symptom screening with symptom feedback and symptom management care pathways was associated with improved symptom scores and increased symptom-specific interventions. Future work should integrate symptom screening into routine clinical care.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04614662.

PMID:39535768 | DOI:10.1001/jama.2024.19585

Transl Vis Sci Technol. 2024 Nov 4;13(11):10. doi: 10.1167/tvst.13.11.10.

ABSTRACT

PURPOSE: Lifestyle risk factors are implicated in driving the current surge in myopia prevalence yet, paradoxically, known risk factors explain little of the variation in refractive error in the population. Here, we applied “instrumental variable” (IV) methods designed to avoid reverse causation and decrease confounding bias, to gauge lifestyle risk factor effect sizes.

METHODS: Three myopia risk factors (time outdoors, time reading, and sleep duration) were assessed in participants of the Avon Longitudinal Study of Parents and Children: a cross-sectional sample of 2302 children aged 15 years old and a longitudinal sample of 3086 children followed from age 7 to 15 years. Seven IVs were considered jointly: dog ownership, cat ownership, bedtime variability, birth order, and polygenic scores quantifying genetic predisposition to spend additional time outdoors, years in fulltime education, and time asleep overnight.

RESULTS: Risk factor effect sizes were 4-fold to 9-fold higher in the IV analyses compared with conventional regression analyses. In IV analyses, one extra hour spent outdoors every day during childhood was associated with a shift toward hyperopia of +0.53 to +0.94 diopters (D), whereas 1 extra hour spent reading every day was associated with a shift toward myopia of -0.44 to -0.88 D. There was inconsistent evidence that sleep duration influenced refractive error.

CONCLUSIONS: Myopia risk factor effects were underestimated up to 9-fold in conventional analyses in this sample, compared with IV analyses.

TRANSLATIONAL RELEVANCE: We speculate that the effects of lifestyle risk factors for myopia have been underestimated in past studies.

PMID:39535748 | DOI:10.1167/tvst.13.11.10

Transl Vis Sci Technol. 2024 Nov 4;13(11):14. doi: 10.1167/tvst.13.11.14.

ABSTRACT

PURPOSE: To characterize faricimab ocular and systemic pharmacokinetics (PK) in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) and to assess the effect of faricimab ocular exposure on clinical endpoints.

METHODS: A population PK (popPK) model was developed using pooled data from phase 1 to 3 studies in patients with nAMD/DME. The dataset included 1095 faricimab aqueous humor (AH) concentrations from 284 patients and 8372 faricimab plasma concentrations from 2246 patients.

RESULTS: Following intravitreal administration, faricimab PK was accurately described by a linear three-compartment model with sequential vitreous humor (VH), AH, and plasma compartments. Faricimab VH elimination to AH is the slowest process, with an estimated half-life (t1/2) of 7.5 days. Due to flip-flop kinetics, plasma, AH, and VH concentrations declined in parallel. Disease had no effect on faricimab PK. Plasma exposure was ∼6000-fold lower than VH exposure. Age, anti-drug antibodies, body weight, and sex statistically significantly influenced PK parameters but had no clinically meaningful effect on ocular and systemic exposure. VH t1/2 alone could not explain faricimab dosing frequency. Exposure-response analyses showed similar gains in best-corrected visual acuity across faricimab exposure ranges and dosing regimens.

CONCLUSIONS: Faricimab ocular and systemic pharmacokinetics were quantified and accurately described by the popPK model, developed using a large dataset from patients with nAMD/DME. Exposure-response analyses suggest that faricimab phase 3 dosing algorithms are appropriate to select the most suitable dosing regimen.

TRANSLATIONAL RELEVANCE: The popPK analysis suggested that faricimab dosing frequency was influenced by several factors and not by VH t1/2 alone.

PMID:39535744 | DOI:10.1167/tvst.13.11.14

Oncol Ther. 2024 Nov 13. doi: 10.1007/s40487-024-00313-3. Online ahead of print.

ABSTRACT

INTRODUCTION: Prostate cancer and its treatment, particularly androgen deprivation therapy (ADT), can profoundly impact patients’ quality of life. The aim of the prospective observational study reported here was to evaluate the effects of ADT on various aspects of quality of life in men with prostate cancer at a community-based hospital in Southern Italy.

METHODS: Eligible men initiating hormonal therapy were recruited between December 2021 and December 2023. Data were collected at baseline (T₀) and after 3 months (T₁) and 6 months (T₂) of ADT using standardized questionnaires (European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30, EORTC QLQ-PR25) and semi-structured interviews.

