Do people with ME/CFS and joint hypermobility represent a disease subgroup? An analysis using registry data.

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, multifaceted disease that affects millions globally. Despite its significant impact, the disease's etiology remains poorly understood, and symptom heterogeneity poses challenges for diagnosis and treatment. Joint hypermobility, commonly seen in hypermobile Ehlers-Danlos Syndrome (hEDS), has been observed in ME/CFS patients but its prevalence and clinical significance within this population are not well-characterized. Objective: To compare the characteristics of ME/CFS patients with and without joint hypermobility (JH+ and JH-) as assessed using the Beighton scoring system, and to explore whether JH+ ME/CFS patients exhibit distinct disease characteristics, comorbidities, and health-related quality of life (HRQOL). Methods: The study used cross-sectional, self-reported data from 815 participants of the You + ME Registry. Participants were categorized as JH+ or JH- based on self-assessed Beighton scores and compared across demographics, comorbidities, family history, and symptoms. HRQOL was assessed using the Short Form-36 RAND survey and Karnofsky Performance Status. Results: 15.5% (N = 126) of participants were classified as JH+. JH+ participants were more likely to be female, report Ehlers-Danlos Syndrome (EDS), Postural Orthostatic Tachycardia Syndrome (POTS), and a family history of EDS. They experienced worse HRQOL, particularly in physical functioning and pain, and a higher number of autonomic, neurocognitive, headache, gut, and musculoskeletal symptoms. Sensitivity analysis suggested that ME/CFS with concurrent JH+ and EDS was associated with more severe symptoms and greater functional impairment. Conclusion: ME/CFS patients with joint hypermobility, particularly those with EDS, demonstrate distinct clinical characteristics, including more severe symptomatology and reduced HRQOL. These findings highlight the need for comprehensive clinical assessments of ME/CFS patients with joint hypermobility. Understanding these relationships could aid in subgroup identification, improving diagnosis, and informing targeted therapeutic approaches. Further research is warranted to explore these associations and their implications for clinical practice.

Comparative effectiveness of mRNA-1273 and BNT162b2 COVID-19 vaccines in immunocompromised individuals: a systematic review and meta-analysis using the GRADE framework.

Introduction: Despite representing only 3% of the US population, immunocompromised (IC) individuals account for nearly half of the COVID-19 breakthrough hospitalizations. IC individuals generate a lower immune response after vaccination in general, and the US CDC recommended a third dose of either mRNA-1273 or BNT162b2 COVID-19 vaccines as part of their primary series. Influenza vaccine trials have shown that increasing dosage could improve effectiveness in IC populations. The objective of this systematic literature review and pairwise meta-analysis was to evaluate the clinical effectiveness of mRNA-1273 (50 or 100 mcg/dose) vs BNT162b2 (30 mcg/dose) in IC populations using the GRADE framework. Methods: The systematic literature search was conducted in the World Health Organization COVID-19 Research Database. Studies were included in the pairwise meta-analysis if they reported comparisons of mRNA-1273 and BNT162b2 in IC individuals ≥18 years of age; outcomes of interest were symptomatic, laboratory-confirmed SARS-CoV-2 infection, SARS-CoV-2 infection, severe SARS-CoV-2 infection, hospitalization due to COVID-19, and mortality due to COVID-19. Risk ratios (RR) were pooled across studies using random-effects meta-analysis models. Outcomes were also analyzed in subgroups of patients with cancer, autoimmune disease, and solid organ transplant. Risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies. Evidence was evaluated using the GRADE framework. Results: Overall, 17 studies were included in the pairwise meta-analysis. Compared with BNT162b2, mRNA-1273 was associated with significantly reduced risk of SARS-CoV-2 infection (RR, 0.85 [95% CI, 0.75-0.97]; P=0.0151; I2 = 67.7%), severe SARS-CoV-2 infection (RR, 0.85 [95% CI, 0.77-0.93]; P=0.0009; I2 = 0%), COVID-19-associated hospitalization (RR, 0.88 [95% CI, 0.79-0.97]; P<0.0001; I2 = 0%), and COVID-19-associated mortality (RR, 0.63 [95% CI, 0.44-0.90]; P=0.0119; I2 = 0%) in IC populations. Results were consistent across subgroups. Because of sample size limitations, relative effectiveness of COVID-19 mRNA vaccines in IC populations cannot be studied in randomized trials. Based on nonrandomized studies, evidence certainty among comparisons was type 3 (low) and 4 (very low), reflecting potential biases in observational studies. Conclusion: This GRADE meta-analysis based on a large number of consistent observational studies showed that the mRNA-1273 COVID-19 vaccine is associated with improved clinical effectiveness in IC populations compared with BNT162b2.

