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.

Is the driver drunk? Oculomotor sobriety testing

Recently a new test involving observation of ocular pursuit movements, end-point nystagmus and angle of lateral deviation at which nystagmoid movements begin has been used by law enforcement agencies to determine the blood alcohol level of suspected drunk drivers. When properly administered and scored, this test can correctly identify approximately 80% of drivers with alcohol levels of 0.10% or greater. The test is more accurate than the traditional coordination or mental computation tests previously used, but questions may be raised about the use of the test with suspects who have ocular problems such as high refractive errors, chronic nystagmus, etc.     

Are ADDH and ADHD the same or different?

To assess the relationship between the DSM-III criteria for attention deficit disorder with hyperactivity (ADDH) and the DSM-III-R criteria for attention-deficit hyperactivity disorder (ADHD), children from an inner city parochial school were evaluated using a 30-item teacher questionnaire consisting of the DMS-III and DSM-III-R criteria for these disorders, the revised Conners Parent and Teacher Questionnaires, and a continuous performance test. Diagnostic groups were established based on teacher ratings of the DSM items and evaluated in relation to the rating scale data and continuous performance test. While children who were identified by teachers as having ADDH almost always satisfied the criteria for ADHD, a new group of children who were hyperactive and impulsive but less clearly inattentive also met the criteria for ADHD. Implications of the change in diagnostic criteria are discussed.     

Work-related injuries in minors

Since 1938, federal child labor laws have restricted employment of persons under 18 years old, in part to protect them from hazardous occupations. Workers' compensation claims reported to the Supplementary Data System of the Bureau of Labor Statistics were examined to define the current status of occupational injuries among minors. Data tapes from 1980 to 1983 were searched to identify all current claims for injuries and illnesses occurring in 1980 in persons under age 18. Injury rates were calculated using information about employment in 1979 available from the 1980 census. In the 24 states included in this study, 23,823 claims were reported for persons less than 18 years old. Of these claims, approximately 10% were from persons under age 16. Rates of injuries in 16- and 17 year olds were 12.6 per 100 full-time male workers and 6.6 per 100 full-time female workers. Serious injuries included fractures, dislocations, and amputations, accounting for 5.8%, 0.7%, and 0.6% of cases, respectively. California, the only state that coded whether injuries resulted in fatalities, reported 12 deaths in this age group. Machines and vehicles, many of which are restricted under child labor laws, accounted for 8.3% and 5.8% of claims. These data suggest that persons under age 18 years are not adequately protected from occupational injury. Further attention and, possibly, new preventive strategies are needed.     

Suppurative corneal ulceration in Bangladesh

Suppurative keratitis is an important preventable cause of blindness, particularly in the developing world. This study analyses 142 cases of suppurative keratitis referred to Chittagong Eye Infirmary, Bangladesh. Some 53.5% of cases were bacterial and 35.9% were fungal. The five most common pathogens were: Pseudomonas sp. 24%, Streptococcus pneumoniae 17%, Aspergillus sp. 13%, Fusarium sp. 7% and Curvularia sp. 6%. Gram stain and culture results were consistent in 62.6% of cases. Previous antibiotic treatment was a significant factor for failure of culture isolation and less so for Gram stain failure. On Gram stain, 55.9% of pseudomonal cases were missed, but only 2% of fungal cases were missed. Over all, Gram stain had a sensitivity of 62% and positive predictive value of 84% for bacterial cases, and 98% and 94% for fungal cases, respectively. Fungal ulcers were typically filamentous, but an antecedent history of trauma was not common. The most frequent injury was due to rice grains, but the inoculum appeared to be introduced during eye washing with contaminated water. Pseudomonal ulcers occurred most frequently in the monsoon season, and Fusarium cases were seen only in the hot, dry season.     

Nonheme iron in sickle erythrocyte membranes: association with phospholipids and potential role in lipid peroxidation

Previous studies documented the abnormal association of heme and heme proteins with the sickle RBC membrane. We have now examined RBC ghosts and inside-out membranes (IOM) for the presence of nonheme iron as detected by its formation of a colored complex with ferrozine. Sickle ghosts have 33.8 +/- 18.2 nmol nonheme iron/mg membrane protein, and sickle IOM have 4.3 +/- 3.0 nmol/mg. In contrast, normal RBC ghosts and IOM have no detectable nonheme iron. The combination of heme and nonheme iron in sickle IOM averages nine times the amount of membrane- associated iron in normal IOM. Kinetics of the ferrozine reaction show that some of this nonheme iron on IOM reacts slowly and is probably in the form of ferritin, but most (72% +/- 18%) reacts rapidly and is in the form of some other biologic chelate. The latter iron compartment is removed by deferoxamine and by treatment of IOM with phospholipase D, which suggests that it represents an abnormal association of iron with polar head groups of aminophospholipids. The biologic feasibility of such a chelate was demonstrated by using an admixture of iron with model liposomes. Even in the presence of tenfold excess adenosine diphosphate, iron partitions readily into phosphatidylserine liposomes; there is no detectable association with phosphatidylcholine liposomes. To examine the bioavailability of membrane iron, we admixed membranes and t-butylhydroperoxide and found that sickle membranes show a tenfold greater peroxidation response than do normal membranes. This is not due simply to a deficiency of vitamin E, and this is profoundly inhibited by deferoxamine. Thus, while thiol oxidation in sickle membranes previously was shown to correlate with heme iron, the present data suggest that lipid peroxidation is related to nonheme iron. In control studies, we did not find this pathologic association of nonferritin, nonheme iron with IOM prepared from sickle trait, high-reticulocyte, postsplenectomy, or iron-overloaded individuals. These data provide additional support for the concept that iron decompartmentalization is a characteristic of sickle RBCs.     

A groundless hypothesis, megaloblastic madness, and the founding of Duke University.

In a recent issue of Medical Hypotheses, Dr H L Newbold repeats the assertion that the cause of James B Duke's death in 1925 was pernicious anemia. Dr Newbold postulates that Mr Duke was neurologically impaired as a result of vitamin B-12 deficiency and that he suffered from depression. In an attempt to relieve this depression, Dr Newbold argues that James B Duke donated the money necessary to found Duke University. Had he been properly treated for pernicious anemia, James Duke might have not been depressed nor made his donation. The historical record does not substantiate this hypothesis. Dr George Minot, Novel Laureate for his work on pernicious anemia, was a consultant to Mr Duke's physicians, and felt that the patient did not have pernicious anemia. There is no independently verifiable evidence to demonstrate that Mr Duke ever suffered from depression. Duke made his first donations to Trinity College, later named Duke University, in 1900--25 years before his death. The available data discounts the hypothesis that depression related to pernicious anemia played any role in the founding of Duke University.