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1.
Int J Circumpolar Health ; 83(1): 2359162, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38801151

ABSTRACT

We aimed to determine the surgical output for patients from Nunavik undergoing transfer to an urban centre for hysteroscopy, and associated costs. We performed a retrospective chart review of all patients from the 14 villages of Nunavik transferred for hysteroscopic surgery from 2016 to 2021. Diagnoses, surgical intervention, and nature of the procedure were all extracted from the patient charts, and costs/length of stay obtained from logisticians and administrators servicing the Nunavik region. Over a 5-year period, 22 patients were transferred from Nunavik for hysteroscopy, of which all were elective save one. The most common diagnosis was endometrial or cervical polyp and the most common procedure was diagnostic hysteroscopy. The average cost for patient transfer and lodging to undergo hysteroscopy in Montreal ranged from $6,000 to $15,000 CDN. On average, 4-5 patient transfers occur annually for hysteroscopy, most commonly for management of endometrial polyps, at a cost of $6,000 to $15,000 CDN, suggesting the need to investigate local capacity building in Nunavik and assess cost-effectiveness.


Subject(s)
Hysteroscopy , Humans , Female , Quebec , Retrospective Studies , Hysteroscopy/economics , Adult , Middle Aged , Health Services Needs and Demand
2.
JAMA Netw Open ; 7(5): e2413644, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38809555

ABSTRACT

Importance: Sweetened beverage taxes have been associated with reduced purchasing of taxed beverages. However, few studies have assessed the association between sweetened beverage taxes and health outcomes. Objective: To evaluate the association between the Seattle sweetened beverage tax and change in body mass index (BMI) among children. Design, Setting, and Participants: In this longitudinal cohort study, anthropometric data were obtained from electronic medical records of 2 health care systems (Kaiser Permanente Washington [KP] and Seattle Children's Hospital Odessa Brown Children's Clinic [OBCC]). Children were included in the study if they were aged 2 to 18 years (between January 1, 2014, and December 31, 2019); had at least 1 weight measurement every year between 2015 and 2019; lived in Seattle or in urban areas of 3 surrounding counties (King, Pierce, and Snohomish); had not moved between taxed (Seattle) and nontaxed areas; received primary health care from KP or OBCC; did not have a recent history of cancer, bariatric surgery, or pregnancy; and had biologically plausible height and BMI (calculated as weight in kilograms divided by height in meters squared). Data analysis was conducted between August 5, 2022, and March 4, 2024. Exposure: Seattle sweetened beverage tax (1.75 cents per ounce on sweetened beverages), implemented on January 1, 2018. Main Outcomes and Measures: The primary outcome was BMIp95 (BMI expressed as a percentage of the 95th percentile; a newly recommended metric for assessing BMI change) of the reference population for age and sex, using the Centers for Disease Control and Prevention growth charts. In the primary (synthetic difference-in-differences [SDID]) model used, a comparison sample was created by reweighting the comparison sample to optimize on matching to pretax trends in outcome among 6313 children in Seattle. Secondary models were within-person change models using 1 pretax measurement and 1 posttax measurement in 22 779 children and fine stratification weights to balance baseline individual and neighborhood-level confounders. Results: The primary SDID analysis included 6313 children (3041 female [48%] and 3272 male [52%]). More than a third of children (2383 [38%]) were aged 2 to 5 years); their mean (SE) age was 7.7 (0.6) years. With regard to race and ethnicity, 789 children (13%) were Asian, 631 (10%) were Black, 649 (10%) were Hispanic, and 3158 (50%) were White. The primary model results suggested that the Seattle tax was associated with a larger decrease in BMIp95 for children living in Seattle compared with those living in the comparison area (SDID: -0.90 percentage points [95% CI, -1.20 to -0.60]; P < .001). Results from secondary models were similar. Conclusions and Relevance: The findings of this cohort study suggest that the Seattle sweetened beverage tax was associated with a modest decrease in BMIp95 among children living in Seattle compared with children living in nearby nontaxed areas who were receiving care within the same health care systems. Taken together with existing studies in the US, these results suggest that sweetened beverage taxes may be an effective policy for improving children's BMI. Future research should test this association using longitudinal data in other US cities with sweetened beverage taxes.


