Zilebesiran, an RNA Interference Therapeutic Agent for Hypertension.

BACKGROUND: Angiotensinogen is the sole precursor of angiotensin peptides and has a key role in the pathogenesis of hypertension. Zilebesiran, an investigational RNA interference therapeutic agent with a prolonged duration of action, inhibits hepatic angiotensinogen synthesis. METHODS: In this phase 1 study, patients with hypertension were randomly assigned in a 2:1 ratio to receive either a single ascending subcutaneous dose of zilebesiran (10, 25, 50, 100, 200, 400, or 800 mg) or placebo and were followed for 24 weeks (Part A). Part B assessed the effect of the 800-mg dose of zilebesiran on blood pressure under low- or high-salt diet conditions, and Part E the effect of that dose when coadministered with irbesartan. End points included safety, pharmacokinetic and pharmacodynamic characteristics, and the change from baseline in systolic and diastolic blood pressure, as measured by 24-hour ambulatory blood-pressure monitoring. RESULTS: Of 107 patients enrolled, 5 had mild, transient injection-site reactions. There were no reports of hypotension, hyperkalemia, or worsening of renal function resulting in medical intervention. In Part A, patients receiving zilebesiran had decreases in serum angiotensinogen levels that were correlated with the administered dose (r = -0.56 at week 8; 95% confidence interval, -0.69 to -0.39). Single doses of zilebesiran (≥200 mg) were associated with decreases in systolic blood pressure (>10 mm Hg) and diastolic blood pressure (>5 mm Hg) by week 8; these changes were consistent throughout the diurnal cycle and were sustained at 24 weeks. Results from Parts B and E were consistent with attenuation of the effect on blood pressure by a high-salt diet and with an augmented effect through coadministration with irbesartan, respectively. CONCLUSIONS: Dose-dependent decreases in serum angiotensinogen levels and 24-hour ambulatory blood pressure were sustained for up to 24 weeks after a single subcutaneous dose of zilebesiran of 200 mg or more; mild injection-site reactions were observed. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov number, NCT03934307; EudraCT number, 2019-000129-39.).

Antiretroviral Therapy in Pregnancy: A 2023 Review of the Literature.

PURPOSE OF REVIEW: Selection of antiretroviral therapy during pregnancy must consider maternal physiology and resulting pharmacokinetic changes in pregnancy, resistance and efficacy profiles, tolerability and frequency of adverse effects, teratogenicity, and maternal, neonatal, and pregnancy outcomes. The objective of this review is to summarize the underlying data that informs the current clinical perinatal guidelines in the USA. RECENT FINDINGS: Data now supports the use of dolutegravir at all stages of pregnancy with no significant increase in neural tube defects. Safety and pharmacokinetic data on newer antiretroviral medications in pregnancy continue to lag behind the general population. While there are multiple safety and tolerability concerns with older regimens, there are now multiple options of regimens that are highly efficacious and have good safety data in pregnancy. Most pregnant patients who are virally suppressed on a well-tolerated regimen are able to safely continue those medications during pregnancy.

Postoperative Incisional Complications in Gynaecologic Single-Incision Laparoscopic Surgery: Comparing Closure Techniques.

OBJECTIVES: Single-incision laparoscopic surgery (SILS) and robotic SILS (rSILS) have been found to be safe, minimally invasive techniques in gynaecology. However, one major perceived drawback of these techniques is the increased risk of incisional hernia, compared to multiport laparoscopy or robotic surgery. This study's aim was to determine the optimal technique to reduce postoperative incisional complications such as hernia. METHODS: A retrospective cohort study was performed at an academic centre from November 2014 to June 2022 on 1036 women who underwent SILS and rSILS gynaecologic procedures with various closure techniques. Techniques included running absorbable sutures without tagging incision apices (standard closure) and tagging incision apices at the beginning of surgery with the use of permanent suture, absorbable suture, or a combination. RESULTS: Rates of hernia (primary outcome) and incisional issues (secondary outcome) such as separation or infection were analyzed by technique. Hernia rates were lower when incision apices were tagged compared to when not tagged (P < 0.001). Cellulitis/abscess rates were not significantly different. Incision separation was higher when apices were tagged with absorbable and a combination of permanent and absorbable sutures than if apices were tagged with all permanent sutures or not at all. In multivariate analysis, hernia rate decreased in groups with tagged apices, although other incision complications did not vary. CONCLUSIONS: The incidence of incisional hernia after SILS procedures is low, though it does vary by technique. Tagging apices for closure, regardless of suture type, can mitigate one of the biggest concerns of performing SILS by reducing postoperative incisional hernia risk.

