Cefepime-Induced Neurotoxicity Presenting with Nonconvulsive Status Epilepticus Admitted as a Stroke Alert.

BACKGROUND Cefepime-induced neurotoxicity has been described in intensive care units (ICUs) and neuro ICU settings, occurring in patients started on cefepime for management of severe infections and sepsis. Most cases occur within 1 to 10 days after starting the drug. We publish a case that occurred on the general medical ward of a patient who had been on cefepime therapy for 4 weeks prior to admission. The aim of this study was to improve the knowledge of this serious condition to general internists as our patient was being managed on the general medical ward. CASE REPORT A 72-year-old female on prolonged intravenous antibiotics for sacral and pelvic osteomyelitis presented with acute encephalopathy and aphasia in the setting of an acute kidney injury. Due to the acute focal neurologic deficit, she was initially admitted as a stroke alert. After a negative magnetic resonance imaging (MRI) of the brain, an electroencephalogram (EEG) was pursued and showed nonconvulsive status epilepticus (NCSE). NCSE was likely a result of cefepime therapy in the setting of an acute kidney injury. CONCLUSIONS Cefepime-induced neurotoxicity should be suspected in any patient on cefepime therapy who develops acute changes in mental status, myoclonus, or evidence of seizures. Risk factors for the disease include older age, renal dysfunction, critical illness, and inappropriate dosing based upon renal function. A high index of suspicion is required and delays in diagnosis are common as there are frequently multiple possible causes for altered mental status in systemically ill patients requiring treatment with broad-spectrum antibiotics.

Development of a Multidisciplinary Medical Home Program for NICU Graduates.

OBJECTIVE: Typical primary care practices are often not equipped to meet the medical, developmental or social needs of infants discharged from a neonatal intensive care unit (NICU). These needs are exacerbated for infants and caregivers residing in poverty. This article discusses a multidisciplinary, family-centered medical home designed to address the needs of this special population. METHODS: This is a descriptive analysis of a cohort of patients in the Next Steps Program (NSP), a multidisciplinary primary care medical home. Key program elements include: continuity of care from the NICU to primary care, routine developmental surveillance, care coordination, and proactive screening to address medical and social needs. RESULTS: The NSP has become a primary referral source for local NICUs, with a total of 549 medically fragile infants enrolled from its inception in 2011 through 2016. Caregivers and patients experience psychosocial stressors at averages statistically significantly higher than the rest of the Commonwealth of Pennsylvania and the US. Although patients in the program use medical resources beyond that of typically developing infants, hospital utilization among this patient cohort is trending down. DISCUSSION: Caring for medically fragile NICU graduates can be daunting for families given the array of necessary services, supports, and resources to maximize their potential. A multidisciplinary primary care medical home, such as the NSP, is a successful model of patient care demonstrating favorable associations with health care utilization, care coordination, and addressing/improving family functioning and their experience.

Critical gaps in the medical knowledge base of eating disorders.

Eating disorders are unique in that they inherently have much medical comorbidity both as a part of restricting-type eating disorders and those characterized by purging behaviors. Over the last three decades, remarkable progress has been made in the understanding and treatment of the medical complications of eating disorders. Yet, unfortunately, there is much research that is sorely needed to bridge the gap between current medical knowledge and more effective and evidence-based medical treatment knowledge. These gaps exist in many different clinical areas including cardiology, electrolytes, gastrointestinal and bone disease. In this paper, we discuss some of the knowledge gap areas, which if bridged would help develop more effective medical intervention for this population of patients.

Real-time patient experience surveys of hospitalized medical patients.

