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.     

The requirement for platelets in allergen-induced late asthmatic airway obstruction. Eosinophil infiltration and heightened airway responsiveness in allergic rabbits

In these studies, we have used an allergic rabbit model to investigate the role of platelets in the late asthmatic response (LAR) by depleting platelets with a guinea pig antirabbit platelet antiserum (APAS). Allergen exposure of immunized rabbits pretreated with normal guinea pig serum (NGPS) to serve as a control resulted in an early- and late-phase obstructive airway response that persisted for 6 h. When the immunized animals were pretreated with APAS, the magnitude of the LAR in terms of dynamic compliance was reduced by 86.2% (p less than 0.03), but there was no difference in the early response curve. Allergen challenge of animals treated with NGPS resulted in an increased bronchial responsiveness to inhaled histamine: PD50 Cdyn geometric mean +/- SEM before, 2.36 mg/ml (3.43-1.64); after, 0.60 mg/ml (0.67-0.54) (p less than 0.01). PD50 RL before, 1.78 mg/ml (2.4-1.32); after, 0.58 mg/ml (0.81-0.47) (p less than 0.05). In contrast, when animals were treated with APAS, there was a significant inhibition of allergen-induced airway hyperresponsiveness to inhaled histamine: PD50 Cdyn geometric mean +/- SEM before, 1.42 mg/ml (2.06-0.98); after, 1.10 mg/ml (1.41-0.86) (p less than 0.4). PD50 RL before, 1.62 mg/ml (2.22-1.39); after, 1.05 mg/ml (1.35-0.82) (p greater than 0.4). Analysis of bronchoalveolar lavage fluid revealed an increase in the number of neutrophils and eosinophils after allergen exposure in control animals (p less than 0.01). However, in animals rendered thrombocytopenic, the number of eosinophils, but not neutrophils, was significantly reduced (p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)     

T2 values in the human brain: comparison with quantitative assays of iron and ferritin

Magnetic resonance (MR) imaging with a whole-body imager was performed in 10 fresh, unfixed whole human brains selected randomly from cadavers. All subjects were neurologically intact before death. T2 time constants were measured within the caudate nucleus, putamen, globus pallidus, cortical gray matter, subcortical white matter, and optic radiation. These regions were then excised, and T2 values were measured again with a 1.5-T MR spectrometer. Quantitative assays of iron, ferritin, and protein from these areas were then performed. Iron concentration varied significantly among brain regions, whereas ferritin and protein concentrations were constant among brain regions and among individuals. Neither iron nor ferritin concentration showed any consistent correlation with T2 values. Histologic examination of brain micro-sections with iron- and ferritin-specific stains of demonstrated poor correlation with biochemical assays of ferritin and iron concentrations. Results indicate that T2 values correlate poorly with iron and ferritin concentrations found in neurologically intact brains.     

Self-care as a professional imperative: physician burnout,depression, and suicide

Purpose

Burnout has been identified in approximately half of all practicing physicians, including anesthesiologists. In this narrative review, the relationship between burnout, depression, and suicide is explored, with particular attention to the anesthesiologist. Throughout this review, we highlight our professional imperative regarding this epidemic.

Source

The authors searched the existing English language literature via PubMed from 1986 until present using the search terms physician burnout, depression, and suicide, with particular attention to studies regarding anesthesiologists and strategies to address these problems.

Principal findings

Burnout and depression have increased among physicians, while the rate of suicide has remained relatively the same. There are many factors associated with burnout and depression as well as many causes. Certain individual factors include sex, amount of social support, and mental health history. Systems factors that play a role in burnout and depression include work compression, demands of electronic health records, production pressure, and lack of control over one’s professional life. Medical license applications include questions that reinforce the stigma of psychological stresses and discourage physicians from seeking appropriate care.

Conclusion

The concept of physician well-being is multidimensional and includes factors related to each physician as an individual as well as to the working environment. Anesthesiologists must actively engage in self-care. Anesthesiology practices and healthcare organizations should evaluate the balance between demands they place on physicians and the resources provided to sustain an engaged, productive, and satisfied physician workforce. National efforts must be rallied to support physicians seeking help for physical and psychological health problems.

     

Selecting the best and brightest: A comparison of residency match processes in the United States and Canada

BACKGROUND:

Selecting candidates for plastic surgery residency training remains a challenge. In the United States, academic measures (United States Medical Licensing Exam Step I scores, medical school class rank and publications) are used as primary criteria for candidate selection for residency. In contrast, Canadian medical education de-emphasizes academic measures by using a pass-fail grading system. As a result, choosing residents from many qualified applicants may pose a challenge for Canadian programs without objective measures of academic success.

METHODS:

A 25-question online survey was distributed to program directors of Canadian plastic surgery residency-training programs. Program directors commented on number of yearly residents and applicants; application sections (ranked in importance using a Likert scale); interview invitation and rank-order list determination; and their satisfaction with the selection process.