Rapid Methadone Induction in a General Hospital Setting: A Retrospective, Observational Analysis.

BACKGROUND: Outpatient methadone guidelines recommend starting at a low dose and titrating slowly. As fentanyl prevalence and opioid-related mortality increases, there is a need for individuals to rapidly achieve a therapeutic methadone dose. Hospitalization offers a monitored setting for methadone initiation, however dosing practices and safety are not well described. METHODS: Retrospective, observational analysis of hospitalized patients with opioid use disorder seen by an inpatient addiction consult team in an academic medical center who were newly initiated on methadone between 2016 and 2022. We calculated initial daily dose, maximum daily dose, timing interval of dose escalation, whether patients were connected to an opioid treatment program (OTP) prior to discharge, whether adverse effects or safety events occurred during the hospitalization, and whether such events were definitely or probably related versus possibly related or unrelated to methadone. RESULTS: One hundred twelve patients were included. The mean initial daily methadone dose administered was 32 mg (range: 10-90 mg). The mean maximum dose reached was 76.8 mg (range 30-165 mg). The mean number of days from initial to peak dose was 5.6 days (range 1-19 days). Overall, 30% of patients experienced a safety event, most commonly sedation. Only 4 safety events were deemed probably or definitely related to methadone. In regression analyses, there was no significant difference between starting doses among patients with or without sedation but there was a relationship between last dose and the likelihood of any possibly related event, with those ending at a dose of 100 mg or higher having a higher likelihood event, compared to those ending at lower doses (47.8% vs 12.4%, P < .001). Seventy-six percent were connected to OTP before discharge. CONCLUSION: Among hospitalized patients initiating methadone, rapid dose titration was infrequently associated with related safety events and most were connected to community-based methadone treatment before discharge.

Applying Patient and Public Involvement in preclinical research: A co-created scoping review.

BACKGROUND: Patient and Public Involvement (PPI) in research aims to improve the quality, relevance and appropriateness of research. PPI has an established role in clinical research where there is evidence of benefit, and where policymakers and funders place continued emphasis on its inclusion. However, for preclinical research, PPI has not yet achieved the same level of integration. As more researchers, including our team, aim to include PPI in preclinical research, the development of an evidence-based approach is important. Therefore, this scoping review aimed to identify and map studies where PPI has been used in preclinical research and develop principles that can be applied in other projects. METHODS: A scoping review was conducted to search the literature in Medline (PubMed), EMBASE, CINAHL, PsycInfo and Web of Science Core Collection to identify applied examples of preclinical PPI. Two independent reviewers conducted study selection and data extraction separately. Data were extracted relating to PPI in terms of (i) rationale and aims, (ii) approach used, (iii) benefits and challenges, (iv) impact and evaluation and (v) learning opportunities for preclinical PPI. Findings were reviewed collaboratively by PPI contributors and the research team to identify principles that could be applied to other projects. RESULTS: Nine studies were included in the final review with the majority of included studies reporting PPI to improve the relevance of their research, using approaches such as PPI advisory panels and workshops. Researchers report several benefits and challenges, although evidence of formal evaluation is limited. CONCLUSION: Although currently there are few examples of preclinical research studies reporting empirical PPI activity, their findings may support those aiming to use PPI in preclinical research. Through collaborative analysis of the scoping review findings, several principles were developed that may be useful for other preclinical researchers. PATIENT OR PUBLIC CONTRIBUTION: This study was conducted as part of a broader project aiming to develop an evidence base for preclinical PPI that draws on a 5-year preclinical research programme focused on the development of advanced biomaterials for spinal cord repair as a case study. A PPI Advisory Panel comprising seriously injured rugby players, clinicians, preclinical researchers and PPI facilitators collaborated as co-authors on the conceptualization, execution and writing of this review, including refining the findings into the set of principles reported here.

The Impact of COVID-19 on Burnout, Psychological Well-being, and Work Satisfaction in Psychiatry Trainees in Ireland.

