Clinical characteristics of COVID-19 patients with underlying rheumatic diseases in Japan: data from a multicenter observational study using the COVID-19 Global Rheumatology Alliance physician-reported registry

Clinical Rheumatology - To describe clinical characteristics of patients in Japan with coronavirus disease 19 (COVID-19) and pre-existing rheumatic disease and examine the possible risk factors...     

Response to pegylated interferon plus ribavirin in HIV-infected patients with chronic hepatitis C due to genotype 4

SUMMARY: Hepatitis C virus (HCV) genotypes 1 and 4 respond less well to pegylated interferon (pegIFN) plus ribavirin (RBV) therapy. For this reason most studies merge these two genotypes when assessing virological response. However, in most trials the HCV genotype 4 population is rather small, and conclusions are mainly derived from what occurs in HCV-1 patients. All HCV-4 patients coinfected with HIV who received pegIFN plus RBV in two different multicentre studies, PRESCO and ROMANCE, conducted respectively in Spain and Italy, were retrospectively analyzed. Baseline plasma HCV-RNA, proportion of patients with HCV-RNA <10 IU / mL at week 4 (rapid virological response), and HCV-RNA declines >2 logs at week 12 (early virological response, EVR) were all assessed as predictors of sustained virological response (SVR). Overall, 75 patients (60 men) were evaluated. Median age was 40 years and median CD4 count 598 cells / mm(3); 49% had plasma HIV-RNA <50 copies / mL; 71% had elevated liver enzymes and 31% had advanced liver fibrosis (Metavir F3-F4). Median serum HCV-RNA was 5.7 log IU / mL. Rapid virological response was attained by 10 (20%) patients and EVR by 26 (42%). Using intention-to-treat and on-treatment (OT) analyses, SVR was achieved by 21 / 75 (28%) and 21 / 62 (34%) of HCV-4 patients, respectively. In the multivariate analysis (OT), baseline HCV-RNA (OR 0.09 for every log increment; 95% CI: 0.01-0.7) and EVR (OR: 7.08; 95% CI: 1.8-27.2) were significantly and independently associated with SVR. This is the largest series of HIV-infected patients with chronic hepatitis C due to HCV-4 treated with pegIFN plus RBV examined so far and the results show that HCV-4 behaves similarly to HCV-1. Therefore, these patients should be considered as difficult to treat population. Baseline serum HCV-RNA and EVR are the best predictors of SVR in HCV-4 / HIV-coinfected patients.     

The course of inhalation profiles during an exacerbation of obstructive lung disease

BACKGROUND: Acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are associated with increased airflow Limitation, hyperinflation and respiratory muscle fatigue. It is unclear, whether patients are able to perform adequate inhalations through various inhalation devices with different orfices during an exacerbation. The aim of this study was to examine the evolution of inhalation profiles of patients inhaling through Diskus, Turbuhaler, pressurized metered dose inhaler (pMDI) and Volumatic and consequently the appropriateness of using the various devices during an exacerbation. MEASUREMENTS: 15 hospitalized patients participated in this randomized comparison of inhalation profiles through the four placebo-devices. For each device, triplicate inhalation profiles were recorded during day 1-9 of admission and in stable phase (day 50). RESULTS: The mean percentage of patients performing optimum inhalation profiles was 100% for Diskus, 60% for Turbuhaler, 14% for pMDI and 87% for Volumatic over the interval of day 1-9 and day 50. Patients with an inspiratory muscle strength (MIP) of less than 6kPa were generally unable to generate the optimum flow through the Turbuhaler (>60 l/min). CONCLUSION: The Diskus and Volumatic can be used effectively in the acute phase of an exacerbation of asthma or COPD. The Turbuhaler could be optimally used after the fifth day of convalescence. The pMDI is rather unsuitable during an exacerbation.     

Turn-on switch in parathyroid hormone receptor by a two-step parathyroid hormone binding mechanism

Parathyroid hormone (PTH) and its related receptor (PTHR) are essential regulators of calcium homeostasis and bone physiology. PTH activates PTHR by interacting with a ligand-binding site localized within the N-terminal extracellular domain (the N-domain) and the domain comprising the seven transmembrane helices and the connecting extracellular loops (the J-domain). PTH binding triggers a conformational switch in the receptor, leading to receptor activation and subsequent cellular responses. The process of receptor activation occurs rapidly, within approximately 1 s, but the binding event preceding receptor activation is not understood. By recording FRET between tetramethyl-rhodamine in PTH(1-34) and GFP in the N-domain of the receptor, we measured the binding event in real time in living cells. We show that the association time course between PTH(1-34) and PTHR involves a two-step binding process where the agonist initially binds the receptor with a fast time constant (tau approximately 140 ms) and then with slower kinetics (tau approximately 1 s). The fast and slow phases were assigned to hormone association to the receptor N- and J domains, respectively. Our data indicate that the slow binding step to the J-domain coincides with a conformational switch in the receptor, also monitored by FRET between the enhanced cyan fluorescent protein and the enhanced yellow fluorescent protein in the PTHR sensor, PTHR enhanced cyan fluorescent protein/enhanced yellow fluorescent protein (PTHR(CFP/YFP)). These data suggest that the conformational change that switches the receptor into its active state proceeds in a sequential manner, with the first rapid binding step event preceding receptor activation by PTH(1-34).     