BACKGROUND: Real-time feedback about patients' perceptions of the quality of the care they are receiving could provide physicians the opportunity to address concerns and improve these perceptions as they occur, but physicians rarely if ever receive feedback from patients in real time. OBJECTIVE: To evaluate if real-time patient feedback to physicians improves patient experience. DESIGN: Prospective, randomized, quality-improvement initiative. SETTING: University-affiliated, public safety net hospital. PARTICIPANTS: Patients and hospitalist physicians on general internal medicine units. INTERVENTION: Real-time daily patient feedback to providers along with provider coaching and revisits of patients not reporting optimal satisfaction with their care. MEASUREMENTS: Patient experience scores on 3 provider-specific questions from daily surveys on all patients and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores and percentiles on randomly selected patients. RESULTS: Changes in HCAHPS percentile ranks were substantial (communication from doctors: 60th percentile versus 39th, courtesy and respect of doctors: 88th percentile versus 23rd, doctors listening carefully to patients: 95th percentile versus 57th, and overall hospital rating: 87th percentile versus 6th (P = 0.02 for overall differences in percentiles), but we found no statistically significant difference in the top box proportions for the daily surveys or the HCAHPS survey. The median [interquartile range] top box score for the overall hospital rating question on the HCAHPS survey was higher in the intervention group than in the control group (10 [9, 10] vs 9 [8, 10], P = 0.04). CONCLUSIONS: Real-time feedback, followed by coaching and patient revisits, seem to improve patient experience.

Medical complications of bulimia nervosa and their treatments.

PURPOSE: The purpose of this article is to thoroughly review the medical complications associated with bulimia nervosa and their evidenced-based or typical treatments. METHODS: A thorough review of medical literature to cull pertinent and best articles which guide the diagnosis and treatment of the medical complications of bulimia nervosa was performed. RESULTS: There are many different medical complications of bulimia nervosa which are caused by the mode and frequency of purging. Some are fluid and electrolyte alterations from the utilized mode of purging and some are due to the local damaging effects of purging behaviors on those body sites. CONCLUSION: Bulimia nervosa is a serious mental health disorder which has many medical complications associated with it. Most are reversible with treatment.

Cardiovascular complications of anorexia nervosa: A systematic review.

OBJECTIVE: Anorexia nervosa portends the highest mortality among psychiatric diseases, despite primarily being a disease of adolescents and younger adults. Although some of this mortality risk is attributable to suicide, many deaths are likely cardiovascular in etiology. Recent studies suggest that adverse myocardial structural changes occur in this condition, which could underlie the increased mortality. Given limited prevalence of severe anorexia there is a paucity of clinical and autopsy data to discern an exact cause of death. METHODS: Given this background we conducted a systematic review of the medical literature to provide a contemporary summary of the pathobiologic sequelae of severe anorexia nervosa on the cardiovascular system. We sought to elucidate the impact of anorexia nervosa in four cardiovascular domains: structural, repolarization/conduction, hemodynamic, and peripheral vascular. RESULTS: A number of cardiac abnormalities associated with anorexia nervosa have been described in the literature, including pericardial and valvular pathology, changes in left ventricular mass and function, conduction abnormalities, bradycardia, hypotension, and dysregulation in peripheral vascular contractility. Despite the prevalent theory that malignant arrhythmias are implicated as a cause of sudden death in this disorder, data to support this causal relationship are lacking. DISCUSSION: It is reasonable to obtain routine electrocardiography and measurements of orthostatic vital signs in patients presenting with anorexia nervosa. Echocardiography is generally not indicated unless prompted by clinical signs of disease. Admission to an inpatient unit with telemetry monitoring is recommended for patients with severe sinus bradycardia or junction rhythm, marked prolongation of the corrected QT interval, or syncope.

Treatments of medical complications of anorexia nervosa and bulimia nervosa.

Inherent to anorexia nervosa and bulimia nervosa are a plethora of medical complications which correlate with the severity of weight loss or the frequency and mode of purging. Yet, the encouraging fact is that most of these medical complications are treatable and reversible with definitive care and cessation of the eating-disordered behaviours. Herein, these treatments are described for both the medical complications of anorexia nervosa and those which are a result of bulimia nervosa.

Avoiding medical complications during the refeeding of patients with anorexia nervosa.

Nutritional rehabilitation and weight restoration are key underpinnings of the treatment protocol for patients with anorexia nervosa. While their inherent state of malnutrition and weight loss is certainly not a healthy one, ironically, the very essence of the refeeding process, if done injudiciously, can also be unsafe for patients with anorexia nervosa. In this article we will provide a review of the major complications that may arise during refeeding, how best to avoid them, and how to treat them.

