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Forward Light Scattering of the Vitreous Gel After Enzymatic Aging: An In Vitro Model to Study Vitreous Opacification

Invest Ophthalmol Vis Sci. 2024 Mar 5;65(3):36. doi: 10.1167/iovs.65.3.36.

ABSTRACT

PURPOSE: Symptomatic vitreous opacifications, so-called floaters, are difficult to objectively assess majorly limiting the possibility of in vitro studies. Forward light scattering was found previously to be increased in eyes with symptomatic floaters. Using an objective setup to measure forward light scattering, we studied the effects of enzymatically digesting the components of the vitreous body on straylight to develop an in vitro model of vitreous opacifications.

METHODS: Fifty-seven porcine vitreous bodies were digested using hyaluronidase, collagenase, trypsin, and bromelain, as well as using a combination of hyaluronidase + collagenase and hyaluronidase + bromelain. A modified C-Quant setup was used to objectively assess forward light scattering.

RESULTS: Depletion of hyaluronic acid majorly increased vitreous straylight (mean increase 34.4 deg2/sr; P = 0.01), whereas primarily digesting the vitreous gel with collagenase or trypsin did not significantly affect straylight. When collagenase or bromelain is applied in hyaluronic acid depleted vitreous gels, the increase in forward light scattering is reversed partially.

CONCLUSIONS: The age-related loss of hyaluronic acid primarily drives the increase in vitreous gel straylight induced by conglomerates of collagen. This process can be reversed partially by digesting collagen. This in vitro model allows the objective quantification and statistical comparison of straylight burden caused by vitreous opacities and, thus, can serve as a first testing ground for pharmacological therapies, as demonstrated with bromelain.

PMID:38551585 | DOI:10.1167/iovs.65.3.36

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Authorship of Publications Supported by NCI-Funded Grants Involving Low- and Middle-Income Countries

JAMA Netw Open. 2024 Mar 4;7(3):e243215. doi: 10.1001/jamanetworkopen.2024.3215.

ABSTRACT

IMPORTANCE: Scientific publication is an important tool for knowledge dissemination and career advancement, but authors affiliated with institutions in low- and middle-income countries (LMICs) are historically underrepresented on publications.

OBJECTIVE: To assess the country income level distribution of author affiliations for publications resulting from National Cancer Institute (NCI)-supported extramural grants between 2015 and 2019, with international collaborating institutions exclusively in 1 or more LMICs.

DESIGN AND SETTING: This cross-sectional study assessed authorship on publications resulting from NCI-funded grants between October 1, 2015, and September 30, 2019. Grants with collaborators in LMICs were identified in the National Institutes of Health (NIH) Query/View/Report and linked to publications using Dimensions for NIH, published between 2011 and 2020. Statistical analysis was performed from May 2021 to July 2022.

MAIN OUTCOMES AND MEASURES: Author institutional affiliation was used to classify author country and related income level as defined by the World Bank. Relative citation ratio and Altmetric data from Dimensions for NIH were used to compare citation impact measures using the Wilcoxon rank sum test.

RESULTS: In this cross-sectional study, 159 grants were awarded to US institutions with collaborators in LMICs, and 5 grants were awarded directly to foreign institutions. These 164 grants resulted in 2428 publications, of which 1242 (51%) did not include any authors affiliated with an institution in an LMIC. In addition, 1884 (78%) and 2009 (83%) publications had a first or last author, respectively, affiliated with a high-income country (HIC). Publications with HIC-affiliated last authors also demonstrated greater citation impact compared with publications with LMIC-affiliated last authors as measured by relative citation ratios and Altmetric Attention Scores; publications with HIC-affiliated first authors also had higher Altmetric Attention Scores.

CONCLUSIONS AND RELEVANCE: This cross-sectional study suggests that LMIC-affiliated authors were underrepresented on publications resulting from NCI-funded grants involving LMICs. It is critical to promote equitable scientific participation by LMIC institutions in cancer research, including through current and planned programs led by the NCI.

