Suggested approaches for research protocols involving the potential for life-threatening reactions

These guidelines are intended to reduce the potential for serious or life-threatening reactions when clinical research is conducted. The following issues were addressed: identifying the risks involved in the research, providing adequate safeguards in the protocol design and during withholding of medication, anticipating risks, minimizing the chances for human error, providing resuscitative equipment sufficient to deal with the most serious anticipated life-threatening reactions, planning for medical support in case of a life-threatening emergency, and optimizing the use of medical personnel and expertise to handle emergency situations. The guidelines also discuss important general issues about protocol design and implementation and the human subject consent form, which should facilitate the approval of protocols by the governing institutional review board.The guidelines are not meant to be inflexible or applicable to all research situations. However, it is our hope that they will allow for clinical research to be conducted in a manner that affords the research subjects a high degree of protection from unnecessary and possibly fatal injuries.     

Sensitization to soybean hull allergens in subjects exposed to different levels of soybean dust inhalation in Argentina

BACKGROUND: Soybean hulls (SHs) have been identified as the source of aeroallergens responsible for soybean asthma outbreaks. However, the prevalence of sensitization to SH allergens in subjects from Argentina, a country where soybeans are produced, is unknown. OBJECTIVE: The purpose of this study was to determine the prevalence of sensitization to SH by in vivo and in vitro tests in subjects with asthma or allergic rhinitis and in control subjects from Argentina who have been exposed to different levels of soybean dust inhalation (SDI). METHODS: Exposure to SDI is defined as follows: (1) direct = occupational, (2) indirect = proximity to soybean fields or grain elevators, and (3) urban = urbanized areas without a known source of SDI. Two groups were studied. Group 1 consisted of 365 subjects with asthma or allergic rhinitis and group 2 (control group) of 50 healthy individuals. Subjects from both groups were classified according to their exposure to SDI. All subjects completed standard questionnaires. Prick skin tests (STs) with an SH extract and with common allergens were performed on all subjects. Specific IgE and IgG4 to SH were measured in sera of 51 of 56 subjects from group 1 who had a positive ST to SH and in all sera from group 2. RESULTS: Fifty-six (15.3%) subjects from group 1 and no subjects from group 2 had a positive ST to SH (wheal SH/wheal histamine >/=0.5). In group 1, positive STs to SH were 38.7%, 20.3%, and 8.2% in subjects with direct, indirect, and urban exposures, respectively (P <.001). Monosensitization to SH is absent in all subjects from group 1. The percent of subjects with positive STs to mites, pollen, and molds was highest in those with a positive ST to SH versus those with a negative ST to SH (P <.01). Asthmatic patients with a positive ST to SH, compared with those exclusively sensitized to mites, had a higher frequency of daily or weekly symptoms (59.4% vs 25.7%, respectively, P <.001) and a higher percent of glucocorticoid dependence (52.8% vs 34%, respectively, P <.01). Percent positive IgE in group 1 and group 2 were 39.2% and 10% (P <.001) and percents positive IgG4 are 27.4% and 12%, respectively (not significant). In subjects from group 1 and group 2 with direct exposure percents positive IgE are 58.3% and 13.3% (P < .001) and percents positive IgG4 were 75% and 20%, respectively (P < .02). IgG4 in group 1 was significantly higher in subjects with direct exposure compared with subjects with indirect or urban exposure. CONCLUSION: This study demonstrated that there was (1) a high prevalence of sensitivity to SH in subjects with asthma or allergic rhinitis from Argentina and (2) an association between sensitivity to SH and severity of asthma and level of exposure to SDI.     

A multicenter study on skin-test reactivity of human volunteers to venom as compared with whole body Hymenoptera antigens

Twenty-four control and 104 stinging insect—allergic patients were tested in this multicenter study, which compared the utility of individual venom and whole body extract (WBE) preparations for diagnosis. This study indicates that venom skin testing is more specific and more reliable than is testing with WBE. There was a high rate of WBE skin-test reactivity among controls. False-positive skin testing with venom was not a problem at concentrations of 1 μg/ml or less. Only one mild and easily treated adverse reaction occurred in this study.     

The changing face of reoperative parathyroidectomy: a single-centre comparison of 147 parathyroid reoperations

IntroductionReoperative parathyroidectomy for persistent and recurrent primary hyperparathyroidism is dependent on radiology. This study aimed to compare outcomes in reoperative parathyroidectomy at a single centre using a combination of traditional and newer imaging studies.Materials and methodsRetrospective case note review of all reoperative parathyroidectomies for persistent and recurrent primary hyperparathyroidism over five years (June 2014 to June 2019; group A). Imaging modalities used and their positive predictive value, complications and cure rates were compared with a published dataset spanning the preceding nine years (group B).ResultsFrom over 2000 parathyroidectomies, 147 were reoperations (101 in group A and 46 in group B). Age and sex ratios were similar (56 vs 62 years; 77% vs 72% female). Ultrasound use remains high and shows better positive predictive value (76% vs 57 %). 99mTc-sestamibi use has declined (79% vs 91%) but the positive predictive value has improved (74% vs 53%). 4DCT use has almost doubled (61% vs 37%) with better positive predictive value (88% vs 75%). 18F-fluorocholine positron emission tomography-computed tomography and ultrasound-guided fine-needle aspiration for parathyroid hormone are novel modalities only available for group A. Both carried a positive predictive value of 100%. Venous sampling with or without angiography use has decreased (35% vs 39%) but maintains a high positive predictive value (86% vs 91%). Cure rates were similar (96% vs 100%). Group A had 5% permanent hypoparathyroidism, 1% permanent vocal cord palsy and 1% haematoma requiring reoperation. No complications for group B.ConclusionOptimal imaging is key to good cure rates in reoperative parathyroidectomy. High-quality, non-interventional imaging techniques have produced a shift in the preoperative algorithm without compromising outcomes.     

Potential significance of airborne fiber dimensions measured in the U.S. refractory ceramic fiber manufacturing industry.

BACKGROUND: To determine dimensions of airborne fibers in the U.S. refractory ceramic fiber (RCF) manufacturing industry, fibers collected through personal air sampling for employees at RCF manufacturing and processing operations have been measured. METHODS: Data were derived from transmission electron microscopy analyses of 118 air samples collected over a 20-year period. RESULTS: Characteristics of sized fibers include: diameter measurements of <60; 0.19 to 1.0 micron, m of which 75% are less than 0.6 micron and length ranging from < 0.6 to > 20 micron, with 68% of fibers between 2.4 and 20 micron. CONCLUSIONS: Exposures in RCF manufacturing include airborne fibers with dimensions (diameter < 0.1-0.4 micron, length < 10 micron) historically associated with biological effects in pleural tissues. Air sampling data and a review of studies relating fiber size to pleural effects in animals and humans support the belief that information on fiber dimensions is essential for studies with synthetic vitreous fibers.