Motivation for participating in phase 1 vaccine trials: Comparison of an influenza and an Ebola randomized controlled trial

Introduction/Hypothesis

Recruitment of participants into phase 1 vaccine clinical trials can be challenging since these vaccines have not been used in humans and there is no perceived benefit to the participant. Occasionally, as was the case with a phase 1 clinical trial of an Ebola vaccine in Halifax, Canada, during the 2014–2016 West African Ebola virus outbreak, recruitment is less difficult. In this study, we explored the motivations of participants in two phase 1 vaccine trials that were concurrently enrolling at the same centre and compared the motivations of participants in a high-profile phase 1 Ebola vaccine trial to those in a less high-profile phase 1 adjuvanted seasonal influenza vaccine study.

Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

Academic Degrees and Clinical Practice Characteristics: The University of Washington Physician Assistant Program: 1969-2000

CONTEXT: The physician assistant profession has been moving toward requiring master's degrees for new practitioners, but some argue this could change the face of the discipline. PURPOSE: To see if there is an association between physician assistants' academic degrees and practice in primary care, in rural areas, and with the medically underserved. METHODS: Surveys were sent to 880 graduates of the first 32 University of Washington physician assistant classes through 2000. Respondents noted their academic degree at program entry and the highest degree attained at any time up to the time of survey. Relationships between practice characteristics and academic degree levels were tested by unadjusted odds ratios and logistic regression after controlling for year of graduation and sex. RESULTS: Of the 478 respondents, 54% worked in primary care, about 30% practiced in nonmetropolitan communities, and 42% reported providing care for the medically underserved. Respondents with no degree (33% of total at entry, 24% at survey) were significantly more likely than degree holders to work in primary care and nonmetropolitan areas. Respondents with no degree at program entry were significantly more likely, and those with no degree at the time of the survey were marginally more likely, to self-report work with the medically underserved. CONCLUSION: Respondents with no academic degree are significantly more likely to demonstrate a commitment to primary, rural, and underserved health care. These findings may inform the national debate about the impact of required advanced degrees on the practice patterns of nonphysician providers.     

Variations in length of stay and outcomes for six medical and surgical conditions in Massachusetts and California

OBJECTIVES.--To determine the extent to which interinstitutional variations in length of stay are explained by differences in patient characteristics and to determine whether patients in hospitals with shorter lengths of stay had worse outcomes. DESIGN.--We reviewed patients' medical records and surveyed patients between 3 and 12 months after hospital discharge using a questionnaire. SETTING.--Six teaching hospitals in California and Massachusetts. PATIENTS.--A cohort of 2484 selected patients who had been hospitalized for acute myocardial infarction or to rule out acute myocardial infarction, coronary artery bypass graft surgery, total hip replacement, cholecystectomy, or transurethral prostatectomy. Between 73% and 84% of the patients with each condition completed a follow-up questionnaire. OUTCOME MEASURES.--In-hospital complications, deaths, length of stay, functional status after hospital discharge, readmission, and patient satisfaction with hospital care were analyzed. RESULTS.--Significant interinstitutional differences in length of stay were noted for all conditions except rule-out acute myocardial infarction. Statistical adjustment for case-mix differences accounted for most of the interinstitutional differences in length of stay for total hip replacement but explained little of the differences in the other conditions. When we controlled statistically for other predictors, length of stay did not have a significant impact on deaths, functional status after hospital discharge, the probability of readmission, or patient satisfaction with hospital care. CONCLUSION.--More research is needed to determine the medical practices that are related to variations in lengths of stay. Routinely available outcome data may help preserve quality in the face of efforts to decrease costs by effecting more standardized practices of care.     

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

Do forceps biopsies truthfully reflect the nature of endoscopically uncovered polypoid lesions of the colon?