Hemangioma located just above the left main coronary artery, in a subject who had cardiac arrest due to ventricular fibrillation, led to a diagnosis of Brugada syndrome

We report the case of a 38-year-old Asian man with a pericardial hemangioma on the left main coronary artery. The patient presented initially at our hospital after cardiopulmonary resuscitation following an episode of ventricular fibrillation (VF). Because of spontaneous coved-type ST segment elevation on the higher intercostal space V1 to V2 in a 12-lead electrocardiogram, documented VF in the absence of structural heart disease, and a family history of sudden death, he was diagnosed with Brugada syndrome. Transesophageal echocardiography showed a smooth-surfaced mass with well-demarcated borders, directly above the left main coronary artery. Computed tomography confirmed the presence of the mass, which showed no enhancement at early phase, but did demonstrate homogenous enhancement at delay phase by contrast material. There were no findings from either the nuclear medicine or the tumor marker investigations which indicated that the mass located just above the main coronary arteries was malignant. Therefore, taken together, these findings suggested that the tumor might be a pericardial hemangioma. The relationship between the location of the hemangioma just above the left main coronary artery and the occurrence of VF was not clear, i.e. whether the presence of the hemangioma caused the stimulation of the left main coronary artery and as a result, led to the spasm of the left main coronary artery and the occurrence of VF. Furthermore, as the tumor did not extend into any of the adjacent structures, such as the coronary arteries or the right ventricular outflow tract, surgical resection was not performed; instead, the patient received a dual chamber implantable cardioverter-defibrillator.     

The exploration of population pharmacokinetic model for meropenem in augmented renal clearance and investigation of optimum setting of dose

In recent years, augmented renal clearance (ARC), in which renal function is excessively enhanced, has been reported, and its influence on β-lactam antibiotics has been investigated. In this study, we aimed to determine the optimum population pharmacokinetic model of meropenem in patients with sepsis with ARC, and evaluated dosing regimens based on renal function. Seventeen subjects (6 with ARC and 11 without) were enrolled in this study. Predicted meropenem concentrations were evaluated for bias and precision using the Bland–Altman method. To examine the dosing regimen, Monte Carlo simulation was performed to calculate the cumulative fraction of response (CFR). In patients with ARC, the bias (average of the predicted value and measured value residuals) of models constructed by Crandon et al. (2011), Roberts et al. (2009), and Jaruratanasirikul et al. (2015) were 5.96 μg/mL, 10.91 μg/mL, and 4.41 μg/mL, respectively. Following 2 g meropenem every 8 h (180 min infusion), CFR ≥ 90%, a criterion of success for empirical therapy, was achieved, even with creatinine clearance of 130–250 mL/min. For patients with sepsis and ARC, the model of Jaruratanasirikul et al. showed the highest degree of accuracy and precision and confirmed the efficacy of the meropenem dosing regimen in this patient population.     

Physical therapists’ perceptions and experiences about barriers and facilitators of therapeutic patient-centred relationships during outpatient rehabilitation: a qualitative study

Background

Over recent years there has been a paradigm shift towards a patient-centred biopsychosocial care model in physical therapy. This new paradigm features a growing interest in understanding the contextual factors that influence the patient's experience of disease, pain and recovery. This includes generalized consensus regarding the importance of establishing a therapeutic relationship that is centred on the patient.

Role of Institutional Climate on Underrepresented Faculty Perceptions and Decision Making in Use of Work–Family Policies

The authors examined the institutional challenges that underrepresented minority (URM) faculty perceive in higher education with use of family support workplace policies. Evidence reveals that faculty encounter differences in access to information and explanations of how to use workplace–family statutes. A qualitative study of 58 URM faculty members highlighted five particularly notable themes: (a) faculty perceptions of how the institution views their family caregiving responsibilities, (b) inadequate compensation matters in the utilization of formal policies, (c) informal policies are often inaccessible and invisible, (d) social networks affect the inclusiveness of work–family institutional practices, and (e) fear of being regarded as a “red flag” constrains decisions regarding the use of policies. Given the push in higher education to diversify its faculty ranks, if administrators are to successfully implement diversity, equity, and inclusion and retain URM faculty, institutions need to pay particular attention to how URM faculty experience the academic climate regarding work–family balance.     

Palliative Care Symptom Management in The Emergency Department: The ABC's of Symptom Management for The Emergency Physician

Background

Palliative care is a rapidly evolving area of emergency medicine. With an estimated 5,000 to 10,000 baby boomers per day reaching retirement age, emergency departments (EDs) are treating more patients with chronic and serious disease. Palliative care offers comprehensive care for patients with advanced medical illness, aims to alleviate suffering and improve quality of life, and plays an important role in caring for these patients in the ED.