Cefiderocol, formerly S-649266, is a first in its class, an injectable siderophore cephalosporin that combines a catechol-type siderophore and cephalosporin core with side chains similar to cefepime and ceftazidime. This structure and its unique mechanism of action confer enhanced stability against hydrolysis by many b-lactamases, including extended spectrum b-lactamases such as CTX-M, and carbapenemases such as KPC, NDM, VIM, IMP, OXA-23, OXA-48-like, OXA-51-like and OXA-58. Cefiderocol's spectrum of activity encompasses both lactosefermenting and non-fermenting Gram-negative pathogens, including carbapenem-resistant Enterobacterales. Cefiderocol recently received US Food and Drug Administration approval for the treatment of complicated urinary tract infections, including pyelonephritis, and is currently being evaluated in phase III trials for nosocomial pneumonia and infections caused by carbapenem-resistant Gram-negative pathogens. The purpose of this article is to review existing data on the mechanism of action, microbiology, pharmacokinetics, pharmacodynamics, efficacy, and safety of cefiderocol to assist clinicians in determining its place in therapy.

Objective: To describe properties of cobicistat and ritonavir; compare boosting data with atazanavir, darunavir, and elvitegravir; and summarize antiretroviral and comedication interaction studies, with a focus on similarities and differences between ritonavir and cobicistat. Considerations when switching from one booster to another are discussed. Data Sources: A literature search of MEDLINE was performed (1985 to April 2017) using the following search terms: cobicistat, ritonavir, pharmacokinetic, drug interactions, booster, pharmacokinetic enhancer, HIV, antiretrovirals. Abstracts from conferences, article bibliographies, and product monographs were reviewed. Study Selection and Data Extraction: Relevant English-language studies or those conducted in humans were considered. Data Synthesis: Similar exposures of elvitegravir, darunavir, and atazanavir are achieved when combined with cobicistat or ritonavir. Cobicistat may not be as potent a CYP3A4 inhibitor as ritonavir in the presence of a concomitant inducer. Ritonavir induces CYP1A2, 2B6, 2C9, 2C19, and uridine 5′-diphospho-glucuronosyltransferase, whereas cobicistat does not. Therefore, recommendations for cobicistat with comedications that are extrapolated from studies using ritonavir may not be valid. Pharmacokinetic properties of the boosted antiretroviral can also affect interaction outcome with comedications. Problems can arise when switching patients from ritonavir to cobicistat regimens, particularly with medications that have a narrow therapeutic index such as warfarin. Conclusions: When assessing and managing potential interactions with ritonavir- or cobicistat-based regimens, clinicians need to be aware of important differences and distinctions between these agents. This is especially important for patients with multiple comorbidities and concomitant medications. Additional monitoring or medication dose adjustments may be needed when switching from one booster to another.

Use of a vasopressor guideline restricting AVP initiation in septic patients to those on at least 50 µg/min of NE appeared to be safe and did not affect the time to reach goal MAP.

ObjectiveOur aim was to develop evidence-informed recommendations for rehabilitation with older adults living with HIV.DesignWe conducted a knowledge synthesis, combining research evidence specific to HIV, rehabilitation and ageing, with evidence on rehabilitation interventions for common comorbidities experienced by older adults with HIV.MethodsWe included highly relevant HIV-specific research addressing rehabilitation and ageing (stream A) and high-quality evidence on the effectiveness of rehabilitation interventions for common comorbidities experienced by older adults ageing with HIV (stream B). We extracted and synthesised relevant data from the evidence to draft evidence-informed recommendations for rehabilitation. Draft recommendations were refined based on people living with HIV (PLHIV) and clinician experience, values and preferences, reviewed by an interprofessional team for Grading of Recommendations Assessment, Development, and Evaluation (GRADE) (quality) rating and revision and then circulated to PLHIV and clinicians for external endorsement and final refinement. We then devised overarching recommendations to broadly guide rehabilitation with older adults living with HIV.ResultsThis synthesis yielded 8 overarching and 52 specific recommendations. Thirty-six specific recommendations were derived from 108 moderate-level or high-level research articles (meta-analyses and systematic reviews) that described the effectiveness of rehabilitation interventions for comorbidities that may be experienced by older adults with HIV. Recommendations addressed rehabilitation interventions across eight health conditions: bone and joint disorders, cancer, stroke, cardiovascular disease, mental health challenges, cognitive impairments, chronic obstructive pulmonary disease and diabetes. Sixteen specific recommendations were derived from 42 research articles specific to rehabilitation with older adults with HIV. The quality of evidence from which these recommendations were derived was either low or very low, consisting primarily of narrative reviews or descriptive studies with small sample sizes. Recommendations addressed approaches to rehabilitation assessment and interventions, and contextual factors to consider for rehabilitation with older adults living with HIV.ConclusionsThese evidence-informed recommendations provide a guide for rehabilitation with older adults living with HIV.

Normative reference values are essential to identify deviation from normal and evaluate response to treatment. As joint range of motion datasets specific to the pediatric population are infrequently reported in the literature, we determined lower limb passive joint range of motion and bone torsion values from 53 typically developing children aged 4-16 years. Our reference values were consistent with previously published norms, although for some measures, large variability in the literature exists. A clear correlation between joint range and age was observed in most measures. Our results highlight the importance of applying age-matched norms when attempting to identify deviation from normal in the growing child.

This study assessed MR imaging findings in a large cohort demonstrating a significantly increased prevalence of cavum septum pellucidum among fighters. Although cerebral microhemorrhages were higher in fighters than in controls, this finding was not statistically significant, possibly partially due to underpowering of the study.

IMPORTANCE Many studies have investigated the imaging findings showing sequelae of repetitive head trauma, with mixed results.OBJECTIVE To determine whether fighters (boxers and mixed martial arts fighters) with cavum septum pellucidum (CSP) and cavum vergae (CV) have reduced volumes in various brain structures or worse clinical outcomes on cognitive and mood testing.

Case series, Level IV.