Harvard Affiliated Emergency Medicine Residency

Hyperphosphatemia, calcitriol deficiency, and secondary hyperparathyroidism (SHPT) are common complications of chronic kidney disease (CKD). Fibroblast growth factor-23 (FGF-23) is a novel phosphaturic hormone that also inhibits renal 1alpha-hydroxylase activity and thus may be involved in the pathogenesis of SHPT. Several hypotheses were tested: that FGF-23 increases as renal function declines; is linearly associated with serum phosphate levels; is associated with increased phosphaturia independent of parathyroid hormone (PTH); and is associated with decreased calcitriol levels independent of renal function, hyperphosphatemia, and vitamin D stores. FGF-23, PTH, 25(OH)D3, calcitriol, calcium, phosphate, and urinary fractional excretion of phosphate (Fe(PO4)) were measured in 80 CKD patients. Multiple linear regression was used to test the hypotheses. FGF-23 and PTH were inversely associated with estimated GFR (eGFR), whereas calcitriol levels were linearly associated with eGFR. Hyperphosphatemia and hypocalcemia were present in only 12 and 6% of patients, respectively, all of whose eGFR was <30. Increased Fe(PO4) was associated with decreased eGFR, and both increased FGF-23 and PTH were independently associated with increased Fe(PO4). Increased FGF-23 and decreased 25(OH)D3 were independent predictors of decreased calcitriol, but the effects on calcitriol levels of renal function itself and hyperphosphatemia were completely extinguished by adjusting for FGF-23. It is concluded that FGF-23 levels increase early in CKD before the development of serum mineral abnormalities and are independently associated with serum phosphate, Fe(PO4), and calcitriol deficiency. Increased FGF-23 may contribute to maintaining normal serum phosphate levels in the face of advancing CKD but may worsen calcitriol deficiency and thus may be a central factor in the early pathogenesis of SHPT.

IN KITTENS, deprivation of form and light over several months can lead to marked abnormalities in the visual pathway. These include behavioral blind-ness, morphological changes in the lateral geniculate body, and disruption of innately determined cortical connections (2, 6-8). This type of plasticity

We analyze a particular pedagogy for learning to interact productively with students and subject matter, which we call “rehearsal.” Our goal is to specify a way in which teacher educators (TEs) and novice teachers (NTs) can interact around teaching that is both embedded in practice and amenable to analysis. We address two main research questions: (a) What do TEs and NTs do together during the kind of rehearsals we have developed to prepare novices for the complex, interactive work of teaching? and (b) Where, in what they do, are there opportunities for NTs to learn to enact the principles, practices, and knowledge entailed in ambitious teaching? We detail what happens in rehearsals using quantitative and qualitative methods. We begin with the results of our quantitative analyses to characterize how typical rehearsals were structured and what was worked on. We then show how NTs and TEs worked together to enable novices to study principled practice through qualitative analyses of a particularly salient aspect of ambitious teaching, namely, eliciting and responding to students’ performance.

We propose a new white matter atlas creation method that learns a model of the common white matter structures present in a group of subjects. We demonstrate that our atlas creation method, which is based on group spectral clustering of tractography, discovers structures corresponding to expected white matter anatomy such as the corpus callosum, uncinate fasciculus, cingulum bundles, arcuate fasciculus, and corona radiata. The white matter clusters are augmented with expert anatomical labels and stored in a new type of atlas that we call a high-dimensional white matter atlas. We then show how to perform automatic segmentation of tractography from novel subjects by extending the spectral clustering solution, stored in the atlas, using the Nystrom method. We present results regarding the stability of our method and parameter choices. Finally we give results from an atlas creation and automatic segmentation experiment. We demonstrate that our automatic tractography segmentation identifies corresponding white matter regions across hemispheres and across subjects, enabling group comparison of white matter anatomy.

