Sociodemographic,clinical, and psychological factors associated with attrition in a prospective study of cardiovascular prevention: the Heart Strategies Concentrating on Risk Evaluation study

PurposeTo identify factors associated with attrition in a longitudinal study of cardiovascular prevention.MethodsDemographic, clinical, and psychosocial variables potentially associated with attrition were investigated in 1841 subjects enrolled in the southwestern Pennsylvania Heart Strategies Concentrating on Risk Evaluation study. Attrition was defined as study withdrawal, loss to follow-up, or missing 50% or more of study visits.ResultsOver 4 years of follow-up, 291 subjects (15.8%) met criteria for attrition. In multivariable regression models, factors that were independently associated with attrition were black race (odds ratio [OR], 2.21; 95% confidence interval [CI], 1.55–3.16; P < .001), younger age (OR per 5-year increment, 0.88; 95% CI, 0.79–0.99; P < .05), male gender (OR, 1.79; 95% CI, 1.27–2.54; P < .05), no health insurance (OR, 2.04; 95% CI, 1.20–3.47; P < .05), obesity (OR, 1.80; 95% CI, 1.07–3.02; P < .05), CES-D depression score 16 or higher (OR, 2.02; 95% CI, 1.29–3.19; P < .05), and higher ongoing life events questionnaire score (OR, 1.09; 95% CI, 1.04–1.13; P < .001). Having a spouse/partner participating in the study was associated with lower odds of attrition (OR, 0.60; 95% CI, 0.37–0.97; P < .05). A synergistic interaction was identified between black race and depression.ConclusionsAttrition over 4 years was influenced by sociodemographic, clinical, and psychological factors that can be readily identified at study entry. Recruitment and retention strategies targeting these factors may improve participant follow-up in longitudinal cardiovascular prevention studies.     

Ischemic bowel disease

Twenty-five cases with ischemic bowel disease seen over a period of 4 years are presented. Of these, 20 cases presented with acute symptoms and five with chronic symptoms. In the majority of patients, the diagnosis was established at operation and on histopathology. Occlusive disease of the superior mesenteric artery was the commonest cause of acute ischemia. Non-occlusive ischemia was not observed in any case. All the patients were treated by resection and anastomosis of the involved bowel. Vascular procedures were not carried out in any. No planned second-look procedures were carried out. Of the 20 acute cases, eight patients died and three developed complications. One chronic case died and there were no other complications in this group. We suggest that ischemic bowel disease should be considered while dealing with cases presenting as acute abdomen or with chronic abdominal pain.     

The Fortune 500 on health care. Most top executives want to set the market free

The nature of the American health care marketplace is in a state of flux and refinement. The recent attempt by the federal government to change the health care system has brought these issues to the forefront of public and private discourse. This research endeavor examines if these discussions influenced health care decisions by some of the nation's most influential decision makers.     

Effect of impaired renal function and haemodialysis on the pharmacokinetics of aprepitant

BACKGROUND: The neurokinin NK(1)-receptor antagonist aprepitant has demonstrated efficacy in preventing highly emetogenic chemotherapy-induced nausea and vomiting. OBJECTIVE: The objective of the present study was to investigate the effects of impaired renal function on the pharmacokinetics and safety of aprepitant. SUBJECTS AND METHODS: A total of 32 patients and healthy subjects were evaluated in this open-label, two-part study. Pharmacokinetic parameters after a single oral dose of aprepitant 240 mg were measured in eight patients with end-stage renal disease (ESRD) requiring haemodialysis, eight patients with severe renal insufficiency (SRI [24-hour creatinine clearance <30 mL/min/1.73 m(2)]) and 16 healthy and age-, sex- and weight-matched subjects (controls). RESULTS: In ESRD patients, the area under the plasma concentration-time curve (AUC) from 0 to 48 hours (AUC(48)) for aprepitant was on average approximately 36% lower than that observed in control subjects (ratio [ESRD patients/healthy controls] of geometric means = 0.64), but the 90% confidence interval 0.52, 0.78 for the ratio of true mean AUC(48) fell within the predefined target interval of 0.5, 2.0. Also in ESRD patients, there was no statistically or clinically significant difference in unbound aprepitant AUC (which may be more clinically relevant than total aprepitant AUC) when compared with healthy control subjects. Aprepitant pharmacokinetic parameters in ESRD patients were clinically similar when haemodialysis was initiated at 4 hours or 48 hours after aprepitant administration. In SRI patients, the ratio (SRI patients/healthy controls) of aprepitant AUC from zero to infinity (AUC(infinity)) geometric mean value was 0.79 with a 90% confidence interval of 0.56, 1.10. On average, in SRI patients the principal aprepitant pharmacokinetic parameters (AUC(infinity), initial maximum plasma concentration [C(max)], time to initial C(max), and apparent elimination half-life) were not statistically different from those obtained in healthy control subjects. Aprepitant was generally well tolerated in both ESRD and SRI patients. CONCLUSION: The results of this study demonstrate that ESRD, haemodialysis and SRI have no clinically meaningful effect on aprepitant pharmacokinetics. Therefore, no dosage adjustment of aprepitant is warranted in SRI or ESRD patients.     

