How useful are autoantibodies in diagnosing thyroid disorders?

Thyrotropin receptor antibodies (TRAb) may be mildly elevated in a variety of thyroid disorders, but a TRAb level >10 U/L increases the probability of Graves' disease by a moderate to large degree (strength of recommendation [SOR]: B, cross-sectional study). A positive or negative thyroid peroxidase antibody (TPOAb) test increases or decreases the probability of autoimmune thyroid disease by only a small to moderate degree (SOR: B, 3 cross-sectional studies)

Development of hydronephrosis secondary to poorly managed neurogenic bowel requiring surgical disimpaction in a patient with spinal cord injury: A case report

Case of an adult patient with paraplegia managing neurogenic bladder with intermittent catheterization who was not performing a standard bowel program for management of neurogenic bowel

Development of a biomarker mortality risk model in acute respiratory distress syndrome

Background: There is a compelling unmet medical need for biomarker-based models to risk-stratify patients with acute respiratory distress syndrome. Effective stratification would optimize participant selection for clinical trial enrollment by focusing on those most likely to benefit from new interventions. Our objective was to develop a prognostic, biomarker-based model for predicting mortality in adult patients with acute respiratory distress syndrome. Methods: This is a secondary analysis using a cohort of 252 mechanically ventilated subjects with the diagnosis of acute respiratory distress syndrome. Survival to day 7 with both day 0 (first day of presentation) and day 7 sample availability was required. Blood was collected for biomarker measurements at first presentation to the intensive care unit and on the seventh day. Biomarkers included cytokine-chemokines, dual-functioning cytozymes, and vascular injury markers. Logistic regression, latent class analysis, and classification and regression tree analysis were used to identify the plasma biomarkers most predictive of 28-day ARDS mortality. Results: From eight biologically relevant biomarker candidates, six demonstrated an enhanced capacity to predict mortality at day 0. Latent-class analysis identified two biomarker-based phenotypes. Phenotype A exhibited significantly higher plasma levels of angiopoietin-2, macrophage migration inhibitory factor, interleukin-8, interleukin-1 receptor antagonist, interleukin-6, and extracellular nicotinamide phosphoribosyltransferase (eNAMPT) compared to phenotype B. Mortality at 28 days was significantly higher for phenotype A compared to phenotype B (32% vs 19%, p = 0.04). Conclusions: An adult biomarker-based risk model reliably identifies ARDS subjects at risk of death within 28 days of hospitalization.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Antihistamines for Postacute Sequelae of SARS-CoV-2 Infection

Postacute sequelae of SARS-CoV2 (PASC) infection is an emerging global health crisis, variably affecting millions worldwide. PASC has no established treatment. We describe 2 cases of PASC in response to opportune administration of over-the-counter antihistamines, with significant improvement in symptoms and ability to perform activities of daily living. Future studies are warranted to understand the potential role of histamine in the pathogenesis of PASC and explore the clinical benefits of antihistamines in the treatment of PASC

Assessing harmful effects in systematic reviews.

BACKGROUND: Balanced decisions about health care interventions require reliable evidence on harms as well as benefits. Most systematic reviews focus on efficacy and randomised trials, for which the methodology is well established. Methods to systematically review harmful effects are less well developed and there are few sources of guidance for researchers. We present our own recent experience of conducting systematic reviews of harmful effects and make suggestions for future practice and further research. METHODS: We described and compared the methods used in three systematic reviews. Our evaluation focused on the review question, study designs and quality assessment. RESULTS: One review question focused on providing information on specific harmful effects to furnish an economic model, the other two addressed much broader questions. All three reviews included randomised and observational data, although each defined the inclusion criteria differently. Standard methods were used to assess study quality. Various practical problems were encountered in applying the study design inclusion criteria and assessing quality, mainly because of poor study design, inadequate reporting and the limitations of existing tools. All three reviews generated a large volume of work that did not yield much useful information for health care decision makers. The key areas for improvement we identified were focusing the review question and developing methods for quality assessment of studies of harmful effects. CONCLUSIONS: Systematic reviews of harmful effects are more likely to yield information pertinent to clinical decision-making if they address a focused question. This will enable clear decisions to be made about the type of research to include in the review. The methodology for assessing the quality of harmful effects data in systematic reviews requires further development

COVID Symptoms, Symptom Clusters, and Predictors for Becoming a Long-Hauler: Looking for Clarity in the Haze of the Pandemic

Emerging data suggest that the effects of infection with SARS-CoV-2 are far reaching extending beyond those with severe acute disease. Specifically, the presence of persistent symptoms after apparent resolution from COVID-19 have frequently been reported throughout the pandemic by individuals labeled as “long-haulers”. The purpose of this study was to assess for symptoms at days 0-10 and 61+ among subjects with PCR-confirmed SARS-CoV-2 infection. The University of California COvid Research Data Set (UC CORDS) was used to identify 1407 records that met inclusion criteria. Symptoms attributable to COVID-19 were extracted from the electronic health record. Symptoms reported over the previous year prior to COVID-19 were excluded, using nonnegative matrix factorization (NMF) followed by graph lasso to assess relationships between symptoms. A model was developed predictive for becoming a long-hauler based on symptoms. 27% reported persistent symptoms after 60 days. Women were more likely to become long-haulers, and all age groups were represented with those aged 50 ± 20 years comprising 72% of cases. Presenting symptoms included palpitations, chronic rhinitis, dysgeusia, chills, insomnia, hyperhidrosis, anxiety, sore throat, and headache among others. We identified 5 symptom clusters at day 61+: chest pain-cough, dyspnea-cough, anxiety-tachycardia, abdominal pain-nausea, and low back pain-joint pain. Long-haulers represent a very significant public health concern, and there are no guidelines to address their diagnosis and management. Additional studies are urgently needed that focus on the physical, mental, and emotional impact of long-term COVID-19 survivors who become long-haulers