PMID:38551565 | DOI:10.1001/jamanetworkopen.2024.3215

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Cervical Cancer Screening via Visual Inspection With Acetic Acid and Lugol Iodine for Triage of HPV-Positive Women

JAMA Netw Open. 2024 Mar 4;7(3):e244090. doi: 10.1001/jamanetworkopen.2024.4090.

ABSTRACT

IMPORTANCE: Limited evidence supports the performance of human papillomavirus (HPV) DNA testing as a primary screening method, followed by triage with visual inspection with acetic acid, in areas with limited health care resources, as suggested by the 2021 World Health Organization guidelines.

OBJECTIVE: To evaluate the performance of visual inspection with acetic acid and Lugol iodine as a triage method for detecting cervical precancerous lesions among HPV-positive women in 1 visit.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined the implementation of a government-led cervical cancer screening program conducted from January 1, 2016, to December 31, 2020, in Ordos City, China. Female residents, aged 35 to 64 years, who understood the screening procedures and voluntarily participated were included in the study. Women were excluded if they reported never having had sexual intercourse, were pregnant, had a hysterectomy, or had ever undergone treatment for cervical lesions. Statistical analysis was conducted from December 2022 to December 2023.

EXPOSURES: The program used the careHPV DNA assay as the primary screening method, and immediate triage was performed by visual inspection if HPV screening results were positive, with a 5-year screening interval. A colposcopy was performed for the women who had suspected cancer on visual inspection results or who were HPV positive and had abnormal visual inspection results, all in 1 visit.

MAIN OUTCOMES AND MEASURES: The rate of compliance with colposcopy and the detection rate of cervical intraepithelial neoplasia grade 2 or higher (CIN2+).

RESULTS: The study included 187 863 women (median age, 46 years [IQR, 40-52 years]) who participated in the program and had valid HPV test results. The overall prevalence of HPV positivity was 12.8% (24 070 of 187 863), and the adherence to triage with visual inspection among HPV-positive women was 93.9% (22 592 of 24 070). Among HPV-positive women, the rate of compliance with colposcopy was 65.6% (2714 of 4137), and the CIN2+ detection rate was 2.8% (643 of 22 592).

CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that the implementation of HPV testing, visual inspection, and colposcopy within 1 visit may mitigate losses to follow-up, detect precancerous lesions, and hold significant implications for screening in comparable areas with limited health care resources.

PMID:38551562 | DOI:10.1001/jamanetworkopen.2024.4090

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Prevalence, Morbidity, and Mortality of Men With Sex Chromosome Aneuploidy in the Million Veteran Program Cohort

JAMA Netw Open. 2024 Mar 4;7(3):e244113. doi: 10.1001/jamanetworkopen.2024.4113.

ABSTRACT

IMPORTANCE: The reported phenotypes of men with 47,XXY and 47,XYY syndromes include tall stature, multisystem comorbidities, and poor health-related quality of life (HRQOL). However, knowledge about these sex chromosome aneuploidy (SCA) conditions has been derived from studies in the less than 15% of patients who are clinically diagnosed and also lack diversity in age and genetic ancestry.

OBJECTIVES: To determine the prevalence of clinically diagnosed and undiagnosed X or Y chromosome aneuploidy among men enrolled in the Million Veteran Program (MVP); to describe military service metrics of men with SCAs; and to compare morbidity and mortality outcomes between men with SCA with and without a clinical diagnosis vs matched controls.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used a case-control recruitment design to select biological males enrolled in the MVP biobank in the US Veterans Administration health care system from 2011 to 2022. Cases were participants with 47,XXY syndrome or 47,XYY syndrome, matched 1:5 with controls based on sex, age, and genetic ancestry. Data were analyzed from January 2022 to December 2023.

EXPOSURE: Genomic identification of an additional X or Y chromosome.

MAIN OUTCOMES AND MEASURES: Outcomes of interest included prevalence of men with SCAs from genomic analysis; clinical SCA diagnosis; Charlson Comorbidity Index; rates of outpatient, inpatient, and emergency encounters per year; self-reported health outcomes; and standardized mortality ratio.

