Artistic Realization Technologies

Helicobacter pylori (H. pylori) infection is a common worldwide infection that is an important cause of peptic ulcer disease and gastric cancer. H. pylori may also have a role in uninvestigated and functional dyspepsia, ulcer risk in patients taking low-dose aspirin or starting therapy with a non-steroidal anti-inflammatory medication, unexplained iron deficiency anemia, and idiopathic thrombocytopenic purpura. While choosing a treatment regimen for H. pylori, patients should be asked about previous antibiotic exposure and this information should be incorporated into the decision-making process. For first-line treatment, clarithromycin triple therapy should be confined to patients with no previous history of macrolide exposure who reside in areas where clarithromycin resistance amongst H. pylori isolates is known to be low. Most patients will be better served by first-line treatment with bismuth quadruple therapy or concomitant therapy consisting of a PPI, clarithromycin, amoxicillin, and metronidazole. When first-line therapy fails, a salvage regimen should avoid antibiotics that were previously used. If a patient received a first-line treatment containing clarithromycin, bismuth quadruple therapy or levofloxacin salvage regimens are the preferred treatment options. If a patient received first-line bismuth quadruple therapy, clarithromycin or levofloxacin-containing salvage regimens are the preferred treatment options. Details regarding the drugs, doses and durations of the recommended and suggested first-line and salvage regimens can be found in the guideline.

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the "ARRIVE Essential 10," which constitutes the minimum requirement, and the "Recommended Set," which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.

OBJECTIVES: Breath tests (BTs) are important for the diagnosis of carbohydrate maldigestion syndromes and small intestinal bacterial overgrowth (SIBO). However, standardization is lacking regarding indications for testing, test methodology and interpretation of results. A consensus meeting of experts was convened to develop guidelines for clinicians and research. METHODS: Pre-meeting survey questions encompassing five domains; indications, preparation, performance, interpretation of results, and knowledge gaps, were sent to 17 clinician-scientists, and 10 attended a live meeting. Using an evidence-based approach, 28 statements were finalized and voted on anonymously by a working group of specialists. RESULTS: Consensus was reached on 26 statements encompassing all five domains. Consensus doses for lactulose, glucose, fructose and lactose BT were 10, 75, 25 and 25 g, respectively. Glucose and lactulose BTs remain the least invasive alternatives to diagnose SIBO. BT is useful in the diagnosis of carbohydrate maldigestion, methane-associated constipation, and evaluation of bloating/gas but not in the assessment of oro-cecal transit. A rise in hydrogen of ≥20 p.p.m. by 90 min during glucose or lactulose BT for SIBO was considered positive. Methane levels ≥10 p.p.m. was considered methane-positive. SIBO should be excluded prior to BT for carbohydrate malabsorption to avoid false positives. A rise in hydrogen of ≥20 p.p.m. from baseline during BT was considered positive for maldigestion. CONCLUSIONS: BT is a useful, inexpensive, simple and safe diagnostic test in the evaluation of common gastroenterology problems. These consensus statements should help to standardize the indications, preparation, performance and interpretation of BT in clinical practice and research.

OBJECTIVES: Persistent disease activity is associated with a poor prognosis in inflammatory bowel disease (IBD). Therefore, monitoring of patients with intent to suppress subclinical inflammation has emerged as a treatment concept. As endoscopic monitoring is invasive and resource intensive, identification of valid markers of disease activity is a priority. The objective was to evaluate the diagnostic accuracy of C-reactive protein (CRP), fecal calprotectin (FC), and stool lactoferrin (SL) for assessment of endoscopically defined disease activity in IBD. METHODS: Databases were searched from inception to November 6, 2014 for relevant cohort and case-control studies that evaluated the diagnostic accuracy of CRP, FC, or SL and used endoscopy as a gold standard in patients with symptoms consistent with active IBD. Sensitivities and specificities were pooled to generate operating property estimates for each test using a bivariate diagnostic meta-analysis. RESULTS: Nineteen studies (n=2499 patients) were eligible. The pooled sensitivity and specificity estimates for CRP, FC, and SL were 0.49 (95% confidence interval (CI) 0.34-0.64) and 0.92 (95% CI 0.72-0.96), 0.88 (95% CI 0.84-0.90) and 0.73 (95% CI 0.66-0.79), and 0.82 (95% CI 0.73-0.88) and 0.79 (95% CI 0.62-0.89), respectively. FC was more sensitive than CRP in both diseases and was more sensitive in ulcerative colitis than Crohn's disease. CONCLUSIONS: Although CRP, FC, and SL are useful biomarkers, their value in managing individual patients must be considered in specific clinical contexts.