RESULTS:

Ten Canadian plastic surgery program directors responded (90.9% response rate). The most important application components determining invitation to interview were letters of reference from a plastic surgeon (mean importance of 5.0 on the Likert scale), clinical electives in plastic surgery (mean 4.6) and electives with their program (mean 4.5). Applicants invited for interview were assessed on the quality of their responses to questions, maturity and personality. The majority of program directors agreed that a clinical elective with their program was important for consideration on their rank-order list. Program directors were neutral on their satisfaction with the selection process.

CONCLUSION:

Canadian plastic surgery residency programs emphasize clinical electives with their program and letters of reference from colleagues when selecting applicants for interviews. In contrast to their American counterparts, Canadian program directors rely on clinical interactions with prospective residents in the absence of objective academic measures.     

Process Redesign to Improve First Case Surgical Starts in an Academic Institution

Purpose: On time start of the first surgical case improves operating room (OR) utilization, physician, and patient satisfaction and decreases delays in subsequent cases. The goal of our study was to evaluate the effect of a multidisciplinary initiative to improve first patient in the room (FPIR) and first case on time start (FCOTS) metrics in a tertiary care setting. Materials and Methods: A multidisciplinary committee focused on first case start data collection. Reasons for both anesthesia and surgical delays were analyzed. Improvement efforts focused on the timely completion of surgical consent, a requirement of a surgical, anesthesia, and nurse team member presence at the patient's bedside by specific time, and parallel processing in the OR. Results: Over 65,100 OR cases were analyzed between 2007 and 2014. There was a statistically significant improvement in FPIR (82.80% versus 69.60%, p < .0001) and FCOTS (66.60% versus 55.90%, p < .0001). Surgical consent completion rate increased from 35% baseline to 68%–100%, depending on the surgical subspecialty. Improvements appeared sustainable several years following process implementation for both FPIR (84.60% versus 69.60%, p < .0001) and FCOTS (67.60% versus 55.90%, p < .0001). Conclusions: Our study demonstrates a successful targeted, multidisciplinary initiative to improve first case surgical starts in an academic setting. Our approach was organizational rather than punitive or rewarding on an individual basis. Strategies included establishing concrete, time-specific goals and posting them visibly, empowering individuals to fulfill them, and ensuring no compromise in patient safety. In the complex environment of academic medicine including research protocols and teaching in the ORs, our organizational approach proved sustainable over several years.     

A health‐economic analysis of porcine islet xenotransplantation

Beckwith J, Nyman JA, Flanagan B, Schrover R, Schuurman H‐J. A health‐economic analysis of porcine islet xenotransplantation. Xenotransplantation 2010; 17: 233–242. © 2010 John Wiley & Sons A/S. Abstract: Background: Islet cell transplantation is a promising treatment for type 1 diabetes. To overcome the shortage of deceased human pancreas donors, porcine islet cell xenotransplantation is being developed as an alternative to allotransplantation. The objective of this study was to perform a cost‐effectiveness analysis of porcine islet transplantation in comparison with standard insulin therapy. The patient population for this study was young adults, ages 20 to 40, for whom standard medical care is inadequate in controlling blood glucose levels (hypoglycemia unawareness). Since trial data were lacking, estimates used extrapolations from data found in the literature and ongoing trials in clinical allotransplantation. Cost estimates were based on the data available in the USA. Methods: Markov modeling and Monte Carlo simulations using software specifically developed for health‐economic evaluations were used. Outcomes data for ongoing clinical islet allotransplantation from the University of Minnesota were used, along with probabilities of complications from the Diabetes Control and Complications Trial. Quality‐adjusted life years (QALYs) were the effectiveness measure. The upper limit of being cost‐effective is $100 000 per QALY. Cost data from the literature were used and adjusted to 2007 US dollars using the medical care portion of the Consumer Price Index. Results: In both Markov modeling and Monte Carlo simulations, porcine islet xenotransplantation was both more effective and less costly over the course of the 20‐yr model. For standard insulin therapy, cumulative cost per patient was $661 000, while cumulative effectiveness was 9.4 QALYs, for a cost of $71 100 per QALY. Transplantation had a cumulative cost of $659 000 per patient, a cumulative effectiveness of 10.9 QALYs, and a cost per QALY of $60 700. Islet transplantation became cost‐effective at 4 yr after transplantation, and was more cost‐effective than standard insulin treatment at 14 yr. These findings are related to relative high costs in the transplantation arm of the evaluation during the first years while those in the insulin arm became higher later in follow‐up. Throughout the follow‐up period, effectiveness of transplantation was higher than that of insulin treatment. In sensitivity analysis, duplication or triplication of one‐time initial costs such as costs of donor animal, islet manufacturing and transplantation had no effect on long‐term outcome in terms of cost‐saving or cost‐effectiveness, but the outcome of transplantation in terms of diabetes complications in cases with partial graft function could affect cost‐saving and cost‐effectiveness conclusions. Conclusion: Despite limitations in the model and lack of trial data, and under the assumption that islet transplantation outcomes for young adult type 1 diabetes patients are not dependent on the source of islet cells, this health‐economic evaluation suggests that porcine islet cell xenotransplantation may prove to be a cost‐effective and possibly cost‐saving procedure for type 1 diabetes compared to standard management.