Subject(s)
Body Mass Index , Pediatric Obesity , Sugar-Sweetened Beverages , Taxes , Humans , Female , Male , Child , Child, Preschool , Taxes/statistics & numerical data , Sugar-Sweetened Beverages/economics , Sugar-Sweetened Beverages/statistics & numerical data , Adolescent , Washington , Longitudinal Studies , Pediatric Obesity/prevention & control
3.
mBio ; 15(5): e0069024, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38717196

ABSTRACT

Extracellular cytochrome filaments are proposed to serve as conduits for long-range extracellular electron transfer. The primary functional physiological evidence has been the reported inhibition of Geobacter sulfurreducens Fe(III) oxide reduction when the gene for the filament-forming cytochrome OmcS is deleted. Here we report that the OmcS-deficient strain from that original report reduces Fe(III) oxide as well as the wild-type, as does a triple mutant in which the genes for the other known filament-forming cytochromes were also deleted. The triple cytochrome mutant displayed filaments with the same 3 nm diameter morphology and conductance as those produced by Escherichia coli heterologously expressing the G. sulfurreducens PilA pilin gene. Fe(III) oxide reduction was inhibited when the pilin gene in cytochrome-deficient mutants was modified to yield poorly conductive 3 nm diameter filaments. The results are consistent with the concept that 3 nm diameter electrically conductive pili (e-pili) are required for G. sulfurreducens long-range extracellular electron transfer. In contrast, rigorous physiological functional evidence is lacking for cytochrome filaments serving as conduits for long-range electron transport. IMPORTANCE: Unraveling microbial extracellular electron transfer mechanisms has profound implications for environmental processes and advancing biological applications. This study on Geobacter sulfurreducens challenges prevailing beliefs on cytochrome filaments as crucial components thought to facilitate long-range electron transport. The discovery of an OmcS-deficient strain's unexpected effectiveness in Fe(III) oxide reduction prompted a reevaluation of the key conduits for extracellular electron transfer. By exploring the impact of genetic modifications on G. sulfurreducens' performance, this research sheds light on the importance of 3-nm diameter electrically conductive pili in Fe(III) oxide reduction. Reassessing these mechanisms is essential for uncovering the true drivers of extracellular electron transfer in microbial systems, offering insights that could revolutionize applications across diverse fields.


Subject(s)
Cytochromes , Ferric Compounds , Geobacter , Oxidation-Reduction , Electron Transport , Geobacter/genetics , Geobacter/metabolism , Cytochromes/metabolism , Cytochromes/genetics , Ferric Compounds/metabolism , Fimbriae, Bacterial/metabolism , Fimbriae, Bacterial/genetics , Fimbriae Proteins/genetics , Fimbriae Proteins/metabolism
4.
J Child Neurol ; : 8830738241252849, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38751200

ABSTRACT

Background and Purpose: Children with developmental disabilities have increased risk of epilepsy and need for overnight video electroencephalographic (EEG) monitoring. However, video EEGs have historically been considered difficult to complete for this population. An autism support service at a pediatric tertiary care hospital implemented a coordinated team approach to help children with developmental disability tolerate overnight video EEGs. The project included completion of a caregiver-report preprocedure questionnaire that then was shared with the multidisciplinary team and used to create individualized care plans. The current study aims to describe rates of video EEG completion and need for lead placement under general anesthesia among children with autism and related disabilities who received these supports. Methods: Rates of video EEG completion and general anesthesia use were analyzed for children referred to the support service between April 2019 and November 2021. Results: A total of 182 children with developmental disability (mean age = 10.3 years, 54.9% diagnosed with autism) met inclusion criteria. 92.9% (n = 169) of children successfully completed EEG (leads on ≥12 hours). Only 19.2% (n = 35) required general anesthesia for video EEG lead placement. The majority (80.2%) of parents (n = 146) completed the preprocedure questionnaire. Video EEG outcomes did not differ based on completion of the questionnaire. Parent-reported challenges with communication and cooperation were associated with shorter video EEG duration and greater use of general anesthesia. Conclusions: These findings suggest that most children with developmental disability can complete video EEG with sufficient support. Preprocedure planning can identify children who would benefit from additional accommodations. Further research is necessary to clarify which supports are most helpful.