RESULTS: Of 595 612 genotyped males in the MVP, 862 had an additional X chromosome (47,XXY) and 747 had an extra Y chromosome (47,XYY), with the highest prevalence among men with East Asian (47,XXY: 10 of 7313 participants; 47,XYY: 14 of 7313 participants) and European (47,XXY: 725 of 427 143 participants; 47,XYY: 625 of 427 143 participants) ancestry. Mean (SD) age at assessment was 61 (12) years, at which point 636 veterans (74.X%) with 47,XXY and 745 veterans (99%) with 47,XYY remained undiagnosed. Individuals with 47,XXY and 47,XYY had similar military service history, all-cause standardized mortality ratio, and age of death compared with matched controls. Individuals with SCA, compared with controls, had higher Charlson Comorbidity Index scores (47,XXY: mean [SD], 4.30 [2.72] vs controls: mean [SD], 3.90 [2.47]; 47,XYY: mean [SD], 4.45 [2.90] vs controls: mean [SD], 3.82 [2.50]) and health care utilization (eg, median [IQR] outpatient encounters per year: 47,XXY, 22.6 [11.8-37.8] vs controls, 16.8 [9.4-28]; 47,XYY: 21.4 [12.4-33.8] vs controls: 17.0 [9.4-28.2]), while several measures of HRQOL were lower (eg, mean [SD] self-reported physical function: 47,XXY: 34.2 [12] vs control mean [SD] 37.8 [12.8]; 47,XYY: 36.3 [11.6] vs control 37.9 [12.8]). Men with a clinical diagnosis of 47,XXY, compared with individuals without a clinical diagnosis, had higher health care utilization (eg, median [IQR] encounters per year: 26.6 [14.9-43.2] vs 22.2 [11.3-36.0]) but lower Charlson Comorbidity Index scores (mean [SD]: 3.7 [2.7] vs 4.5 [4.1]).

CONCLUSION AND RELEVANCE: In this case-control study of men with 47,XXY and 47,XYY syndromes, prevalence of SCA was comparable with estimates in the general population. While these men had successfully served in the military, they had higher morbidity and reported poorer HRQOL with aging. Longer longitudinal follow-up of this sample will be informative for clinical and patient-reported outcomes, the role of ancestry, and mortality statistics.

PMID:38551561 | DOI:10.1001/jamanetworkopen.2024.4113

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Trends in Adolescent Suicide by Method in the US, 1999-2020

JAMA Netw Open. 2024 Mar 4;7(3):e244427. doi: 10.1001/jamanetworkopen.2024.4427.

ABSTRACT

IMPORTANCE: Adolescent suicide in the US is a major public health problem, yet temporal trends in suicide methods by demographics are understudied.

OBJECTIVE: To examine national trends in suicide mortality by method (firearm, poisoning, hanging and asphyxiation, and all other means) from 1999 to 2020 by demographic characteristics.

DESIGN, SETTING, AND PARTICIPANTS: This serial cross-sectional study used national death certificate data of adolescent (aged 10-19 years) suicide decedents compiled by the National Center for Health Statistics from January 1, 1999, to December 31, 2020. Data analysis was performed from April 1, 2023, to July 9, 2023.

EXPOSURES: Age, sex, and race and ethnicity.

MAIN OUTCOMES AND MEASURES: Trends in age-standardized mortality rates and average annual percent change (AAPC) in rates were estimated by age, sex, and race and ethnicity for each suicide method.

