Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Relapsing Malaria: A Case Report of Primaquine Resistance

Primaquine (an 8-aminoquinoline malarial therapy) is the only FDA-approved therapy to treat the hypnozoite stage of P. vivax. We think of relapse occurring because of parasitic resistance or poor compliance secondary to drug toxicities. However, in patients with repeated treatment failure, we must consider CYP-450 mutations affecting drug metabolism as an important cause of relapse. A 47-year-old man who travelled to a jungle in Venezuela was diagnosed with P. falciparum and P. vivax in July 2015. He was treated with seven rounds of primaquine-based therapy in the following year, all resulted in relapse without further exposure to endemic areas. On his eighth presentation, he was found to have CYP-4502D6 mutation that affected the metabolism and activation of primaquine. Thereafter, he was treated without relapse. Primaquine efficacy depends on many factors. Understanding the mechanism responsible for malaria relapse is paramount for successful treatment and reduction in morbidity and mortality. This case illustrates the importance of considering cytochrome mutations that affect drug efficacy in cases of relapsing malaria

Difficult Delivery and Neonatal Resuscitation: A Novel Simulation for Emergency Medicine Residents

Introduction: Newborn delivery and resuscitation are rare, but essential, emergency medicine (EM) skills. We evaluated the effect of simulation on EM residents’ knowledge, confidence, and clinical skills in managing shoulder dystocia and neonatal resuscitation.Methods: We developed a novel simulation that integrates a shoulder dystocia with neonatal resuscitation and studied a convenience sample of EM residents. Each 15-minute simulation was run with one learner, a simulated nurse, and a standardized patient in situ in the emergency department. The learner was required to reduce a shoulder dystocia and then perform neonatal resuscitation. We debriefed with plus/delta format, standardized teaching points, and individualized feedback. We assessed knowledge with a nine-question multiple choice test, confidence with five-point Likert scales, and clinical performance using a checklist of critical actions. Residents repeated all measures one year after the simulation.Results: A total of 23 residents completed all measures. At one-year post-intervention, residents scored 15% higher on the knowledge test. All residents increased confidence in managing shoulder dystocia on a five-point Likert scale (1.4 vs 2.8) and 80% increased confidence in performing neonatal resuscitation (1.8 vs 3.0). Mean scores on the checklist of critical actions improved by 19% for shoulder dystocia and by 27% for neonatal resuscitation.Conclusion: Implementing simulation may improve EM residents’ knowledge, confidence, and clinical skills in managing shoulder dystocia and neonatal resuscitation

Difficult Delivery and Neonatal Resuscitation: A Novel Simulation for Emergency Medicine Residents

Introduction: Newborn delivery and resuscitation are rare, but essential, emergency medicine (EM) skills. We evaluated the effect of simulation on EM residents’ knowledge, confidence, and clinical skills in managing shoulder dystocia and neonatal resuscitation.Methods: We developed a novel simulation that integrates a shoulder dystocia with neonatal resuscitation and studied a convenience sample of EM residents. Each 15-minute simulation was run with one learner, a simulated nurse, and a standardized patient in situ in the emergency department. The learner was required to reduce a shoulder dystocia and then perform neonatal resuscitation. We debriefed with plus/delta format, standardized teaching points, and individualized feedback. We assessed knowledge with a nine-question multiple choice test, confidence with five-point Likert scales, and clinical performance using a checklist of critical actions. Residents repeated all measures one year after the simulation.Results: A total of 23 residents completed all measures. At one-year post-intervention, residents scored 15% higher on the knowledge test. All residents increased confidence in managing shoulder dystocia on a five-point Likert scale (1.4 vs 2.8) and 80% increased confidence in performing neonatal resuscitation (1.8 vs 3.0). Mean scores on the checklist of critical actions improved by 19% for shoulder dystocia and by 27% for neonatal resuscitation.Conclusion: Implementing simulation may improve EM residents’ knowledge, confidence, and clinical skills in managing shoulder dystocia and neonatal resuscitation

The Columbia-Bronx VA amalgamative clerkship: an effective, 12-week, integrated, longitudinal clinical experience

Background: Many medical schools have adopted the longitudinal integrated clerkship (LIC) model in response to calls for increased continuity in clinical learning environments. However, because of implementation challenges, such programs are not feasible at some institutions or are limited to a small number of students. Objective: In January 2014, Columbia University College of Physicians and Surgeons (P&S) recognized the need to explore different LIC formats and began offering four, 12-week amalgamative clerkships (AC). Students within this curricular track experienced primary care, internal medicine ‘away’, orthopedic surgery, urology, and an elective in an integrated format. Design: P&S developed the AC in partnership with the James J. Peters VA Medical Center in Bronx, NY (BVA). All patient care and educational conferences took place at the BVA during the 12-week experience. The learning objectives of the AC were aligned to the learning objectives of a 52-week LIC also offered at Columbia. An evaluation process was developed to determine student learning experiences and preliminary outcomes, including how well the LIC-related objectives could be achieved in a shorter period of time. Results: In 2015, P&S collected AC evaluation data through three student feedback sessions. Students reported that the AC provided opportunity for patient continuity, patient-centered care approaches, meaningful roles for students, career development opportunities, and health systems awareness. Conclusions: Early outcomes indicate that the BVA AC provides a degree of longitudinality that can influence student perceptions of patient care, career development, and health systems, consistent with the larger LIC. The team continues to gather additional data on students’ experiences and investigate additional sites that have potential to serve as future AC learning environments

Liver Stiffness Decreases Rapidly in Response to Successful Hepatitis C Treatment and Then Plateaus

<div><p>Background and Aim</p><p>To investigate the impact of a sustained virological response (SVR) to hepatitis C virus (HCV) treatment on liver stiffness (LS).</p><p>Methods</p><p>LS, measured by transient elastography (FibroScan), demographic and laboratory data of patients treated with interferon (IFN)-containing or IFN-free regimens who had an SVR24 (undetectable HCV viral load 24 weeks after the end of treatment) were analyzed using two-tailed paired t-tests, Mann-Whitney Wilcoxon Signed-rank tests and linear regression. Two time intervals were investigated: pre-treatment to SVR24 and SVR24 to the end of follow-up. LS scores ≥ 12.5 kPa indicated LS-defined cirrhosis. A p-value below 0.05 was considered statistically significant.</p><p>Results</p><p>The median age of the patients (n = 100) was 60 years [IQR (interquartile range) 54–64); 72% were male; 60% were Caucasian; and 42% had cirrhosis pre-treatment according to the FibroScan measurement. The median LS score dropped from 10.40 kPa (IQR: 7.25–18.60) pre-treatment to 7.60 kPa (IQR: 5.60–12.38) at SVR24, p <0.01. Among the 42 patients with LS-defined cirrhosis pre-treatment, 25 (60%) of patients still had LS scores ≥ 12.5 kPa at SVR24, indicating the persistence of cirrhosis. The median change in LS was similar in patients receiving IFN-containing and IFN-free regimens: -1.95 kPa (IQR: -5.75 –-0.38) versus -2.40 kPa (IQR: -7.70 –-0.23), p = 0.74. Among 56 patients with a post-SVR24 LS measurement, the LS score changed by an additional -0.90 kPa (IQR: -2.98–0.5) during a median follow-up time of 1.17 (IQR: 0.88–1.63) years, which was not a statistically significant decrease (p = 0.99).</p><p>Conclusions</p><p>LS decreased from pre-treatment to SVR24, but did not decrease significantly during additional follow-up. Earlier treatment may be needed to reduce the burden of liver disease.</p></div