Accreditation of residency programs and certification of physicians requires assessment of competence in communication and interpersonal skills. Residency and continuing medical education program directors seek ways to teach and evaluate these competencies. This report summarizes the methods and tools used by educators, evaluators, and researchers in the field of physician-patient communication as determined by the participants in the "Kalamazoo II" conference held in April 2002. Communication and interpersonal skills form an integrated competence with two distinct parts. Communication skills are the performance of specific tasks and behaviors such as obtaining a medical history, explaining a diagnosis and prognosis, giving therapeutic instructions, and counseling. Interpersonal skills are inherently relational and process oriented; they are the effect communication has on another person such as relieving anxiety or establishing a trusting relationship. This report reviews three methods for assessment of communication and interpersonal skills: (1) checklists of observed behaviors during interactions with real or simulated patients; (2) surveys of patients' experience in clinical interactions; and (3) examinations using oral, essay, or multiple-choice response questions. These methods are incorporated into educational programs to assess learning needs, create learning opportunities, or guide feedback for learning. The same assessment tools, when administered in a standardized way, rated by an evaluator other than the teacher, and using a predetermined passing score, become a summative evaluation. The report summarizes the experience of using these methods in a variety of educational and evaluation programs and presents an extensive bibliography of literature on the topic. Professional conversation between patients and doctors shapes diagnosis, initiates therapy, and establishes a caring relationship. The degree to which these activities are successful depends, in large part, on the communication and interpersonal skills of the physician. This report focuses on how the physician's competence in professional conversation with patients might be measured. Valid, reliable, and practical measures can guide professional formation, determine readiness for independent practice, and deepen understanding of the communication itself.

We analyzed the clinical and laboratory characteristics of 50 patients with catastrophic antiphospholipid syndrome (APS) (5 from our clinics and 45 from a MEDLINE computer-assisted review of the literature from 1992 through 1996). Thirty-three (66%) patients were female and 17 (34%) were male. Twenty-eight (56%) patients had primary APS, 15 (30%) had defined systemic lupus erythematosus (SLE), 6 (12%) had "lupus-like" syndrome, and 1 (2%) had rheumatoid arthritis. Mean age of patients in this series was 38 +/- 14 years (range, 11-74 yr). Three (6%) patients developed the clinical picture of catastrophic APS under the age of 15 years, and 11 (22%) were 50 years old or more. In 11 (22%) patients, precipitating factors contributed to the development of catastrophic APS (infections in 3, drugs in 3, minor surgical procedures in 3, anticoagulation withdrawal in 2, and hysterectomy in 1). The presentation of the acute multi-organ failure was usually complex, involving multiple organs simultaneously or in a very short period of time. The majority of patients manifested microangiopathy--that is, occlusive vascular disease affecting predominantly small vessels of organs, particularly kidney, lungs, brain, heart, and liver--with a minority of patients experiencing only large vessel occlusions. Thrombocytopenia was reported in 34 (68%) patients, hemolytic anemia in 13 (26%), disseminated intravascular coagulation in 14 (28%), and schistocytes in 7 (14%). The following antibodies were detected: lupus anticoagulant (94%), anticardiolipin antibodies (94%), anti-dsDNA (87% of patients with SLE), antinuclear antibodies (58%), anti-Ro/SS-A (8%), anti-RNP (8%), and anti-La/SS-B (2%). Anticoagulation was used in 70% of the patients, steroids in 70%, plasmapheresis in 40%, cyclophosphamide in 34%, intravenous gammaglobulins in 16%, and splenectomy in 4%. Most patients, however, received a combination of nonsurgical therapies. Death occurred in 25 of the 50 (50%) patients. In most, cardiac problems seemed to be the major cause of death. In several of these, respiratory failure was also present, usually due to acute respiratory distress syndrome and diffuse alveolar hemorrhage. Among the 20 patients who received the combination of anticoagulation, steroids, and plasmapheresis or intravenous gammaglobulins, recovery occurred in 14 (70%) patients. The use of ancrod and defibrotide appeared to be effective in the 2 respective patients in whom they were used.