Hepatic sortilin regulates both apolipoprotein B secretion and LDL catabolism.

Genome-wide association studies (GWAS) have identified a genetic variant at a locus on chromosome 1p13 that is associated with reduced risk of myocardial infarction, reduced plasma levels of LDL cholesterol (LDL-C), and markedly increased expression of the gene sortilin-1 (SORT1) in liver. Sortilin is a lysosomal sorting protein that binds ligands both in the Golgi apparatus and at the plasma membrane and traffics them to the lysosome. We previously reported that increased hepatic sortilin expression in mice reduced plasma LDL-C levels. Here we show that increased hepatic sortilin not only reduced hepatic apolipoprotein B (APOB) secretion, but also increased LDL catabolism, and that both effects were dependent on intact lysosomal targeting. Loss-of-function studies demonstrated that sortilin serves as a bona fide receptor for LDL in vivo in mice. Our data are consistent with a model in which increased hepatic sortilin binds intracellular APOB-containing particles in the Golgi apparatus as well as extracellular LDL at the plasma membrane and traffics them to the lysosome for degradation. We thus provide functional evidence that genetically increased hepatic sortilin expression both reduces hepatic APOB secretion and increases LDL catabolism, providing dual mechanisms for the very strong association between increased hepatic sortilin expression and reduced plasma LDL-C levels in humans.

Scaling up for the "bottom billion": "5 x 5" implementation of community mental health care in low-income regions.

Common mental disorders pose tremendous health and social burdens in the poorest countries. This Open Forum describes a planning framework to advance effective, sustainable design and implementation of mental health services in these settings. It builds on research in treatment dissemination and on the authors' experience in several initiatives-including the Millennium Villages Project in sub-Saharan Africa and the Partners In Health system in Haiti (Zanmi Lasante). The authors describe a "pyramid of care" approach that specifies five key skill packages to address common mental disorders in low-resource settings and five implementation rules: assess context first; identify priority care pathways and map them across skill packages; specify decision supports, supervision, and triage rules; use quality improvement practices; and plan for sustainability and capacity building. The framework addresses the need for a shared vocabulary and a set of tools to coordinate and compare efforts to scale-up mental health treatment across diverse settings.

From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus.

Recent genome-wide association studies (GWASs) have identified a locus on chromosome 1p13 strongly associated with both plasma low-density lipoprotein cholesterol (LDL-C) and myocardial infarction (MI) in humans. Here we show through a series of studies in human cohorts and human-derived hepatocytes that a common noncoding polymorphism at the 1p13 locus, rs12740374, creates a C/EBP (CCAAT/enhancer binding protein) transcription factor binding site and alters the hepatic expression of the SORT1 gene. With small interfering RNA (siRNA) knockdown and viral overexpression in mouse liver, we demonstrate that Sort1 alters plasma LDL-C and very low-density lipoprotein (VLDL) particle levels by modulating hepatic VLDL secretion. Thus, we provide functional evidence for a novel regulatory pathway for lipoprotein metabolism and suggest that modulation of this pathway may alter risk for MI in humans. We also demonstrate that common noncoding DNA variants identified by GWASs can directly contribute to clinical phenotypes.

Antibodies immobilized as arrays to profile protein post-translational modifications in mammalian cells.

Previously, we demonstrated that antibodies printed on a solid support were able to detect protein-protein interaction in mammalian cells. Here we further developed the antibody array system for detecting proteins with various post-translational modifications in mammalian cells. In this novel approach, immunoprecipitated proteins were labeled with fluorescent dye followed by incubation over antibody arrays. Targeted proteins, captured by the antibodies immobilized on PVDF membrane or glass slide, were detected by means of near infrared fluorescent scanner or fluorescent microscopy. To demonstrate the application of the antibody arrays in protein post-translational modifications, we profiled protein tyrosine phosphorylation, ubiquitination, and acetylation in mammalian cells under different conditions. Our results indicate that antibody array technology can provide a powerful means of profiling a large number of proteins with different post-translational modifications in cells.