There is currently growing interest in using mobile phones to support the treatment of psychotic disorders, such as schizophrenia. However, the widespread implementation of these interventions will ultimately depend upon patients' access to mobile devices and their willingness to engage with mobile health ("mHealth"). Thus, we conducted a systematic review and meta-analysis to assess mobile phone ownership and interest in mHealth among patients with psychosis. An electronic search of Ovid MEDLINE, Embase, PsycINFO, CENTRAL, AMED, Health Technology Assessment Database, and Health Management Information Consortium Database was conducted, using search terms synonymous with mobile phones and psychotic disorders. The initial literature search yielded 2572 results. Fifteen studies matched eligibility criteria, reporting data from 12 independent samples of psychiatric patients (n = 3227). Data pertaining to mobile phone ownership, usage, and opinions on mHealth among patients with psychotic disorders were extracted from these studies, and meta-analytic techniques were applied. The overall mobile phone ownership rate was 66.4% (95% CI = 54.1%-77.6%). However, we found strong statistical evidence that mobile phone ownership has been significantly increasing since 2007, and the rate among patients surveyed in the last 2 years was 81.4% (n = 454). Furthermore, in surveys of mHealth acceptability, the majority of patients responded in favor of using mobile phones to enhance contact with services and support self-management. Considering the increasing availability of mobile phones and the broad acceptability of mHealth among patients, there is now a need to develop and evaluate mHealth interventions to enhance healthcare services for people with psychosis.

Growing use of U.S. emergency departments, cited as a key contributor to rising health care costs, has become a leading target of health care reform. Since 1993, emergency departments have played an increasing role in hospital admissions for almost all conditions.

BACKGROUND: Accurate reporting of patient symptoms is critical for diagnosis and therapeutic monitoring in psychiatry. Smartphones offer an accessible, low-cost means to collect patient symptoms in real time and aid in care. OBJECTIVE: To investigate adherence among psychiatric outpatients diagnosed with major depressive disorder in utilizing their personal smartphones to run a custom app to monitor Patient Health Questionnaire-9 (PHQ-9) depression symptoms, as well as to examine the correlation of these scores to traditionally administered (paper-and-pencil) PHQ-9 scores. METHODS: A total of 13 patients with major depressive disorder, referred by their clinicians, received standard outpatient treatment and, in addition, utilized their personal smartphones to run the study app to monitor their symptoms. Subjects downloaded and used the Mindful Moods app on their personal smartphone to complete up to three survey sessions per day, during which a randomized subset of PHQ-9 symptoms of major depressive disorder were assessed on a Likert scale. The study lasted 29 or 30 days without additional follow-up. Outcome measures included adherence, measured by the percentage of completed survey sessions, and estimates of daily PHQ-9 scores collected from the smartphone app, as well as from the traditionally administered PHQ-9. RESULTS: Overall adherence was 77.78% (903/1161) and varied with time of day. PHQ-9 estimates collected from the app strongly correlated (r=.84) with traditionally administered PHQ-9 scores, but app-collected scores were 3.02 (SD 2.25) points higher on average. More subjects reported suicidal ideation using the app than they did on the traditionally administered PHQ-9. CONCLUSIONS: Patients with major depressive disorder are able to utilize an app on their personal smartphones to self-assess their symptoms of major depressive disorder with high levels of adherence. These app-collected results correlate with the traditionally administered PHQ-9. Scores recorded from the app may potentially be more sensitive and better able to capture suicidality than the traditional PHQ-9.

Emergency medicine (EM) presents many cognitive, social, and systems challenges to practitioners. Coordination and communication under stress between and among individuals and teams representing a number of disciplines are critical for optimal care of the patient. The specialty is characterized by uncertainty, complexity, rapidly shifting priorities, a dependence on teamwork, and elements common to other risky domains such as perioperative medicine and aviation. High-fidelity simulators have had a long tradition in aviation, and in the past few years have begun to have a significant impact in anesthesiology. A national, multicenter research program to document the costs of teamwork failures in EM and provide a remedy in the form of an Emergency Team Coordination Course has developed to the point that high-fidelity medical simulators will be added to the hands-on training portion of the course. This paper describes an evolving collaborative effort by members of the Center for Medical Simulation, the Harvard Emergency Medicine Division, and the MedTeams program to design, demonstrate, and refine a high-fidelity EM simulation course to improve EM clinician performance, increase patient safety, and decrease liability. The main objectives of the paper are: 1) to present detailed specifications of tools and techniques for high-fidelity medical simulation; 2) to share the results of a proof-of-concept EM simulation workshop introducing multiple mannequin/ three-patient scenarios; and 3) to focus on teamwork applications. The authors hope to engage the EM community in a wide-ranging discussion and handson exploration of these methods.

