A double-blind, randomised, parallel group, multinational, multicentre study comparing a single dose of ondansetron 24 mg p.o. with placebo and metoclopramide 10 mg t.d.s. p.o. in the treatment of opioid-induced nausea and emesis in cancer patients

Nausea and emesis are common side effects of opioid drugs administered for pain relief in cancer patients. The aim of this study was to compare the anti-emetic efficacy and safety of ondansetron, placebo and metoclopramide in the treatment of opioid-induced nausea and emesis (OIE) in cancer patients. This was a multinational, multicentre, double-blind, parallel group study in which cancer patients who were receiving a full opioid agonist for cancer pain were randomised to receive one of oral ondansetron 24 mg once daily, metoclopramide 10 mg three times daily, or placebo. Study medication was started only if the patient experienced nausea and/or emesis following opioid administration. Efficacy and safety assessments were made over a study period of 24 h from the time of the first dose of anti-emetics/placebo. The study was terminated prematurely because of the difficulties in recruiting patients satisfying the stringent entry criteria. Ninety-two patients were included in the intent-to-treat population: 30 patients received placebo, 29 patients ondansetron and 33 patients metoclopramide. There was no statistically significant difference between the groups in the proportion achieving complete control of emesis (33% of patients on placebo, 48% on ondansetron and 52% on metoclopramide) or complete control of nausea (23% of patients on placebo, 17% on ondansetron and 36% on metoclopramide). Rescue anti-emetics were required in 8 of 33 patients on metoclopramide, 4 of 29 on ondansetron, and 3 of 30 on placebo. The incidence of adverse events was very low and similar in all treatment groups. Neither ondansetron 24 mg once daily nor metoclopromide 10 mg t.d.s. given orally was significantly more effective than placebo in the control of OIE in cancer patients.     

Are 1 or 2 dangerous? Clozapine and olanzapine exposure in toddlers

Clozapine (Clozaril) and olanzapine (Zyprexa) are two relatively new atypical antipsychotics that are structurally and pharmacologically related. There are currently no therapeutic indications for these pharmaceuticals in infants and toddlers.Presumably, as the usage of these medications in adults increases, the frequency of unintentional pediatric ingestions will increase. In 2001 the annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System included a separate subcategory for atypical antipsychotics under the heading of sedatives/hypnotics/antipsychotics. The toxidrome resulting from these drugs is predominately central nervous system depression and anticholinergic effects. Although the desirable lack of extrapyramidal symptoms in adults results in their greatest clinical utility, several reports of toxic ingestions in small children are noteworthy for having extrapyramidal manifestations. We review here the available reported clinical experience with toxic doses of these medications that in small children may amount to as little as a single tablet. Although such doses may be lethal, supportive care and gastrointestinal decontamination in this population will generally lead to a good outcome.     

Validation of a Novel Surgical Data Capturing System Following Total Hip Arthroplasty

Background

The OrthoMiDaS (Orthopedic Minimal Data Set) Episode of Care (OME) database was developed in an effort to advance orthopedic outcome measurements on a national scale. This study was designed to evaluate if the OME data capture system would increase the quality of data collected in the context of primary and revision total hip arthroplasty (THA) compared to conventional operative notes.

Direct quantitative measurement of the kinetics of HLA-specific antibody interactions with isolated HLA proteins

HLA specific antibodies vary in their pathogenicity and this is likely to be the net effect of constant chain usage, quantity, specificity, and affinity. Here we have measured the affinity of human monoclonal antibodies for a range of HLA proteins. Purified antibodies and ligands allowed dynamic interactions to be measured directly by surface plasmon resonance. Physiochemical differences between pairs of ligands were quantified using electrostatic mismatch and hydrophobic mismatch scores.All antibodies were characterized by fast on-rates and slow off rates but with a wide range of association rates (k_on, 3.63–24.25?×?10⁵ per mol per second) and dissociation rates (k_off, 0.99–10.93?×?10^?3 per second). Dissociation constants (K_D) ranged from 5.9?×?10^?10?M to 3.0?×?10^?8?M. SN320G6 has approximately a twenty-fold greater affinity for HLA A2 compared with SN607D8, but has a similar affinity for HLA-A2 and B57. In contrast, SN607D8 has greater than a twofold greater affinity for HLA-A2 compared with A68. Similarly, WK1D12 has about a threefold greater affinity for HLA-B27 compared with B7. The higher affinity interactions correlate with the specificity of stimulating antigen. This is the first study to directly measure the binding kinetics and affinity constants for human alloantibodies against HLA.     

Role of Established Type 2 Diabetes–Susceptibility Genetic Variants in a High Prevalence American Indian Population

Several single nucleotide polymorphisms (SNPs) associated with type 2 diabetes mellitus (T2DM) have been identified, but there is little information on their role in populations at high risk for T2DM. We genotyped SNPs at 63 T2DM loci in 3,421 individuals from a high-risk American Indian population. Nominally significant (P < 0.05) associations were observed at nine SNPs in a direction consistent with the established association. A genetic risk score derived from all loci was strongly associated with T2DM (odds ratio 1.05 per risk allele, P = 6.2 × 10⁻⁶) and, in 292 nondiabetic individuals, with lower insulin secretion (by 4% per copy, P = 4.1 × 10⁻⁶). Genetic distances between American Indians and HapMap populations at T2DM markers did not differ significantly from genomic expectations. Analysis of U.S. national survey data suggested that 66% of the difference in T2DM prevalence between African Americans and European Americans, but none of the difference between American Indians and European Americans, was attributable to allele frequency differences at these loci. These analyses suggest that, in general, established T2DM loci influence T2DM in American Indians and that risk is mediated in part through an effect on insulin secretion. However, differences in allele frequencies do not account for the high population prevalence of T2DM.     

