Risk of Chronic Obstructive Pulmonary Disease and Receipt of a Breathing Test in 26 States and the District of Columbia, 2017-2018.

We estimated the prevalence of respiratory symptoms, chronic obstructive pulmonary disease (COPD) risk level, and receipt of a breathing test among adults without reported COPD in 26 states and the District of Columbia by using 2017-2018 Behavioral Risk Factor Surveillance System data. Among adults without reported COPD, the 3 respiratory symptoms indicating COPD (chronic cough, phlegm or mucus production, shortness of breath) were common (each >10%). About 15.0% were at higher COPD risk (based on the number of symptoms, age, and smoking status); 41.4% of adults at higher risk reported receipt of a breathing test. Patient-provider recognition and communication of risk symptoms, appropriate screening, and follow-up are important for early diagnosis and treatment.

A phase 2 randomized trial with autologous polyclonal expanded regulatory T cells in children with new-onset type 1 diabetes.

CD4+CD25hiCD127lo/-FOXP3+ regulatory T cells (Tregs) play a key role in preventing autoimmunity. In autoimmune type 1 diabetes (T1D), adoptive transfer of autologous polyclonal Tregs has been shown to be safe in adults in phase 1 clinical trials. We explored factors contributing to efficacy of autologous polyclonal expanded Tregs (expTregs) in a randomized phase 2 multi-center, double-blind, clinical trial (Sanford/Lisata Therapeutics T-Rex phase 2 trial, ClinicalTrials.gov NCT02691247). One hundred ten treated children and adolescents with new-onset T1D were randomized 1:1:1 to high-dose (20 × 106 cells/kilogram) or low-dose (1 × 106 cells/kilogram) treatments or to matching placebo. Cytometry as well as bulk and single-cell RNA sequencing were performed on selected expTregs and peripheral blood samples from participants. The single doses of expTregs were safe but did not prevent decline in residual ß cell function over 1 year compared to placebo (P = 0.94 low dose, P = 0.21 high dose), regardless of age or baseline C-peptide. ExpTregs were highly activated and suppressive in vitro. A transient increase of activated memory Tregs was detectable 1 week after infusion in the high-dose cohort, suggesting effective transfer of expTregs. However, the in vitro fold expansion of expTregs varied across participants, even when accounting for age, and lower fold expansion and its associated gene signature were linked with better C-peptide preservation regardless of Treg dose. These results suggest that a single dose of polyclonal expTregs does not alter progression in T1D; instead, Treg quality may be an important factor.

Lumbar vertebral diskitis-osteomyelitis with mycotic abdominal aortic aneurysm caused by Streptococcus mitis.

Vertebral osteomyelitis is a well-documented disease entity in literature with various known etiologies. However, vertebral diskitis-osteomyelitis secondary to an infected aortic aneurysm is an uncommon and life-threatening complication. We present the case of a 65-year-old male patient who presented with chronic low back pain that acutely worsened for 1 to 1.5 months and was diagnosed with vertebral diskitis-osteomyelitis secondary to a contiguous infection from an adjacent mycotic aortic aneurysm. To our knowledge, this is one of the few cases reported of vertebral diskitis-osteomyelitis secondary to mycotic aortic aneurysm. We discuss the findings on CT and MRI, as well as the value of imaging in guiding management.

Pediatric Endocrine Society Statement on Considerations for Use of Teplizumab (Tzield™) in Clinical Practice.

Teplizumab (TzieldTM, Provention Bio), a monoclonal antibody directed at t-cell marker CD3, is the first medication approved by the FDA to delay progression from Stage 2 to Stage 3 type 1 diabetes (T1D). To date, the overwhelming majority of pediatric endocrinologists do not have experience using immunotherapeutics and seek guidance the use of teplizumab in clinical practice. To address this need, the Pediatric Endocrine Society (PES) Diabetes Special Interest Group (Diabetes SIG) and Drug and Therapeutics Committee assembled a task force to review clinical trial data and solicit expert recommendations on the approach to teplizumab infusions. We present considerations on all aspects of teplizumab administration, utilizing evidence where possible and providing a spectrum of expert opinions on unknown aspects. We discuss patient selection and prescreening, highlighting the safety and considerations for monitoring and treatment of side effects. We propose a schedule of events, a protocol for administration and discuss practice management aspects. We advocate for the need for further long-term systematic surveillance studies to continue evaluating the efficacy and safety of teplizumab.

