Hospital admission for neurologic disorders among 5-year survivors of noncentral nervous system tumors in childhood: A cohort study within the Adult Life after Childhood Cancer in Scandinavia study

Large, comprehensive studies of the risk for neurologic disorders among long-term survivors of noncentral nervous system (CNS) childhood cancers are lacking. Thus, the aim of our study was to assess the lifetime risk of Nordic non-CNS childhood cancer survivors for neurologic disorders. We identified 15,967 5-year survivors of non-CNS childhood cancer diagnosed in Denmark, Iceland, Finland and Sweden in 1943–2008, and 151,118 matched population comparison subjects. In-patient discharge diagnoses of neurologic disorders were used to calculate relative risks (RRs) and absolute excess risks (AERs). A neurologic disorder was diagnosed in 755 of the survivors while 370 were expected, yielding a RR of 2.0 (95% confidence interval (CI) 1.9–2.2). The highest risks were found among survivors of neuroblastoma (4.1; 95% CI 3.2–5.3) and leukemia (2.8; 95% CI 2.4–3.2). The AER decreased from 331 (278–383) excess neurologic disorders per 100,000 person-years 5–9 years after diagnosis to 82 (46–118) ≥ 20 years after diagnosis. Epilepsy was the most common diagnosis (n = 229, 1.4% of all survivors), and significantly increased risks were seen among survivors of eight out of 12 types of childhood cancer. Survivors of neuroblastoma had remarkably high risks (RR ≥ 10) for hospitalization for paralytic syndromes and hydrocephalus, while survivors of leukemia had additional high risks for dementia and encephalopathy. In conclusion, survivors of non-CNS childhood cancer are at high risk for neurologic disorders, especially within the first decade after diagnosis. Therefore, intensive follow-up to identify those who require close management is needed.     

Stories of despair: a Kierkegaardian read of suffering and selfhood in survivorship

Medicine, Health Care and Philosophy - A life-threatening illness such as cancer can bring about much existential suffering and a disconnect to self in spite of surviving cancer. In my recent...     

Opioid overdose prevention education for medical students: Adopting harm reduction into mandatory clerkship curricula

Abstract

Background: Opioid overdose deaths constitute a public health crisis in the United States. Strategies for reducing opioid-related harm are underutilized due in part to clinicians’ low knowledge about harm reduction theory and limited preparedness to prescribe naloxone. Educational interventions are needed to improve knowledge and attitudes about, and preparedness to address, opioid overdoses among medical students. Methods: Informed by the Department of Veterans Affairs’ Overdose Education and Naloxone Distribution (OEND) program and narrative medicine, we developed and led a mandatory workshop on harm reduction for clerkship medical students. Using validated scales, we assessed students’ knowledge and attitudes about, and preparedness to address, opioid overdoses before the workshop and 6 weeks after. Results: Of 75 participating students from February through December 2017, 55 (73%) completed pre-workshop and 38 (51%) completed both pre- and post-workshop surveys. At baseline, 40 (73%) encountered patients with perceived at-risk opioid use in the previous 6 weeks, but only 11 (20%) recalled their teams prescribing naloxone for overdose prevention. Among those completing both surveys, knowledge about and preparedness to prevent overdose showed large improvement (Cohen’s d?=?0.85, P?<?.001; Cohen’s d?=?1.24, P?<?.001, respectively) and attitudes showed moderate improvement (Cohen’s d?=?0.32, P = .04). Discussion: Educational interventions grounded in harm reduction theory can increase students’ knowledge and attitudes about, and preparedness to address, opioid overdoses.     