6.
Neurol Neuroimmunol Neuroinflamm ; 11(4): e200255, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38728608

ABSTRACT

OBJECTIVES: To estimate the incidence of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. METHODS: We conducted a retrospective cohort study of >10 million person-years of observation from members of Kaiser Permanente Southern California, 2011-2022. The electronic health record of individuals with text-string mention of NMDA and encephalitis were reviewed to identify persons who met diagnostic criteria for anti-NMDAR encephalitis. Age-standardized and sex-standardized incidences stratified by race and ethnicity were estimated according to the 2020 US Census population. RESULTS: We identified 70 patients who met diagnostic criteria for anti-NMDAR encephalitis. The median age at onset was 23.7 years (IQR = 14.2-31.0 years), and 45 (64%) were female patients. The age-standardized and sex-standardized incidence of anti-NMDAR encephalitis per 1 million person-years was significantly higher in Black (2.94, 95% CI 1.27-4.61), Hispanic (2.17, 95% CI 1.51-2.83), and Asian/Pacific Island persons (2.02, 95% CI 0.77-3.28) compared with White persons (0.40, 95% CI 0.08-0.72). Ovarian teratomas were found in 58.3% of Black female individuals and 10%-28.6% in other groups. DISCUSSION: Anti-NMDA receptor encephalitis disproportionately affected Black, Hispanic, or Asian/Pacific Island persons. Ovarian teratomas were a particularly common trigger in Black female individuals. Future research should seek to identify environmental and biological risk factors that disproportionately affect minoritized individuals residing in the United States.


Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis , Humans , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/ethnology , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/epidemiology , Female , Adult , Male , Incidence , Young Adult , Retrospective Studies , Adolescent , California/epidemiology , Hispanic or Latino/statistics & numerical data , Health Status Disparities , White People/ethnology , Black or African American/ethnology , Ovarian Neoplasms/ethnology , Ovarian Neoplasms/epidemiology , Teratoma/epidemiology , Teratoma/ethnology , Middle Aged , Ethnicity
7.
Autism ; : 13623613241249878, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38725306

ABSTRACT

LAY ABSTRACT: Previous research has shown that girls/women are diagnosed later than boys/men with autism. Individuals who are diagnosed later in life, especially girls/women, have greater anxious and depressive symptoms. Previous research has been limited due to narrow inclusionary criteria for enrollment in studies. The present study uses two samples-one clinic-based, large "real-world" sample and another research-based sample with strict criteria for autism diagnosis-to understand the relationships between diagnostic age, sex assigned at birth, and symptoms of anxiety/depression. In both samples, those who were diagnosed later had greater anxious/depressive symptoms, and anxiety was not predicted by sex. In the clinic-based but not research-based sample, those assigned female at birth were diagnosed later than those assigned male at birth. In the clinic-based sample only, individuals assigned female at birth and who were later diagnosed experienced greater symptoms of anxiety/depression compared to those assigned male who benefited from earlier diagnostic timing. Within the research-based sample, those assigned female at birth had greater depressive symptoms than those assigned male. These findings highlight the importance of timely identification of autism, especially for girls/women who are often diagnosed later. Community-based samples are needed to better understand real-world sex-based and diagnostic age-based disparities in mental health.