OBJECTIVES: To compare outcomes of patients admitted to postacute skilled nursing facilities with delirium, subsyndromal delirium, and no delirium. DESIGN: Observational cohort study. SETTING: Seven skilled nursing facilities that specialize in postacute care within a single metropolitan region. PARTICIPANTS: Five hundred four subjects chosen from 1,248 consenting subjects aged 65 and older who underwent mental status testing within 5 days of admission to the participating facilities. Subjects who met full Confusion Assessment Method (CAM) criteria were classified as delirious, those with one or more CAM criteria were classified as having subsyndromal delirium, and those with no CAM features were classified as having no delirium. All subjects with delirium and with available medical records were included. A random subset of subjects with no delirium and subsyndromal delirium with available medical records was included. MEASUREMENTS: The medical records of all subjects underwent a structured review by trained research nurses who were masked to the subjects' initial delirium status. Records were reviewed for the development of new complications within the postacute setting and to determine whether the subjects were discharged within 30 days and, if so, the discharge destination. The National Death Index was used to assess 6-month mortality. RESULTS: Subjects with delirium were more likely to experience one or more complications than subjects with no delirium (73% vs 41%, P < .01). Within 30 days of postacute admission, subjects with delirium were more than twice as likely to be rehospitalized (30% vs 13%), and less than half as likely to be discharged to the community (30% vs 73%) than subjects without delirium (differences P < .01). Subjects with subsyndromal delirium had outcomes intermediate between those with and without delirium. Finally, subjects admitted to the postacute setting with delirium experienced a 6-month mortality rate of 25.0%, compared with 5.7% in subjects admitted without delirium. Subjects with subsyndromal delirium had a 6-month mortality rate of 18.3%. CONCLUSION: Patients admitted to postacute skilled nursing facilities with delirium are more likely to experience complications, rehospitalization, and death than patients without delirium. These findings support the need for improved case finding and management of delirium in postacute care.

BACKGROUND: Debate regarding the optimal initial treatment for anterior cruciate ligament (ACL) injuries in children and adolescents has not resulted in a clear consensus for initial nonoperative treatment or operative reconstruction. HYPOTHESIS/PURPOSE: The purpose of this meta-analysis was to systematically analyze aggregated data from the literature to determine if a benefit exists for either nonoperative or early operative treatment for ACL injuries in the pediatric patient. The hypothesis was that combined results would favor early operative reconstruction with respect to posttreatment episodes of instability/pathological laxity, symptomatic meniscal tears, clinical outcome scores, and return to activity. STUDY DESIGN: Meta-analysis. METHODS: A literature selection process included the extraction of data on the following clinical variables: symptomatic meniscal tears, return to activities, clinical outcome scores, return to the operating room, and posttreatment instability/pathological laxity. A symptomatic meniscal tear was defined as occurring after the initial presentation, limiting activity, and requiring further treatment. Instability/pathological laxity was defined for the sake of this study as having an episode of giving way, a grade ≥2 Lachman/pivot-shift test result, or a side-to-side difference of >4 mm as measured by the KT-1000 arthrometer. All studies were evaluated using a formal study quality analysis. Meta-analysis was conducted for aggregated data in each category. RESULTS: Six studies (217 patients) comparing operative to nonoperative treatment and 5 studies (353 patients) comparing early to delayed reconstruction were identified. Three studies reported posttreatment instability/pathological laxity; 13.6% of patients after operative treatment experienced instability/pathological laxity compared with 75% of patients after nonoperative treatment (P < .01). Two studies reported symptomatic meniscal tears; patients were over 12 times more likely to have a medial meniscal tear after nonoperative treatment than after operative treatment (35.4% vs 3.9%, respectively; P = .02). A significant difference in scores between groups was noted in 1 of 2 studies reporting International Knee Documentation Committee (IKDC) scores (P = .002) and in 1 of 2 studies reporting Tegner scores (P = .007). Two studies reported return to activity; none of the patients in the nonoperative groups returned to their previous level of play compared with 85.7% of patients in the operative groups (P < .01). Study quality analysis revealed that the majority of the studies were inconsistent in reporting outcomes. CONCLUSION: Meta-analysis revealed multiple trends that favor early surgical stabilization over nonoperative or delayed treatment. Patients after nonoperative and delayed treatment experienced more instability/pathological laxity and inability to return to previous activity levels than did patients treated with early surgical stabilization.