Down-titration of biologics for the treatment of rheumatoid arthritis: A systematic literature review

Biologic therapies have improved the management of rheumatoid arthritis (RA) and the treat-to-target approach has resulted in many patients achieving remission. In the current treatment landscape, clinicians have begun considering dose reduction/tapering for their patients. Rheumatology guidelines in Asia, Europe, and the United States include down-titration of biologics but admit that the level of evidence is moderate. We conducted a systematic literature review to assess the published studies that evaluate down-titration of biologics in RA. The published literature was searched for studies that down-titrated the following biologics: abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, and tocilizumab. Eligible studies included randomized controlled trials (RCTs), non-RCTs, observational, and pharmacoeconomic studies. The outcomes of interest were (1) efficacy and health-related quality of life, (2) disease flares, and (3) impact on cost. Eleven full-text publications were identified; only three were RCTs. Study results suggest that dosing down may be an option in many patients who have achieved remission or low disease activity. However, some patients are likely to experience a disease flare. Across the studies, the definition of disease flare and the down-titration criteria were inconsistent, making it difficult to conclude which patients may be appropriate and when to attempt down-titration. Studies have evaluated the practice of dosing down biologic therapy in patients with RA; however, a relatively small number of RCTs have been published. Although down-titration may be an option for some patients in LDA or remission, additional RCTs are needed to provide guidance on this practice

The Fischer 344 Rat Reflects Human Susceptibility to Francisella Pulmonary Challenge and Provides a New Platform for Virulence and Protection Studies

Background: The pathogenesis of Francisella tularensis, the causative agent of tularemia, has been primarily characterized in mice. However, the high degree of sensitivity of mice to bacterial challenge, especially with the human virulent strains of F. tularensis, limits this animal model for screening of defined attenuated vaccine candidates for protection studies. Methods and Findings: We analyzed the susceptibility of the Fischer 344 rat to pulmonary (intratracheal) challenge with three different subspecies (subsp) of F. tularensis that reflect different levels of virulence in humans, and characterized the bacterial replication profile in rat bone marrow-derived macrophages (BMDM). In contrast to the mouse, Fischer 344 rats exhibit a broader range of sensitivity to pulmonary challenge with the human virulent subsp. tularensis and holarctica. Unlike mice, Fischer rats exhibited a high degree of resistance to pulmonary challenge with LVS (an attenuated derivative o

COVID-19 Survivors’ Reports of the Timing, Duration, and Health Impacts of Post-Acute Sequelae of SARS-CoV-2 (PASC) Infection

IMPORTANCE Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) is a major public health concern. Studies suggest that 1 in 3 infected with SARS-CoV-2 may develop PASC, including those without initial symptoms or with mild COVID-19 disease.1, 2 OBJECTIVE To evaluate the timing, duration, and health impacts of PASC reported by a large group of primarily non-hospitalized COVID-19 survivors. DESIGN, SETTING, AND PARTICIPANTS A survey of 5,163 COVID-19 survivors reporting symptoms for more than 21 days following SARS-CoV-2 infection. Participants were recruited from Survivor Corps and other online COVID-19 survivor support groups. MAIN OUTCOMES AND MEASURES Participants reported demographic information, as well as the timing, duration, health impacts, and other attributes of PASC. The temporal distribution of symptoms, including average time of onset and duration of symptoms were determined, as well as the perceived distress and impact on ability to work. RESULTS On average, participants reported 21.4 symptoms and the number of symptoms ranged from 1 to 93. The most common symptoms were fatigue (79.0%), headache (55.3%), shortness of breath (55.3%), difficulty concentrating (53.6%), cough (49.0%), changed sense of taste (44.9%), diarrhea (43.9%), and muscle or body aches (43.5%). The timing of symptom onset varied and was best described as happening in waves. The longest lasting symptoms on average for all participants (in days) were “frequently changing” symptoms (112.0), inability to exercise (106.5), fatigue (101.7), difficulty concentrating (101.1), memory problems (100.8), sadness (99.2), hormone imbalance (99.1), and shortness of breath (96.9). The symptoms that affected ability to work included the relapsing/remitting nature of illness (described by survivors as “changing symptoms”), inability to concentrate, fatigue, and memory problems, among others. Symptoms causing the greatest level of distress (on scale of 1 “none” to 5 “a great deal”) were extreme pressure at the base of the head (4.4), syncope (4.3), sharp or sudden chest pain (4.2), brain pressure (4.2), headache (4.2), persistent chest pain or pressure (4.1), and bone pain in extremities (4.1). CONCLUSIONS AND RELEVANCE PASC is an emerging public health priority characterized by a wide range of changing symptoms, which hinder survivors’ ability to work. PASC has not been fully characterized and the trajectory of symptoms and long-term outcomes are unknown. There is no treatment for PASC, and survivors report distress in addition to a host of ongoing symptoms. Capturing patient reports of symptoms through open-ended inquiry is a critical first step in accurately and comprehensively characterizing PASC to ensure that medical treatments and management strategies best meet the needs of individual patients and help mitigate health impacts of this new disease