Mortality and mortality disparities among people with epilepsy in the United States, 2011-2021.

Studies on epilepsy mortality in the United States are limited. We used the National Vital Statistics System Multiple Cause of Death data to investigate mortality rates and trends during 2011-2021 for epilepsy (defined by the International Classification of Diseases, 10th Revision, codes G40.0-G40.9) as an underlying, contributing, or any cause of death (i.e., either an underlying or contributing cause) for U.S. residents. We also examined epilepsy as an underlying or contributing cause of death by selected sociodemographic characteristics to assess mortality rate changes and disparities in subpopulations. During 2011-2021, the overall age-standardized mortality rates for epilepsy as an underlying (39 % of all deaths) or contributing (61 % of all deaths) cause of death increased 83.6 % (from 2.9 per million to 6.4 per million population) as underlying cause and 144.1 % (from 3.3 per million to 11.0 per million population) as contributing cause (P < 0.001 for both based on annual percent changes). Compared to 2011-2015, in 2016-2020 mortality rates with epilepsy as an underlying or contributing cause of death were higher overall and in nearly all subgroups. Overall, mortality rates with epilepsy as an underlying or contributing cause of death were higher in older age groups, among males than females, among non-Hispanic Black or non-Hispanic American Indian/Alaska Native persons than non-Hispanic White persons, among those living in the West and Midwest than those living in the Northeast, and in nonmetro counties compared to urban regions. Results identify priority subgroups for intervention to reduce mortality in people with epilepsy and eliminate mortality disparity.

Fluoroscopy-Assisted Computer Navigation Accurately Determines Cup Position and Leg Length for Anterior Hip Arthroplasty.

BACKGROUND: Recently, fluoroscopy-assisted computer navigation has been developed to assess intraoperative cup inclination/anteversion and leg-length discrepancy (LLD) in the operating room. However, there is a relative dearth of studies investigating the accuracy of this software compared with postoperative radiographs. MATERIALS AND METHODS: We prospectively enrolled 211 navigated anterior total hip arthroplasties using fluoroscopy-assisted computer navigation software. Intraoperative navigated measurements were compared with postoperative anteroposterior radiographs to assess accuracy of cup inclination/anteversion and LLD. Continuous variables were analyzed using the Student's t test, and categorical variables were analyzed using Fisher's exact test. RESULTS: On postoperative radiographs, 94.3% of cups (199 of 211) were positioned within the Lewinnek "safe zone," compared with 99.1% navigated intraoperatively (P=.01). Eighty-two percent of hips (174 of 211) were navigated intraoperatively to LLDs within ±2 mm; on postoperative radiographs, 65% of hips (138 of 211) had LLDs within ±2 mm (P=.0001). Intraoperatively, 100% of hips (211 of 211) were navigated to LLDs within ±5 mm; similarly, on postoperative radiographs, 98% of hips (207 of 211) had LLDs within ±5 mm (P=.12). CONCLUSION: A novel fluoroscopy-assisted computer navigation platform accurately assessed intraoperative cup position and LLD during anterior total hip arthroplasty. Careful attention to fluoroscopic technique, positioning of radiographic landmarks, and knowledge of the limitations of fluoroscopy, including parallax effect, are important concepts that surgeons should incorporate into their decision algorithm. [Orthopedics. 202x;4x(x):xx-xx.].

Understanding primary care providers' attitudes towards preventive screenings to patients with inflammatory bowel disease.