ISSLS PRIZE IN CLINICAL SCIENCE 2017: Is infection the possible initiator of disc disease? An insight from proteomic analysis

Study design

Proteomic and 16S rDNA analysis of disc tissues obtained in vivo.

Objective

To address the controversy of infection as an aetiology for disc disorders through protein profiling.

Summary of background data

There is raging controversy over the presence of bacteria in human lumbar discs in vivo, and if they represent contamination or infection. Proteomics can provide valuable insight by identifying proteins signifying bacterial presence and, also host defence response proteins (HDRPs), which will confirm infection.

Methods

22 discs (15-disc herniations (DH), 5-degenerate (DD), 2-normal in MRI (NM) were harvested intraoperatively and immediately snap frozen. Samples were pooled into three groups and proteins extracted were analysed with liquid chromatography-tandem mass spectrometry (LC–MS/MS). Post identification, data analysis was performed using Uniprotdb, Pantherdb, Proteome discoverer and STRING network. Authentication for bacterial presence was performed by PCR amplification of 16S rDNA.

Results

LC–MS/MS analysis using Orbitrap showed 1103 proteins in DH group, compared to 394 in NM and 564 in DD. 73 bacterial specific proteins were identified (56 specific for Propionibacterium acnes; 17 for Staphylococcus epidermidis). In addition, 67 infection-specific HDRPs, unique or upregulated, such as Defensin, Lysozyme, Dermcidin, Cathepsin-G, Prolactin-Induced Protein, and Phospholipase-A2, were identified confirming presence of infection. Species-specific primers for P. acnes exhibited amplicons at 946 bp (16S rDNA) and 515 bp (Lipase) confirming presence of P. acnes in both NM discs, 11 of 15 DH discs, and all five DD discs. Bioinformatic search for protein–protein interactions (STRING) documented 169 proteins with close interactions (protein clustering co-efficient 0.7) between host response and degenerative proteins implying that infection may initiate degradation through Ubiquitin C.

Conclusion

Our study demonstrates bacterial specific proteins and host defence proteins to infection which strengthen the hypothesis of infection as a possible initiator of disc disease. These results can lead to a paradigm shift in our understanding and management of disc disorders.

     

Diagnostic stromal histomorphology in fibroepithelial breast lesions: a fresh perspective

Histopathologic parameters were studied in fibroepithelial breast lesions comprising of Fibroadenomas (FAs), Juvenile cellular fibroadenomas (JCFs) as well as benign, borderline and malignant phyllodes tumours (B/Bo/MPTs). H & E stained sections of 67 cases (25 ICFA, 5 Mixed FA, 10 PCFA, 12 JCF and 15 PT) were retrieved from archival material and the microscopic features of each lesion, reviewed by two independent observers. A diagnosis was arrived at by consensus. Diagnostic criteria were laid down for each of the above lesions based on a statistical analysis of data obtained from a previously drawn up semiquantitative grading system for various stromal histomorphologic parameters. An increasing grade of stromal cellularity, pleomorphism, overgrowth and mitotic index was observed, from the benign to the borderline and overtly malignant lesions included in the spectrum. A semiquantitative grading of relevant stromal histomorphologic variables was found to be of immense diagnostic significance in fibroepithelial breast lesions and served to elucidate cases falling into the diagnostic grey zones of the spectrum.