RESULTS: This study assessed data from 47 217 adolescent suicide decedents. From 1999 to 2020, suicide by firearm (AAPC, 1.0; 95% CI, 0.1-1.9), poisoning (AAPC, 2.7; 95% CI, 1.0-4.4), hanging and asphyxiation (AAPC, 2.4; 95% CI, 0.2-4.6), and other means (AAPC, 2.9; 95% CI, 1.2-4.6) increased. Rapidly increasing rates were observed among female adolescents for poisoning (AAPC, 4.5; 95% CI, 2.3-6.7) and hanging and asphyxiation (AAPC, 5.9; 95% CI, 5.0-6.8) suicides. From 2007 to 2020, firearm suicides sharply increased among female (annual percent change [APC], 7.8; 95% CI, 6.0-9.5) and male (APC, 5.3; 95% CI, 4.3-6.3) adolescents. Firearm suicide rates increased among Black adolescents from 2012 to 2020 (APC, 14.5; 95% CI, 9.7-19.5), Asian and Pacific Islander adolescents from 2008 to 2020 (APC, 12.0; 95% CI, 9.7-14.5), American Indian and Alaska Native adolescents from 2014 to 2020 (APC, 10.6; 95% CI, 2.6-19.3), and Hispanic or Latino adolescents from 2011 to 2020 (APC, 10.2; 95% CI, 6.3-13.8). During the study period, Black adolescents had the highest average increase in hanging and asphyxiation suicides (AAPC, 4.2; 95% CI, 3.2-5.2). From 2011 to 2020, poisoning suicide deaths increased (APC, 12.6; 95% CI, 8.5-16.7) among female adolescents.

CONCLUSIONS AND RELEVANCE: Suicide rates increased across all methods from 1999 to 2020. Differences were noted by sex, age, and race and ethnicity. Increasing suicide rates among racial and ethnic minoritized youth are especially concerning, and effective prevention strategies are urgently needed.

PMID:38551558 | DOI:10.1001/jamanetworkopen.2024.4427

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The Effect of Therapeutic Play on Children’s Pain, Anxiety and Mothers’ Anxiety during Pre- and Postcircumcision Period

J Perianesth Nurs. 2024 Mar 26:S1089-9472(23)01102-4. doi: 10.1016/j.jopan.2023.12.015. Online ahead of print.

ABSTRACT

PURPOSE: The study was conducted to determine the effect of the therapeutic play method implemented on the pre- and postcircumcision pain and anxiety levels of children and mothers’ anxiety levels in the pediatric surgery clinic.

DESIGN: Prospective, randomized clinical trial.

METHODS: The study consisted of children between the ages of 3 to 6 admitted to the pediatric surgery clinic and their mothers (N = 120; Therapeutic playgroup = 60, Control group = 60). As a therapeutic play method the children and their mothers used play dough during the structured conversation for about 10 minutes before and after the operation. A questionnaire, the Face, Legs, Activity, Cry, Consolability (FLACC) pain scale, the Children’s Emotional Manifestation Scale (CEMS) anxiety scale, and State-Trait Anxiety Inventory-S (STAI-S) anxiety scale for parents were used to collect data.

FINDINGS: In the pre- and postcircumcision period, the pain and anxiety levels of children and mothers’ anxiety levels in the therapeutic playgroup were statistically lower compared to the control group (P < .05). In the postoperative period, a positive and significance correlation was found between anxiety levels of the mothers and pain and anxiety levels of children in the control group (P < .05).

CONCLUSIONS: The therapeutic play method was effective in reducing the pain and anxiety levels of children and mothers’ anxiety in the pre- and postcircumcision period.

PMID:38551545 | DOI:10.1016/j.jopan.2023.12.015

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Metabolic Syndrome and Metabolic Dysfunction-Associated Steatotic Liver Disease in Premenopausal Women: Global Trends and Projections to 2040

Mayo Clin Proc. 2024 Mar 28:S0025-6196(24)00035-1. doi: 10.1016/j.mayocp.2023.12.025. Online ahead of print.

ABSTRACT

OBJECTIVE: To quantify the burden of metabolic dysfunction-associated steatotic liver disease (MASLD) and related metabolic disorders in premenopausal women.

PATIENTS AND METHODS: Between 2010 and 2019, global evaluations of prevalence, mortality, disability-adjusted life years (DALYs), and their age-standardized rate (ASR) were conducted for metabolic conditions such as MASLD, type 2 diabetes mellitus, dyslipidemia, hypertension (HTN), obesity, and polycystic ovarian syndrome. Subgroup assessments were conducted according to geographical regions and the sociodemographic index. The predictive models were established to estimate mortality and DALYs through 2040.

