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In some patients with chronic obstructive pulmonary disease (COPD), type 2 inflammation may increase exacerbation risk and may be indicated by elevated blood eosinophil counts. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation. In a phase 3, double-blind, randomized trial, we assigned patients with COPD who had a blood eosinophil count of at least 300 per microliter and an elevated exacerbation risk despite the use of standard triple therapy to receive dupilumab (300 mg) or placebo subcutaneously once every 2 weeks. The primary end point was the annualized rate of moderate or severe exacerbations of COPD. Key secondary and other end points that were corrected for multiplicity were the change in the prebronchodilator forced expiratory volume in 1 second (FEV ) and in the scores on the St. George's Respiratory Questionnaire (SGRQ; range, 0 to 100, with lower scores indicating a better quality of life) and the Evaluating Respiratory Symptoms in COPD (E-RS-COPD; range, 0 to 40, with lower scores indicating less severe symptoms). A total of 939 patients underwent randomization: 468 to the dupilumab group and 471 to the placebo group. The annualized rate of moderate or severe exacerbations was 0.78 (95% confidence interval [CI], 0.64 to 0.93) with dupilumab and 1.10 (95% CI, 0.93 to 1.30) with placebo (rate ratio, 0.70; 95% CI, 0.58 to 0.86; P<0.001). The prebronchodilator FEV increased from baseline to week 12 by a least-squares (LS) mean of 160 ml (95% CI, 126 to 195) with dupilumab and 77 ml (95% CI, 42 to 112) with placebo (LS mean difference, 83 ml; 95% CI, 42 to 125; P<0.001), a difference that was sustained through week 52. At week 52, the SGRQ score had improved by an LS mean of -9.7 (95% CI, -11.3 to -8.1) with dupilumab and -6.4 (95% CI, -8.0 to -4.8) with placebo (LS mean difference, -3.4; 95% CI, -5.5 to -1.3; P = 0.002). The E-RS-COPD score at week 52 had improved by an LS mean of -2.7 (95% CI, -3.2 to -2.2) with dupilumab and -1.6 (95% CI, -2.1 to -1.1) with placebo (LS mean difference, -1.1; 95% CI, -1.8 to -0.4; P = 0.001). The numbers of patients with adverse events that led to discontinuation of dupilumab or placebo, serious adverse events, and adverse events that led to death were balanced in the two groups. Among patients with COPD who had type 2 inflammation as indicated by elevated blood eosinophil counts, those who received dupilumab had fewer exacerbations, better lung function and quality of life, and less severe respiratory symptoms than those who received placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; BOREAS ClinicalTrials.gov number, NCT03930732.).

Electronic nicotine product use is increasing in the U.S., but few studies have addressed its effects on oral health. The goal of this work was to determine the association between electronic nicotine product use and periodontal disease. Population Assessment of Tobacco and Health adult survey data from 2013–2016 (waves 1, 2 and 3) was used for the analysis. Longitudinal electronic nicotine product users used electronic nicotine products regularly every day or somedays in all three waves. Participants with new cases of gum disease reported no history of gum disease in wave 1 but reported being diagnosed with gum disease in waves 2 or 3. Odds ratios (OR) were calculated to determine the association between electronic nicotine product use and new cases of gum disease after controlling for potential confounders. Compared to never users, longitudinal electronic nicotine product users had increased odds of being diagnosed with gum disease (OR 1.76, 95% Confidence Interval (CI) 1.12–2.76) and bone loss around teeth (OR 1.67, 95% CI 1.06–2.63). These odds were higher for participants with a history of marijuana and a history of illicit or non-prescribed drug use. Our findings show that e-cigarettes may be harmful to oral health.

Hospitalization of the elderly for invasive pneumococcal disease is frequently accompanied by the occurrence of an adverse cardiac event; these are primarily new or worsened heart failure and cardiac arrhythmia. Herein, we describe previously unrecognized microscopic lesions (microlesions) formed within the myocardium of mice, rhesus macaques, and humans during bacteremic Streptococcus pneumoniae infection. In mice, invasive pneumococcal disease (IPD) severity correlated with levels of serum troponin, a marker for cardiac damage, the development of aberrant cardiac electrophysiology, and the number and size of cardiac microlesions. Microlesions were prominent in the ventricles, vacuolar in appearance with extracellular pneumococci, and remarkable due to the absence of infiltrating immune cells. The pore-forming toxin pneumolysin was required for microlesion formation but Interleukin-1β was not detected at the microlesion site ruling out pneumolysin-mediated pyroptosis as a cause of cell death. Antibiotic treatment resulted in maturing of the lesions over one week with robust immune cell infiltration and collagen deposition suggestive of long-term cardiac scarring. Bacterial translocation into the heart tissue required the pneumococcal adhesin CbpA and the host ligands Laminin receptor (LR) and Platelet-activating factor receptor. Immunization of mice with a fusion construct of CbpA or the LR binding domain of CbpA with the pneumolysin toxoid L460D protected against microlesion formation. We conclude that microlesion formation may contribute to the acute and long-term adverse cardiac events seen in humans with IPD.

