identifier ChiCTR2000029955.Tuberculosis (TB) kills more people than any other infectious disease. Challenges for developing better treatments include the complex pathology due to within-host immune dynamics, interpatient variability in disease severity and drug pharmacokinetics-pharmacodynamics (PK-PD), and the growing emergence of resistance. Model-informed drug development using quantitative and translational pharmacology has become increasingly recognized as a method capable of drug prioritization and regimen optimization to efficiently progress compounds through TB drug development phases. In this review, we examine translational models and tools, including plasma PK scaling, site-of-disease lesion PK, host-immune and bacteria interplay, combination PK-PD models of multidrug regimens, resistance formation, and integration of data across nonclinical and clinical phases.We propose a workflow that integrates these tools with computational platforms to identify drug combinations that have the potential to accelerate sterilization, reduce relapse rates, and limit the emergence of resistance. (1) To identify factors associated with severe dysfunctional larynx leading to total laryngectomy after curative treatment of head and neck squamous cell carcinoma and (2) to describe swallowing and voice outcomes. Retrospective single-institution case-control study. Tertiary care referral center. A 10-year chart review was performed for patients who had previously undergone radiation or chemoradiation for head and neck mucosal squamous cell carcinoma and planned to undergo total laryngectomy for dysfunctional larynx, as well as a control group of matched patients. Controls were patients who had undergone radiation or chemoradiation for mucosal squamous cell carcinoma but did not have severe dysfunction warranting laryngectomy; these were matched to cases by tumor subsite, T stage, and time from last treatment to video swallow study. Main outcomes assessed were postoperative diet, alaryngeal voice, pharyngeal dilations, and complications. Twenty-six patients were scheduled for laryngectomy for dysfunctional larynx, of which 23 underwent surgery. Originally treated tumor subsites included the larynx, oropharynx, hypopharynx, oral cavity, and a tumor of unknown origin. The median time from end of cancer treatment to laryngectomy was 11.5 years. All cases were feeding tube or tracheostomy dependent or both prior to laryngectomy. As compared with matched controls, cases were significantly less likely to have undergone IMRT (intensity-modified radiotherapy) and more likely to have pulmonary comorbidities. Eighty-nine percent of cases with follow-up achieved functional alaryngeal voice, and all were able to have oral intake. Non-IMRT approaches and pulmonary comorbidities are associated with laryngectomy for dysfunction after radiation or chemoradiation.Non-IMRT approaches and pulmonary comorbidities are associated with laryngectomy for dysfunction after radiation or chemoradiation.School nurses across Massachusetts and the nation rose to the challenges presented by the pandemic of the coronavirus disease 2019 (COVID-19). One of the many ways in which school nurses responded to the pandemic was to work in collaboration with their Local Boards of Health in a variety of capacities. The essential functions of a school nurse uniquely prepare them for the roles of case investigators and contact tracing monitors as a means to ensure population health. In addition to both individual and population health within the school setting, school nurses are effective partner in emergency planning and can help inform decision making and policy making within communities.The proportion of patients with residual olfactory and gustatory dysfunction after COVID-19 is increasing, and practical health care strategies need to be developed to manage this novel situation in otolaryngology services worldwide. Starting from our experience in a large Italian hospital, we estimated that >1500 people will complain of some form of olfactory and gustatory dysfunction in the future months in our region. We want to share our logistical and clinical integrated pathway that is aimed to screen and refer each patient to the most appropriate level of care in order to optimize resources and avoid overwhelming the available clinics. To offer pragmatic, evidence-informed advice on nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line therapy after surgery. This companion to the American Academy of Otolaryngology-Head & Neck Surgery (AAO-HNS) clinical practice guideline (CPG), "Opioid Prescribing for Analgesia After Common Otolaryngology Operations," presents data on potency, bleeding risk, and adverse effects for ibuprofen, naproxen, ketorolac, meloxicam, and celecoxib. National Guidelines Clearinghouse, CMA Infobase, National Library of Guidelines, NICE, SIGN, New Zealand Guidelines Group, Australian National Health and Medical, Research Council, TRIP database, PubMed, Guidelines International Network, Cochrane Library, EMBASE, CINAHL, BIOSIS Previews, ISI Web of Science, AHRQ, and HSTAT. AAO-HNS opioid CPG literature search strategy, supplemented by PubMed/MEDLINE searches on NSAIDs, emphasizing systematic reviews and randomized controlled trials. NSAIDs provide highly effective analgesia for postoperative pain, partic pain control with greater safety than opioid-based regimens. Nutlin-3a datasheet The AAO-HNS opioid prescribing CPG therefore prioritizes multimodal, nonopioid analgesia as first-line therapy, recommending that opioids be reserved for severe or refractory pain. This state-of-the-art review provides strategies for safely incorporating NSAIDs into acute postoperative pain regimens.Background Action potential alternans can induce ventricular tachyarrhythmias and manifest on the surface ECG as T-wave alternans (TWA) and QRS alternans (QRSA). We sought to evaluate microvolt QRSA in cardiomyopathy patients in relation to TWA and ventricular tachyarrhythmia outcomes. Methods and Results Prospectively enrolled cardiomyopathy patients (n=100) with prophylactic defibrillators had 12-lead ECGs recorded during ventricular pacing from 100 to 120 beats/min. QRSA and TWA were quantified in moving 128-beat segments using the spectral method. Segments were categorized as QRSA positive (QRSA+) and/or TWA positive (TWA+) based on ≥2 precordial leads having alternans magnitude >0 and signalnoise >3. Patients were similarly categorized based on having ≥3 consecutive segments with alternans. TWA+ and QRSA+ occurred together in 31% of patients and alone in 18% and 14% of patients, respectively. Although TWA magnitude (1.4±0.4 versus 4.7±1.0 µV, P120 ms (HR, 4.1; 95% CI, 1.3-12; P=0.014) to predict events. Conclusions Microvolt QRSA is novel phenomenon in cardiomyopathy patients that can exist without TWA and is associated with QRS prolongation.