Screening for Inhibition of Vibrio cholerae VipA-VipB Interaction Identifies Small-Molecule Compounds Active against Type VI Secretion

The type VI secretion system (T6SS) is the most prevalent bacterial secretion system and an important virulence mechanism utilized by Gram-negative bacteria, either to target eukaryotic cells or to combat other microbes. The components show much variability, but some appear essential for the function, and two homologues, denoted VipA and VipB in Vibrio cholerae, have been identified in all T6SSs described so far. Secretion is dependent on binding of an α-helical region of VipA to VipB, and in the absence of this binding, both components are degraded within minutes and secretion is ceased. The aim of the study was to investigate if this interaction could be blocked, and we hypothesized that such inhibition would lead to abrogation of T6S. A library of 9,600 small-molecule compounds was screened for their ability to block the binding of VipA-VipB in a bacterial two-hybrid system (B2H). After excluding compounds that showed cytotoxicity toward eukaryotic cells, that inhibited growth of Vibrio, or that inhibited an unrelated B2H interaction, 34 compounds were further investigated for effects on the T6SS-dependent secretion of hemolysin-coregulated protein (Hcp) or of phospholipase A₁ activity. Two compounds, KS100 and KS200, showed intermediate or strong effects in both assays. Analogues were obtained, and compounds with potent inhibitory effects in the assays and desirable physicochemical properties as predicted by in silico analysis were identified. Since the compounds specifically target a virulence mechanism without affecting bacterial replication, they have the potential to mitigate the virulence with minimal risk for development of resistance.     

Educational Inequalities in Post‐Hip Fracture Mortality: A NOREPOS Studys

Hip fractures are associated with high excess mortality. Education is an important determinant of health, but little is known about educational inequalities in post‐hip fracture mortality. Our objective was to investigate educational inequalities in post‐hip fracture mortality and to examine whether comorbidity or family composition could explain any association. We conducted a register‐based population study of Norwegians aged 50 years and older from 2002 to 2010. We measured total mortality according to educational attainment in 56,269 hip fracture patients (NORHip) and in the general Norwegian population. Both absolute and relative educational inequalities in mortality in people with and without hip fracture were compared. There was an educational gradient in post‐hip fracture mortality in both sexes. Compared with those with primary education only, the age‐adjusted relative risk (RR) of mortality in hip fracture patients with tertiary education was 0.82 (95% confidence interval [CI] 0.77–0.87) in men and 0.79 (95% CI 0.75–0.84) in women. Additional adjustments for Charlson comorbidity index, marital status, and number of children did not materially change the estimates. Regardless of educational attainment, the 1‐year age‐adjusted mortality was three‐ to fivefold higher in hip fracture patients compared with peers in the general population without fracture. The absolute differences in 1‐year mortality according to educational attainment were considerably larger in hip fracture patients than in the population without hip fracture. Absolute educational inequalities in mortality were higher after hip fracture compared with the general population without hip fracture and were not mediated by comorbidity or family composition. Investigation of other possible mediating factors might help to identify new targets for interventions, based on lower educational attainment, to reduce post‐hip fracture mortality. © 2015 American Society for Bone and Mineral Research.     

B‐Type Natriuretic Peptide Levels Predict Ventricular Arrhythmia Post Left Ventricular Assist Device Implantation

B‐type natriuretic peptide (BNP) levels have been shown to predict ventricular arrhythmia (VA) and sudden death in patients with heart failure. We sought to determine whether BNP levels before left ventricular assist device (LVAD) implantation can predict VA post LVAD implantation in advanced heart failure patients. We conducted a retrospective study consisting of patients who underwent LVAD implantation in our institution during the period of May 2009–March 2013. The study was limited to patients receiving a HeartMate II or HeartWare LVAD. Acute myocardial infarction patients were excluded. We compared between the patients who developed VA within 15 days post LVAD implantation to the patients without VA. A total of 85 patients underwent LVAD implantation during the study period. Eleven patients were excluded (five acute MI, four without BNP measurements, and two discharged earlier than 13 days post LVAD implantation). The incidence of VA was 31%, with 91% ventricular tachycardia (VT) and 9% ventricular fibrillation. BNP remained the single most powerful predictor of VA even after adjustment for other borderline significant factors in a multivariate logistic regression model (P < 0.05). BNP levels are a strong predictor of VA post LVAD implantation, surpassing previously described risk factors such as age and VT in the past.