While 30-day readmissions following hospitalization for pneumonia have been well-studied in the elderly, their burden in young adults remains poorly understood. To study patterns of readmissions following hospitalization for pneumonia across age groups and insurance payers. In the Nationwide Readmission Database for the years 2013 and 2014 we identified all adults (≥18 years) discharged alive after a hospitalization with the primary diagnosis of pneumonia, and examined rates of readmissions within 30-days of discharge. Using covariates included in the Center for Medicare & Medicaid Services risk-adjustment model for pneumonia readmissions in a multivariable regression model for survey data, we identified predictors of 30-day readmission. We identified 629,939 index pneumonia hospitalizations with a weighted estimate of 1,472,069 nationally. Overall, 16.2% of patients were readmitted within 30 days of their hospitalization for pneumonia, with 30-day readmission rates of 12.4% in the 18-44 year age-group, 16.1% in the 45-64 year age-group, and 16.7% in the ≥65-year age-group. In risk-adjusted analyses, compared with elderly, middle-aged adults were more likely to be readmitted (risk-adjusted OR 1.05, 95% CI 1.03-1.07). Mean cost per readmission was also highest for this age group at $15,976. Middle-aged adults experience substantial rates of 30-day readmission that are comparable to those over 65 years of age, with a higher cost per readmission event. Future efforts are needed to identify potential interventions to alleviate the high burden of pneumonia readmissions in middle-aged adults.

Background Our study examined what demographic and health factors were associated with motivations for e-cigarette use in those with asthma and COPD. Methods The analysis included participants ≥ 18 years old in Wave 5 of the Population Assessment of Tobacco and Health who reported e-cigarette use and had asthma or COPD. We used multivariable logistic regression models, adjusted for survey weights, to examine the associations of potential reasons for e-cigarette use, including affordability and attempts to minimize or quit cigarette smoking. Results Seven hundred twenty-five participants (weighted n  = 2,588,403) met the inclusion criteria. Factors associated with using e-cigarettes to help reduce cigarette use included being > 45 years old (odds ratio 1.9, 95% confidence interval 1.1–3.2) and having experienced wheezing in the past year (2.1, 1.3–3.4). Experiencing wheezing was also the only factor associated with using e-cigarettes to help quit smoking (2.6, 1.5–4.5). Being Hispanic and being moderately to very worried about the health impacts of any tobacco product usage, which includes electronic products, conferred a lower likelihood of using e-cigarettes to cut down on cigarettes (0.5, 0.3–0.98; 0.4, 0.3–0.8). Those who identified as male or being moderately to very worried about the health impacts of their tobacco product usage were significantly less likely to have initiated e-cigarettes for smoking cessation (0.6, 0.4–0.9; 0.3, 0.2–0.5). Conclusions Factors associated with the uptake of e-cigarettes as a smoking cessation tool include age, gender, and ethnicity. Wheezing, as a symptom of respiratory illness, appears to have the strongest association with e-cigarette usage as a form of smoking cessation. At the same time, concern about the health impacts of tobacco products is the strongest negative predictor.

The use of electronic cigarettes (e-cigarettes) has increased in the US, but little is known about the effects of these products on lung health. The main purpose of this study was to examine the association between e-cigarette use and a participant’s report of being diagnosed with chronic obstructive pulmonary disease (COPD) in a nationally representative sample of adults. Methods: The first wave of the Population Assessment of Tobacco and Health (PATH) survey adult data was used (N = 32,320). Potential confounders between e-cigarette users and non-users were balanced using propensity score matching. Odds ratios (OR) were calculated to examine the association between e-cigarette use and COPD in the propensity-matched sample, the entire sample, different age groups, and in nonsmokers. Replicate weights and balanced repeated replication methods were utilized to account for the complex survey design. Results: Of the 3642 participants who met the criteria for e-cigarette use, 2727 were propensity matched with 2727 non e-cigarette users. In the propensity-matched sample, e-cigarette users were more likely to report being diagnosed with COPD (OR 1.43, 95% confidence interval [CI] 1.12–1.85) than non-e-cigarette users after adjusting for confounders. The result was similar in the entire sample and in the different age subgroups. Among nonsmokers, the odds of reporting a COPD diagnosis were even greater among e-cigarette users (OR 2.94, 95% CI 1.73–4.99) compared to non-e-cigarette users. Conclusion: Our findings demonstrate that e-cigarette use was associated with a reported diagnosis of COPD among adults in the US. Further research is necessary to characterize the nature of this association and on the long-term effects of using e-cigarettes.