Markov chain Monte Carlo (MCMC) sampling strategies can be used to simulate hidden Markov model (HMM) parameters from their posterior distribution given observed data. Some MCMC methods used in practice (for computing likelihood, conditional probabilities of hidden states, and the most likely sequence of states) can be improved by incorporating established recursive algorithms. The most important of these is a set of forward-backward recursions calculating conditional distributions of the hidden states given observed data and model parameters. I show how to use the recursive algorithms in an MCMC context and demonstrate mathematical and empirical results showing a Gibbs sampler using the forward-backward recursions mixes more rapidly than another sampler often used for HMMs. Iintroduce an augmented variables technique for obtaining unique state labels in HMMs and finite mixture models. I show how recursive computing allows the statistically efficient use of MCMC output when estimating the hidden states. I directly calculate the posterior distribution of the hidden chain's state-space size by MCMC, circumventing asymptotic arguments underlying the Bayesian information criterion, which is shown to be inappropriate for a frequently analyzed dataset in the HMM literature. The use of log-likelihood for assessing MCMC convergence is illustrated, and posterior predictive checks are used to investigate application specific questions of model adequacy.

PURPOSE: To determine if medical students who demonstrate unprofessional behavior in medical school are more likely to have subsequent state board disciplinary action. METHOD: A case-control study was conducted of all University of California, San Francisco, School of Medicine graduates disciplined by the Medical Board of California from 1990-2000 (68). Control graduates (196) were matched by medical school graduation year and specialty choice. Predictor variables were male gender, undergraduate grade point average, Medical College Admission Test scores, medical school grades, National Board of Medical Examiner Part 1 scores, and negative excerpts describing unprofessional behavior from course evaluation forms, dean's letter of recommendation for residencies, and administrative correspondence. Negative excerpts were scored for severity (Good/Trace versus Concern/Problem/Extreme). The outcome variable was state board disciplinary action. RESULTS: The alumni graduated between 1943 and 1989. Ninety-five percent of the disciplinary actions were for deficiencies in professionalism. The prevalence of Concern/Problem/Extreme excerpts in the cases was 38% and 19% in controls. Logistic regression analysis showed that disciplined physicians were more likely to have Concern/Problem/Extreme excerpts in their medical school file (odds ratio, 2.15; 95% confidence interval, 1.15-4.02; p =.02). The remaining variables were not associated with disciplinary action. CONCLUSION: Problematic behavior in medical school is associated with subsequent disciplinary action by a state medical board. Professionalism is an essential competency that must be demonstrated for a student to graduate from medical school.

BACKGROUND: Several quality of recovery (QoR) health status scales have been developed to quantify the patient's experience after anesthesia and surgery, but to date, it is unclear what constitutes the minimal clinically important difference (MCID). That is, what minimal change in score would indicate a meaningful change in a patient's health status? METHODS: The authors enrolled a sequential, unselected cohort of patients recovering from surgery and used three QoR scales (the 9-item QoR score, the 15-item QoR-15, and the 40-item QoR-40) to quantify a patient's recovery after surgery and anesthesia. The authors compared changes in patient QoR scores with a global rating of change questionnaire using an anchor-based method and three distribution-based methods (0.3 SD, standard error of the measurement, and 5% range). The authors then averaged the change estimates to determine the MCID for each QoR scale. RESULTS: The authors enrolled 204 patients at the first postoperative visit, and 199 were available for a second interview; a further 24 patients were available at the third interview. The QoR scores improved significantly between the first two interviews. Triangulation of distribution- and anchor-based methods results in an MCID of 0.92, 8.0, and 6.3 for the QoR score, QoR-15, and QoR-40, respectively. CONCLUSION: Perioperative interventions that result in a change of 0.9 for the QoR score, 8.0 for the QoR-15, or 6.3 for the QoR-40 signify a clinically important improvement or deterioration.

