Recruitment and baseline epidemiologic profile of participants in the first phase 3 HIV vaccine efficacy trial

OBJECTIVE: To describe recruitment and baseline epidemiologic characteristics of volunteers in the first phase 3 placebo-controlled trial of a recombinant gp120 HIV vaccine (AIDSVAX B/B). METHODS: Volunteers were gay/bisexual men or women at risk for sexually transmitted HIV infection. Recruitment strategies, demographics, and risk factors were assessed. HIV status was determined by standard HIV-1 antibody assays. Seronegative/viremic HIV infection at enrollment was determined using the HIV-1 nucleic acid test. RESULTS: From June 1998 through October 1999, 5417 of 7185 volunteers screened were enrolled at 61 sites in the United States, Canada, and The Netherlands. Successful recruitment methods included distribution of study information at gay venues, advertising and media coverage, and referrals from volunteers. Most volunteers were altruistically motivated, men (98%), young (median, 36 years), white (83%), well educated (61% college education or more), and at high risk for HIV during the 6 months before enrollment. At baseline, 14 were HIV infected (12 were seronegative but viremic; 2 were seropositive and viremic). CONCLUSION: Men and women at high risk for sexually transmitted HIV infection were successfully recruited for the first phase 3 HIV vaccine efficacy trial. Knowledge of recruitment and baseline epidemiologic characteristics of participants in this trial will provide valuable guidance for designing and conducting future trials.     

Asthma/Emphysema Complication of Electroconvulsive Therapy: A Case Study

The authors describe an elderly depressed patient with asthma/emphysema who developed severe postictal bronchospasm immediately after one electroconvulsive treatment. Possible problems and considerations in treating such patients are discussed.     

Does your hospital need a robot or a management trainer?

Executives of small hospitals and home health services have heard that this is the Age of Computers, Telecommunications, Robotics, and Gene Engineering, and they wonder if their organizations might benefit from the high technology and advanced management tools employed by big corporations and “leading edge” hospitals. But they are too tired and busy to greatly expand their technical/managerial expertise, especially since there are so many choices among possible innovations, ranging from robotics to management training, each choice demanding different new expertise, and each requiring an investment of time and energy. We helped several health care executives to identify their options for innovation. We offered a scoring scheme to sort out the innovation options (a simple but effective way to decide what innovation would be “right” for their organization), and a simple, “back of the envelope” tutorial on robotics in health care. The principle is to allow the administrators to make a quick evaluation of the paths they might wish to travel. Our point here is that for every “natural-born” innovator, there must be dozens of interested but uncommitted persons who need some gentle, simple help. To the extent that the diffusion of medical systems depends on a mass market, these fence-sitters must receive help and guidance.     

Does hospital competition lead to medical equipment expansion? Evidence on the medical arms race

Health Care Management Science - With the implementation of a series of pro-competition policies in China, the hospital market competition has been intensified dramatically over the past decade....     

Baseline Assessment of Circulating MicroRNAs Near Diagnosis of Type 1 Diabetes Predicts Future Stimulated Insulin Secretion

Type 1 diabetes is an autoimmune disease resulting in severely impaired insulin secretion. We investigated whether circulating microRNAs (miRNAs) are associated with residual insulin secretion at diagnosis and predict the severity of its future decline. We studied 53 newly diagnosed subjects enrolled in placebo groups of TrialNet clinical trials. We measured serum levels of 2,083 miRNAs, using RNA sequencing technology, in fasting samples from the baseline visit (<100 days from diagnosis), during which residual insulin secretion was measured with a mixed meal tolerance test (MMTT). Area under the curve (AUC) C-peptide and peak C-peptide were stratified by quartiles of expression of 31 miRNAs. After adjustment for baseline C-peptide, age, BMI, and sex, baseline levels of miR-3187-3p, miR-4302, and the miRNA combination of miR-3187-3p/miR-103a-3p predicted differences in MMTT C-peptide AUC/peak levels at the 12-month visit; the combination miR-3187-3p/miR-4723-5p predicted proportions of subjects above/below the 200 pmol/L clinical trial eligibility threshold at the 12-month visit. Thus, miRNA assessment at baseline identifies associations with C-peptide and stratifies subjects for future severity of C-peptide loss after 1 year. We suggest that miRNAs may be useful in predicting future C-peptide decline for improved subject stratification in clinical trials.     

Small animal jet injection technique results in enhanced immunogenicity of hantavirus DNA vaccines

DNA vaccine evaluation in small animals is hampered by low immunogenicity when the vaccines are delivered using a needle and syringe. To overcome this technical hurdle we tested the possibility that a device developed for human intradermal medicine delivery might be adapted to successfully deliver a DNA vaccine to small animals. Disposable syringe jet injection (DSJI) does not currently exist for small animals. However, a commercialized, human intradermal device used to to administer medicines to the human dermis in a 0.1 mL volume was evaluated in Syrian hamsters. Here, we found that hantavirus DNA vaccines administered to hamsters using DSJI were substantially more immunogenic than the same vaccines delivered by needle/syringe or particle mediated epidermal delivery (gene gun) vaccination. By adjusting how the device was used we could deliver vaccine to either subcutaneous tissues, or through the skin into the muscle. RNA and/or antigen expression was detected in epidermal, subepidermal and fibroblast cells. We directly compared six optimized and non-optimized hantavirus DNA vaccines in hamsters. Optimization, including codon-usage and mRNA stability, did not necessarily result in increased immunogenicity for all vaccines tested; however, optimization of the Andes virus (ANDV) DNA vaccine protected vaccinated hamsters from lethal disease. This is the first time active vaccination with an ANDV DNA vaccine has shown protective efficacy in the hamster model. The adaptation of a human intradermal jet injection device for use as a method of subcutaneous and intramuscular jet injection of DNA vaccines will advance the development of nucleic acid based medical countermeasures for diseases modeled in hamsters.     

A prospective study of the accuracy of preoperative computed tomographic staging of patients with biopsy-proven rectal carcinoma

From June 1983 to January 1986, 91 patients with biopsy-proven adenocarcinoma of the rectum had computed tomographic scans of the pelvis performed before treatment as part of a "sandwich" radiotherapy-surgery regimen. Two experienced diagnostic radiologists performed locoregional staging of all scans according to the University of California at San Francisco criteria; one of these radiologists repeated this staging at a later time to test the reproducibility of a single observer. Staging was performed without the use of any other radiographic studies or of any clinical information except the patients' age, sex, and the diagnosis of rectal carcinoma, to test the value of computed tomographic scans alone for staging. Agreement between the two stagings performed by the first observer was 51 percent, and interobserver agreement was only 37 percent. Agreement with Dukes' staging was only 33 percent. Therefore, preoperative pelvic computed tomographic scanning of primary rectal adenocarcinoma should not be relied upon for staging or for the selection of patients for treatment options.