8.
Nurs Outlook ; 72(4): 102189, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38810535

ABSTRACT

BACKGROUND: Poorer leadership communication during COVID-19 may have contributed to the moral distress of nurses in hospitals where Black patients predominantly access their care (BSH). PURPOSE: To compare nurse moral distress and leadership communication during the COVID-19 pandemic in hospitals that serve disproportionately many or few patients of Black race. METHODS: In a national hospital sample (n = 90), nurse survey data were collected (March 2021). Nurse moral distress was analyzed in linear regression models. The key covariates were BSH category (Medicare Black patient percentage) and leadership communication. DISCUSSION: Nurses in high-BSH had significantly greater moral distress and more difficulty accessing personal protective equipment than nurses in low-BSH. The percentage of nurses in high-BSHs with high moral distress was double that of nurses in low-BSHs. Poorer leadership communication in BSHs accounted for the nurses' greater moral distress. CONCLUSION: Policies should improve leadership communication, mitigate distress, and support nurses in under-resourced settings.

9.
J Vis Exp ; (206)2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38647333

ABSTRACT

Microvascular endothelial cells (MVECs) have many critical roles, including control of vascular tone, regulation of thrombosis, and angiogenesis. Significant heterogeneity in endothelial cell (EC) genotype and phenotype depends on their vascular bed and host disease state. The ability to isolate MVECs from tissue-specific vascular beds and individual patient groups offers the opportunity to directly compare MVEC function in different disease states. Here, using subcutaneous adipose tissue (SAT) taken at the time of insertion of cardiac implantable electronic devices (CIED), we describe a method for the isolation of a pure population of functional human subcutaneous adipose tissue MVEC (hSATMVEC) and an experimental model of hSATMVEC-adipocyte cross-talk. hSATMVEC were isolated following enzymatic digestion of SAT by incubation with anti-CD31 antibody-coated magnetic beads and passage through magnetic columns. hSATMVEC were grown and passaged on gelatin-coated plates. Experiments used cells at passages 2-4. Cells maintained classic features of EC morphology until at least passage 5. Flow cytometric assessment showed 99.5% purity of isolated hSATMVEC, defined as CD31+/CD144+/CD45-. Isolated hSATMVEC from controls had a population doubling time of approximately 57 h, and active proliferation was confirmed using a cell proliferation imaging kit. Isolated hSATMVEC function was assessed using their response to insulin stimulation and angiogenic tube-forming potential. We then established an hSATMVEC-subcutaneous adipocyte co-culture model to study cellular cross-talk and demonstrated a downstream effect of hSATMVEC on adipocyte function. hSATMVEC can be isolated from SAT taken at the time of CIED insertion and are of sufficient purity to both experimentally phenotype and study hSATMVEC-adipocyte cross-talk.


Subject(s)
Adipocytes , Endothelial Cells , Subcutaneous Fat , Humans , Adipocytes/cytology , Endothelial Cells/cytology , Endothelial Cells/metabolism , Subcutaneous Fat/cytology , Cell Communication/physiology
10.
Mult Scler Relat Disord ; 86: 105577, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38579569

ABSTRACT

We sought to determine whether a history of traumatic brain injury (TBI) could explain the lower symbol digit modalities test (SDMT) scores observed among newly diagnosed multiple sclerosis (MS) and control participants identifying as Black or Hispanic versus white in the MS Sunshine Study (n = 1172). 330 (29.2 %) participants reported a history of ≥1 TBI. Accounting for TBI did not explain the significant independent associations between having MS, being Black or Hispanic and lower SDMT. The pervasive effects of systemic racism in the United States remain the best explanation for the lower SDMT scores observed in Black and Hispanic participants.