BACKGROUND: Although the association between exposure to particulate matter (PM) mass and mortality is well established, there remains uncertainty about which chemical components of PM are most harmful to human health. METHODS: A hierarchical approach was used to determine how the association between daily PM2.5 mass and mortality was modified by PM2.5 composition in 25 US communities. First, the association between daily PM2.5 and mortality was determined for each community and season using Poisson regression. Second, we used meta-regression to examine how the pooled association was modified by community and season-specific particle composition. RESULTS: There was a 0.74% (95% confidence interval = 0.41%-1.07%) increase in nonaccidental deaths associated with a 10 microg/m3 increase in 2-day averaged PM2.5 mass concentration. This association was smaller in the west (0.51% [0.10%-0.92%]) than in the east (0.92% [0.23%-1.36%]), and was highest in spring (1.88% [0.23%-1.36%]). It was increased when PM2.5 mass contained a higher proportion of aluminum (interquartile range = 0.58%), arsenic (0.55%), sulfate (0.51%), silicon (0.41%), and nickel (0.37%). The combination of aluminum, sulfate, and nickel also modified the effect. These species proportions explained residual variability between the community-specific PM2.5 mass effect estimates. CONCLUSIONS: This study shows that certain chemical species modify the association between PM2.5 and mortality and illustrates that mass alone is not a sufficient metric when evaluating health effects of PM exposure.

Tissue engineering approaches for promoting the repair of skeletal tissues have focused on cell-based therapies involving multipotent stromal cells. Recent studies have identified such cells in several tissues in the adult human, including skin, muscle, bone marrow, and subcutaneous fat. This study examined the hypothesis that the infrapatellar fat pad of the adult knee contains progenitor cells that have the ability to differentiate into chondrocytes, osteoblasts, or adipocytes under appropriate culture conditions. Cells isolated from the fat pad stroma had a profile of cell-surface molecules similar but not identical to that of bone marrow-derived mesenchymal stem cells. Using defined culture conditions, fat pad-derived stromal cells were induced to differentiate cells with phenotypic characteristics of: (1) chondrocytes, synthesizing cartilage matrix molecules; (2) adipocytes, producing lipid vacuoles and leptin; or (3) osteoblasts, forming mineralized tissue. The culture conditions also modulated the expression of characteristic gene markers for each lineage. This study supports the hypothesis that multipotent stromal cells are present in many connective tissues in the adult human. Given its location and accessibility, the fat pad may prove to be a potential source of progenitor cells for musculoskeletal tissue engineering.

OBJECTIVES: Many studies around the world addressed the post-colonoscopy complications, but their pooled prevalence and time trends are unknown. We performed a systematic review and meta-analysis of population-based studies to examine the pooled prevalence of post-colonoscopy complications ("perforation", "bleeding", and "mortality"), stratified by colonoscopy indication. Temporal variability in the complication rate was assessed. METHODS: We queried Pubmed, Embase, and the Cochrane library for population-based studies examining post-colonoscopy complications (within 30 days), performed from 2001 to 2015 and published by 1 December 2015. We determined pooled prevalence of perforations, post-colonoscopy bleeding, post-polypectomy bleeding, and mortality. RESULTS: We retrieved 1,074 studies, of which 21 met the inclusion criteria. Overall, pooled prevalences for perforation, post-colonoscopy bleeding, and mortality were 0.5/1,000 (95% confidence interval (CI) 0.4-0.7), 2.6/1,000 (95% CI 1.7-3.7), and 2.9/100,000 (95% CI 1.1-5.5) colonoscopies. Colonoscopy with polypectomy was associated with a perforation rate of 0.8/1,000 (95% CI 0.6-1.0) and a post-polypectomy bleeding rate of 9.8/1,000 (95% CI 7.7-12.1). Complication rate was lower for screening/surveillance than for diagnostic examinations. Time-trend analysis showed that post-colonoscopy bleeding declined from 6.4 to 1.0/1,000 colonoscopies, whereas the perforation and mortality rates remained stable from 2001 to 2015. Overall, considerable heterogeneity was observed in most of the analyses. CONCLUSIONS: Worldwide, the post-colonoscopy complication rate remained stable or even declined over the past 15 years. The findings of this meta-analysis encourage continued efforts to achieve and maintain safety targets in colonoscopy practice.