Dislocation is one of the most common complications after total hip arthroplasty (THA). Risk factors include neuromuscular and cognitive disorders, patient non-compliance, and previous hip surgery. Surgical considerations that must be addressed include approach, soft-tissue tension, component positioning, impingement, head size, acetabular liner profile, and surgeon experience. Recent improvements in posterior soft-tissue repair after primary THA have shown a reduced incidence of dislocation. When dislocation occurs, a thorough history, physical examination, and radiographic assessment help in choosing the proper intervention. Closed reduction usually is possible, and nonsurgical management frequently succeeds in preventing recurrence. When these measures fail, first-line revision options should target the underlying etiology. This most often involves tensioning or augmentation of soft tissues, as in capsulorrhaphy or trochanteric advancement; correction of malpositioned components; or improving the head-to-neck ratio. If instability persists, or if a primary THA repeatedly dislocates without a clear cause, a constrained cup or bipolar femoral prosthesis may be as effective as a salvage procedure.

BACKGROUND: Despite growing interest in mobile mental health and utilization of smartphone technology to monitor psychiatric symptoms, there remains a lack of knowledge both regarding patient ownership of smartphones and their interest in using such to monitor their mental health. OBJECTIVE: To provide data on psychiatric outpatients' prevalence of smartphone ownership and interest in using their smartphones to run applications to monitor their mental health. METHODS: We surveyed 320 psychiatric outpatients from four clinics around the United States in order to capture a geographically and socioeconomically diverse patient population. These comprised a state clinic in Massachusetts (n=108), a county clinic in California (n=56), a hybrid public and private clinic in Louisiana (n=50), and a private/university clinic in Wisconsin (n=106). RESULTS: Smartphone ownership and interest in utilizing such to monitor mental health varied by both clinic type and age with overall ownership of 62.5% (200/320), which is slightly higher than the average United States' rate of ownership of 58% in January 2014. Overall patient interest in utilizing smartphones to monitor symptoms was 70.6% (226/320). CONCLUSIONS: These results suggest that psychiatric outpatients are interested in using their smartphones to monitor their mental health and own the smartphones capable of running mental healthcare related mobile applications.

Dynamic and reversible RNA modifications such as N6-methyladenosine (m6A) can play important roles in regulating messenger RNA (mRNA) splicing, export, stability and translation. Defective mRNA modification through altered expression of the methyltransferase and/or demethylases results in developmental defects and cancer progression. Identifying modified mRNAs, annotating the distribution of modification sites across the mRNA, as well as characterizing and comparing other modification features are essential for studying the function and elucidating the mechanism of mRNA modifications. Several methods including methylated RNA immunoprecipitation and sequencing (MeRIP-seq) are available for the detection of mRNA modifications. However, a convenient and comprehensive tool to annotate diverse kinds of mRNA modifications in different species is lacking. Here, we developed RNAmod (https://bioinformatics.sc.cn/RNAmod), an interactive, one-stop, web-based platform for the automated analysis, annotation, and visualization of mRNA modifications in 21 species. RNAmod provides intuitive interfaces to show outputs including the distribution of RNA modifications, modification coverage for different gene features, functional annotation of modified mRNAs, and comparisons between different groups or specific gene sets. Furthermore, sites of known RNA modification, as well as binding site data for hundreds of RNA-binding proteins (RBPs) are integrated in RNAmod to help users compare their modification data with known modifications and to explore the relationship with the binding sites of known RBPs. RNAmod is freely available and meets the emerging need for a convenient and comprehensive analysis tool for the fast-developing RNA modification field.