RESULTS: Of the 52 participants, 43 completed all three assessments. The EORTC QLQ-C30 showed a statistically significant worsening in physical functioning (mean score decrease from 83.8 at T₀ to 76.7 at T₂; p < 0.001), increased fatigue (from 23.7 to 35.2; p < 0.001), and insomnia (from 23.7 to 31.8; p = 0.048) following ADT initiation. The QLQ-PR25 revealed a significant decline in sexual functioning (from 59 to 26.9; p < 0.001) and sexual activity (from 27.3 to 12; p = 0.001). Interviews revealed a significant rise in the number of patients reporting depressed mood. Interviews also highlighted a worsening in body image perception and sexuality, increased feelings of dependence, and challenges in the social and relational spheres.

CONCLUSIONS: ADT significantly impacts various aspects of quality of life in men with prostate cancer, particularly physical functioning, fatigue, sexual function, body image, and emotional well-being. These results underscore the critical importance of a comprehensive, patient-centered approach that addresses both the physical and psychosocial aspects of care.

PMID:39535725 | DOI:10.1007/s40487-024-00313-3

MAGMA. 2024 Nov 13. doi: 10.1007/s10334-024-01213-3. Online ahead of print.

ABSTRACT

OBJECTIVE: To optimize high-resolution 7 T MRI of the cochlea and measure normal cochlea and the cochlear nerve morphometry in vivo.

MATERIALS AND METHODS: Eight volunteers with normal hearing were scanned at 7 T using an optimized protocol. Two neuroradiologists independently scored image quality. The basal turn lumen diameter (BTLD), height, width, length and volume of the cochlear, long (LD) and short (SD) diameter the calculated cross-sectional area (CSA) of the cochlear nerve were measured. Intra and inter-observer reliability was assessed using intraclass correlation (ICC).

RESULTS: 3D T2W DRIVE combined with dielectric pads, allowed acquisition of high-resolution images showing detailed structures, such as the crista ampullaris in the semicircular canals. The overall grading scores from neuroradiologists were excellent. In the left ear, averaging over all subjects gave BTLD of 2.6 ± 0.05 mm, height of 4.9 ± 0.1 mm, width of 4.4 ± 0.2 mm, length of 36.5 ± 0.4 mm, volume of 0.16 ± 0.02 ml, LD of 1.31 ± 0.1 mm, SD of 1.06 ± 0.1 mm, and CSA of 1.1 ± 0.1 mm². The right ear gave BTLD of 2.6 ± 0.04 mm, height of 4.9 ± 0.1 mm, width of 4.4 ± 0.3 mm, length of 35.5 ± 0.4 mm, volume of 0.16 ± 0.02 ml, LD of 1.29 ± 0.1 mm, SD of 1.07 ± 0.1 mm, and CSA of 1.10 ± 0.2 mm². No statistically significant difference was found between the sides of the head (p-value > 0.05). The intra-observer reliability was high (0.77-0.94), while the inter-observer reliability varied from moderate to high (0.55-0.81).

CONCLUSION: 7 T MRI can provide excellent visualization of the internal structure of the cochlear and of the vestibulocochlear nerve in vivo.

PMID:39535680 | DOI:10.1007/s10334-024-01213-3

Clin Exp Med. 2024 Nov 13;25(1):4. doi: 10.1007/s10238-024-01519-5.

ABSTRACT

Existing challenges in accurately diagnosing various rheumatic diseases (RDs) have stimulated the search for novel biomarkers to aid clinical evaluation and monitoring. We conducted a systematic review and meta-analysis of studies investigating the candidate biomarker endoglin (CD105), a transmembrane glycoprotein expressed in endothelial, myeloid, and lymphoid cells, in RD patients and healthy controls. We searched PubMed, Scopus, and Web of Science from inception to 10 August 2024 to identify relevant studies. We evaluated the risk of bias using the JBI Critical Appraisal Checklist and the certainty of evidence using GRADE (PROSPERO registration number: CRD42023581008). Overall, circulating endoglin concentrations were significantly higher in RD patients compared to controls (13 studies; standard mean difference, SMD = 0.64, 95% CI 0.13 to 1.14, p = 0.014; low certainty of evidence). The effect size of the between-group differences in endoglin concentrations was not significantly associated with age, male-to-female ratio, year of publication, number of participants, or mean RD duration. By contrast, the effect size was statistically significant in studies conducted in the European region (p = 0.033), involving patients with systemic sclerosis (p = 0.032), and measuring serum (p = 0.019). The results of this systematic review and meta-analysis suggest the potential pathophysiological role of endoglin in RDs. This, however, requires further investigation in prospective studies, particularly in patients with systemic sclerosis.

PMID:39535678 | DOI:10.1007/s10238-024-01519-5

Int J Cardiovasc Imaging. 2024 Nov 13. doi: 10.1007/s10554-024-03278-6. Online ahead of print.