BACKGROUND: We sought to determine nationwide, population-based trends in rates of venous thromboembolism (VTE) among hospitalized inflammatory bowel disease (IBD) patients in the United States and to determine its mortality and economic impact. METHODS: We analyzed discharges from the Nationwide Inpatient Sample and used ICD-9-CM codes to identify Crohn's disease (CD) and ulcerative colitis (UC) between 1998 and 2004. Rates of VTE were compared between those with and without IBD. The impact of VTE on in-hospital mortality and resource utilization was quantified using regression analysis. RESULTS: After multivariate adjustment, both UC (OR 1.85, 95% CI 1.70-2.01) and CD discharges (OR 1.48, 95% CI 1.35-1.62) had higher rates of VTE compared to non-IBD discharges. Prevalence of VTE was greater among UC compared to CD discharges (OR 1.32, 95% CI 1.17-1.48). Among CD patients, active fistulizing disease was independently associated with greater VTE (OR 1.39, 95% CI 1.13-1.70). There was an annual 17% rise in odds of VTE among IBD admissions over 7 yr. VTE was associated with greater mortality among IBD patients (adjusted OR 2.50, 95% CI 1.83-3.43). This age- and comorbidity-adjusted excess mortality from VTE was 2.1-fold higher for IBD than for non-IBD patients (P < 0.0001). IBD patients with VTE had longer length of stay (11.7 vs 6.1 days, P < 0.0001) and incurred higher hospital charges ($47,515 vs $21,499; P < 0.0001). CONCLUSIONS: VTE is increasingly prevalent among hospitalized IBD patients and has substantial mortality and economic impact. These findings drive the need for widespread prophylaxis against and early detection of VTE among IBD inpatients.

Evaluation of needle biopsies and extensive clinicopathological correlation play an important role in the determination of liver allograft dysfunction occurring more than 1 year after transplantation. Interpretation of these biopsies can be quite difficult because of the high incidence of recurrent diseases that show histopathological, clinical, and serological features that overlap with each other and with rejection. Also, more than one insult can contribute to allograft injury. In an attempt to enable centers to compare and pool results, improve therapy, and better understand pathophysiological disease mechanisms, the Banff Working Group on Liver Allograft Pathology herein proposes a set of consensus criteria for the most common and problematic causes of late liver allograft dysfunction, including late-onset acute and chronic rejection, recurrent and new-onset viral and autoimmune hepatitis, biliary strictures, and recurrent primary biliary cirrhosis and primary sclerosing cholangitis. A discussion of differential diagnosis is also presented.

The author presents reflections from medical anthropology on the institutional culture of medicine and medical education, which sees itself as a "culture of no culture" and which systematically tends to foster static and essentialist conceptions of "culture" as applied to patients. Even though requirements designed to address cultural competence are increasingly incorporated into medical school curricula, medical students as a group may be forgiven for failing to take these very seriously as long as they perceive that they are quite distinct from the real competence that they need to acquire. To change this situation will require challenging the tendency to assume that "real" and "cultural" must be mutually exclusive terms. Physicians' medical knowledge is no less cultural for being real, just as patients' lived experiences and perspectives are no less real for being cultural. Whether this lesson can be effectively conveyed within existing curricular frameworks remains an open question. Cultural competence curricula will, perhaps, achieve their greatest success if and when they put themselves out of business-if and when, that is, medical competence itself is transformed to such a degree that it is no longer possible to imagine it as not also being "cultural."

When patients with inflammatory bowel disease (IBD) are admitted to the hospital with a flare of acute severe colitis, the possibility of a concurrent cytomegalovirus (CMV) infection causing or worsening the colitis is often considered. IBD patients are usually immunosuppressed, and therefore presumably at increased risk for active CMV infection and disease. Multiple techniques are used to diagnose CMV infection, including endoscopy, histology, serology, viral culture, CMV antigen testing, and CMV DNA testing. Immunohistochemistry (IHC) performed on colon biopsy specimens with monoclonal antibodies directed against CMV immediate early antigen is considered by most to be the current gold standard for diagnosis. The prevalence of CMV infection in acute severe colitis appears to be 21-34%, and the prevalence of CMV infection in the steroid refractory subgroup of these patients is 33-36%. After antiviral therapy, colitis remission rates in IBD patients with CMV infection range from 67% to 100%, though CMV histological infection or the presence of circulating virus alone is not always associated with steroid resistance, and may not require antiviral therapy.