BACKGROUND: Preventive care is important for managing inflammatory bowel disease (IBD), yet primary care providers (PCPs) often face challenges in delivering such care due to discomfort and unfamiliarity with IBD-specific guidelines. This study aims to assess PCPs' attitudes towards, and practices in, providing preventive screenings for IBD patients, highlighting areas for improvement in guideline dissemination and education. METHODS: Using a web-based opt-in panel of PCPs (DocStyles survey, spring 2022), we assessed PCPs' comfort level with providing/recommending screenings and the reasons PCPs felt uncomfortable (n = 1,503). Being likely to provide/recommend screenings for depression/anxiety, skin cancer, osteoporosis, and cervical cancer were compared by PCPs' comfort level and frequency of seeing patients with IBD. We estimated adjusted odd ratios (AORs) of being likely to recommend screenings and selecting responses aligned with IBD-specific guidelines by use of clinical practice methods. RESULTS: About 72% of PCPs reported being comfortable recommending screenings to patients with IBD. The top reason identified for not feeling comfortable was unfamiliarity with IBD-specific screening guidelines (55%). Being comfortable was significantly associated with being likely to provide/recommend depression/anxiety (AOR = 3.99) and skin cancer screenings (AOR = 3.19) compared to being uncomfortable or unsure. Percentages of responses aligned with IBD-specific guidelines were lower than those aligned with general population guidelines for osteoporosis (21.7% vs. 27.8%) and cervical cancer screenings (34.9% vs. 43.9%), and responses aligned with IBD-specific guidelines did not differ by comfort level for both screenings. Timely review of guidelines specific to immunosuppressed patients was associated with being likely to provide/recommend screenings and selecting responses aligned with IBD-specific guidelines. CONCLUSIONS: Despite a general comfort among PCPs in recommending preventive screenings for IBD patients, gaps in knowledge regarding IBD-specific screening guidelines persist. Enhancing awareness and understanding of these guidelines through targeted education and resource provision may bridge this gap.

Islet autoantibodies as precision diagnostic tools to characterize heterogeneity in type 1 diabetes: a systematic review.

BACKGROUND: Islet autoantibodies form the foundation for type 1 diabetes (T1D) diagnosis and staging, but heterogeneity exists in T1D development and presentation. We hypothesized that autoantibodies can identify heterogeneity before, at, and after T1D diagnosis, and in response to disease-modifying therapies. METHODS: We systematically reviewed PubMed and EMBASE databases (6/14/2022) assessing 10 years of original research examining relationships between autoantibodies and heterogeneity before, at, after diagnosis, and in response to disease-modifying therapies in individuals at-risk or within 1 year of T1D diagnosis. A critical appraisal checklist tool for cohort studies was modified and used for risk of bias assessment. RESULTS: Here we show that 152 studies that met extraction criteria most commonly characterized heterogeneity before diagnosis (91/152). Autoantibody type/target was most frequently examined, followed by autoantibody number. Recurring themes included correlations of autoantibody number, type, and titers with progression, differing phenotypes based on order of autoantibody seroconversion, and interactions with age and genetics. Only 44% specifically described autoantibody assay standardization program participation. CONCLUSIONS: Current evidence most strongly supports the application of autoantibody features to more precisely define T1D before diagnosis. Our findings support continued use of pre-clinical staging paradigms based on autoantibody number and suggest that additional autoantibody features, particularly in relation to age and genetic risk, could offer more precise stratification. To improve reproducibility and applicability of autoantibody-based precision medicine in T1D, we propose a methods checklist for islet autoantibody-based manuscripts which includes use of precision medicine MeSH terms and participation in autoantibody standardization workshops.

Islet autoantibodies are markers found in the blood when insulin-producing cells in the pancreas become damaged and can be used to predict future development of type 1 diabetes. We evaluated published literature to determine whether characteristics of islet antibodies (type, levels, numbers) could improve prediction and help understand differences in how individuals with type 1 diabetes respond to treatments. We found existing evidence shows that islet autoantibody type and number are most useful to predict disease progression before diagnosis. In addition, the age when islet autoantibodies first appear strongly influences rate of progression. These findings provide important information for patients and care providers on how islet autoantibodies can be used to understand future type 1 diabetes development and to identify individuals who have the potential to benefit from intervention or prevention therapy.

