Craig A. Piquette

Premature discontinuation of patients: A potential bias in COPD clinical trials

Premature discontinuation from clinical trials may bias results against effective therapies. In the present study mortality rates were retrospectively reviewed in a 6-month, randomised, placebo-controlled trial in which tiotropium 18 μg daily was shown to decrease chronic obstructive pulmonary disease exacerbations. Patients participated for 6 months even if trial medication was prematurely discontinued. Exposure-adjusted incidence rates (IRs) were calculated for randomisation–end trial, randomisation–end trial drug (0–ED) and end trial drug–end trial (ED–ET). Of 1,829 patients (forced expiratory volume in one second 1.04 L (36% predicted), mean age 68 yrs, 99% male), 16% tiotropium and 27% placebo patients prematurely stopped trial medication. The number of fatal events for the entire cohort was: 62 all cause, including 16 cardiac and 16 lower respiratory. IRs for fatal events per 100 patient-yrs were higher in the discontinued period: 1.9 (0–ED) versus 23.0 (ED–ET) in the tiotropium group and 1.8 versus 19.0 in the placebo group. Respective IRs for fatal cardiac events were 0.7 versus 2.8 (tiotropium) and 0.5 versus 6.2 (placebo); for fatal lower respiratory events were 0.7 versus 2.8 (tiotropium) and 0.8 versus 5.4 (placebo). Rate ratios (tiotropium/placebo) for fatal events were lower in the discontinued period: 1.4 versus 0.5 for cardiac and 0.9 versus 0.5 for lower respiratory. Higher incidence rates of fatal events occurred following premature discontinuation of study medication. Incomplete information from rate ratios occurs as a result of failure to consider outcomes of patients who discontinue early from clinical trials.

Lessons learned: critical care management of patients with Ebola in the United States.

Objective:This report will describe the preparations for and the provision of care of two patients with Ebola virus disease in the biocontainment unit at the University of Nebraska Medical Center. Data Sources:Patient medical records. Study Selection:Not applicable. Data Extraction:Not applicable. Data Synthesis:Not applicable. Conclusions:Safe and effective care of patients with Ebola virus disease requires significant communication and planning. Adherence to a predetermined isolation protocol is essential, including proper donning and doffing of personal protective equipment. Location of the patient care area and the logistics of laboratory testing, diagnostic imaging, and the removal of waste must be considered. Patients with Ebola virus disease are often dehydrated and need adequate vascular access for fluid resuscitation, nutrition, and phlebotomy for laboratory sampling. Advanced planning for acute life-threatening events and code status must be considered. Intensivist scheduling should account for the significant amount of time required for the care of patients with Ebola virus disease. With appropriate precautions and resources, designated hospitals in the United States can safely provide care for patients with Ebola virus disease.

Entrustable Professional activities and curricular milestones for fellowship training in pulmonary and critical care medicine: Executive summary from the multi-society working group

Assessment of graduate medical trainee progress via the accomplishment of competency milestones is an important element of the Next Accreditation System of the Accreditation Council for Graduate Medical Education. This article summarizes the findings of a multisociety working group that was tasked with creating the entrustable professional activities and curricular milestones for fellowship training in pulmonary medicine, critical care medicine, and combined programs. Using the Delphi process, experienced medical educators from the American College of Chest Physicians, American Thoracic Society, Society of Critical Care Medicine, and Association of Pulmonary and Critical Care Medicine Program Directors reached consensus on the detailed curricular content and expected skill set of graduates of these programs. These are now available to trainees and program directors for the purposes of curriculum design, review, and trainee assessment.

Training Pathway for Critical Care Medicine

To the Editor: Drs Kaplan and Shaw focused on the critical care medicine (CCM) workforce shortage. However, their proposal for a single training pathway in CCM did not address the underlying complexities of the problem. The reasons behind the separate training pathways to critical care certification in the United States are lengthy and complex, as would be any attempt to align all key US stakeholders to consolidate training standards and credentialing into a single pathway similar to Europe’s CoBaTrICE. More importantly, there is no evidence that a single CCM training pathway would either improve patient care or attract more trainees to the field. Kaplan and Shaw suggested that multiple pathways may discourage students and residents from choosing CCM training, citing a program fill rate of approximately 50% for surgery CCM. However, the much larger pool of pulmonary CCM programs filled 97% of their positions, and data from 2004 to 2009 demonstrate growth of enrolled fellows in 3 pathways: anesthesia CCM from 43 to 80, surgery CCM from 106 to 155, and internal medicine CCM from 1182 to 1433. One major limitation to further growth is that despite growing societal needs, willing educators and health systems, interested candidates, and even bills introduced in Congress, the Centers for Medicare & Medicaid Services (CMS) has continued its 14-year-old freeze on sponsored physician training positions. Without additional funding, it is unlikely any changes in CCM training will affect this shortage. More robust growth may also be constrained by perceptions of physician burnout or lifestyle issues, but we believe confusion among trainees about which pathway to pick is unlikely to be playing a major role. We agree that cross-discipline training in a variety of intensive care unit (ICU) settings is important, and this is currently required for internal medicine CCM. A multisociety task force recently published competency-based criteria for internal medicine CCM that included many competencies historically associated with nonmedical ICUs. Efforts to consolidate CCM training across physician specialties are ongoing, such as the work of the internal medicine and emergency medicine boards toward a jointly sponsored CCM certification. A single CCM training pathway would have to compensate for the diverse preparatory experiences of medical, surgical, and anesthesiology residencies. This risks further extending the duration of training. We suggest a broader approach to this issue by inviting educators, professional societies, and funding agencies to begin discussing meaningful solutions to the problem of a CCM workforce shortage that is not going away on its own.