BACKGROUND: Total excision of colonic polyps is not always attainable and in some patients it is clinically contraindicated. Also, a resected polyp may be lost at any step between its endoscopic removal and its embedding in paraffin. The aim of this study was to compare the histological features of colonic polyps as analysed by the study of biopsy-forceps obtained samples with those assessed on scrutinizing the totally resected growths. PATIENTS AND METHODS: This prospective study included a cohort of 59 patients in whom, in the course of an elective colonoscopy, a total excision of a 6 mm-sized or larger polyp was called for. Sizeable biopsies were obtained by means of an Olympus Multibyte forceps prior to the total polypectomy. Subsequent to the study of the polypectomy specimens, the forceps biopsy samples were submitted for histological examination. The pathologists were blinded as to the source of the tissue they were studying. The diagnoses rendered by evaluating the biopsy samples and polypectomy specimens of each patient were contrasted with each other. RESULTS: Major discrepancies between the histological features of the fragments captured by the biopsy-forceps and the factual nature of the totally removed polyps were uncovered in 11 (18.6%) of 59 cases. Intriguingly, the grade of the tumours was underrated in all the 11 cases, as judged by contrasting the tentative diagnoses of the forceps-biopsies with the decisive diagnoses of the polypectomies. Importantly, 2 adenocarcinomas would have been missed by just looking at the forceps-retrieved sample. CONCLUSIONS: In our experience, a discordance of 18.6% is to be expected between the diagnoses rendered after examining forceps-biopsies of and totally excised colonic polyps. Nevertheless, it is advisable to procure biopsies prior to the excision of the growths, because on those occasions in which patients' growths cannot be removed or have not been retrieved for one reason or another, a small forceps-captured tissue sample correctly reflects the characteristics of the polyp in 81.4% of the cases. Finally, the biopsies may be discarded in the event that total removal was successful.     

Heightened risk of breast cancer following pregnancy: could lasting systemic immune alterations contribute?

The protective effect of having a first full-term pregnancy (FFTP) at a younger age on women's lifetime risk of breast cancer is well known. Less appreciated is the increased risk seen in the years immediately following pregnancy. This adverse effect is more pronounced and more prolonged in women with later age at FFTP. The mechanisms responsible for this increased risk are still poorly understood. In the present paper, we put forward the hypothesis that the marked peripheral immune changes induced by pregnancy may account for these effects. We highlight immune changes that characterize the unique immune state of pregnancy (a combination of cellular immunosuppression and enhanced inflammatory response), note the resemblance of these changes to cancer escape mechanisms, and discuss why such immune changes may be critical for the development of breast cancer following pregnancy. We further support this idea by initial findings from our own laboratory that the age at FFTP is negatively related to natural killer cell cytotoxicity many years later and propose possible models for the kinetics of the immune changes during and following pregnancy. The effect of age at FFTP on the immune function is currently understudied. Its potential relevance to the development of breast cancer stresses the need for further research.     

A case study in planning for public health education: the organ and tissue donation experience.

The chasm between the supply and demand of donated organs and tissues continues to grow despite widespread public awareness of transplantation and numerous efforts to educate the public about organ donation. It is fast becoming a significant public health problem in this country. The need for more effective public education is well documented in the literature on transplantation and is a primary objective of organizations in the transplant field. In response to this need, the Division of Organ Transplantation in the Health Resources and Services Administration of the Public Health Service initiated a project to examine the nature and scope of donation education initiatives throughout the country, to identify shortcomings, and to suggest ways the Federal Government could contribute to the effectiveness of public education in organ and tissue donation. The project resulted in the development of a protocol that also is applicable to other health education programs. Its major steps consisted of assessing the status of donation-related public education in the United States, identifying existing needs in donation education by applying principles learned from other public health education programs, and identifying roles that could be assumed to help strengthen the American public''s commitment to organ and tissue donation. These roles, which could be adopted by an transplant-related organization, were as broker of knowledge, producer of educational strategies, energizer through communications research, and catalyst by bringing together other groups. This approach to needs assessment and planning may provide useful insights both for those concerned with transplants and for professionals conducting education campaigns related to other public health issues.