The rule that exempts women from rituals that need to be performed at specific times (so-called timebound, positive commandments) has served for centuries to stabilize Jewish gender. It has provided ...a rationale for women's centrality at home and their absence from the synagogue. Departing from dominant popular and scholarly views, Elizabeth Shanks Alexander argues that the rule was not conceived to structure women's religious lives, but rather became a tool for social engineering only after it underwent shifts in meaning during its transmission. Alexander narrates the rule's complicated history, establishing the purposes for which it was initially formulated and the shifts in interpretation that led to its being perceived as a key marker of Jewish gender. At the end of her study, Alexander points to women's exemption from particular rituals (Shema, tefillin and Torah study), which, she argues, are better places to look for insight into rabbinic gender.
The increasing incidence of multidrug-resistant Gram negatives, such as carbapenem-resistant
(CRE), has resulted in a critical need for new antimicrobials. Most studies of new antimicrobials have ...been performed in patients with nondrug-resistant pathogens. We performed a retrospective analysis of patients with CRE infections to inform the design of phase 3 clinical trials.
This was a retrospective study at 22 centers in 4 countries. Baseline data, treatment, and outcomes were collected in patients with complicated urinary tract infection (cUTI)/acute pyelonephritis (AP), hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), and bacteremia due to CRE.
Two hundred fifty-six cases of CRE infection were identified: 75 cUTI/AP, 21 HABP, 20 VABP, and 140 bacteremia. The patient population had significant comorbidities: 32.8% had chronic renal insufficiency, and 26.2% were immunocompromised. Illness severity at presentation was high: 29.3% presented with septic shock. Treatment regimens varied widely; however, a majority of patients received combination therapy. Outcomes were universally poor (28-day mortality was 28.1%) across all sites of infection, particularly in dialysis patients and those with sepsis.
The CRE infections occured in patients with substantial comorbidities and were associated with high mortality and low rates of clinical cure with available antibiotics. Patients with these comorbidities are often excluded from enrollment in clinical trials for registration of new drugs. These results led to changes in the inclusion/exclusion criteria of a phase 3 trial to better represent the patient population with CRE infections and enable enrollment. Observational studies may become increasingly important to guide clinical trial design, inform on the existing standard of care, and provide an external control for subsequent trials.
Abstract
Background
Five hundred milligrams of intravenous (IV) sotrovimab has been shown to be well tolerated and efficacious against pre-Omicron strains in treating patients with mild to moderate ...coronavirus disease 2019 (COVID-19) at high risk for disease progression.
Methods
This was an open-label, single-arm substudy of phase 3 COMET-TAIL (NCT04913675) assessing the safety and tolerability of a 2000 mg IV dose of sotrovimab. Symptomatic patients (aged ≥18 years) with COVID-19 at high risk for progression were enrolled from June 30 through July 11, 2022, when Omicron BA.5, BA.2.12.1, and BA.4 were the predominant circulating variants in the United States. The primary end point was the occurrence of adverse events (AEs), serious AEs (SAEs), AEs of special interest, and COVID-19 disease-related events (DREs) through day 8. Safety, pharmacokinetics, viral load, and hospitalization >24 hours for acute management of illness or death through day 29 were assessed.
Results
All participants (n = 81) were Hispanic, 58% were female, and 51% were aged ≥55 years. Through day 8, no AEs, including infusion-related reactions or hypersensitivity, were reported; 2 participants reported DREs (mild cough, n = 2). One SAE (acute myocardial infarction), which was considered unrelated to sotrovimab or COVID-19 by the investigator, occurred on day 27 and was the only hospitalization reported. Maximum serum concentration (geometric mean) was 745.9 µg/mL. Viral load decreased from baseline through day 29; only 2 (3%) participants had a persistently high viral load (≥4.1 log10 copies/mL) at day 8.
Conclusions
Two thousand milligrams of IV sotrovimab was well tolerated, with no safety signals observed.
Trial registration
ClinicalTrials.gov Identifier: NCT04913675.
Background & aims
This study investigated the perceptions of educational professionals in regard to the effectiveness of visual communication systems and their applications as a functional ...communication intervention for individuals with Autism Spectrum Disorder (ASD).
Methods
One hundred and one individuals from diverse educational backgrounds, school districts, educational services, and various states were surveyed for this study. All participants in this study served individuals with Autism Spectrum Disorder in a clinical and/or school setting.