Film production during the Covid-19 pandemic.

BACKGROUND: The COVID-19 pandemic created unprecedented challenges for the film industry. Following a shutdown of productions, The Safe Way Forward document was developed to outline disease mitigation protocols. Despite this framework, many unanticipated scenarios arose during reopening of film production with the ongoing pandemic. AIMS: To identify and document promising practices for mitigating COVID-19 transmission in the film industry that can inform future pandemics and other industries. METHODS: We conducted a literature search to review research regarding COVID-19 disease mitigation efforts in the film industry. Through client-facing consultancy and consultant group meetings, we identified those factors most important for disease mitigation in the film industry and applicable to future pandemics and other industries. The Delphi Method enabled experts to review lessons learned as studio consultants during the COVID-19 pandemic; learnings were coded and analyzed for recurring themes. RESULTS: We identified anxiety, mistrust, and poor communication as key contributors to decreased compliance with COVID-19 protocols. In response, our team demonstrated multi-specialty expertise, provided scientific explanations, and developed trust by listening empathetically and responding with clear, consistent messaging. These measures served to alleviate anxiety, improve compliance, and provide a safe return to production. CONCLUSIONS: This study demonstrates the ability and agility of multi-disciplinary experts acting in the absence of clear guidance to support a safe return to film production. Workplace anxiety and non-compliance can be alleviated through effective communication by trusted experts. Lessons learned by our consultancy group can help protect workers across diverse industries in future pandemics.

Injury Among Home Care Workers in Washington State.

Home Care Aides (HCAs) have nearly four times the rate of injury as the general U.S. work force. In 2015, the Service Employees International Union 775 Benefits Group conducted a health and safety survey with 672 HCAs in Washington State. The goal was to identify the risk factors for injury and to better assess injury rates through self-report. Quantitative analyses assessed injury prevalence and barriers in reporting injury. Overall, 13 percent responded that they had ever had an injury that required medical attention while working as an HCA. These rates are significantly higher for HCAs employed by home care agencies compared with HCAs who work independently. Over a third reported moderate to high levels of hesitancy in reporting an on-the-job injury; these rates were even higher for independent providers. Study findings suggest that HCAs are well informed about appropriate next steps following workplace injury, but strong barriers may prevent them from attempting the reporting process.

Safety of union home care aides in Washington State.

INTRODUCTION: A rate-based understanding of home care aides' adverse occupational outcomes related to their work location and care tasks is lacking. METHODS: Within a 30-month, dynamic cohort of 43 394 home care aides in Washington State, injury rates were calculated by aides' demographic and work characteristics. Injury narratives and focus groups provided contextual detail. RESULTS: Injury rates were higher for home care aides categorized as female, white, 50 to <65 years old, less experienced, with a primary language of English, and working through an agency (versus individual providers). In addition to direct occupational hazards, variability in workload, income, and supervisory/social support is of concern. CONCLUSIONS: Policies should address the roles and training of home care aides, consumers, and managers/supervisors. Home care aides' improved access to often-existing resources to identify, manage, and eliminate occupational hazards is called for to prevent injuries and address concerns related to the vulnerability of this needed workforce.

Causes and Disparities in Death Rates Among Urban American Indian and Alaska Native Populations, 1999-2009.

