Allogeneic hematopoietic cell transplantation (HCT) has been used for 40 years to ameliorate or cure primary immune deficiency (PID) diseases, including severe combined immunodeficiency (SCID) and ...non-SCID PID. There is a critical need for evaluation of the North American experience of different HCT approaches for these diseases to identify best practices and plan future investigative clinical trials. Our survey of incidence and prevalence of PID in North American practice sites indicates that such studies are feasible. A conference of experts in HCT treatment of PID has recommended (1) a comprehensive cross-sectional and retrospective analysis of HCT survivors with SCID; (2) a prospective study of patients with SCID receiving HCT, with comparable baseline and follow-up testing across participating centers; (3) a pilot study of newborn screening for SCID to identify affected infants before compromise by infection; and (4) studies of the natural history of disease in patients who do or do not receive HCT for the non-SCID diseases of Wiskott-Aldrich syndrome and chronic granulomatous disease. To accomplish these goals, collaboration by a consortium of institutions in North America is proposed. Participation of immunologists and HCT physicians having interest in PID and experts in laboratory methods, clinical outcomes assessment, databases, and analysis will be required for the success of these studies.
We report a case of Cryptococcus neoformans pneumonia in a patient taking ruxolitinib, a janus kinase 1,2 inhibitor approved for the treatment of myelofibrosis. We hypothesize that ruxolitinib ...contributed to this infection through its effects on cell-mediated immunity. Clinicians should be aware of the potential for intracellular or opportunistic infections associated with this novel drug class.
Background We sought to determine the prevalence of and clinical variables associated with learned helplessness, a psychologic state characterized by reduced motivation, difficulty in determining ...causality, and depression, in family members of patients admitted to ICUs. Methods We conducted an observational survey study of a prospectively defined cohort of family members, spouses, and partners of patients admitted to surgical, medical, and trauma ICUs at a large academic medical center. Two validated instruments, the Learned Helplessness Scale and the Perceived Stress Scale, were used, and self-report of patient clinical characteristics and subject demographics were collected. Results Four hundred ninety-nine family members were assessed. Of these, 238 of 460 (51.7%) had responses consistent with a significant degree of learned helplessness. Among surrogate decision-makers, this proportion was 50% (92 of 184). Characteristics associated with significant learned helplessness included grade or high school education (OR, 3.27; 95% CI, 1.29-8.27; P = .01) and Perceived Stress Scale score > 18 (OR, 4.15; 95% CI, 2.65-6.50; P < .001). The presence of a patient advance directive or do not resuscitate (DNR) order was associated with reduced odds of significant learned helplessness (OR, 0.56; 95% CI, 0.32-0.98; P = .05). Conclusions The majority of family members of patients in the ICU experience significant learned helplessness. Risk factors for learned helplessness include lower educational levels, absence of an advance directive or DNR order, and higher stress levels among family members. Significant learned helplessness in family members may have negative implications in the collaborative decision-making process.
The Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols ...address the natural history of patients treated for severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, and chronic granulomatous disease through retrospective, prospective, and cross-sectional studies. The PIDTC additionally seeks to encourage training of junior investigators, establish partnerships with European and other International colleagues, work with patient advocacy groups to promote community awareness, and conduct pilot demonstration projects. Future goals include the conduct of prospective treatment studies to determine optimal therapies for primary immunodeficiency diseases. To date, the PIDTC has funded 2 pilot projects: newborn screening for SCID in Navajo Native Americans and B-cell reconstitution in patients with SCID after hematopoietic stem cell transplantation. Ten junior investigators have received grant awards. The PIDTC Annual Scientific Workshop has brought together consortium members, outside speakers, patient advocacy groups, and young investigators and trainees to report progress of the protocols and discuss common interests and goals, including new scientific developments and future directions of clinical research. Here we report the progress of the PIDTC to date, highlights of the first 2 PIDTC workshops, and consideration of future consortium objectives.
Background Learning health care systems apply the experiences of prior patients to inform care and help to guide decision making for current patients. These systems should help to deliver more ...effective, efficient, and appropriate care. Most examples of learning systems derive from integrated care delivery systems and examples of such systems in the community at large have been lacking. Methods The comparative effectiveness research translation network (CERTAIN) is a learning system bringing together hospitals and outpatient clinics across Washington State. CERTAIN leverages existing medical record-based data collection taking place at nearly all statewide hospitals and links this data collection with patient-reported information about function and quality of life. Results We have described the components of the CERTAIN infrastructure, the elements of a pilot project evaluating treatments of claudication, and the opportunities and challenges of developing and implementing a “real world” learning system. Examples in the areas of vascular disease, spine care, gastrointestinal disease, and urology. Conclusion Learning health care systems face many operational challenges but hold great promise for discovery and implementation of more effective clinical practices.
Objectives The purpose of this study was to compare the safety and efficacy of surgical, stent, and balloon angioplasty (BA) treatment of native coarctation acutely and at follow-up. Background ...Controversy surrounds the optimal treatment for native coarctation of the aorta. This is the first multicenter study evaluating acute and follow-up outcomes of these 3 treatment options in children weighing >10 kg. Methods This is a multicenter observational study. Baseline, acute, short-term (3 to 18 months), and intermediate (>18 months) follow-up hemodynamic, imaging data, and complications were recorded. Results Between June 2002 and July 2009, 350 patients from 36 institutions were enrolled: 217 underwent stent, 61 underwent BA, and 72 underwent surgery. All 3 arms showed significant improvement acutely and at follow-up in resting systolic blood pressure and upper to lower extremity systolic blood pressure gradient (ULG). Stent was superior to BA in achieving lower ULG acutely. Surgery and stent were superior to BA at short-term follow-up in achieving lower ULG. Stent patients had shorter hospitalization than surgical patients (2.4 vs. 6.4 days; p < 0.001) and fewer complications than surgical and BA patients (2.3%, 8.1%, and 9.8%; p < 0.001). The BA patients were more likely to encounter aortic wall injury, both acutely and at follow-up (p < 0.001). Conclusions Stent patients had significantly lower acute complications compared with surgery patients or BA patients, although they were more likely to require a planned reintervention. At short-term and intermediate follow-up, stent and surgical patients achieved superior hemodynamic and integrated aortic arch imaging outcomes compared with BA patients. Because of the nonrandomized nature of this study, these results should be interpreted with caution.
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