Results
The study found that aided augmentative and alternative communication (AAC) systems were widely utilized, and participants perceived these systems as the most effective for individuals with Autism Spectrum Disorder. It also found that the use of low level tech aided augmentative communication systems such as Picture Exchange System and high level tech systems such as voice output systems that were strictly computer based, were dependent on the individual's abilities and needs. Finally, the study found that the use of photography and photo journaling techniques had positive outcomes for individuals diagnosed with Autism Spectrum Disorder and other students in the learning environment.
Conclusions
The results revealed that the overall consensus of educational professionals that serve individuals with ASD agreed that aided AAC systems were more effective methods to foster and enhance functional communication. In terms of effectiveness of the level of technology utilized within the system, it depends on the needs and abilities of the individual with ASD. Participants, however, did agree that photography and photo journaling techniques may provide positive attributes to all students and not only those diagnosed with ASD.
Implications
The ability to modify or alter the ways in which AAC systems are created and implemented may address the need to individualize the systems in terms of the needs and abilities of the individual with ASD. The results inform educational practices as they highlight that a majority of the professionals that participated in this study need further professional development with the understanding and application of these systems in order to better understand their benefits and what they have to offer individuals with ASD. The results also provided a lens through the professionals' experiences into the classrooms by providing information from professionals that utilize and implement these systems daily including their successes in aiding communication effectively.
To date, NIPT in the UK has been predominately used in the health service for early sexing of pregnancies at known risk of sex-linked conditions. Developments in the technology are broadening its use ...to diagnostic testing for paternally inherited genetic conditions and for detection of aneuploidy. This study aimed to examine the experiences of UK genetic counselors with offering NIPT for sexing, and to explore their views on future uses of the technology. Twenty interviews with practicing GC’s from four centres were audiotaped, transcribed, and analyzed using modified grounded theory. Participants all had experience of counseling patients around prenatal diagnosis and 18/20 had experience of offering NIPT. GCs reported initially feeling cautious about offering the test, although they saw it as a positive advance for their patients at genetic risk. Emphasis was placed on accuracy, adequate counseling provision and gatekeeping with concerns expressed about broadening its use in the routine antenatal setting. Findings indicate the genetics model for offering prenatal testing to high risk patients can incorporate NIPT and the profession may have a role in informing its implementation in wider healthcare settings. In a wider context this study highlights the challenges new technologies bring to genetic counselors’ practice and service structure.
Chronic sleep loss is a potent catabolic stressor, increasing the risk of metabolic dysfunction and loss of muscle mass and function. To provide mechanistic insight into these clinical outcomes, we ...sought to determine if acute sleep deprivation blunts skeletal muscle protein synthesis and promotes a catabolic environment. Healthy young adults (N = 13; seven male, six female) were subjected to one night of total sleep deprivation (DEP) and normal sleep (CON) in a randomized cross‐over design. Anabolic and catabolic hormonal profiles were assessed across the following day. Postprandial muscle protein fractional synthesis rate (FSR) was assessed between 13:00 and 15:00 and gene markers of muscle protein degradation were assessed at 13:00. Acute sleep deprivation reduced muscle protein synthesis by 18% (CON: 0.072 ± 0.015% vs. DEP: 0.059 ± 0.014%·h‐1, p = .040). In addition, sleep deprivation increased plasma cortisol by 21% (p = .030) and decreased plasma testosterone by 24% (p = .029). No difference was found in the markers of protein degradation. A single night of total sleep deprivation is sufficient to induce anabolic resistance and a procatabolic environment. These acute changes may represent mechanistic precursors driving the metabolic dysfunction and body composition changes associated with chronic sleep deprivation.
Acute sleep deprivation decreases muscle protein synthesis in young, healthy males and females. Acute sleep deprivation promotes a catabolic hormonal environment. Future research should investigate sex‐specific differences.
Academic Health Centers (AHCs) across the nation are experiencing a reawakening to the importance of Diversity, Equity, and Inclusion (DEI). Such work impacts both employees and patients served by ...healthcare institutions. Yet, for departments without previously existing formal channels for this work, it is not always apparent where to begin. The current manuscript details a process for creating a committee as a vehicle for championing DEI efforts at the department level within an AHC. The authors present a six-step model for forming a DEI Committee and progress monitoring measures to remain accountable to identified objectives. In each step, the authors provide examples of their work with the goal for readers to tailor and apply each step to their own departments’ DEI efforts. The current paper also identifies lessons learned with regard to barriers and facilitators of department-level DEI work. Reflections and next steps for DEI work beyond the proposed model are also discussed.
Abstract
Background
Convenient administration of coronavirus disease 2019 (COVID-19) treatment in community settings is desirable. Sotrovimab is a pan-sarbecovirus dual-action monoclonal antibody ...formulated for intravenous (IV) or intramuscular (IM) administration for early treatment of mild/moderate COVID-19.