OBJECTIVES: To characterize the leading causes of death for the urban American Indian/Alaska Native (AI/AN) population and compare with urban White and rural AI/AN populations. METHODS: We linked Indian Health Service patient registration records with the National Death Index to reduce racial misclassification in death certificate data. We calculated age-adjusted urban AI/AN death rates for the period 1999-2009 and compared those with corresponding urban White and rural AI/AN death rates. RESULTS: The top-5 leading causes of death among urban AI/AN persons were heart disease, cancer, unintentional injury, diabetes, and chronic liver disease and cirrhosis. Compared with urban White persons, urban AI/AN persons experienced significantly higher death rates for all top-5 leading causes. The largest disparities were for diabetes and chronic liver disease and cirrhosis. In general, urban and rural AI/AN persons had the same leading causes of death, although urban AI/AN persons had lower death rates for most conditions. CONCLUSIONS: Urban AI/AN persons experience significant disparities in death rates compared with their White counterparts. Public health and clinical interventions should target urban AI/AN persons to address behaviors and conditions contributing to health disparities.

The association of depression with diabetes management among urban American Indians/Alaska Natives in the United States, 2011.

OBJECTIVE: To determine the relationship between depression and diabetes management among urban American Indians/Alaska Natives (AI/ANs). DESIGN: Retrospective, cross-sectional analysis of medical records. SETTING: 33 Urban Indian Health Organizations that participated in the Indian Health Service Diabetes Care and Outcomes Audit. PATIENTS: 3,741 AI/AN patient records. MAIN OUTCOME MEASURES: Diabetes management outcomes, including HbA1c, smoking, BMI, systolic blood pressure, creatinine, total cholesterol, and receipt of preventive services. RESULTS: Individuals with depression and diabetes were 1.5 times more likely to smoke than individuals with diabetes but without depression (OR=1.51; 95% Cl: 1.23, 1.86), controlling for age, sex, and facility. After adjustment, the geometric mean BMI in diabetes patients with depression was 3% higher than in patients without depression (ß=.034; 95% CI: .011, .057). CONCLUSIONS: Urban AI/ANs with diabetes and depression are more likely to smoke and have higher BMI than those with diabetes but without depression. These findings inform programmatic efforts to address the care of patients with both depression and diabetes.

Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005-2010.

The neuropathologic examination is considered to provide the gold standard for Alzheimer disease (AD). To determine the accuracy of currently used clinical diagnostic methods, clinical and neuropathologic data from the National Alzheimer's Coordinating Center, which gathers information from the network of National Institute on Aging (NIA)-sponsored Alzheimer Disease Centers (ADCs), were collected as part of the National Alzheimer's Coordinating Center Uniform Data Set (UDS) between 2005 and 2010. A database search initially included all 1198 subjects with at least one UDS clinical assessment and who had died and been autopsied; 279 were excluded as being not demented or because critical data fields were missing. The final subject number was 919. Sensitivity and specificity were determined based on "probable" and "possible" AD levels of clinical confidence and 4 levels of neuropathologic confidence based on varying neuritic plaque densities and Braak neurofibrillary stages. Sensitivity ranged from 70.9% to 87.3%; specificity ranged from 44.3% to 70.8%. Sensitivity was generally increased with more permissive clinical criteria and specificity was increased with more restrictive criteria, whereas the opposite was true for neuropathologic criteria. When a clinical diagnosis was not confirmed by minimum levels of AD histopathology, the most frequent primary neuropathologic diagnoses were tangle-only dementia or argyrophilic grain disease, frontotemporal lobar degeneration, cerebrovascular disease, Lewy body disease and hippocampal sclerosis. When dementia was not clinically diagnosed as AD, 39% of these cases met or exceeded minimum threshold levels of AD histopathology. Neurologists of the NIA-ADCs had higher predictive accuracy when they diagnosed AD in subjects with dementia than when they diagnosed dementing diseases other than AD. The misdiagnosis rate should be considered when estimating subject numbers for AD studies, including clinical trials and epidemiologic studies.

Hormonal exposures and the risk of intracranial meningioma in women: a population-based case-control study.

