Drug-induced thrombocytopenia is associated with increased binding of IgG to platelets both in vivo and in vitro

Thrombocytopenia is a common serious adverse effect of drug treatment. A variety of in vitro diagnostic techniques to confirm the diagnosis are available, but the majority lack sufficient sensitivity to detect all cases of drug-induced thrombocytopenia. We studied 19 patients with suspected drug-induced thrombocytopenia and demonstrated that platelet- associated IgG (PAIgG) was elevated in all at the time of thrombocytopenia, and PAIgG returned to normal levels as the thrombocytopenia resolved. In the majority of patients, the platelet count rapidly returned to normal after the drug was discontinued; however, in six patients, the thrombocytopenia persisted well beyond the period of time that the offending drug would be expected to be cleared from the blood. In 13 patients, serum obtained after recovery was used to identify the drug responsible for the thrombocytopenia in an in vitro assay. In all cases, the addition of the drug historically associated with the thrombocytopenic episode was associated with an increased binding of IgG to control platelets. For uncertain reasons, the concentration of drug required to increase the in vitro binding of IgG to test platelets was often more than the concentration usually achieved in vivo. Wider application of these techniques may provide better understanding of the clinical characteristics and mechanisms responsible for drug-induce thrombocytopenia.     

Test–retest repeatability of [18F]Flortaucipir PET in Alzheimer’s disease and cognitively normal individuals

The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [¹⁸F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [¹⁸F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr_80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr_80–100 and SUVr_110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods.     

Assuring the quality of intravenous admixture programs.

Several aspects of quality assurance (QA) methods in i.v. admixture programs are discussed, and a basic framework for developing QA programs for admixture services is presented. The objective of QA is to insure that admixture products: (1) are therapeutically and pharmaceutically appropriate to the patient; (2) are free from microbial and pyrogenic contaminants; (3) are free from undesirable levels of particulate or toxic contaminants; (4) contain drugs in correct amounts; and (5) are labeled, stored and distributed under principles of good drug control. Three types of QA criteria bases which may be used as indicators of quality are discussed (resources, facilities and organization; required procedures; end-products or results). Because end-product monitoring has certain limitations in the admixture setting, QA must rely heavily on procedure-centered review methods. General guidelines for developing QA programs are outlined. Adherence to procedure is the key to assuring the quality of admixture products. In developing a QA program, the highest priority should be given to the education and training of admixture personnel, particularly with respect to aseptic technique and pharmaceutical calculations.     

Colposcopic genital findings in prepubertal girls assessed for sexual abuse

After the introduction of the colposcope for the examination of children suspected of being sexually abused in Leeds, a study was undertaken to describe the findings in detail. A total of 109 consecutive prepubertal girls, mean age 70.4 months were assessed including colposcopic genital and anal examination, and peer group review of reports and photographs. Fifty nine children had signs consistent with blunt force penetrating trauma (hymenal transection/major notch, scar, or hymenal attenuation). Transections were encountered most commonly at 6 o'clock (directly posterior). In 46 the hymenal orifice was gaping with thigh abduction only and in 47 the hymenal orifice transverse diameter was greater than 4 mm on labial separation. Overall, physical findings were commonly present and in only two cases were no signs recorded. Non-specific and frequent findings included patterns of labial and introital reddening. Supportive hymenal signs including swelling, rounding of edge, thickening, distortion, and loss of symmetry were common. Labial fusion was present in 20. Urethral dilatation with labial separation was noted in 14. Physical findings including normality are consistent with abuse and even minor anogenital signs as well as negative findings should be documented. Colposcopy and photography are valuable tools in peer review, teaching, and case management.     

Service systems integration and outcomes for mentally ill homeless persons in the ACCESS program. Access to Community Care and Effective Services and Supports

OBJECTIVE: The authors evaluated the second of the two core questions around which the ACCESS (Access to Community Care and Effective Services and Supports) evaluation was designed: Does better integration of service systems improve the treatment outcomes of homeless persons with severe mental illness? METHODS: The ACCESS program provided technical support and about $250,000 a year for four years to nine sites to implement strategies to promote systems integration. These sites, along with nine comparison sites, also received funds to support outreach and assertive community treatment programs to assist 100 clients a year at each site. Outcome data were obtained at baseline and three and 12 months later from 7,055 clients across four annual cohorts at all sites. RESULTS: Clients at all sites demonstrated improvement in outcome measures. However, the clients at the experimental sites showed no greater improvement on measures of mental health or housing outcomes across the four cohorts than those at the comparison sites. More extensive implementation of systems integration strategies was unrelated to these outcomes. However, clients of sites that became more integrated, regardless of the degree of implementation or whether the sites were experimental sites or comparison sites, had progressively better housing outcomes. CONCLUSIONS: Interventions designed to increase the level of systems integration in the ACCESS demonstration did not result in better client outcomes.