Method
This multicenter phase 3 study based on a randomized open-label design tested the noninferiority of IM to IV administration according to an absolute noninferiority margin of 3.5%. From June to August 2021, patients aged ≥12 years with COVID-19, who were neither hospitalized nor receiving supplemental oxygen but were at high risk for progression, were randomized 1:1:1 to receive sotrovimab as a single 500-mg IV infusion or a 500- or 250-mg IM injection. The primary composite endpoint was progression to (1) all-cause hospitalization for >24 hours for acute management of illness or (2) all-cause death through day 29.
Results
Sotrovimab 500 mg IM was noninferior to 500 mg IV: 10 (2.7%) of 376 participants vs 5 (1.3%) of 378 met the primary endpoint, respectively (absolute adjusted risk difference, 1.06%; 95% CI, −1.15% to 3.26%). The 95% CI upper limit was lower than the prespecified noninferiority margin of 3.5%. The 250-mg IM group was discontinued early because of the greater proportion of hospitalizations vs the 500-mg groups. Serious adverse events occurred in <1% to 2% of participants across groups. Four participants experienced serious disease-related events and died (500 mg IM, 2/393, <1%; 250 mg IM, 2/195, 1%).
Conclusions
Sotrovimab 500-mg IM injection was well tolerated and noninferior to IV administration. IM administration could expand outpatient treatment access for COVID-19.
Clinical Trials Registration
ClinicalTrials.gov: NCT04913675.
Sotrovimab administered intramuscularly at 500 mg was noninferior to 500 mg administered intravenously for treatment of mild/moderate COVID-19 in patients at high risk, as measured by all-cause hospitalization >24 hours or death through day 29, and it was well tolerated. Intramuscular sotrovimab should provide easier outpatient access to COVID-19 treatment.
The “particular plaintiffs” provision of PLRA, 18 U.S.C. § 3626(a)(1), has had little success in restricting prisoners' access to class certification. Nonetheless, prisoners may now be largely unable ...to pursue class action litigation. InWal-Mart Stores, Inc. v. Dukes, the Supreme Court last year announced new restrictions on class certification that may make such litigation nearly unavailable in most civil rights cases, including those filed by prisoners. As a further irony, the Supreme Court's decision from the same term inBrown v. Platademonstrates that the new standards announced inDukesare unrelated to distinguishing cases in which class certification promotes judicial efficiency and fairness. This sequence of events underlines the importance of the federal courts' hostility to civil rights in exacerbating the effects of PLRA on prisoners' rights, and the Supreme Court's expression of that hostility through procedural decisions.
•Lefamulin showed potent activity against the most common community-acquired bacterial pneumonia (CABP) pathogens.•Bacterial baseline pathogens were identified by real-time quantitative PCR and ...standard diagnostic tests.•Lefamulin efficacy was high regardless of baseline pathogen or presence of drug-resistant strains/polymicrobial infection.
Lefamulin, a pleuromutilin antibiotic approved for community-acquired bacterial pneumonia (CABP), was evaluated for microbiological efficacy in a prespecified pooled analysis of LEAP 1 and 2 phase 3 clinical trial data in patients with CABP.
In LEAP 1, adults (PORT risk class III‒V) received intravenous (IV) lefamulin 150 mg every 12 h (q12h) for 5‒7 days or moxifloxacin 400 mg every 24 h (q24h) for 7 days, with optional IV-to-oral switch. In LEAP 2, adults (PORT II‒IV) received oral lefamulin 600 mg q12h for 5 days or moxifloxacin 400 mg q24h for 7 days. Primary outcomes were early clinical response (ECR) at 96 ± 24 h after treatment start and investigator assessment of clinical response (IACR) 5‒10 days after the last dose. Secondary outcomes included ECR and IACR in patients with a baseline CABP pathogen (detected via culture, urinary antigen testing, serology and/or real-time PCR).
Baseline CABP pathogens were detected in 709/1289 patients (55.0%; microbiological intention-to-treat population). The most frequently identified pathogens were Streptococcus pneumoniae (61.9% of patients) and Haemophilus influenzae (29.9%); 25.1% had atypical pathogens and 33.1% had polymicrobial infections. Pathogens were identified most frequently by PCR from sputum, followed by culture from respiratory specimens. In patients with baseline CABP pathogens, ECR rates were 89.3% (lefamulin) and 93.0% (moxifloxacin); IACR success rates were 83.2% and 86.7%, respectively. Results were consistent across CABP pathogens, including drug-resistant isolates and polymicrobial infections.
Lefamulin is a valuable IV and oral monotherapy option for empirical and directed CABP treatment in adults.
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