Subject(s)
Black or African American , Brain Injuries, Traumatic , Hispanic or Latino , Multiple Sclerosis , White People , Humans , Multiple Sclerosis/ethnology , Multiple Sclerosis/diagnosis , Male , Female , Adult , Middle Aged , Brain Injuries, Traumatic/ethnology , Brain Injuries, Traumatic/diagnosis , Brain Injuries, Traumatic/complications , Hispanic or Latino/statistics & numerical data , Black or African American/ethnology , White People/ethnology , United States/ethnology , Cognitive Dysfunction/ethnology , Cognitive Dysfunction/etiology , Cognitive Dysfunction/diagnosis , Neuropsychological Tests , Racism/ethnology
11.
Nat Microbiol ; 9(5): 1231-1243, 2024 May.
Article in English | MEDLINE | ID: mdl-38649413

ABSTRACT

The 2022 mpox virus (MPXV) outbreak was sustained by human-to-human transmission; however, it is currently unclear which factors lead to sustained transmission of MPXV. Here we present Mastomys natalensis as a model for MPXV transmission after intraperitoneal, rectal, vaginal, aerosol and transdermal inoculation with an early 2022 human outbreak isolate (Clade IIb). Virus shedding and tissue replication were route dependent and occurred in the presence of self-resolving localized skin, lung, reproductive tract or rectal lesions. Mucosal inoculation via the rectal, vaginal and aerosol routes led to increased shedding, replication and a pro-inflammatory T cell profile compared with skin inoculation. Contact transmission was higher from rectally inoculated animals. This suggests that transmission might be sustained by increased susceptibility of the anal and genital mucosae for infection and subsequent virus release.


Subject(s)
Mucous Membrane , Poxviridae Infections , Virus Shedding , Animals , Female , Mucous Membrane/virology , Poxviridae Infections/transmission , Poxviridae Infections/virology , Poxviridae Infections/veterinary , Humans , Virus Replication , Disease Models, Animal , Rodentia/virology , Male , Rats , Vagina/virology , Disease Outbreaks
12.
Autism ; : 13623613241243117, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38587289

ABSTRACT

LAY ABSTRACT: Later autism diagnosis is associated with risk for mental health problems. Understanding factors related to later autism diagnosis may help reduce mental health risks for autistic people. One characteristic associated with later autism diagnosis is female sex. However, studies often do not distinguish sex assigned at birth and gender identity. Gender diversity may be more common in autistic relative to neurotypical people, and autism is more common in gender-diverse populations. We studied age at autism diagnosis by sex assigned at birth, gender identity, and gender diversity (gender-diverse vs cisgender) status, separately. We studied three separate autistic samples, each of which differed in how they were diagnosed and how they were recruited. The samples included 193 persons (8.0-18.0 years) from a research-recruited academic medical center sample; 1,550 people (1.3-25.4 years) from a clinic-based sample; and 244 people (18.2-30.0 years) from a community-enriched sample. We found significant differences in the clinic-based and community-enriched samples. People assigned female sex at birth were diagnosed with autism significantly later than people assigned male at birth. People of female gender were diagnosed significantly later than people of male gender. Gender-diverse people were diagnosed significantly later than cisgender people. Sex assigned at birth, gender identity, and gender diversity may each show unique relationships with age of autism diagnosis. Differences in how autistic people are diagnosed and recruited are important to consider in studies that examine sex assigned at birth or gender identity. More research into autism diagnosis in adulthood is needed.

13.
Discov Immunol ; 3(1): kyad028, 2024.
Article in English | MEDLINE | ID: mdl-38567292

ABSTRACT

Mast cells are infamous for mediating allergic and inflammatory diseases due to their capacity of rapidly releasing a wide range of inflammatory mediators stored in cytoplasmic granules. However, mast cells also have several important physiological roles that involve selective and agonist-specific release of these active mediators. While a filtering mechanism at the plasma membrane could regulate the selective release of some cargo, the plethora of stored cargo and the diversity of mast cell functions suggests the existence of granule subtypes with distinct trafficking pathways. The molecular mechanisms underlying differential trafficking and exocytosis of these granules are not known, neither is it clear how granule trafficking is coupled to the stimulus. In endothelial cells, a Rab GTPase, Rab46, responds to histamine but not thrombin signals, and this regulates the trafficking of a subpopulation of endothelial-specific granules. Here, we sought to explore, for the first time, if Rab46 plays a role in mast cell function. We demonstrate that Rab46 is highly expressed in human and murine mast cells, and Rab46 genetic deletion has an effect on mast cell degranulation that depends on both stimuli and mast cell subtype. This initial insight into the contribution of Rab46 to mast cell function and the understanding of the role of Rab46 in stimuli-dependent trafficking in other cell types necessitates further investigations of Rab46 in mast cell granular trafficking so that novel and specific therapeutic targets for treatment of the diverse pathologies mediated by mast cells can be developed.