A Sleep Medicine Curriculum for Pulmonary and Pulmonary / Critical Care Fellowship Programs – A Multi-Society Expert Panel Report

BACKGROUND: Pulmonary medicine specialists find themselves responsible for the diagnosis and management of patients with sleep disorders. Despite the increasing prevalence of many of these conditions, many sleep medicine fellowship training slots go unfilled, leading to a growing gap between the volume of patients seeking care for sleep abnormalities and the number of physicians formally trained to manage them. To address this need, we convened a multisociety panel to develop a list of curricular recommendations related to sleep medicine for pulmonary fellowship training programs. METHODS: Surveys of pulmonary and pulmonary/critical care fellowship program directors and recent graduates of these programs were performed to assess the current state of sleep medicine education in pulmonary training, as well as the current scope of practice of pulmonary specialists. These data were used to inform a modified Delphi process focused on developing curricular recommendations relevant to sleep medicine. RESULTS: Surveys confirmed that pulmonary medicine specialists are often responsible for the diagnosis and treatment of a number of sleep conditions, including several that are not traditionally considered related to respiratory medicine. Through five rounds of voting, the panel crafted a list of 52 curricular competencies relevant to sleep medicine for recommended inclusion in pulmonary training programs. CONCLUSIONS: Practicing pulmonary specialists require a broad knowledge of sleep medicine to provide appropriate care to patients they will be expected to manage. Training program directors may use the list of competencies as a framework to ensure adequate mastery of important content by graduating fellows.

RHINOSCLEROMA IN A YOUNG ADULT WITH CHRONIC RHINITIS AND DYSPNEA

FIXED DRUG ERUPTION CAUSED BY AMOXICILLIN-CLAVULANIC Fixed drug eruptions caused by penicillin derivates are infrequent, and very few cases have been reported.1–4 Fixed drug eruption is characterized by sudden onset of round and/or oval, edematous, dusky-red macules on the skin and/or mucous membranes, accompanied by burning and/or itching. In addition, some cases may show the formation of vesicles, bullae, and denuded skin.5 A 26-year-old woman with Down syndrome was given Augmentine (GlaxoSmithKline SA, Madrid, Spain), 500 mg 3 times a day, for treatment of an infection. Four hours after ingestion of the fourth tablet, she had itching and erythema on her palms and plantae. Two days later, the patient presented with denuded skin of her palms. Finally, the patient’s symptoms cleared in 1 week with corticosteroid treatment. She had previously tolerated this antibiotic. Prick and intradermal test results with benzylpenicilloyl polylysine as the major determinant at a concentration of 0.04 mg/mL and minor determinant mixture at 0.5 mg/mL were negative. Both major and minor determinants were purchased from Diater SA (Madrid, Spain). Skin test results with benzylpenicillin, 10,000 UI/mL (Normon SA, Madrid, Spain); amoxicillin, 20 mg/mL and 25 mg/mL (GlaxoSmithKline SA, Madrid, Spain); ampicillin, 20 mg/mL (Normon SA); cefuroxime, 20 mg/mL (GlaxoSmithKline SA); and ceftazidime, 20 mg/mL (Combino Pharm SL, Barcelona, Spain) were all negative. Specific IgE antibodies to penicillin V, penicillin G, amoxicillin, and ampicillin (CAP-FEIA; Phadia, Uppsala, Sweden) were negative. Patch tests were performed on the patient’s upper back skin and palms with penicillin, amoxicillin, and amoxicillinclavulanic, at a concentration of 10% in petroleum jelly. No reactions were observed at 48 and 96 hours. After the patient gave informed consent, we performed a singleblinded oral challenge with amoxicillin-clavulanic, with a positive result. Four hours after being given 825 mg of amoxicillin-clavulanic, the patient had erythema on the palms and plantae; 24 hours later, she had denuded skin of her palms. To investigate possible cross-reactivity among other -lactams, we performed an oral challenge with cefuroxime and ceftazidime that produced negative results. Therefore, we recommended the use of cefuroxime and ceftazidime for future treatments that would require -lactam antibiotics. Penicillins are the drugs most frequently implicated in immunologic adverse reactions, such as IgE-mediated immediate reactions, maculopapular exanthemas, erythema multiforme, and fixed drug eruptions.2,4 Patch testing is a simple and safe method to identify certain causative agents of fixed drug eruptions, but it cannot be relied on if results are negative.1 In our case, we performed the patch test on normal and previously affected skin with amoxicillin, amoxicillinclavulanic, and ampicillin, all of them in 10% petroleum jelly, with negative results. In the literature, Saenz de San Pedro Morera et al1 described a fixed drug eruption to amoxicillin with a positive patch test result on the back and on previously involved skin. Jiménez et al2 described a case of fixed drug eruption caused by amoxicillin with a negative epicutaneous open test result (10% in petroleum jelly), performed on the patient’s upper back and palms, with penicillin, amoxicillin, and amoxicillin-clavulanic. The diagnosis was confirmed by oral challenge. On the other hand, Arias et al4 described a woman with a selective fixed drug eruption to amoxicillin with no reaction to other -lactam drugs. Patch test results from normal and residual pigmented skin were also negative. We report a fixed drug eruption to amoxicillin-clavulanic that was confirmed by oral challenge. To our knowledge, this is the first case published with this drug.