Economic insecurities and patient-reported outcomes in patients with systemic lupus erythematosus in the USA: a cross-sectional analysis of data from the California Lupus Epidemiology Study.

BACKGROUND: Social determinants of health are consistently associated with systemic lupus erythematosus (SLE) outcomes. However, social determinants of health are typically measured with conventional socioeconomic status factors such as income or education. We assessed the association of economic insecurities (ie, food, housing, health care, and financial insecurity) with patient-reported outcomes in a cohort of patients with SLE. METHODS: In this cross-sectional analysis, data were derived from the California Lupus Epidemiology Study based in the San Francisco Bay Area, CA, USA. Participants were recruited between Feb 25, 2015, and Jan 10, 2018, from rheumatology clinics. Inclusion criteria were Bay Area residency; oral fluency in English, Spanish, Cantonese, or Mandarin; 18 years or older; ability to provide informed consent; and a physician confirmed SLE diagnosis. Food, housing, health care, and financial economic insecurities were assessed by validated screening tools. Patient-reported outcomes were obtained using PROMIS, Quality of Life in Neurological Disorders (known as Neuro-QoL) Cognitive Function short form, Patient Health Questionnaire (PHQ)-8, and General Anxiety Disorder (GAD)-7 instruments. Poverty was defined as household income of 125% or less of the federal poverty limit. Lower education was defined as less than college-graduate education. The association of economic insecurities with patient-reported outcomes was assessed by multivariable linear regression models adjusting for demographics, SLE disease characteristics, and comorbidities. We tested for interactions of insecurities with poverty and education. FINDINGS: The final cohort included 252 participants. Mean age was 49·7 (SD 13·4) years, 228 (90%) of 252 were women and 24 (10%) were men. 80 (32%) individuals self-identified as Asian, 26 (10%) as Black, 101 (40%) as White, eight (3%) as mixed race, and 37 (15%) as other race; 59 (23%) self-identified as Hispanic. 135 (54%) individuals had at least one insecurity. Insecurities were highly prevalent, and more common in those with poverty and lower education. Adjusted multivariate analyses revealed that participants with any insecurity had significantly worse scores across all measured patient-reported outcomes. For physical function, no insecurity had an adjusted mean score of 48·9 (95% CI 47·5-50·3) and any insecurity had 45·7 (44·3-47·0; p=0·0017). For pain interference, no insecurity was 52·0 (50·5-53·5) and any insecurity was 54·4 (53·0-55·8; p=0·031). For fatigue, no insecurity was 50·5 (48·8-52·3) and any insecurity was 54·9 (53·3-56·5; p=0·0005). For sleep disturbance, no insecurity was 49·9 (48·3-51·6) and any insecurity was 52·9 (51·4-54·5; p=0·012). For cognitive function, no insecurity was 49·3 (47·7-50·9) and any insecurity was 45·6 (44·1-47·0; p=0·0011). For PHQ-8, no insecurity was 4·4 (3·6-5·1) and any insecurity was 6·1 (5·4-6·8; p=0·0013). For GAD-7, no insecurity was 3·3 (2·6-4·1) and any insecurity was 5·2 (4·5-5·9; p=0·0008). Individuals with more insecurities had worse patient-reported outcomes. There were no statistically significant interactions between insecurities and poverty or education. INTERPRETATION: Having any economic insecurity was associated with worse outcomes for people with SLE regardless of poverty or education. The findings of this study provide insight into the relationship between economic insecurities and SLE outcomes and underscore the need to assess whether interventions that directly address these insecurities can reduce health disparities in SLE. FUNDING: US Centers for Disease Control, Rheumatology Research Foundation, and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Concurrent warming and browning eliminate cold-water fish habitat in many temperate lakes.