OBJECTIVE: Prior to the pandemic, trainee doctors were at higher risk of psychological ill health. There is limited evidence measuring the impact of COVID-19 on psychiatry trainees. This study evaluates levels of burnout, work satisfaction, and psychological well-being in psychiatry junior doctors in Ireland and identifies potential contributing factors. METHODS: The authors carried out a cross-sectional online survey measuring demographic and work-related variables. Questions including exposure to COVID-19 and stress-related factors were included. We evaluated burnout, work satisfaction, and psychological well-being using the Abbreviated-Maslach Burnout Inventory, Basic Needs Satisfaction at Work Scale, and WHO-5 Well-being Index. RESULTS: One hundred and five doctors responded (21%). The biggest stressor reported was reduced face-to-face contact with family and friends (73%). Forty one percent reported weekly supervision changes. Sixty five percent met the criteria for burnout, compared with 36.2% in 2018. Significant factors associated with burnout included staff shortages, longer hours, and less experience. Changes in supervision and working in non-European Working Time Directive compliant rotas were associated with lower scores across all subdomains of the BNSW Scale. The WHO-5 Well-being Index identified 48% scored low in personal well-being, indicating these trainees met the threshold for depression. Changes in regular supervision (p=0.010) were a significant predictor of low personal well-being. CONCLUSIONS: High prevalence of burnout and low levels of well-being in this vulnerable cohort, particularly those who are inexperienced, have changes in supervision, and working longer hours is concerning. This study highlights the importance of regular supervision and support for this group.

Initiating Pharmacologic Treatment in Tobacco-Dependent Adults. An Official American Thoracic Society Clinical Practice Guideline.

Background: Current tobacco treatment guidelines have established the efficacy of available interventions, but they do not provide detailed guidance for common implementation questions frequently faced in the clinic. An evidence-based guideline was created that addresses several pharmacotherapy-initiation questions that routinely confront treatment teams.Methods: Individuals with diverse expertise related to smoking cessation were empaneled to prioritize questions and outcomes important to clinicians. An evidence-synthesis team conducted systematic reviews, which informed recommendations to answer the questions. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to rate the certainty in the estimated effects and the strength of recommendations.Results: The guideline panel formulated five strong recommendations and two conditional recommendations regarding pharmacotherapy choices. Strong recommendations include using varenicline rather than a nicotine patch, using varenicline rather than bupropion, using varenicline rather than a nicotine patch in adults with a comorbid psychiatric condition, initiating varenicline in adults even if they are unready to quit, and using controller therapy for an extended treatment duration greater than 12 weeks. Conditional recommendations include combining a nicotine patch with varenicline rather than using varenicline alone and using varenicline rather than electronic cigarettes.Conclusions: Seven recommendations are provided, which represent simple practice changes that are likely to increase the effectiveness of tobacco-dependence pharmacotherapy.

Salpingectomy versus Tubal Occlusion for Permanent Contraception during Cesarean Delivery: Outcomes and Physician Attitudes.

STUDY OBJECTIVE: Compare clinical outcomes and physician attitudes toward tubal occlusion and salpingectomy during cesarean section. DESIGN: Retrospective cohort study with survey. SETTING: Private hospital in Cincinnati, Ohio. PATIENTS: Women aged ≥18 years undergoing permanent contraception during cesarean delivery with and without salpingectomy from January 2016 to December 2017. INTERVENTIONS: Rate measurements of permanent contraception during cesarean section by salpingectomy versus tubal occlusion. Online survey assessment of study population physicians' attitudes toward salpingectomy. MEASUREMENTS AND MAIN RESULTS: Study subjects identified using Current Procedural Terminology codes. Subject demographics, operative details, and perioperative morbidity indicators were identified by chart review. A total of 363 subjects were included: 116 (32%) had salpingectomies, and 247 (68%) had tubal occlusions. Study variables were compared using Wilcoxon rank sum and Fisher exact tests. Despite similar cohort demographics, salpingectomy increased mean operative time by 6.5 minutes compared with tubal occlusion (p = .001). Compared with subjects who had a salpingectomy, those who had a tubal occlusion had more postoperative symptomatic anemia (5.7% vs 0.9%) and infection (6.9% vs 1.7%). The primary surgeon was identified by logistic regression as the factor most predictive of salpingectomy (p <.001). Of 30 physicians, 23 (77%) completed the survey, and these physicians performed 80% of procedures. Physicians did not differ by sex, age, years of practice, solo vs group practice, or hospital-employed vs private practice when compared with the number or rate of salpingectomies performed. Cancer risk reduction was the most common physician-identified salpingectomy benefit (17 of 23, 74%). A total of 65% believed that salpingectomy posed additional risks, but 70% believed the benefits were equal to or greater than the risks. Of the 23 (87%) who completed the survey, 20 believed that salpingectomy added no additional operative time and was cost-neutral. CONCLUSION: Relative to tubal ligation, salpingectomy during cesarean section increases operative time but not perioperative morbidity. Physicians do not seem biased against salpingectomy and express awareness of published benefits and risks, yet it is not the dominant surgical approach.

