Background Socioeconomic status (SES) is associated with asthma morbidity in observational studies, but the factors underlying this association are uncertain. Objective We investigated whether 3 SES ...correlates—low income, low education, and high perceived stress—were independent risk factors for treatment failure and asthma exacerbations in the context of a randomized controlled trial. Methods The effect of low SES (household income of <$50,000/y and household educational level of less than a Bachelor's degree) and high perceived stress (defined as a score of >20 on a perceived stress scale) on asthma morbidity was analyzed in 381 participants by using Poisson regression models. The primary outcome was treatment failure (defined in the trial protocol as a significant clinical or airflow deterioration), and the secondary outcome was asthma exacerbations requiring systemic corticosteroids. Results Fifty-four percent of participants had a low income, 40% had a low educational level, and 17% had high perceived stress levels. Even after adjusting for race and other important confounders, participants with lower income had higher rates of both treatment failures (rate ratio, 1.6; 95% CI, 1.1-2.3; P = .03) and exacerbations (rate ratio, 1.9; 95% CI, 1.1-3.3; P = .02). Adherence with inhaled corticosteroids was similarly high for both income categories. Education and perceived stress were not significantly associated with either outcome. Conclusions In the context of a randomized controlled trial, participants with lower income were more likely to experience adverse asthma outcomes independent of education, perceived stress, race, and medication adherence.
The purpose of this study was to develop a radiation therapy (RT) contouring atlas and recommendations for women with postoperative and locally advanced vulvar carcinoma.
An international committee ...of 35 expert gynecologic radiation oncologists completed a survey of the treatment of vulvar carcinoma. An initial set of recommendations for contouring was discussed and generated by consensus. Two cases, 1 locally advanced and 1 postoperative, were contoured by 14 physicians. Contours were compared and analyzed using an expectation-maximization algorithm for simultaneous truth and performance level estimation (STAPLE), and a 95% confidence interval contour was developed. The level of agreement among contours was assessed using a kappa statistic. STAPLE contours underwent full committee editing to generate the final atlas consensus contours.
Analysis of the 14 contours showed substantial agreement, with kappa statistics of 0.69 and 0.64 for cases 1 and 2, respectively. There was high specificity for both cases (≥99%) and only moderate sensitivity of 71.3% and 64.9% for cases 1 and 2, respectively. Expert review and discussion generated consensus recommendations for contouring target volumes and treatment for postoperative and locally advanced vulvar cancer.
These consensus recommendations for contouring and treatment of vulvar cancer identified areas of complexity and controversy. Given the lack of clinical research evidence in vulvar cancer radiation therapy, the committee advocates a conservative and consistent approach using standardized recommendations.
Background Compositional differences in the bronchial bacterial microbiota have been associated with asthma, but it remains unclear whether the findings are attributable to asthma, to aeroallergen ...sensitization, or to inhaled corticosteroid treatment. Objectives We sought to compare the bronchial bacterial microbiota in adults with steroid-naive atopic asthma, subjects with atopy but no asthma, and nonatopic healthy control subjects and to determine relationships of the bronchial microbiota to phenotypic features of asthma. Methods Bacterial communities in protected bronchial brushings from 42 atopic asthmatic subjects, 21 subjects with atopy but no asthma, and 21 healthy control subjects were profiled by using 16S rRNA gene sequencing. Bacterial composition and community-level functions inferred from sequence profiles were analyzed for between-group differences. Associations with clinical and inflammatory variables were examined, including markers of type 2–related inflammation and change in airway hyperresponsiveness after 6 weeks of fluticasone treatment. Results The bronchial microbiome differed significantly among the 3 groups. Asthmatic subjects were uniquely enriched in members of the Haemophilus , Neisseria , Fusobacterium , and Porphyromonas species and the Sphingomonodaceae family and depleted in members of the Mogibacteriaceae family and Lactobacillales order. Asthma-associated differences in predicted bacterial functions included involvement of amino acid and short-chain fatty acid metabolism pathways. Subjects with type 2–high asthma harbored significantly lower bronchial bacterial burden. Distinct changes in specific microbiota members were seen after fluticasone treatment. Steroid responsiveness was linked to differences in baseline compositional and functional features of the bacterial microbiome. Conclusion Even in subjects with mild steroid-naive asthma, differences in the bronchial microbiome are associated with immunologic and clinical features of the disease. The specific differences identified suggest possible microbiome targets for future approaches to asthma treatment or prevention.