BACKGROUND: American Thyroid Association guidelines currently recommend the selective use of radioactive iodine (RAI) therapy in patients with well differentiated thyroid cancer (WDTC). Despite these guidelines, RAI ablation has been used routinely in all but the very lowest risk patients with thyroid cancer over the last 30 years. The objective of this study was to evaluate patterns of RAI use and elevated risk of secondary primary malignancies (SPM) in patients with low-risk (T1N0) WDTC. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to analyze trends in RAI use over time in the United States. To determine the excess risk of SPM, the standardized incidence ratio (SIR) and excess absolute risk (EAR) of various cancers were calculated in the 2 cohorts. Between 1973 and 2007, 37,176 patients with WDTC were followed in the SEER Program, equating to 408,750 person-years at risk (PYR). In total, 14,589 patients received RAI, and SPMs were observed in 3223 patients. RESULTS: During the study period, the rate of RAI use in patients with low-risk (T1N0) WDTC increased from 3.3% to 38.1%. For low-risk patients, the SIR of SPM was 1.21 (95% confidence interval [CI], 0.93-1.54), and the EAR was 4.6 excess cases per 10,000 PYR. SPM with significantly elevated risk because of RAI were salivary gland malignancies (SIR = 11.13; 95% CI, 1.35-40.2) and leukemia (SIR = 5.68; 95% CI, 2.09-12.37). The excess risk of leukemia was significantly greater in patients aged <45 years (SIR = 5.32; 95% CI, 2.75-9.30) compared with the excess risk in older patients (SIR = 2.26; 95% CI, 1.43-3.39). CONCLUSIONS: The increased risk of a SPM in patients with low-risk (T1N0) WDTC, along with a lack of data demonstrating improved survival outcomes with adjuvant RAI, provide a compelling argument in favor of rationing the use of RAI in this patient population.

Birmingham, Patrick K. MD; Cheney, Frederick W. MD; Ward, Richard J. MD, MEd Author Information

We have generated an optimized inducible recombination system for conditional gene targeting based on a Cre recombinase-steroid receptor fusion. This configuration allows efficient Cre-mediated recombination in most organs of the mouse upon induction, without detectable background activity. An ES cell line, was established that carries the inducible recombinase and a loxP-flanked lacZ reporter gene. Out of this line, completely ES cell-derived mice were efficiently produced through tetraploid blastocyst complementation, without the requirement of mouse breeding. Our findings provide a new concept allowing the generation of inducible mouse mutants within 6 months, as compared to 14 months using the current protocol.

PURPOSE: To identify and model the effects of sleep loss and fatigue on resident-physicians' professional lives and personal well-being. METHOD: In 2001-02, 149 residents at five U.S. academic health centers and from six specialties (obstetrics-gynecology, emergency medicine, family medicine, internal medicine, pediatrics, surgery) were recruited for the study. Residents were all in good standing in their programs. In a mixed-methods design, focus groups consisted of an average of seven (range, three to 14) individuals in the same year of training and residency program, for a total of 60 interns and 89 senior residents. Trained moderators conducted focus groups using a standardized, semistructured discussion guide. Participants also completed a 30-item quantitative questionnaire assessing sleepiness and workplace sleep attitudes that included the Epworth Sleepiness Scale (ESS). RESULTS: Residents described multiple adverse effects of sleep loss and fatigue on learning and cognition; job performance, including professionalism and task performance; and personal life, including personal well-being and relationships with spouse or significant other and family. Only 16% of the sample scored within the "normal" range on the ESS; 84% scored in the range for which clinical intervention is indicated. Sleepiness was consistent across institution, specialty, years of training, age, gender, marital status, and having children. CONCLUSIONS: More residents perceived that sleep loss and fatigue had major impact on their personal lives during residency, leaving many personal and social activities and meaningful personal pleasures deferred or postponed. Sleep loss and fatigue also had major impact on residents' abilities to perform their work. This finding further substantiates the growing concern about the potential impact on professional development. These observations should be taken into account in developing new training guidelines and educational interventions for housestaff.