Burnout, Work Satisfaction, and Well-being Among Non-consultant Psychiatrists in Ireland.

OBJECTIVE: The aim of this study was to explore the areas of psychological well-being, satisfaction at work, and burnout among non-consultant psychiatrists in Ireland, and to assess for potential contributory factors. METHODS: The College of Psychiatrists of Ireland distributed the survey online to 100 non-consultant psychiatry doctors working in Ireland. The survey contained questions relating to demographic and work-related variables, the Abbreviated-Maslach Burnout Inventory (a-MBI), Basic Needs Satisfaction at Work (BNSW) scale, and WHO-5 Well-being Index. Descriptive statistics were used by the authors to summarize the data and univariate associations were explored between baseline data and subscales. RESULTS: Sixty-nine percent of our sample completed the survey. Thirty-six percent of the sample met the criteria for burnout, with lack of supervision the only variable significantly associated with this. Lack of regular supervision was associated with lower scores across all work satisfaction domains of the BNSW scale. The WHO-5 Well-being Index identified that 30% of respondents scored low in personal well-being, indicating that this proportion screened positive for depression, based on international diagnostic criteria. Lack of regular supervision was found to be significantly associated with low psychological well-being. CONCLUSION: This study indicates that lack of supervision is significantly associated with burnout, lower satisfaction at work, and poorer psychological well-being. Close evaluation of these areas is important to identify vulnerable individuals and areas of training which can be improved upon, which may lead to relevant measures being implemented for the benefit of psychiatrists, patients, and the wider society.

The development of natural polymer scaffold-based therapeutics for osteochondral repair.

Due to the limited regenerative capacity of cartilage, untreated joint defects can advance to more extensive degenerative conditions such as osteoarthritis. While some biomaterial-based tissue-engineered scaffolds have shown promise in treating such defects, no scaffold has been widely accepted by clinicians to date. Multi-layered natural polymer scaffolds that mimic native osteochondral tissue and facilitate the regeneration of both articular cartilage (AC) and subchondral bone (SCB) in spatially distinct regions have recently entered clinical use, while the transient localized delivery of growth factors and even therapeutic genes has also been proposed to better regulate and promote new tissue formation. Furthermore, new manufacturing methods such as 3D bioprinting have made it possible to precisely tailor scaffold micro-architectures and/or to control the spatial deposition of cells in requisite layers of an implant. In this way, natural and synthetic polymers can be combined to yield bioactive, yet mechanically robust, cell-laden scaffolds suitable for the osteochondral environment. This mini-review discusses recent advances in scaffolds for osteochondral repair, with particular focus on the role of natural polymers in providing regenerative templates for treatment of both AC and SCB in articular joint defects.

Clinical and neuroimaging correlates of cognition in HIV.

This study investigated whether HIV-positive participants, stable on combined antiretroviral therapy (cART), showed cognitive impairments relative to HIV-negative controls; and whether clinical and neuroimaging factors correlated with cognitive function in the HIV-positive participants. One hundred and twenty-six white men who have sex with men, of whom 78 were HIV-positive and stable on cART and 48 were HIV negative, were recruited to this cross-sectional study. The median age of HIV-positive participants in this study was 47. They underwent clinical and neuropsychological evaluation and magnetic resonance imaging of the brain, including diffusion tensor imaging (DTI). Cognitive scores for both groups were compared, and regression models were run to explore the influence of clinical, psychiatric, lifestyle, and neuroimaging variables on cognition. The prevalence of neurocognitive impairment, using the multivariate normative comparison criteria, was 28% in HIV-positive participants and 5% in HIV-negative participants. After covarying for age, years of education, and non-English speaking background, there were significant differences between the HIV group and the controls across four cognitive domains. The HIV group showed significantly higher mean diffusivity (MD) and lower fractional anisotropy (FA) than the control group on DTI. Although anxiety levels were clinically low, anxiety and DTI measures were the only variables to show significant correlations with cognitive function. In the HIV group, poorer cognitive performance was associated with higher MD and lower FA on DTI and higher (albeit clinically mild) levels of anxiety. Our findings suggest that white matter changes and subtle anxiety levels contribute independently to cognitive impairment in HIV.