Cold-water species in temperate lakes face two simultaneous climate-driven ecosystem changes: warming and browning of their waters. Browning refers to reduced transparency arising from increased dissolved organic carbon (DOC), which absorbs solar energy near the surface. It is unclear whether the net effect is mitigation or amplification of climate warming impacts on suitable oxythermal habitat (<20 °C, >5 mgO/L) for cold-loving species because browning expands the vertical distribution of both cool water and oxygen depletion. We analyzed long-term trends and high-frequency sensor data from browning lakes in New York's Adirondack region to assess the contemporary status of summertime habitat for lacustrine brook trout. Across two decades, surface temperatures increased twice as fast and bottom dissolved oxygen declined >180% faster than average trends for temperate lakes. We identify four lake categories based on oxythermal habitat metrics: constrained, squeezed, overheated, and buffered. In most of our study lakes, trout face either seasonal loss (7 of 15) or dramatic restriction (12 to 21% of the water column; 5 of 15) of suitable habitat. These sobering statistics reflect rapid upward expansion of oxygen depletion in lakes with moderate or high DOC relative to compression of heat penetration. Only in very clear lakes has browning potentially mitigated climate warming. Applying our findings to extensive survey data suggests that decades of browning have reduced oxythermal refugia in most Adirondack lakes. We conclude that joint warming and browning may preclude self-sustaining cold-water fisheries in many temperate lakes; hence, oxythermal categorization is essential to guide triage strategies and management interventions.

Comparison of computational fluid dynamics with transcranial Doppler ultrasound in response to physiological stimuli.

Cerebrovascular haemodynamics are sensitive to multiple physiological stimuli that require synergistic response to maintain adequate perfusion. Understanding haemodynamic changes within cerebral arteries is important to inform how the brain regulates perfusion; however, methods for direct measurement of cerebral haemodynamics in these environments are challenging. The aim of this study was to assess velocity waveform metrics obtained using transcranial Doppler (TCD) with flow-conserving subject-specific three-dimensional (3D) simulations using computational fluid dynamics (CFD). Twelve healthy participants underwent head and neck imaging with 3 T magnetic resonance angiography. Velocity waveforms in the middle cerebral artery were measured with TCD ultrasound, while diameter and velocity were measured using duplex ultrasound in the internal carotid and vertebral arteries to calculate incoming cerebral flow at rest, during hypercapnia and exercise. CFD simulations were developed for each condition, with velocity waveform metrics extracted in the same insonation region as TCD. Exposure to stimuli induced significant changes in cardiorespiratory measures across all participants. Measured absolute TCD velocities were significantly higher than those calculated from CFD (P range < 0.001-0.004), and these data were not correlated across conditions (r range 0.030-0.377, P range 0.227-0.925). However, relative changes in systolic and time-averaged velocity from resting levels exhibited significant positive correlations when the distinct techniques were compared (r range 0.577-0.770, P range 0.003-0.049). Our data indicate that while absolute measures of cerebral velocity differ between TCD and 3D CFD simulation, physiological changes from resting levels in systolic and time-averaged velocity are significantly correlated between techniques.

Impact of Water- and Land-Based Exercise Training on Risk Factors and Vascular Function in Middle-Aged and Older Men and Women.

INTRODUCTION: Exercise improves vascular function, but it is unclear whether benefits are mediated by traditional cardiovascular risk factors or whether sex differences in training effects exist in older adults. We hypothesized that exercise would improve cardiovascular risk factors, that males and females would benefit similarly, and that improvements in risk factors would correlate with changes in vascular function. METHODS: Seventy-two healthy middle-aged/older adults (age, 62 ± 7 yr; 26%♂) were randomized to a land-walking ( n = 23), water-walking ( n = 25), or a nonexercise control group (C; n = 23). The exercise groups undertook supervised and monitored training three times a week for 50 min per session, across 24 wk. Blood pressure, body composition (dual x-ray absorptiometry), blood lipids and glucose, and flow-mediated brachial artery dilation were assessed in all participants at weeks 0 and 24. To maximize power for sex differences and correlation analyses, we pooled the training groups (land-walking + water-walking). RESULTS: Training prevented increases in LDL and total cholesterol/HDL ratio observed in the nonexercise control group. No group by time interactions were observed for other risk factors. Sex differences in training effects existed for visceral fat (-187 ± 189 g♂ vs -15 ± 161 g♀; P = 0.006) and lean mass (-352 ± 1045 g♂ vs 601 ± 1178 g♀; P = 0.008). Improvement in flow-mediated brachial artery dilation was correlated with decreased waist girth ( r = -0.450, P = 0.036), but not with other risk factors. CONCLUSIONS: Exercise training prevented deterioration in lipid levels, whereas sex differences existed for body composition changes with training. Improvement in vascular function was not dependent on changes in risk factors in middle-aged/older adults, suggesting that artery health may be dependent on other exercise-related stimuli.

