Evaluation of the extent of under-reporting of serious adverse drug reactions: the case of toxic epidermal necrolysis.

INTRODUCTION: Toxic epidermal necrolysis (TEN) is a life-threatening adverse drug reaction (ADR) that is primarily the result of drug exposure (incidence 0.4-1.3 per million person-years). Life-threatening ADRs such as TEN should be reported to ADR monitoring programmes, which collect reports for suspected ADRs and alert the public and medical practitioners to new drug hazards. In Canada, reports are made to the Canadian Adverse Drug Reaction Monitoring Program (CADRMP). OBJECTIVE: To examine the extent of under-reporting for TEN in Canada. DESIGN: A retrospective case series design was used to collect all TEN cases for the period January 1995 to December 2000. METHODS: The CADRMP and 22 burn centres across Canada were contacted for all TEN patients treated during the specified time period. PATIENT GROUPS STUDIED: The study population consisted of patients admitted to burn treatment sites across Canada, patient cases reported to the CADRMP and patient cases recorded by the Canadian Institute for Health Information (CIHI) hospital discharge summaries as the International Classification of Diseases Version 9 Clinical Modification (ICD-9-CM) code 695.1. RESULTS: Twenty-five TEN cases (six fatal) were reported to CADRMP from January 1995 to December 2000. During this period, 14 (63.6%) burn treatment sites reported admission of 250 TEN cases. Hospital discharge summaries using the ICD-9-CM code 695.1 indicated that 4349 cases were admitted to hospital during this time period and it was estimated that 15.5% (n = 674) of these cases were TEN. Using the burn facility data as the denominator, 10% (25 of 250) of TEN cases were reported to CADRMP. Using CIHI data as a denominator, only 4% (25 of 674) of TEN cases were reported to CADRMP. CONCLUSIONS: There is serious under-reporting of TEN. Lack of reporting of life-threatening ADRs can compromise population safety. There is a need to increase awareness of ADR reporting programmes.     

SARS-CoV-2 Variants in Paraguay: Detection and Surveillance with an Economical and Scalable Molecular Protocol

SARS-CoV-2 variant detection relies on resource-intensive whole-genome sequencing methods. We sought to develop a scalable protocol for variant detection and surveillance in Paraguay, pairing rRT-PCR for spike mutations with Nanopore sequencing. A total of 201 acute-phase nasopharyngeal samples were included. Samples were positive for the SARS-CoV-2 N2 target and tested with the Spike SNP assay to detect mutations associated with the following variants: alpha (501Y), beta/gamma (417variant/484K/501Y), delta (452R/478K), and lambda (452Q/490S). Spike SNP calls were confirmed using amplicon (Sanger) sequencing and whole-genome (Nanopore) sequencing on a subset of samples with confirmed variant lineages. Samples had a mean N2 Ct of 20.8 (SD 5.6); 198/201 samples (98.5%) tested positive in the Spike SNP assay. The most common genotype was 417variant/484K/501Y, detected in 102/198 samples (51.5%), which was consistent with the P.1 lineage (gamma variant) in Paraguay. No mutations (K417 only) were found in 64/198 (32.3%), and K417/484K was identified in 22/198 (11.1%), consistent with P.2 (zeta). Seven samples (3.5%) tested positive for 452R without 478K, and one sample with genotype K417/501Y was confirmed as B.1.1.7 (alpha). The results were confirmed using Sanger sequencing in 181/181 samples, and variant calls were consistent with Nanopore sequencing in 29/29 samples. The Spike SNP assay could improve population-level surveillance for mutations associated with SARS-CoV-2 variants and inform the judicious use of sequencing resources.     

Bioethics as care work

German philosopher Martin Heidegger argued that humans are defined by care. The term he used, “Sorge,” picks out a wide range of caring relations, including sorrow, worry, the making of arrangements, and even fending for another. Since coming to The Hastings Center, I've been struck by the genuine care definitive of its scholars’ relationship to their work. Care about newborns, the elderly, and nonhuman animals. Care about doctors, nurses, and health care institutions. Care expressed in the panoply of ways biomedical knowledge and practices inform our havings, doings, and beings in the world. Perhaps in its better moments, bioethics just is care work. But care work is hard and messy.     

Acquired Immunodeficiency Syndrome (AIDS)

The Acquired Immunodeficiency Syndrome (AIDS), caused by the human immunodeficiency virus (HIV), also called the human T-lymphotropic virus type III/lymphadenopathy-associated virus [HTLV-III/LAV], has affected over 23,000 people; more than half of those with the disease have died. The actual case fatality rate approaches 100%. AIDS affects all groups and classes of people, although some are at special risk. Distribution of the disease is worldwide. The illness' effects on the body are widespread; of special interest are the ophthalmologic manifestations. The eye may be infected by various viruses (cytomegalovirus, varicella-zoster virus, herpes simples virus or HIV itself), toxoplasma gondii, candida sp, cryptococcus neoformans, M. tuberculosis, or M. avium-intracellulare. Kaposi's sarcoma may affect the eye as well. Retinal vascular abnormalities (e.g., cotton-wool spots, vasculitis) are not uncommon in AIDS. The syndrome may present with neuro-ophthalmologic manifestations. No effective treatment for the illness is currently available, although several hold promise and there is hope for an AIDS vaccine. Prevention of infection through reduction of risks appears to be the only defense against AIDS at this time.     

Imaging in glaucoma

Structural assessment using the imaging technologies discussed herein provides reproducible quantitative measurements of posterior segment ocular structures. These measurements have been found to provide useful data for glaucoma detection in various regions of the posterior segment. Further studies are needed to evaluate the utility of these technologies for pre-perimetric glaucoma detection and for monitoring glaucoma progression over an extended period.     

Parathyroid surgery and methylene blue: A review with guidelines for safe intraoperative use

Methylene blue has been used to help facilitate parathyroid surgery for over 30 years. Its use has been widely considered both safe and cost effective. Twenty‐six cases of a toxic metabolic encephalopathy, however, have been reported with its use. As a result, some surgeons have stopped using this technique altogether. It is now known that methylene blue is a monoamine oxidase inhibitor. When combined with drugs that increase central serotonin neurotransmission, serotonin toxicity results. This is the cause of the encephalopathy described in the literature. A case report, review of the literature, and guidelines as to its proper use are presented so as to allow for safe parathyroid surgery. Laryngoscope, 2009