Recommendations for the Appropriate Structure, Communication, and Investigation of Tobacco Harm Reduction Claims. An Official American Thoracic Society Policy Statement.

RATIONALE: The tobacco harm reduction literature is replete with vague language, far-reaching claims, and unwarranted certainty. The American Thoracic Society has increasingly recognized the need for a framework for reliably making such claims. Evidence-based standards improving the scientific value and transparency of harm reduction claims are expected to improve their trustworthiness, clarity, and consistency. METHODS: Experts from relevant American Thoracic Society committees identified key topic areas for discussion. Literature search strategy included English language articles across Medline, Google Scholar, and the Cochrane Collaborative databases, with expanded search terms including tobacco, addiction, smoking, cigarettes, nicotine, and harm reduction. Workgroup members synthesized their evidentiary summaries into a list of candidate topics suitable for inclusion in the final report. Breakout groups developed detailed content maps of each topic area, including points to be considered for suggested recommendations. Successive draft recommendations were modified using an iterative consensus process until unanimous approval was achieved. Patient representatives ensured the document's relevance to the lay public. RESULTS: Fifteen recommendations were identified, organized into four framework elements dealing with: estimating harm reduction among individuals, making claims on the basis of population impact, appropriately careful use of language, and ethical considerations in harm reduction. DISCUSSION: This statement clarifies important principles guiding valid direct and inferential harm reduction claims. Ideals for effective communication with the lay public and attention to unique ethical concerns are also delineated. The authors call for formal systems of grading harm reduction evidence and regulatory assurances of longitudinal surveillance systems to document the impact of harm reduction policies.

Psychogenic amnesia: syndromes, outcome, and patterns of retrograde amnesia.

There are very few case series of patients with acute psychogenic memory loss (also known as dissociative/functional amnesia), and still fewer studies of outcome, or comparisons with neurological memory-disordered patients. Consequently, the literature on psychogenic amnesia is somewhat fragmented and offers little prognostic value for individual patients. In the present study, we reviewed the case records and neuropsychological findings in 53 psychogenic amnesia cases (ratio of 3:1, males:females), in comparison with 21 consecutively recruited neurological memory-disordered patients and 14 healthy control subjects. In particular, we examined the pattern of retrograde amnesia on an assessment of autobiographical memory (the Autobiographical Memory Interview). We found that our patients with psychogenic memory loss fell into four distinct groups, which we categorized as: (i) fugue state; (ii) fugue-to-focal retrograde amnesia; (iii) psychogenic focal retrograde amnesia following a minor neurological episode; and (iv) patients with gaps in their memories. While neurological cases were characterized by relevant neurological symptoms, a history of a past head injury was actually more common in our psychogenic cases (P = 0.012), perhaps reflecting a 'learning episode' predisposing to later psychological amnesia. As anticipated, loss of the sense of personal identity was confined to the psychogenic group. However, clinical depression, family/relationship problems, financial/employment problems, and failure to recognize the family were also statistically more common in that group. The pattern of autobiographical memory loss differed between the psychogenic groups: fugue cases showed a severe and uniform loss of memories for both facts and events across all time periods, whereas the two focal retrograde amnesia groups showed a 'reversed' temporal gradient with relative sparing of recent memories. After 3-6 months, the fugue patients had improved to normal scores for facts and near-normal scores for events. By contrast, the two focal retrograde amnesia groups showed less improvement and continued to show a reversed temporal gradient. In conclusion, the outcome in psychogenic amnesia, particularly those characterized by fugue, is better than generally supposed. Findings are interpreted in terms of Markowitsch's and Kopelman's models of psychogenic amnesia, and with respect to Anderson's neuroimaging findings in memory inhibition.

Does the modified Glasgow Prognostic Score (mGPS) have a prognostic role in esophageal cancer?

