Adverse drug reactions in a tertiary care teaching hospital in India: analysis of spontaneously reported cases

Background: Epidemiological data are limited regarding clinical characteristic of adverse drug reactions (ADRs) in India.Aim: The aim was to assess ADRs with reference to the causative drugs, seriousness and their other clinical characteristics in Indian tertiary care teaching hospital.Methods: A spontaneous reporting based ADR monitoring study was conducted over a period of 2 years. The World Health Organization (WHO) definition of an ADR and its seriousness was adopted. The organ system involvement was labeled by WHO-ADR terminology. ADRs were analyzed for causality by Naranjo’s algorithm, preventability by modified Schumock and Thornton’s criteria and types of reactions by Rawlins and Thompson classification. Subgroup analysis was performed between serious and non-serious reactions.Results: Of the total of 135 reactions reported 111 reactions from 97 patients were included for analysis. The incidences of overall and serious ADRs were 0.25 and 0.06 per 1000 patients, respectively. The most commonly implicated organ systems were skin and appendages (52.25%). The major causative drug classes were antimicrobials (40.28%), central nervous system (23.61%) and autacoids (15.97%). About two-thirds of the reactions (65.77%) were classified as probable and one-tenth (8.10%) as preventable. The factors significantly associated with serious reactions were age group 40-60 years (odds ratio [OR]: 5.51), parenteral drugs (OR: 2.96), central and peripheral nervous system disorders (OR: 5.06), body as a whole - general disorders (OR: 9.05) and acute onset reactions (OR: 52.62).Conclusion: Antimicrobials are common causative agents. Cohort study is recommended to confirm the risk factors of serious ADRs in Indian population

Oxygen treatment reduces neurological deficits and demyelination in two animal models of multiple sclerosis

AIMS: To explore the importance of tissue hypoxia in causing neurological deficits and demyelination in the inflamed CNS, and the value of inspiratory oxygen treatment, using both active and passive experimental autoimmune encephalomyelitis (EAE). METHODS: Normobaric oxygen treatment was administered to Dark Agouti rats with either active or passive EAE, compared with room air-treated, and naïve, controls. RESULTS: Severe neurological deficits in active EAE were significantly improved after just 1 hour of breathing ~95% oxygen. The improvement was greater and more persistent when oxygen was applied either prophylactically (from immunization for 23 days), or therapeutically from the onset of neurological deficits for 24, 48, or 72 hours. Therapeutic oxygen for 72 hours significantly reduced demyelination and the integrated stress response in oligodendrocytes at the peak of disease, and protected from oligodendrocyte loss, without evidence of increased oxidative damage. T-cell infiltration and cytokine expression in the spinal cord remained similar to that in untreated animals. The severe neurological deficit of animals with passive EAE occurred in conjunction with spinal hypoxia and was significantly reduced by oxygen treatment initiated before their onset. CONCLUSIONS: Severe neurological deficits in both active and passive EAE can be caused by hypoxia and reduced by oxygen treatment. Oxygen treatment also reduces demyelination in active EAE, despite the autoimmune origin of the disease

A multispectral microscope for in vivo oximetry of rat dorsal spinal cord vasculature

Quantification of blood oxygen saturation (SO2) in vivo is essential for understanding the pathogenesis of diseases in which hypoxia is thought to play a role, including inflammatory disorders such as multiple sclerosis (MS) and rheumatoid arthritis (RA). We describe a low-cost multispectral microscope and oximetry technique for calibration-free absolute oximetry of surgically exposed blood vessels in vivo. We imaged the vasculature of the dorsal spinal cord in healthy rats, and varied inspired oxygen (FiO2) in order to evaluate the sensitivity of the imaging system to changes in SO2. The venous SO2 was calculated as 67.8  ±  10.4% (average  ±  standard deviation), increasing to 83.1  ±  11.6% under hyperoxic conditions (100% FiO2) and returning to 67.4  ±  10.9% for a second normoxic period; the venous SO2 was 50.9  ±  15.5% and 29.2  ±  24.6% during subsequent hypoxic states (18% and 15% FiO2 respectively). We discuss the design and performance of our multispectral imaging system, and the future scope for extending this oximetry technique to quantification of hypoxia in inflamed tissue

Management of transfusion needs in a case of immunizing anti-M antibody in a patient with acute myeloid leukemia

Anti-M is a relatively common "naturally occurring" antibody. Unexpected alloantibodies in patient's serum other than ABO isoagglutinins (e.g., anti-M) may cause a discrepancy in the reverse grouping. As long as anti-M does not react at 37°C, it is clinically insignificant for transfusion. However, we found this antibody to be of "immunizing" type which was reactive at 37°C and AHG phase and showing problems in blood grouping and crossmatch. This antibody had both IgM and IgG components. When "M" antibodies active at 37°C are encountered, antigen-negative or red cells that are compatible with an indirect antiglobulin test should be provided

Overdose and risk factors for coronavirus disease 2019.