Adjuvant effect of inhaled particulate matter containing free radicals following house-dust mite induction of asthma in mice.

INTRODUCTION: Exposures to particulate matter (PM) from combustion sources can exacerbate preexisting asthma. However, the cellular and molecular mechanisms by which PM promotes the exacerbation of asthma remain elusive. We used a house dust mite (HDM)-induced mouse model of asthma to test the hypothesis that inhaled DCB230, which are PM containing environmentally persistent free radicals (EPFRs), will aggravate asthmatic responses. METHODS: Groups of 8-10-week-old C57BL/6 male mice were exposed to either air or DCB230 aerosols at a concentration of 1.5 mg/m3 4 h/day for 10 days with or without prior HDM-induction of asthma. RESULTS: Aerosolized DCB230 particles formed small aggregates (30-150 nm). Mice exposed to DCB230 alone showed significantly reduced lung tidal volume, overexpression of the Muc5ac gene, and dysregulation of 4 inflammation related genes, Ccl11, Ccl24, Il-10, and Tpsb2. This suggests DCB230 particles interacted with the lung epithelium inducing mucous hypersecretion and restricting lung volume. In addition to reduced lung tidal volume, compared to respective controls, the HDM + DCB230-exposed group exhibited significantly increased lung tissue damping and up-regulated expression of Muc5ac, indicating that in this model, mucous hypersecretion may be central to pulmonary dysfunction. This group also showed augmented lung eosinophilic inflammation accompanied by an up-regulation of 36 asthma related genes. Twelve of these genes are part of IL-17 signaling, suggesting that this pathway is critical for DCB230 induced toxicity and adjuvant effects in lungs previously exposed to HDM. CONCLUSION: Our data indicate that inhaled DCB230 can act as an adjuvant, exacerbating asthma through IL-17-mediated responses in a HDM mouse model.

Forecasting individual exercise sweat losses from forecast air temperature and energy expenditure.

Introduction: Recent success in predicting individual sweat losses from air temperature and energy expenditure measurements suggests a potential for forecasting individual sweat losses for future combinations of environment and exercise. The purpose of this study is to determine the plausibility of accurately forecasting exercise sweat losses from meteorological air temperature forecasts and individual running energy expenditure forecasts. The potential impact on plasma sodium is also estimated when setting drinking rates equal to forecast sweat losses. Materials and methods: Individual exercise sweat losses (equated to water needs) and energy expended while running were measured in 33 participants along with air temperature and compared with forecasts of the same. Forecast inputs were used in a web app to forecast exercise sweat losses for comparison with observed values. The bias between forecast and observed exercise sweat losses was used to calculate the potential drinking impact on plasma sodium. Results: The concordance correlation coefficient between forecast and observed values was 0.95, 0.96, and 0.91 for air temperature, energy expenditure, and exercise sweat losses, respectively, indicating excellent agreement and no significant differences observed via t-test. Perfect matching of water intake to sweat losses would lower plasma sodium concentrations from 140 to 138 mmol/L; calculations using the 95% limits of agreement for bias showed that drinking according to forecast exercise sweat losses would alter plasma sodium concentrations from 140 to between 136 and 141 mmol/L. Conclusions: The outcomes support the strong potential for accurately forecasting exercise sweat losses from commonly available meteorological air temperature forecasts and energy expenditure from forecast running distance.