BACKGROUND: The modified Glasgow Prognostic Score (mGPS), which combines indices of decreased plasma albumin and elevated CRP, has reported independent prognostic significance in colorectal cancer, but its value in upper gastrointestinal cancer is unclear. The aim of this study was to assess the prognostic significance of mGPS in patients with operable esophageal malignancy. METHODS: Patients undergoing resection with curative intent between January 2008 and June 2013 were included. The mGPS was scored as 0, 1, or 2 based on CRP(>10 mg/L) and albumin(<35g/L). The mGPS score (0 vs. 1/2 combined) was correlated with patient and tumor characteristics, and operative and oncologic outcomes. RESULTS: Two hundred and twenty-three patients were included. Median (range) follow-up was 21(12-70) months. The mGPS was 0 in 174 patients(78%). mGPS was significantly associated with positive nodal status(P = 0.008) and stage ≥III (P = 0.017). There was a significant improvement in overall survival in patients with mGPS = 0 (47.8 vs. 37.5 months, P = 0.014) but in multivariate analysis, only TNM-stage and nodal status were found to be independent prognostic indicators. CONCLUSIONS: mGPS is associated with advanced stage but has no independent prognostic significance and does not impact on operative outcomes. Consequently, this data does not support its routine application in patient selection or prognostication. J. Surg. Oncol. 2016;113:732-737. © 2016 Wiley Periodicals, Inc.

Pre-measurement rest time affects magnitude and reliability of toe pressure measurements.

OBJECTIVES: Toe pressures are used to evaluate lower extremity healing capacity and screen for peripheral arterial disease (PAD). Although toe pressures are commonly used clinically both as an independent measure and in the calculation of the toe-brachial index, the effect of pre-measurement rest duration on the magnitude and reliability of toe pressures is unknown. This study investigated the effect of pre-measurement rest duration on toe pressures. METHODS: Seventy community-based participants meeting guidelines for PAD screening were recruited. Systolic toe pressures either at the left or right hallux were manually measured using photoplethysmography following 5, 10 and 15 min of rest in a supine horizontal position. Testing was repeated 7-10 days later. RESULTS: A significant drop in toe pressure (3.86 mmHg) occurred between 5 and 10 min (p = 0.001). No significant change occurred between 10 and 15 min. Reliability after 5 min was excellent (intra-class correlation coefficient, ICC = 0.80, 95% CI 0.68-0.89), increasing slightly at 10 and 15 min (ICC = 0.86, 95% CI 0.77-0.92 and ICC = 0.82, 95% CI 0.69-0.89). CONCLUSIONS: Toe pressures stabilize after 10 min of rest in a supine horizontal position. Longer periods of pre-measurement rest did not improve reliability significantly.

Donor brain death exacerbates complement-dependent ischemia/reperfusion injury in transplanted hearts.

BACKGROUND: Brain death (BD) can immunologically prime the donor organ and is thought to lead to exacerbated ischemia/reperfusion injury after transplantation. Using a newly developed mouse model of BD, we investigated the effect of donor BD on posttransplantation cardiac ischemia/reperfusion injury. We further investigated the therapeutic effect of a targeted complement inhibitor in recipients of BD donor hearts and addressed the clinical relevance of these studies by analyzing human heart biopsies from BD and domino (living) donors. METHODS AND RESULTS: Hearts from living or BD donor C57BL/6 mice were transplanted into C57BL/6 or BALB/c recipients. Recipient mice were treated with the complement inhibitor CR2-Crry or vehicle control (n=6). Isografts were analyzed 48 hours after transplantation for injury, inflammation, and complement deposition, and allografts were monitored for graft survival. Human cardiac biopsies were analyzed for complement deposition and inflammatory cell infiltration. In the murine model, donor BD exacerbated ischemia/reperfusion injury and graft rejection, as demonstrated by increased myocardial injury, serum cardiac troponin, cellular infiltration, complement deposition, inflammatory chemokine and cytokine levels, and by decreased graft survival. CR2-Crry treatment of recipients significantly reduced all measured outcomes in grafts from both BD and living donors compared with controls. Analysis of human samples documented the relevance of our experimental findings and revealed exacerbated complement deposition and inflammation in grafts from BD donors compared with grafts from living donors. CONCLUSIONS: BD exacerbates posttransplantation cardiac ischemia/reperfusion injury in mice and humans and decreases survival of mouse allografts. Furthermore, targeted complement inhibition in recipient mice ameliorates BD-exacerbated ischemia/reperfusion injury.