Psychotic disorders due to a known medical illness or substance use are collectively termed secondary psychoses. In this paper, we first review the historic evolution of the concept of secondary versus primary psychosis and how this distinction supplanted the earlier misleading classification of psychoses into organic and functional. We then outline the clinical features and approach to the diagnosis of secondary psychotic disorders. Features such as atypical presentation, temporal relation to detectable medical cause, evidence of direct physiological causal relationship to the etiological agent, and the absence of evidence of a primary psychotic illness that may better explain the presentation suggest consideration of a secondary psychosis. Finally, we discuss how careful studies of secondary psychotic disorders can help elucidate the pathophysiology of primary, or idiopathic, psychotic disorders such as schizophrenia. We illustrate this issue through a discussion of three secondary psychotic disorders - psychoses associated with temporal lobe epilepsy, velocardiofacial syndrome, and N-methyl D-aspartate (NMDA) receptor encephalitis - that can, respectively, provide neuroanatomical, genetic, and neurochemical models of schizophrenia pathogenesis.

Radiation therapy is a critical treatment modality in the management of patients with gynecologic tumors. New highly conformal external-beam and brachytherapy techniques have led to important reductions in recurrence and patient morbidity and mortality. However, patients who receive pelvic radiation for gynecologic malignancies may experience a unique constellation of toxicity because of the anatomic locations, combination with concurrent chemotherapy and/or surgery, as well as potential surgical interventions. Although side effects are often categorized into acute versus late toxicities, several late toxicities represent continuation and evolution of the same pathologic process. Comorbidities and radiation dose can significantly increase the risk of morbidity. Current understanding of the incidence of various morbidities in patients treated with current radiation techniques for gynecologic malignancies, the impact of chemotherapy and surgery, treatment options for those effects, and future areas of research are highlighted.

STUDY DESIGN: Systematic review of the literature and analysis of pooled data. OBJECTIVES: To better understand the incidence of thromboembolic disease in postoperative spinal patients, and to establish a starting point for defining appropriate postoperative prophylaxis protocols. SUMMARY OF BACKGROUND DATA: The risk of thromboembolic disease is well studied for some orthopedic procedures. However, the incidence of postoperative thromboembolic disease is less well-defined in patients who have had spinal surgery. METHODS: The MEDLINE database was queried using the search terms deep venous thrombosis or DVT, pulmonary embolus, thromboembolic disease, and spinal or spine surgery. Abstracts of all identified articles were reviewed. Detailed information from eligible articles was extracted. Data were compiled and analyzed by simple summation methods when possible to stratify rates of DVT and/or pulmonary embolus for a given prophylaxis protocol, screening method, and type of spinal surgery. RESULTS: Twenty-five articles were eligible for full review. DVT risk ranged from 0.3% to 31%, varying between patient populations and methods of surveillance. Pooling data from the 25 studies, the overall rate of DVT was 2.1%. DVT rate was influenced by prophylaxis method: no prophylaxis, 2.7%; compression stockings (CS), 2.7%; pneumatic sequential compression device (PSCD), 4.6%; PSCD and CS, 1.3%; chemical anticoagulants, 0.6%; and inferior vena cava filters with/without another method of prophylaxis, 22%. DVT rate was also influenced by the method of diagnosis, ranging from 1% to 12.3%. CONCLUSION: As risk of DVT after routine elective spinal surgery is fairly low, it seems reasonable to use CS with PSCD as a primary method of prophylaxis. There is insufficient evidence to support or refute the use of chemical anticoagulants in routine elective spinal surgery. In addition, there is insufficient evidence to suggest that screening patients undergoing elective spinal surgery with ultrasound or venogram is routinely warranted.

Four hundred sixty-seven adult victims of blunt trauma undergoing cervical spine radiography (CSR) were prospectively studied to identify any clinical parameters which would aid in the selective application of CSR. Eight persons (1.7%), six of whom were alert and two who presented comatose, sustained cervical spine injuries. In this study, persons injured in falls demonstrated a statistically significant greater risk of cervical spine injury compared to those injured in motor vehicle accidents (p = 0.001). In alert trauma victims, a statistical correlation with cervical spine injury was noted for individuals who had complaints of neck discomfort (p = 0.028) and for patients who manifested tenderness to neck palpation (p = 0.000039). No cervical spine injury was noted in any alert, not intoxicated, neurologically intact patient who had no complaints of neck discomfort upon questioning or palpation. We conclude that alert trauma victims with no complaints of neck discomfort upon questioning and with no tenderness on neck palpation need not undergo CSR.