Background Anaphylaxis is a potentially life-threatening allergic reaction. The risk of anaphylaxis after vaccination has not been well described in adults or with newer vaccines in children. ...Objective We sought to estimate the incidence of anaphylaxis after vaccines and describe the demographic and clinical characteristics of confirmed cases of anaphylaxis. Methods Using health care data from the Vaccine Safety Datalink, we determined rates of anaphylaxis after vaccination in children and adults. We first identified all patients with a vaccination record from January 2009 through December 2011 and used diagnostic and procedure codes to identify potential anaphylaxis cases. Medical records of potential cases were reviewed. Confirmed cases met the Brighton Collaboration definition for anaphylaxis and had to be determined to be vaccine triggered. We calculated the incidence of anaphylaxis after all vaccines combined and for selected individual vaccines. Results We identified 33 confirmed vaccine-triggered anaphylaxis cases that occurred after 25,173,965 vaccine doses. The rate of anaphylaxis was 1.31 (95% CI, 0.90-1.84) per million vaccine doses. The incidence did not vary significantly by age, and there was a nonsignificant female predominance. Vaccine-specific rates included 1.35 (95% CI, 0.65-2.47) per million doses for inactivated trivalent influenza vaccine (10 cases, 7,434,628 doses given alone) and 1.83 (95% CI, 0.22-6.63) per million doses for inactivated monovalent influenza vaccine (2 cases, 1,090,279 doses given alone). The onset of symptoms among cases was within 30 minutes (8 cases), 30 to less than 120 minutes (8 cases), 2 to less than 4 hours (10 cases), 4 to 8 hours (2 cases), the next day (1 case), and not documented (4 cases). Conclusion Anaphylaxis after vaccination is rare in all age groups. Despite its rarity, anaphylaxis is a potentially life-threatening medical emergency that vaccine providers need to be prepared to treat.
Background Combined pulmonary fibrosis and emphysema (CPFE) is increasingly recognized, but its prevalence and prognosis remain unclear. We sought to determine the prevalence, clinical features, and ...prognosis of CPFE in idiopathic pulmonary fibrosis (IPF), using a standardized and reproducible definition. Methods Patients with IPF were identified from two ongoing cohorts. Two radiologists scored emphysema and fibrosis severity on high-resolution CT (HRCT) scans. CPFE was defined as ≥ 10% emphysema on HRCT scan. Clinical characteristics and outcomes of patients with CPFE and IPF and those with non-CPFE IPF were compared with unadjusted analysis and then analysis after adjustment for HRCT fibrosis score. Mortality was compared using competing risks regression to handle lung transplantation. Sensitivity analyses were performed using Cox proportional hazards, including time to death (transplantation censored) and time to death or transplant. Results CPFE criteria were met in 29 of 365 patients with IPF (8%), with high agreement between radiologists (κ = 0.74). Patients with CPFE had less fibrosis on HRCT scans and higher FVC, but greater oxygen requirements ( P ≤ .01 for all comparisons). Findings were maintained with adjustment for fibrosis severity. Inhaled therapies for COPD were used by 53% of patients with CPFE. There was no significant difference in mortality comparing patients with CPFE and IPF to those with non-CPFE IPF (hazard ratio, 1.14; 95% CI, 0.61-2.13; P = .69). Conclusions CPFE was identified in 8% of patients with IPF and is a distinct, clinical phenotype with potential therapies that remain underutilized. Patients with CPFE and IPF and those with non-CPFE IPF have similar mortality.