ABSTRACT

Left ventricular mechanical dyssynchrony (LVMD) is an important prognostic factor for heart failure (HF). Phase analysis of myocardial perfusion SPECT is actively being researched to evaluate LVMD. We performed a systematic review and meta-analysis on the prognostic significance of LVMD using gated SPECT in HF patient. PubMed, Embase, and the Cochrane library were searched until January 10, 2024, for studies reporting the prognostic value of LVMD in HF patients using gated SPECT for outcomes of all-cause death, cardiac death, or major adverse cardiovascular event (MACE). Hazard ratios (HRs) along with their corresponding 95% confidence intervals (CIs) were combined through meta-analysis employing a random-effects model. Funnel plots and Egger’s tests were utilized to evaluate publication bias, and trim-and-fill method were applied where bias was identified. Ten studies (2585 patients) were included; six on MACE and five on all-cause or cardiac death. Prognoses were worse in patients with LVMD assessed by SPECT than in those without LVMD, with the overall pooled HR for MACE being 2.05 (95% CI, 1.65-2.54). The pooled HR for all-cause or cardiac death was 2.08 (95% CI, 1.10-3.94); however, publication bias was present (p = 0.0024), and after adjustment, the prognostic value of LVMD was not statistically significant (HR, 1.24; 95% CI, 0.68-2.23). Assessing LVMD through myocardial perfusion SPECT proves to be a significant indicator of subsequent adverse cardiac events in HF patients. Utilizing phase analysis of SPECT could offer valuable insights for risk assessment and decision-making regarding therapy in HF patients.

PMID:39535673 | DOI:10.1007/s10554-024-03278-6

Inflammation. 2024 Nov 13. doi: 10.1007/s10753-024-02169-1. Online ahead of print.

ABSTRACT

Our two previous studies observed that cell division cycle 42 (CDC42) was lower and correlated with improved renal function and inflammation in diabetic nephropathy (DN) patients, and CDC42 inhibited renal tubular epithelial cell fibrosis and inflammation under high glucose condition. Sequentially, this current study aimed to investigate the effect of CDC42 on improving renal function, fibrosis, and inflammation in DN mice, and its interaction with T cell receptor (TCR) related pathways. Mice were treated by streptozotocin to construct early-stage DN model, then transfected with CDC42 overexpression adenovirus, followed by simultaneous treatment of LY294002 (PI3K/AKT inhibitor) and CI-1040 (ERK inhibitor), respectively. CDC42 reduced blood glucose, creatinine, and 24 h urine protein in DN mice, but only showed a tendency to decrease blood urea nitrogen without statistical significance. Hematoxylin&eosin staining revealed that CDC42 descended the glomerular volume, basement membrane thickness, and inflammatory cell infiltration in kidney. Meanwhile, CDC42 lowered fibronectin, TGF-β1, and Collagen I expressions in kidney, but not decreased α-SMA significantly. Besides, CDC42 decreased T-helper (Th) 1 and Th17 cells in kidney, and reduced serum IFN-γ, IL-1β, IL-17A, and TNF-α but not IL-6. Regarding TCR-related pathways, CDC42 activated AKT and ERK pathways but not JNK pathway. However, the treatment of LY294002 and CI-1040 had limited effect on attenuating CDC42’s functions on renal function and fibrotic markers. CDC42 improves renal functions, fibrosis, Th1/Th17 infiltration and inflammation to some degree in DN mice, these functions may be independent to AKT and ERK pathways.

PMID:39535664 | DOI:10.1007/s10753-024-02169-1

Eur J Nutr. 2024 Nov 13;64(1):2. doi: 10.1007/s00394-024-03521-9.

ABSTRACT

OBJECTIVES: The potential association between oral health and nutritional status of the very old, has been poorly investigated. Thus, we carried out the cross-sectional study to evaluate the association of oral health with the nutritional status of the older adults.

METHODS: 210 participants aged over 75 years were included in the study. Nutritional status was assessed by the Short-form Mini-Nutritional Assessment (MNA-SF) and body composition measurement. Data were available for self-reported oral health (10-item Eating Assessment Tool (EAT-10) and Chewing Function Questionnaire (CFQ)) and specific experimental tests including salivary flow, tongue and lip pressure, occlusal force, water swallow test and taste test for the detection of oral functions. Spearman rank correlation was used to analyze the correlation between body composition and oral health. Logistic regression and restricted cubic spline models were applied to examine the association of oral health with malnutrition.

RESULTS: The study reveals that poor oral health is related to the malnutrition. The tongue pressure and molar occlusal force were significantly associated with malnutrition in an L-shaped dose-response relationship after adjustment for potential confounding factors. The higher the tongue pressure and molar occlusal force, the lower the risk of malnutrition. Besides, the CFQ score, salty, sour, and bitter taste, are risk factors for malnutrition.

CONCLUSIONS: The presence of malnutrition is significantly associated with poor oral health in older adults. Our study supposes that the design of food suitable for oral conditions of the older adults may be another feasible solution to the nutritional problems among them.

PMID:39535606 | DOI:10.1007/s00394-024-03521-9