BACKGROUND: Worldwide, one-seventh of cervical cancers occur in China, which lacks a national screening program. By evaluating the diagnostic accuracy of self-collected cervicovaginal specimens tested for human papillomavirus (HPV) DNA (Self-HPV testing) in China, we sought to determine whether Self-HPV testing may serve as a primary cervical cancer screening method in low-resource settings. METHODS: We compiled individual patient data from five population-based cervical cancer-screening studies in China. Participants (n = 13 140) received Self-HPV testing, physician-collected cervical specimens for HPV testing (Physician-HPV testing), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Screen-positive women underwent colposcopy and confirmatory biopsy. We analyzed the accuracies of pooled Self-HPV testing, Physician-HPV testing, VIA, and LBC to detect biopsy-confirmed cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and CIN3+. All statistical tests were two-sided. RESULTS: Of 13 004 women included in the analysis, 507 (3.9%) were diagnosed as CIN2+, 273 (2.1%) as CIN3+, and 37 (0.3%) with cervical cancer. Self-HPV testing had 86.2% sensitivity and 80.7% specificity for detecting CIN2+ and 86.1% sensitivity and 79.5% specificity for detecting CIN3+. VIA had statistically significantly lower sensitivity for detecting CIN2+ (50.3%) and CIN3+ (55.7%) and higher specificity for detecting CIN2+ (87.4%) and CIN3+ (86.9%) (all P values < .001) than Self-HPV testing, LBC had lower sensitivity for detecting CIN2+ (80.7%, P = .015), similar sensitivity for detecting CIN3+ (89.0%, P = .341), and higher specificity for detecting CIN2+ (94.0%, P < .001) and CIN3+ (92.8%, P < .001) than Self-HPV testing. Physician-HPV testing was more sensitive for detecting CIN2+ (97.0%) and CIN3+ (97.8%) but similarly specific for detecting CIN2+ (82.7%) and CIN3+ (81.3%) (all P values <.001) than Self-HPV testing. CONCLUSIONS: The sensitivity of Self-HPV testing compared favorably with that of LBC and was superior to the sensitivity of VIA. Self-HPV testing may complement current screening programs by increasing population coverage in settings that do not have easy access to comprehensive cytology-based screening.

The Millennium Development Goals have ended and the Sustainable Development Goals have begun, marking a shift in the global health landscape. The frame of reference has changed from a focus on 8 development priorities to an expansive set of 17 interrelated goals intended to improve the well-being of all people. In this time of change, several groups, including the Lancet Commission on Global Surgery, have brought a critical problem to the fore: 5 billion people lack access to safe, affordable surgical and anaesthesia care when needed. The magnitude of this problem and the world's new focus on strengthening health systems mandate reimagined roles for and renewed commitments from high income country actors in global surgery. To discuss the way forward, on 6 May 2015, the Commission held its North American launch event in Boston, Massachusetts. Panels of experts outlined the current state of knowledge and agreed on the roles of surgical colleges and academic medical centres; trainees and training programmes; academia; global health funders; the biomedical devices industry, and news media and advocacy organisations in building sustainable, resilient surgical systems. This paper summarises these discussions and serves as a consensus statement providing practical advice to these groups. It traces a common policy agenda between major actors and provides a roadmap for maximising benefit to surgical patients worldwide. To close the access gap by 2030, individuals and organisations must work collectively, interprofessionally and globally. High income country actors must abandon colonial narratives and work alongside low and middle income country partners to build the surgical systems of the future.

Smith, Benjamin D. MD; Arthur, Douglas W. MD; Buchholz, Thomas A. MD; Haffty, Bruce G. MD; Hahn, Carol A. MD; Hardenbergh, Patricia H. MD; Julian, Thomas B. MD; Marks, Lawrence B. MD; Todor, Dorin A. PhD; Vicini, Frank A. MD; Whelan, Timothy J. MD; White, Julia MD; Wo, Jennifer Y. MD; Harris, Jay R. MD Author Information