RESULTS: In 2019, the most significant ASR of deaths was found in HTN (11.37; 9.52 to 13.45), followed by obesity (10.49; 7.57 to 13.64). In contrast, the greatest ASR of DALYs was attributed to obesity (816.13; 581.41 to 1073.32), followed by HTN (634.73; 536.75 to 744.77). The mortality rates for dyslipidemia (0.55%) and HTN (0.72%) have been decreasing over time, but there has been an increase in obesity (+0.58%), type 2 diabetes mellitus (+0.85%), and MASLD (+0.51%). Lower sociodemographic index countries exhibit a higher disability-to-prevalence ratio. In 2040, obesity is predicted to cause the most deaths (+41.59% from 2019).

CONCLUSION: The escalating impact of metabolic syndrome, the rising trends in death rates linked to obesity, and the disparities based on region and socioeconomic status in premenopausal women underscore the alarming increase in the global burden of metabolic syndrome.

PMID:38551541 | DOI:10.1016/j.mayocp.2023.12.025

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Urine Albumin-Creatinine Ratio Variability in People With Type 2 Diabetes: Clinical and Research Implications

Am J Kidney Dis. 2024 Mar 15:S0272-6386(24)00620-6. doi: 10.1053/j.ajkd.2023.12.018. Online ahead of print.

ABSTRACT

RATIONALE & OBJECTIVE: Evidence has demonstrated that albuminuria is a key diagnostic and prognostic marker of diabetic chronic kidney disease, but the impact of its day-to-day variability has not been adequately considered. This study quantified within-individual variability of albuminuria in people with type 2 diabetes to inform clinical albuminuria monitoring.

STUDY DESIGN: Descriptive cross-sectional analysis.

SETTING & PARTICIPANTS: People with type 2 diabetes (n=826, 67.1 [IQR, 60.3-72.4] years, 64.9% male) participating in the Progression of Diabetic Complications (PREDICT) cohort study.

EXPOSURE: Four spot urine collections for measurement of urinary albumin-creatinine ratio (UACR) within 4 weeks.

OUTCOME: Variability of UACR.

ANALYTICAL APPROACH: We characterized within-individual variability (coefficient of variation [CV], 95% limits of random variation, intraclass correlation coefficient), developed a calculator displaying probabilities that any observed difference between a pair of UACR values truly exceeded a 30% difference, and estimated the ranges of diagnostic uncertainty to inform a need for additional UACR collections to exclude or confirm albuminuria. Multiple linear regression examined factors influencing UACR variability.

RESULTS: We observed high within-individual variability (CV 48.8%; 95% limits of random variation showed a repeated UACR to be as high/low as 3.78/0.26 times the first). If a single-collection UACR increased from 2 to 5mg/mmol, the probability that UACR actually increased by at least 30% was only 50%, rising to 97% when 2 collections were obtained at each time point. The ranges of diagnostic uncertainty were 2.0-4.0mg/mmol after an initial UACR test, narrowing to 2.4-3.2 and 2.7-2.9mg/mmol for the mean of 2 and 3 collections, respectively. Some factors correlated with higher (female sex; moderately increased albuminuria) or lower (reduced estimated glomerular filtration rate and sodium-glucose cotransporter 2 inhibitor/angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment) within-individual UACR variability.

LIMITATIONS: Reliance on the mean of 4 UACR collections as the reference standard for albuminuria.

CONCLUSIONS: UACR demonstrates a high degree of within-individual variability among individuals with type 2 diabetes. Multiple urine collections for UACR may improve capacity to monitor changes over time in clinical and research settings but may not be necessary for the diagnosis of albuminuria.

PLAIN-LANGUAGE SUMMARY: Albuminuria (albumin in urine) is a diagnostic and prognostic marker of diabetic chronic kidney disease. However, albuminuria can vary within an individual from day to day. We compared 4 random spot urinary albumin-creatinine ratio (UACR) samples from 826 participants. We found that a second UACR collection may be as small as a fourth or as large as almost 4 times the first sample’s UACR level. This high degree of variability presents a challenge to our ability to interpret changes in albuminuria. Multiple collections have been suggested as a solution. We have constructed tools that may aid clinicians in deciding how many urine collections are required to monitor and diagnose albuminuria. Multiple urine collections may be required for individual monitoring but not necessarily for diagnosis.