14.
Pediatrics ; 153(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38495019

ABSTRACT

BACKGROUND AND OBJECTIVES: The Community Eligibility Provision (CEP), a universal free school meals policy, increases school meal participation by allowing schools in low-income areas to provide free breakfast and lunch to all students; however, its impact on obesity remains uncertain. The objective of this study is to estimate the association of CEP with child obesity. METHODS: School obesity prevalence was calculated using BMI measurements collected annually between 2013 and 2019 from students in California public schools in grades 5, 7, and 9. To estimate the association of CEP with obesity, we used a difference-in-differences approach for staggered policy adoption with an outcome regression model conditional on covariates, weighted by student population size. RESULTS: The analysis included 3531 CEP-eligible schools using school-level obesity prevalence calculated from 3 546 803 BMI measurements. At baseline, on average, 72% of students identified as Hispanic, 11% identified as white, 7% identified as Black, and 80% were eligible for free or reduced-price meals. Baseline obesity prevalence was 25%. Schools that participated in CEP were associated with a 0.60-percentage-point net decrease in obesity prevalence after policy adoption (95% confidence interval: -1.07 to -0.14 percentage points, P = .01) compared with eligible, nonparticipating schools, corresponding with a 2.4% relative reduction, given baseline prevalence. Meals served increased during this period in CEP-participating schools only. CONCLUSIONS: In a balanced sample of California schools, CEP participation was associated with a modest net decrease in obesity prevalence compared with eligible, nonparticipating schools. These findings add to the growing literature revealing potential benefits of universal free school meals for children's well-being.


Subject(s)
Food Services , Pediatric Obesity , Humans , Child , Pediatric Obesity/epidemiology , Pediatric Obesity/prevention & control , Meals , Schools , Lunch , Breakfast
15.
Curr Opin Gastroenterol ; 40(3): 143-147, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38547333

ABSTRACT

PURPOSE OF REVIEW: Ischemic hepatitis (IH) refers to diffuse liver injury secondary to hypoperfusion. The condition is usually seen in the critical care setting and is associated with significant mortality. IH typically occurs in the setting of systemic hypotension superimposed on some form of underlying cardiac dysfunction. This review aims to report what is known and what is new about the etiology, pathophysiology, and clinical features associated with IH. RECENT FINDINGS: In recent years, studies on IH have largely confirmed earlier reports regarding etiologies, comorbid conditions, and associated mortality. Recent study has also shed light on the potential treatment of IH with N -acetyl-cysteine (NAC). SUMMARY: IH is typically associated with underlying cardiac disease, and patients with IH have a very high mortality rate. Treatment remains largely supportive, although the utility of agents such as NAC are being explored.


Subject(s)
Hepatitis , Humans , Hepatitis/complications , Acetylcysteine/therapeutic use
16.
J Adv Nurs ; 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38515225