Prior studies demonstrated marked increases in Clostridium difficile infection (CDI) in the United States (U.S.) in recent years. The objective of this study was to describe the epidemiology of initial and recurrent CDI in a national Veterans Health Administration (VHA) cohort over a 12-year period. This was a retrospective cohort study of all adult VHA beneficiaries with CDI (ICD-9-CM code 008.45) plus a positive CDI stool test between October 1, 2002 and September 30, 2014. Data were obtained from the VA Informatics and Computing Infrastructure. Recurrence was defined as a second ICD-9-CM code plus a new course of CDI therapy following a minimum three-day gap after the initial therapy was completed. CDI incidence and outcomes were presented descriptively and longitudinally. Overall, 30,326 patients met study inclusion criteria. CDI incidence increased from FY 2003 (1.6 per 10,000) to FY 2013 (5.1 per 10,000). Thereafter, CDI incidence decreased through FY 2014 (4.6 per 10,000). A total of 5,011 patients (17%) experienced a first recurrence and, of those, 1,713 (34%) experienced a second recurrence. Recurrence incidence increased 10-fold over the study period, from (0.1 per 10,000) in FY 2003, to (1.0 per 10,000) in FY 2014. Overall, 30-day mortality and median hospital length of stay (LOS) decreased among initial episodes over the study period. Mortality was higher for initial episodes (21%) compared to first recurrences (11%) and second recurrences (7%). Median hospital LOS was longer for first episodes (13 days) compared to first (9 days) and second recurrences (8 days). Initial and recurrent CDI episodes increased among veterans over a 12-year period. Outcomes, such as mortality and hospital LOS improved in recent years; both of these outcomes are worse for initial CDI episodes than recurrent episodes.

Background Statin use is associated with increased incidence of diabetes and possibly with increased body weight and reduced exercise capacity. Data on the long-term effects of these associations in healthy adults, however, are very limited. In addition, the relationship between these effects and diabetic complications has not been adequately studied. Objective To examine the association between statin use and new-onset diabetes, diabetic complications, and overweight/obesity in a cohort of healthy adults. Research Design This was a retrospective cohort study. Participants Subjects were Tricare beneficiaries who were evaluated between October 1, 2003 and March 1, 2012. Patients were divided into statin users and nonusers. Intervention We excluded patients who, at baseline, had a preexisting disease indicative of cardiovascular diseases, any positive element of the Charlson comorbidity index (including diabetes mellitus), or life-limiting chronic diseases. Using 42 baseline characteristics, we generated a propensity score to match statin users and nonusers. Main Measures Outcomes assessed included new-onset diabetes, diabetic complications, and overweight/obesity. Key Results A total of 25,970 patients (3982 statin users and 21,988 nonusers) were identified as healthy adults at baseline. Of these, 3351 statins users and 3351 nonusers were propensity score-matched. Statin users had higher odds of new-onset diabetes (odds ratio [OR] 1.87; 95 % confidence interval [95 % CI] 1.67–2.01), diabetes with complications (OR 2.50; 95 % CI 1.88–3.32), and overweight/obesity (OR 1.14; 95 % CI 1.04–1.25). Secondary and sensitivity analyses demonstrated similar findings. Conclusions Diabetes, diabetic complications, and overweight/obesity were more commonly diagnosed among statin-users than similar nonusers in a healthy cohort of adults. This study demonstrates that short-term clinical trials might not fully describe the risk/benefit of long-term statin use for primary prevention.

Invasive pneumococcal disease (IPD) is a leading cause of death. Rheumatoid arthritis (RA) patients are at risk of IPD due to immunosuppressant medications. Up until 2022, two pneumococcal vaccines, the 13-valent Pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide vaccine (PPSV23), were recommended. Despite the recommendation change to give a single 20-valent PCV vaccine (PCV20), some still require multiple vaccinations. There is a need to identify barriers to vaccine uptake. We conducted a retrospective cohort study to assess the on-time vaccination rates for PCV13 and PPSV23 in treated RA patients between 2010 and 2018 using national Veterans Affairs data. Patients > 18 years of age diagnosed with RA and newly initiated on RA treatment were included. Pneumococcal vaccine compliance was assessed by measuring on-time receipt of PCV13 and PPSV23 vaccinations. We identified factors using multivariate logistic regression and described the occurrence of these factors using descriptive statistics. A total of 39,243 patients were included in the study. Most patients were white (75.8 %), male (85.4 %), on methotrexate therapy (41.4 %). The average age was 62.3 years. The proportion of patients considered vaccine compliant is 43.9 %. The primary independent risk factors for vaccine non-compliance were black/African American race (Odds Ratio [OR] 1.26, 95 % Confidence Interval [CI] 1.19–1.34) or missing/unknown race (OR 1.45, 95 % CI 1.31–1.61), missing/unknown ethnicity (OR 1.21, 1.02–1.43), never married (OR 1.10, 95 % CI 1.02–1.19) or widowed (OR 1.23, 95 % CI 1.12–1.34), diagnosed with congestive heart failure (OR 1.10, 95 % CI 1.00–1.22), or dementia (OR 1.48, 95 % CI 1.16–1.91). The proportion of patients who were non-compliant in patients who were vaccine naïve was 32.1 % and the non-compliance rate for non-naïve patients was 65.3 %. Providers should identify barriers to pneumococcal vaccination in RA patients to improve compliance. Efforts to increase vaccination should be tailored to specific high-risk groups.