PMID:38551531 | DOI:10.1053/j.ajkd.2023.12.018

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Quadriceps femoris muscle ultrasound in sarcoidosis: an observational case-control study

Eur J Phys Rehabil Med. 2024 Mar 29. doi: 10.23736/S1973-9087.24.08232-7. Online ahead of print.

ABSTRACT

BACKGROUND: Although loss of muscle mass may be associated with general weakness, intolerance to physical activity and fatigue, it is underestimated and poorly understood in patients with sarcoidosis.

AIM: To compare the quadriceps femoris muscle (QFM) thickness measured by ultrasonography (US) between the female patients with sarcoidosis and controls, secondly to assess the correlation between the muscle strength, fatigue and QFM thickness.

DESIGN: Observational, case-control study.

SETTING: Physical Medicine and Rehabilitation Department of a University Hospital.

POPULATION: Thirty-one women with sarcoidosis and 27 healthy volunteers were included in the study.

METHODS: The participants were evaluated for the following outcomes: 1) handgrip strength; 2) QFM thickness measured using US; and 3) sonographic thigh adjustment ratio (STAR). The sarcoidosis group was also evaluated with the 30-second chair stand test (30s-CST) and Fatigue Severity Scale (FSS).

RESULTS: The QFM thickness and STAR values of the patients with sarcoidosis were significantly lower than those of the controls (P=0.0001). However, no statistically significant difference was observed between the handgrip strengths of the groups (P=0.581). There was no statistically significant correlation between the STAR values and handgrip strength in the sarcoidosis group; however, there was a significant positive correlation between the STAR values and 30s-CST (r=0.467, P=0.008).

CONCLUSIONS: Loss of muscle mass is one of the musculoskeletal conditions in patients with sarcoidosis that may be associated with nonspecific symptoms, such as general debility, intolerance to physical activity, and fatigue. In the present study, no difference was observed in hand grip strength between the groups, while we found that QFM thickness was affected in patients with sarcoidosis when compared to the controls. The ultrasonographic QFM evaluation seems to be an innovative tool which may be used at all stages of sarcoidosis patient follow-up.

CLINICAL REHABILITATION IMPACT: The grip strength is a commonly used test to detect muscle weakness, but onset of a decrease in muscle mass in the lower extremities may occur earlier. Considering the increased burden of musculoskeletal problems in this population, performing 30s-CST and sonographic QFM thickness is practical methods to identify risky patients.

PMID:38551519 | DOI:10.23736/S1973-9087.24.08232-7

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Development and preliminary validation of the Clinician Affective REsponse (CARE) scale

Res Psychother. 2024 Mar 21. doi: 10.4081/ripppo.2024.736. Online ahead of print.

ABSTRACT

The present study reports on the development and validation of the clinician affective response (CARE) scale. The CARE scale was designed as a self-report measure of therapists’ patterns of thoughts, feelings, and behaviors toward the patient during an individual psychotherapy session. An initial pool of 116 items was generated, and its quality was evaluated by subject matter experts. Validation data were gathered from licensed psychotherapists (n=554). We used exploratory factor analysis and item response theory-graded response modeling to select items, confirmatory factor analysis to test how well the factor structure fit the data, and k-fold cross-validation to ascertain the robustness of the model. Criterion validity was evaluated by correlating the scores of the scale with the characteristics of therapists, patients, and treatment. The selected model consists of 15 items and a 3-factor structure, which showed excellent model fit, good internal consistency, and evidence of criterion validity. The CARE scale, short and quick to complete, enables therapists to reflect on and recognize their inner experiences and quantify these experiences in ways conducive to statistical analysis and research. Furthermore, the monitoring of these affective reactions toward their patients can guide therapeutic interventions and inform clinical supervisors.

PMID:38551502 | DOI:10.4081/ripppo.2024.736