ABSTRACT

AIM(S): The aim of this systematic literature review was to determine the extent and quality of quantitative evidence regarding associations between hospital organizational features, person-centred care (PCC) and nursing-sensitive outcomes among persons with dementia in the acute care setting. DESIGN: Systematic review. METHODS: Key terms were utilized to guide searches in four databases. The two reviewers deduplicated articles and came to a consensus for the final sample using inclusion and exclusion criteria. DATA SOURCES: MEDLINE/OVID, CINHAL, COCHRANE and WEB OF SCIENCE. RESULTS: There were 10 studies included. PCC was associated with better outcomes for persons with dementia (i.e. decreased restraint use, decreased length of stay, increased involvement with families and the patient, and increased nurse confidence and competence in caring for this population). Of the studies, none explicitly identified an association between nursing-sensitive outcomes, PCC and hospital organizational features in the acute care setting among persons with dementia. CONCLUSION: This review highlights a clinically significant gap in knowledge regarding associations between hospital organizational features, PCC and nursing sensitive outcomes. The impact of face-to-face dementia competency training as a standard practice among acute care facilities, the importance of leadership engagement, support and involvement to improve nurse confidence and competence in caring for persons with dementia needs to be explored. IMPACT STATEMENT: These findings support future research to understand the relationship between organization features and patient-centred care and how these collectively impact nursing-sensitive outcomes, specifically in persons with dementia in acute care settings.

17.
Neurol Neuroimmunol Neuroinflamm ; 11(3): e200211, 2024 May.
Article in English | MEDLINE | ID: mdl-38507657

ABSTRACT

BACKGROUND AND OBJECTIVES: B-cell-depleting therapies increase the risk of infections and hypogammaglobulinemia. These relationships are poorly understood. The objectives of these analyses were to estimate how much of this rituximab-associated infection risk is mediated by hypogammaglobulinemia and to identify other modifiable risk factors in persons with multiple sclerosis (pwMS). METHODS: We conducted a retrospective cohort study of rituximab-treated pwMS from January 1, 2008, to December 31, 2020, in Kaiser Permanente Southern California. Cumulative rituximab dose was defined as ≤2, >2 and ≤4, or >4 g. Serious infections were defined as infections requiring or prolonging hospitalizations, and recurrent outpatient infections as seeking care for ≥3 within 12 months. Exposures, outcomes, and covariates were collected from the electronic health record. Adjusted hazard ratios (aHRs) were estimated using Andersen-Gill hazards models, and generalized estimating equations were used to examine correlates of IgG values. Cross-sectional causal mediation analyses of rituximab and hypogammaglobulinemia were conducted. RESULTS: We identified 2,482 pwMS who were treated with rituximab for a median of 2.4 years (interquartile range = 1.3-3.9). The average age at rituximab initiation was 43.0 years, 71.9% were female, 49.7% were White, non-Hispanic patients, and 29.6% had advanced disability (requiring walker or worse). Seven hundred patients (28.2%) developed recurrent outpatient infections, 155 (6.2%) developed serious infections, and only 248 (10.0%) had immunoglobulin G (IgG) < 700 mg/dL. Higher cumulative rituximab dose (>4 g) was correlated with lower IgG levels (Beta = -58.8, p < 0.0001, ref ≤2 g) and, in models mutually adjusted for hypogammaglobulinemia, both were independently associated with an increased risk of serious (>4 g, aHR = 1.56, 95% CI 1.09-2.24; IgG < 500, aHR = 2.98, 95% CI 1.56-5.72) and outpatient infections (>4 g, aHR = 1.73, 95% CI 1.44-2.06; IgG < 500 aHR = 2.06, 95% CI 1.52-2.80; ref = IgG ≥ 700). Hypogammaglobulinemia explained at most 17.9% (95% CI -47.2-119%) of serious infection risk associated with higher cumulative rituximab exposure but was not significant for outpatient infections. Other independent modifiable risk factors were advanced physical disability for serious (aHR = 5.51, 95% CI 3.71-8.18) and outpatient infections (aHR = 1.24, 95% CI 1.06-1.44) and COPD (aHR = 1.68, 95% CI 1.34-2.11) and obesity (aHR = 1.25, 95% CI 1.09-1.45) for outpatient infections. DISCUSSION: Higher cumulative rituximab doses increase the risk of infections even in this population where 90% of patients maintained normal IgG levels. Clinicians should strive to use minimally effective doses of rituximab and other B-cell-depleting therapies and consider important comorbidities to minimize risks of infections.