BACKGROUND: There have been significant efforts to respond to the two public health emergencies of coronavirus disease 2019 (COVID-19) and overdose in British Columbia (BC), Canada. The purpose of this study was to quantify the prevalence of known risk factors associated with mortality due to COVID-19 for persons who have had a non-fatal overdose during 2015-2017 in comparison to persons who have not had an overdose. METHODS: Data were extracted from the BC Provincial Overdose Cohort which includes a 20 % random sample of BC residents and persons who have had a non-fatal overdose in BC from January 2015 to December 2017. Chi-square tests and logistic regression were used to compare risk factors by overdose history. RESULTS: Persons who had a non-fatal overdose were significantly more likely to have three (chronic pulmonary disease, diabetes, coronary heart disease) of the four known chronic conditions associated with the development of severe illness due to COVID-19 compared to persons who did not have a previous non-fatal overdose event. CONCLUSION: Persons who had an overdose were more likely to have several chronic conditions associated with the development of severe illness due to COVID-19. The increased likelihood of having these risk factors is reflective of the social and health inequities experienced by persons who have a history of overdose

Subretinal Aβ injections induce a localised, early CNV phenotype in C57BL/6 mice

Purpose : Amyloid β (Aβ) is associated with clinical hallmarks of Age-related macular degeneration (AMD), yet its potential role in AMD pathogenesis remains unknown. The purpose of this study was to test Aβ induced morphological/functional changes to the outer retina in situ by conducting non-invasive retinal imaging techniques in a mouse model.Methods : Female C57BL/6 mice aged 117±4 days were subject to subretinal injection with 1.5μl 625nM human oligomeric Aβ1-42(n=7), sham(n=6) or 625nM BSA(n=5). At 8 and 15 days post injection full-field electroretinography (ffERG) and optical coherence tomography (OCT) were performed to assess treatment effects compared to baseline. Scotopic ffERGs were conducted by stimulation with 1.5mm diameter, 6.8 cd-s/m2 white LED light for 1ms in 2 sweeps with a 120s interval, from which average A-wave and B-wave amplitudes, and T(A) and T(B) implicit times were calculated. OCT images were acquired as 1.4mm volumetric scans (100 B-scans comprising 1000 A-scans). Scans were segmented at 24 locations using the InVivoVue 2.4 Diver software for Inner segments (IS), Outer segments (OS), Photoreceptor end tips (ETPRS) and the RPE, to assess treatment effects on layer thickness. One-way ANOVA with Tukey’s post hoc test assessed statistical comparisons with individual mice as the statistical unit. Data is presented as mean ± SEM.Results : Localised subretinal hyperreflective exudation (SHE) and subretinal hyper-reflective material (SHRM) were evident in OCT scans after Aβ1-42 and BSA treatment at 8 and 15 days, with SHE/SHRM reduction associated with subretinal cystic spaces on day 15. No significant difference was seen in global thickness of the IS(p=0.46,p=0.80), OS(p=0.97,p=0.81), ETPRS(p=0.95,p=1.0) or RPE(p=0.95,p=0.28) compared to sham at 8 and 15 days respectively. Similarly, ffERGs saw no significant difference in the A-wave(p=0.94,p=1.00), B-wave(p=0.87,0.89), T(A) (p=0.43,p=0.19) and T(B) (p=0.94,p=0.82) between Aβ and sham at 8 and 15 days.Conclusions : Aβ exposure induced pathology consistent with an early-CNV phenotype. However, this did not translate to a global reduction in IS, OS, ETPRS or RPE thickness, or retinal function, likely due to the localised nature of pathology observed. Nonetheless, our findings suggest a pro-angiogenic role for Aβ, where cumulative damage over time may cause statistically significant thickness/functional deficits

Analysis of annualized bleeding rates and baseline characteristics in subjects with a 14-day or longer dosing interval in the phase 3 b-long study of recombinant factor IX FC fusion protein

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Association of opioid and stimulant use disorder diagnoses with fatal and nonfatal overdose among people with a history of incarceration.

Importance: Studies have suggested a rise in opioid- and stimulant-involved overdoses in recent years in North America. This risk may be acute for individuals who have had contact with the criminal justice system, who are particularly vulnerable to overdose risk. Question: What is the association between opioid and/or stimulant use disorder diagnoses and fatal and nonfatal overdose among people with a history of incarceration? Findings: In this cohort study of 6816 individuals with a history of incarceration, people with both opioid and stimulant use disorder diagnoses had approximately 2.5 times the hazard of overdose compared with people with no substance use disorder diagnoses. Stimulant use disorder alone was associated with a similar hazard of fatal overdose as opioid use disorder alone. Meaning: These findings suggest that in the context of an ongoing overdose public health emergency that disproportionally impacts people with histories of incarceration, there is an urgent need for attention to the service needs of individuals who have had contact with the criminal justice system who co-use opioids and stimulants

Tissue Hypoxia and Associated Innate Immune Factors in Experimental Autoimmune Optic Neuritis

Visual loss in acute optic neuritis is typically attributed to axonal conduction block due to inflammatory demyelination, but the mechanisms remain unclear. Recent research has highlighted tissue hypoxia as an important cause of neurological deficits and tissue damage in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) and, here, we examine whether the optic nerves are hypoxic in experimental optic neuritis induced in Dark Agouti rats. At both the first and second peaks of disease expression, inflamed optic nerves labelled significantly for tissue hypoxia (namely, positive for hypoxia inducible factor-1α (HIF1α) and intravenously administered pimonidazole). Acutely inflamed nerves were also labelled significantly for innate markers of oxidative and nitrative stress and damage, including superoxide, nitric oxide and 3-nitrotyrosine. The density and diameter of capillaries were also increased. We conclude that in acute optic neuritis, the optic nerves are hypoxic and come under oxidative and nitrative stress and damage. Tissue hypoxia can cause mitochondrial failure and thus explains visual loss due to axonal conduction block. Tissue hypoxia can also induce a damaging oxidative and nitrative environment. The findings indicate that treatment to prevent tissue hypoxia in acute optic neuritis may help to restore vision and protect from damaging reactive oxygen and nitrogen species