Multimorbidity in systemic lupus erythematosus in a population-based cohort: the lupus Midwest network.

OBJECTIVES: To assess the prevalence and incidence of multimorbidity and the association with the SLICC/ACR damage index (SDI) among patients with systemic lupus erythematosus (SLE). METHODS: Using prevalent and incident population-based cohorts of patients with SLE and their matched comparators, we assessed 57 chronic conditions. Chronic conditions were categorized as SDI-related or SDI-unrelated. Multimorbidity was defined as the presence of 2+ chronic conditions. Multimorbidity at prevalence and incidence/index was compared between cohorts using logistic regression. Cox models were used to examine development of multimorbidity after SLE incidence. RESULTS: The prevalent cohort included 449 patients with established SLE on January 1, 2015. They were three times more likely to have multimorbidity compared with non-SLE comparators (OR 2.98, 95% CI 2.18-4.11). The incident cohort included 270 patients with new-onset SLE. At SLE incidence, patients with SLE were more likely to have multimorbidity than comparators (OR 2.27, 95% CI 1.59-3.27). After incidence, the risk of developing multimorbidity was 2-fold higher among patients with SLE than comparators (hazard ratio (HR) 2.11, 95% CI 1.59-2.80). Development of multimorbidity was higher in patients with SLE based on SDI-related (HR 2.91, 95% CI 2.17-3.88) and SDI-unrelated conditions (HR 1.73, 95% CI, 1.32-2.26). CONCLUSION: Patients with SLE have a higher burden of multimorbidity, even before the onset of the disease. The risk disparity continues after SLE classification and is also seen in a prevalent SLE cohort. Multimorbidity is driven both by SDI-related and unrelated conditions.

Trends in the Prevalence of Chronic Obstructive Pulmonary Disease Among Adults Aged ≥18 Years - United States, 2011-2021.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death in the United States. Overall COPD prevalence declined during 1999-2011. Trends in COPD prevalence during the previous decade have not been reported. CDC analyzed 2011-2021 Behavioral Risk Factor Surveillance System data to assess trends and differences in self-reported physician-diagnosed COPD prevalence among U.S. adults aged ≥18 years. Age-standardized prevalence of COPD did not change significantly from 2011 (6.1%) to 2021 (6.0%). Prevalence was stable for most states and subgroups; however, it decreased significantly among adults aged 18-44 years (average annual percent change [AAPC] = -2.0%) and increased significantly among those aged ≥75 years (AAPC = 1.3%), those living in micropolitan counties (0.8%), and among current (1.5%) or former (1.2%) smokers. COPD prevalence remained elevated in the following groups: women, adults aged ≥65 years, those with a lower education level, unable to work, living in rural areas, and who ever smoked. Evidence-based strategies, especially those tailored for adults disproportionately affected, can reduce COPD prevalence, and address the continued need for prevention, early diagnosis, treatment, and management.

Disease-modifying therapies and features linked to treatment response in type 1 diabetes prevention: a systematic review.

BACKGROUND: Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Prevention efforts have focused on immune modulation and supporting beta cell health before or around diagnosis; however, heterogeneity in disease progression and therapy response has limited translation to clinical practice, highlighting the need for precision medicine approaches to T1D disease modification. METHODS: To understand the state of knowledge in this area, we performed a systematic review of randomized-controlled trials with ≥50 participants cataloged in PubMed or Embase from the past 25 years testing T1D disease-modifying therapies and/or identifying features linked to treatment response, analyzing bias using a Cochrane-risk-of-bias instrument. RESULTS: We identify and summarize 75 manuscripts, 15 describing 11 prevention trials for individuals with increased risk for T1D, and 60 describing treatments aimed at preventing beta cell loss at disease onset. Seventeen interventions, mostly immunotherapies, show benefit compared to placebo (only two prior to T1D onset). Fifty-seven studies employ precision analyses to assess features linked to treatment response. Age, beta cell function measures, and immune phenotypes are most frequently tested. However, analyses are typically not prespecified, with inconsistent methods of reporting, and tend to report positive findings. CONCLUSIONS: While the quality of prevention and intervention trials is overall high, the low quality of precision analyses makes it difficult to draw meaningful conclusions that inform clinical practice. To facilitate precision medicine approaches to T1D prevention, considerations for future precision studies include the incorporation of uniform outcome measures, reproducible biomarkers, and prespecified, fully powered precision analyses into future trial design.