Isolation and genetic characterization of Toxoplasma gondii from alpaca (Vicugna pacos) and sheep (Ovis aries).

Alpacas are important to the economy of several countries. Little is known of Toxoplasma gondii infection in alpacas worldwide. In the present study, T. gondii was isolated and genetically characterized from alpacas for the first time. Alpacas (n = 16) and rams (n = 12) pastured on a farm in Virginia, USA, were examined at necropsy. Antibodies to T. gondii were determined by the modified agglutination test (MAT, 1:25) and found in 6 of 16 alpacas with titers of 1:100 (2 alpaca), 1:400 (2 alpacas), 1:800 (1 alpaca), and 1:1,600 (1 alpaca), and 5 of 12 rams in titers of 1:50 in one, 1:400 in one, 1:800 in one, 1:1,600 in one, and 1:3,200 in one. Tissues of all 16 alpacas were bioassayed in mice or in cats. Muscles (heart, skeletal muscle) of nine alpacas with MAT titers of 1:25 were fed to T. gondii-free cats; the cats did not shed oocysts. Viable T. gondii was isolated from tissues of two of six seropositive alpacas by bioassay in mice. Viable T. gondii was isolated from three of three seropositive sheep by bioassay in mice. Genotyping using cell-cultured tachyzoites revealed four genotypes, including one for ToxoDB PCR-RFLP genotype #2 (type III), one for genotype #3 (type II variant), one for genotype #170, and two for a new genotype designated as ToxoDB PCR-RFLP genotype #230. Thus, four of the five T. gondii isolates in the present study belonged to different genotypes. These results indicate a higher genetic diversity among T. gondii isolates circulating in the USA than previously realized.

A survey of contraceptive method use among patients with delayed permanent contraception due to the COVID-19 pandemic.

OBJECTIVES: Evaluate contraception usage in patients awaiting permanent contraception during COVID-19 pandemic. STUDY DESIGN: Patients awaiting permanent contraception between March 2020 and July 2022 completed a survey assessing contraceptive usage. Descriptive statistics were analyzed. RESULTS: One hundred and twenty-three patients consented to the survey. Ninety seven percent identified as Black, Indigenous, and people of color. Eighty three percent used alternative forms of contraception, with 31% using long acting, reversible contraceptives. Eighty nine percent still desired surgery. CONCLUSIONS: Despite delays, most patients still desired surgery. Patients alternatively chose intrauterine devices and implants. IMPLICATIONS: Hospitals should prioritize permanent contraception to avoid delays in access to desired reproductive healthcare options.

Linkage to Care Outcomes Following Treatment in A Low-Threshold Substance Use Disorder Bridge Clinic.

BACKGROUND: Treatment for substance use disorders (SUD) remains low in the United States. To better meet needs of people who use alcohol and other drugs, low threshold bridge clinics which offer treatment without barrier and harm reduction services have gained prevalence. Bridge clinics work to surmount barriers to care by providing same day medication and treatment for SUD and eventually transitioning patients to community-based treatment providers. In this study, we examine SUD treatment outcomes among patients who transitioned out of a bridge clinic. METHODS: This is a retrospective cohort study of posttreatment outcomes of patients seen at an urban medical center's bridge clinic between 2017 and 2022. The primary outcome was being in care anywhere at time of follow-up. We also examined the proportion of patients who completed each step of the cascade of care following transfer: connection to transfer clinic, completion of a clinic visit, retention in care, and medication use among those remaining in care at the transfer clinic. We examined the association of different bridge clinic services with still being in care anywhere and the association between successful transfer with being in care and taking medication at follow-up. RESULTS: Of 209 eligible participants, 63 were surveyed. Sixty-five percent of participants identified as male, 74% as white, 12% as Hispanic, 6% as Black, and 16% were unhoused. Most participants (78%) reported being connected to SUD treatment from the Bridge Clinic, and 37% remained in care at the same facility at the time of survey. Eighty-four percent reported being in treatment anywhere and 68% reported taking medication for SUD at follow-up, with most participants reporting taking buprenorphine (46%). CONCLUSION: Of those participants who transitioned out of a bridge clinic into community-based SUD care, 78% were successfully connected to ongoing care and 84% were still in care at follow-up.