Globally, reverse shoulder arthroplasty (RSA) has moved away from the Grammont design to modern prosthesis designs. The purpose of this 2-part study was to systematically review each of the most ...common complications of RSA, limiting each search to publications in 2010 or later. In this part (part I), we examined (1) scapular notching (SN), (2) periprosthetic infection (PJI), (3) mechanical failure (glenoid or humeral component), and (4) neurologic injury (NI).
Four separate PubMed database searches were performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Overall, 113 studies on SN, 62 on PJI, 34 on mechanical failure, and 48 on NI were included in our reviews. Univariate analysis was performed with the χ2 or Fisher exact test.
The Grammont design had a higher SN rate vs. all other designs combined (42.5% vs. 12.3%, P < .001). The onlay humeral design had a lower rate than the lateralized glenoid design (10.5% vs. 14.8%, P < .001). The PJI rate was 2.4% for primary RSA and 2.6% for revision RSA. The incidence of glenoid and humeral component loosening was 2.3% and 1.4%, respectively. The Grammont design had an increased NI rate vs. all other designs combined (0.9% vs. 0.1%, P = .04).
Focused systematic reviews of the recent literature with a large volume of RSAs demonstrate that with the use of non-Grammont modern prosthesis designs, complications including SN, PJI, glenoid component loosening, and NI are significantly reduced compared with previous studies. As the indications for RSA continue to expand, it is imperative to accurately track the rates and types of complications to justify its cost and increased indications.
Summary Background Bisphosphonates are thought to act through the osteoclast by changing bone microenvironment. Previous findings of adjuvant clodronate trials in different populations with operable ...breast cancer have been mixed. The National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-34 aims to ascertain whether oral clodronate can improve outcomes in women with primary breast cancer. Methods NSABP B-34 is a multicentre, randomised, double-blind, placebo-controlled study in 3323 women with stage 1–3 breast cancer. After surgery to remove the tumour, patients were stratified by age, axillary nodes, and oestrogen and progesterone receptor status and randomly assigned in a 1:1 ratio to either oral clodronate 1600 mg daily for 3 years (n=1662) or placebo (1661). The primary endpoint was disease-free survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00009945. Findings Median follow-up was 90·7 months (IQR 82·7–100·0) and 3311 patients had data for this period. Disease-free survival did not differ between groups (286 events in the clodronate group vs 312 in the placebo group; hazard ratio 0·91, 95% CI 0·78–1·07; p=0·27). Moreover, no differences were recorded for overall survival (0·84, 0·67–1·05; p=0·13), recurrence-free interval (0·83, 0·67–1·04; p=0·10), or bone metastasis-free interval (0·77, 0·55–1·07; p=0·12). Non-bone metastasis-free interval was slightly increased with clodronate (0·74, 0·55–1·00; p=0·047). Analyses in women age 50 years or older on study entry showed benefits of clodronate for recurrence-free interval (0·75, 0·57–0·99; p=0·045), bone metastasis-free interval (0·62, 0·40–0·95; p=0·027), and non-bone metastasis-free interval (0·63, 0·43–0·91; p=0·014), but not for overall survival (0·80, 0·61–1·04, p=0·094). Adherence to treatment at 3 years was 56% for the clodronate group and 60% for the placebo group. Grade 3 or higher liver dysfunction was noted in 23 of 1612 patients in the clodronate group and 12 of 1623 patients in the placebo group; grade 3–4 diarrhoea was noted in 28 patients in the clodronate group and in ten in the placebo group. There was one possible case of osteonecrosis of the jaw in the clodronate group. Interpretation Findings of NSABP B-34 suggest that bisphosphonates might have anticancer benefits for older postmenopausal women. A meta-analysis of adjuvant bisphosphonate trials is suggested before recommendations for use in non-osteoporotic postmenopausal women with primary breast cancer are made. Funding National Cancer Institute, Bayer Oy (formerly Schering Oy).
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