BACKGROUND: The role of exogenous hormone exposures in the development of meningioma is unclear, but these exposures have been proposed as one hypothesis to explain the over-abundance of such tumors in women. METHODS: The association between oral contraception (OC) or hormone replacement therapy (HRT) and intracranial meningioma in women was investigated using a population-based, matched case-control study. Exposures for 143 cases and 286 controls matched on age within five years were obtained by interview. Diagnoses were confirmed histopathologically and estrogen and progesterone receptor assays conducted. RESULTS: Although risk of meningioma appeared modestly elevated in past OC users (OR = 1.5, 95% CI 0.8 - 2.7), and in current users (OR = 2.5, 95% CI 0.5 - 12.6), the confidence intervals were wide. No significant association between meningioma risk and duration of OC use was found. Likewise, risk of meningioma was only weakly associated with past use of HRT (OR = 0.7, 95% CI 0.4 - 1.3), and not at all with current use of HRT (OR = 1.0, 95% CI 0.5 - 2.2). Of 142 available specimens, 2 (1%) expressed estrogen receptors, whereas 130 (92%) expressed progesterone receptors (PR). OC use was associated with increased risk of a meningioma expressing less rather than more PR (OR = 3.2, 95% CI 1.3 - 8.0). Overall, in post menopausal women, HRT use appeared to confer a non-significant protective effect, and was not associated with low or high PR expressing meningiomas. CONCLUSION: This study found little evidence of associations between meningioma and exogenous hormone exposures in women but did suggest that some hormonal exposures may influence tumor biology in those women who develop meningioma.

Active and passive cigarette smoking and risk of intracranial meningioma.

Motivated by prior studies, we examined associations between cigarette smoking and risk of intracranial meningioma in a population-based case-control study, including 200 cases and 2 controls matched to each case on age and sex. Subjects were asked to recall their history of active and passive cigarette smoking occurring 10 or more years before the date of meningioma surgery. Ever active smoking was associated with an increased risk of meningioma in men (OR = 2.1; 95% CI 1.1-4.2) but not in women (OR = 0.7; 95% CI 0.5-1.1). The statistical interaction by gender was significant (p = 0.01). In men, risk increased with increasing number of cigarettes smoked daily (p for trend = 0.04). In women, the trend was opposite (p for trend = 0.08). Among never active smokers, passive smoking from a spouse was associated with increased risk in both sexes (OR 2.0; 95% CI 1.1-3.5), and risk increased with increasing duration of exposure (p for trend = 0.02). Uncertain is whether these findings reflect a true biological phenomenon or result from chance or uncontrolled confounding.

Dental X-rays and the risk of intracranial meningioma: a population-based case-control study.

BACKGROUND: Ionizing radiation is a likely cause of intracranial meningioma. The authors determined whether the risk of intracranial meningioma was associated with past dental X-rays-specifically, posterior bitewings, full-mouth series, and lateral cephalometric and panoramic radiographs. METHODS: The authors conducted a population-based case-control study of residents of King, Pierce, and Snohomish counties in western Washington State. Case patients (n = 200) had an incident intracranial meningioma that was confirmed histologically during life between January 1995 and June 1998. The authors used random-digit dialing and Medicare eligibility lists to identify two control subjects to be matched to each case patient based on age and gender. Exposures were determined during an in-person interview. The authors compared self-report and dental records in a subset of study participants. RESULTS: Of the 4 dental X-ray procedures evaluated, only the full-mouth series (specifically, > or = 6 over a lifetime) was associated with a significantly increased risk of meningioma (odds ratio, 2.06; 95% confidence limits, 1.03-4.17). However, evidence for a dose-response relation was lacking (P for trend = 0.33). The risk was elevated with the aggregate number of full-mouth series in 10-year periods from approximately 15-40 years before diagnosis, with significant elevations in the 10-year periods beginning 22-30 years before diagnosis. The risks in these analyses were even greater when only women were considered. CONCLUSIONS: Dental X-rays involving full-mouth series performed 15-40 years ago, when radiation exposure from full-mouth series was much greater than it is now, were associated with an increased risk of meningioma. The authors did not observe an increased risk with bitewings, lateral cephalometric, and panoramic radiographs.