Type 1 diabetes (T1D) is a condition that results from the destruction of a type of cell in the pancreas that produces the hormone insulin, leading to lifelong dependence on insulin injections. T1D prevention remains a challenging goal, largely due to the immense variability in disease processes and progression. Therapies tested to date in medical research settings (clinical trials) work only in a subset of individuals, highlighting the need for more tailored prevention approaches. We reviewed clinical trials of therapies targeting the disease process in T1D. While the overall quality of trials was high, studies testing individual features affecting responses to treatments were low. This review reveals an important need to carefully plan high-quality analyses of features that affect treatment response in T1D, to ensure that tailored approaches may one day be applied to clinical practice.

Comment on Rosa et al. Optic Nerve Drusen Evaluation: A Comparison between Ultrasound and OCT. J. Clin. Med. 2022, 11, 3715.

We read with interest the paper by Rosa et al., entitled "Optic Nerve Drusen Evaluation: A Comparison between Ultrasound and OCT", published in June of 2022 [...].

Posterior Capsule Reconstruction with Polypropylene Mesh After Total Hip Arthroplasty.

Instability remains a challenge after total hip arthroplasty (THA). We have previously utilized a monofilament polypropylene mesh to reconstruct the posterior capsule for unstable THA. This study identified 24 hips that underwent mesh reconstruction of the posterior capsule for instability. Survivorship was 70.8% at mean 6.5 years (range 6 weeks-20.1 years). Six patients underwent re-operation, and one patient had the mesh removed. Of eight hips, five (62.5%) with a history of prior revision re-dislocated, while only 2/16 hips (12.5%) with no previous revision history re-dislocated (p = 0.02). Posterior capsule reconstruction with polypropylene mesh has reasonable mid-term survivorship in this challenging population. (Journal of Surgical Orthopaedic Advances 32(2):092-096, 2023).

Comparison of Visual Methods to Reanalyze Provocative Test Data from Randomized Controlled Clinical Trials in New- or Recent-Onset Type 1 Diabetes.

INTRODUCTION: Over the last 13 years, the Immune Tolerance Network (ITN), has conducted trials of agents to abrogate the autoimmunity underlying type 1 diabetes. Primary endpoints center on the change of C-peptide production during mixed meal tolerance tests (MMTT), measured as the area under the curve (AUC) or AUC mean over 2-3 years. Studies permit rapid-acting insulin until a few hours before the MMTT, and thus do not exclude overnight hyperglycemia prior to testing. We hypothesize that overnight or fasting hyperglycemia will deplete pre-formed insulin and impact measurements of first-phase insulin secretion and C-peptide AUC. METHODS: Publicly available, deidentified, subject-level data were obtained from ITN TrialShare. We developed several graphical analyses to reexamine results from each MMTT including combined glucose and C-peptide response curves, the centroids of polygons of MMTT timepoints, and ratios comparing extents of excursions of glucose and c-peptide production. RESULTS: We have applied these graphical analyses to 1161 MMTT from 245 subjects in 8 studies. Graphical analyses of MMTT results for individuals over the course of the follow-up period reflect the expected loss of c-peptide and higher blood glucose during MMTT; centroids move accordingly, upwards and leftwards. CONCLUSIONS: We were able to analyze MMTT data from ITN studies with several graphical analyses. We are poised to apply these approaches to test our central hypothesis by comparing how deviations from modeled rates of predicted changes for an individual over time correlate with blood glucose levels in the hours before a MMTT. This may lead to refinement of future trial protocols to ensure tighter regulation of glycemic excursions ahead of provocative testing.