Subject(s)
Agammaglobulinemia , Infections , Multiple Sclerosis , Humans , Female , Male , Rituximab/adverse effects , Agammaglobulinemia/chemically induced , Agammaglobulinemia/epidemiology , Multiple Sclerosis/drug therapy , Multiple Sclerosis/complications , Retrospective Studies , Cross-Sectional Studies , Immunoglobulin G , Infections/chemically induced , Infections/epidemiology
18.
Article in English | MEDLINE | ID: mdl-38502828

ABSTRACT

The proportion of older adults in the U.S. is growing, and the older adult population is also becoming increasingly diverse. However, there are limited data on the aging process and older adults in underserved populations. Equitable participation in research studies on aging, the research workforce, and the healthcare workforce is critical to improve health outcomes for the entire U.S. population. Health disparities frameworks offer researchers and healthcare professionals the tools to develop and evaluate aging research that addresses all levels of analysis and domains of influence. Although there have been efforts to diversify the healthcare and research workforce, significant disparities in representation remain. In this perspective, we discuss existing aging health disparities, health disparities frameworks to use as tools to better conduct aging research, methods to enhance the proportion of underrepresented populations in aging research, and the current gaps in as well as efforts to enhance the diversity of the healthcare and research workforces.

19.
Sci Rep ; 14(1): 6219, 2024 03 14.
Article in English | MEDLINE | ID: mdl-38485999

ABSTRACT

Radiation-induced cystitis is an inflammatory condition affecting the urinary bladder, which can develop as a side effect of abdominopelvic radiotherapy, specifically external-beam radiation therapy or myeloablative radiotherapy. A possible involvement of mast cells in the pathophysiology of radiation-induced cystitis has been indicated in cases of external-beam radiation therapy; however, there is no evidence that these findings apply to the myeloablative aetiology. As such, this study investigated potential changes to urinary bladder mast cell prevalence when exposed to myeloablative radiation. Lethally irradiated C57BL/6J mice that received donor rescue bone marrow cells exhibited an increased mast cell frequency amongst host leukocytes 1 week following irradiation. By 4 weeks, no significant difference in either frequency or cell density was observed. However mast cell diameter was smaller, and a significant increase in mast cell number in the adventitia was observed. This study highlights that mast cells constitute a significant portion of the remaining host leukocyte population following radiation exposure, with changes to mast cell distribution and decreased cell diameter four weeks following radiation-induced injury.


Subject(s)
Cystitis , Urinary Bladder , Mice , Animals , Mast Cells/physiology , Mice, Inbred C57BL , Cystitis/etiology , Pelvis
20.
Autism ; : 13623613241236112, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38456360

ABSTRACT

LAY ABSTRACT: The current demand for autism diagnostic services exceeds the ability of the workforce to assess and diagnose children in a timely manner. One solution may be to equip primary care providers (PCPs) with the tools and expertise needed to diagnose autism within their practice. PCPs are often trusted professionals who have many touchpoints with children during early development, in which they can identify early signs of autism. Recent initiatives have focused on bolstering PCPs' diagnostic capabilities; however, no studies have examined how the rates of autism diagnosis in primary care have changed over time. We aimed to evaluate whether autism diagnosis in primary care has changed over time and how diagnosis in primary care relates to a child's age at the time of diagnosis. We found that the likelihood of a child being diagnosed by a PCP decreased by about 2% with every passing year from 2004 to 2019 when accounting for demographic characteristics. In our sample, PCPs diagnosed children approximately 1 year earlier than non-PCPs (e.g., psychologists and psychiatrists). Further research is needed to understand why the proportion of children diagnosed by PCPs decreases over time. However, this decrease suggests more work is needed to get capacity-building initiatives into community primary care practice. Though we must continue to find effective ways to build community PCPs' ability to diagnose autism, the present findings support the crucial role PCPs can play in early autism diagnosis.

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