In-Room Ultraviolet Air Filtration Units Reduce Airborne Particles During Total Joint Arthroplasty

Reducing airborne bioburden in total joint arthroplasty (TJA) is of critical importance. The efficacy of crystalline ultraviolet-C (C-UVC) filtration in reducing bioburden in a dynamic operating room (OR) environment has not been evaluated. We assessed whether C-UVC filtration reduced (i) total particle counts (TPC); (ii) viable particle counts (VPC); and (iii) colony-forming units (CFUs). Fifty primary TJA cases were performed in a positive-pressure OR; 25 cases with the C-UVC unit and 25 cases without. The air was sampled by a particle counter and an impact air sampler to measure particle counts and CFUs, respectively. To compare TPC, VPC, and CFU/m³ between groups, independent t tests and multivariate regression, adjusted for number of OR staff and door openings, were performed. The C-UVC group had significantly lower TPC (2.6 × 10⁶ vs. 4.7 × 10⁶ particles, p = 0.001) and VPC (18,605 vs. 27,516 particles, p = 0.001). There were fewer CFUs in the C-UVC group (10.9 CFU/m³ vs. 13.7 CFU/m³, p = 0.163). Multivariate analysis identified C-UVC filtration as a significant predictor of decreased TPC (β = −0.44, p = 0.002) and VPC (β = −0.47, p = 0.001) after accounting for door openings and number of OR staff. The reduction in CFUs was not significant on multivariate analysis. In this prospective pilot study, a C-UVC air disinfection and recirculation unit led to a significant reduction in both TPC and VPC and a non-significant reduction in CFU. Statement of clinical significance: Further studies are needed to investigate the effects of C-UVC filtration units on surgical-site infection rates. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:431-437, 2020     

A Practical Guide for Navigating the Design,Build, and Clinical Integration of Electronic Patient-Reported Outcomes in the Radiation Oncology Department

The development and integration of electronic patient-reported outcomes (ePROs) into the radiation oncology clinic workflow provide novel opportunities, accompanied by unique design considerations and implementation challenges. The processes required for implementation of ePROs are entirely distinct from standard paper-based surveys, with the majority of time devoted to conception and design before initiating questionnaire build, detailed workflow process mapping including development of new workflows, comprehensive communication of the vision between providers and the information technology team, and quality assurance. Based on our experience with implementation of ePROs in our radiation oncology department, we developed a stepwise framework for approaching ePRO conceptual design, build, workflow integration, and the electronic health record interface. Here, we provide a guide for the numerous considerations, decision points, and solutions associated with the implementation of ePROs in the radiation oncology department setting. Although various ePRO tools and electronic health record capabilities impose different requirements, opportunities, and limitations, the conceptual processes and many of the electronic build considerations are broadly applicable.     

Enhanced hematopoietic activity of a human granulocyte/macrophage colony-stimulating factor-interleukin 3 fusion protein.

Granulocyte/macrophage colony-stimulating factor-interleukin 3 (GM-CSF-IL-3) fusion proteins were generated by construction of a plasmid in which the coding regions of human GM-CSF and IL-3 cDNAs were connected by a synthetic linker sequence followed by subsequent expression in yeast. Both GM-CSF-IL-3 and IL-3-GM-CSF fusion proteins were purified to homogeneity and shown to bind to cell-surface receptors through either their GM-CSF or IL-3 domains. The fusion proteins exhibited enhanced receptor affinity, proliferative activity, and hematopoietic colony-stimulating activity compared with either IL-3 and/or GM-CSF alone. This suggests that GM-CSF-IL-3 fusion proteins may hold future promise as therapeutic agents.     

The spectrum of therapeutic influences and integrative health care: classifying health care practices by mode of therapeutic action

The growing popularity of complementary and alternative medicine (CAM) and integrative medicine (IM) highlight the need for a clinically relevant system for classifying health care practices. All systems, modalities, and techniques of health care (conventional, complementary, alternative, and traditional) can be organized in categories of "primary mode of therapeutic action." This results in six categories: biochemical; biomechanical; mind-body; energy; psychological (symbolic); and nonlocal. In each category, there are subdivisions. Organizing health care by primary mode of therapeutic action has numerous benefits: (1) conventional and CAM practitioners, and the public, can readily see some of the general similarities and differences among practices; (2) health care educators gain a common foundation and shared language for explaining CAM and IM; (3) professionals and the public, wishing to combine dissimilar practices, gain a common framework for evaluating the meaning of integration; and (4) the crossover problem can be understood as a natural occurrence in health care, not a confusing intellectual dilemma. The National Center for Complementary and Alternative Medicine (NCCAM) system of categories for CAM is briefly critiqued.