Risk Factors for Recurrence Following Arthroscopic Bankart Repair - A Systematic.

BACKGROUND: Recurrent instability remains a major source of morbidity following arthroscopic Bankart repair. Many risk factors and predictive tools have been described, but there remains a lack of consensus surrounding individual risk factors and their contribution to outcomes. PURPOSE: To systematically review the literature to identify and quantify risk factors for recurrence following arthroscopic Bankart repair. METHODS: A literature search was performed using the PubMed/Medline databases based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Studies were included if they evaluated risk factors for recurrent instability following arthroscopic Bankart repair. RESULTS: Overall, 111 studies were included in the analysis, including a total of 19,307 patients and 2,750 episodes of recurrent instability with 45 risk factors described. Age at operation was reported by 60 studies, with 35 finding increased risk at younger ages. Meta-analysis showed a two-fold recurrence rate of 27.0% (171/634) for patients under 20 years old compared to 13.3% (197/1485) for older patients (p<0.001). Seventeen studies completed multivariable analysis, 13 of which were significant (Odds Ratio 1.3-14.0). Glenoid bone loss was evaluated by 39 studies, with 20 finding an increased risk. Multivariable analysis in 9 studies found OR ranging from 0.7-35.1; 6 were significant. Off-track Hill-Sachs lesions were evaluated in 21 studies (13 significant), with 3 of 4 studies that conducted multivariable analysis finding a significant association with odds ratio of 2.9-8.9 of recurrence. The number of anchors used in repair was reported by 25 studies, with 4 finding increased risk with fewer anchors. Pooled analysis demonstrated a 25.0% (29/156) risk of recurrence with 2 anchors compared to 18.1% (89/491) with 3 or more anchors (p=0.06). Other frequently described risk factors included glenohumeral joint hyperlaxity (46% of studies reporting a significant association), number of preoperative dislocations (31%), contact sport participation (20%), competitive sport participation (46%), patient sex (7%), and concomitant SLAP tear (0%). CONCLUSION: Younger age, glenoid bone loss, and off-track Hill-Sachs lesions, are established risk factors for recurrence following arthroscopic Bankart repair. Other commonly reported risk factors included contact and competitive sports participation, number of fixation devices, and patient sex.

Naloxone Use During Pregnancy-Data from 26 US Jurisdictions, 2019-2020.

OBJECTIVES: We aimed to determine the prevalence of self-reported naloxone use during pregnancy among people in the United States with a recent live birth. A secondary objective was to characterize people at increased risk of overdose who did and did not use naloxone. METHODS: We analyzed data from the Pregnancy Risk Assessment Monitoring System from 26 US jurisdictions that conducted an opioid supplement survey from 2019 to 2020. Respondents with increased risk of experiencing an opioid overdose were identified based on self-reported use of illicit amphetamines, heroin, cocaine, or receiving medication for opioid use disorder (MOUD) during pregnancy. Weighted prevalence estimates and 95% confidence intervals were calculated for reported naloxone use at any point during pregnancy among people with an increased risk of overdose. RESULTS: Naloxone use during pregnancy was reported by <1% of the overall study population (unweighted N = 88/34,528). Prevalence of naloxone use was 5.0% (95% CI: 0.0-10.6) among respondents who reported illicit amphetamine use, 15.2% (1.8-28.6) among those who reported heroin use, and 17.6% (0.0-38.1) among those who reported cocaine use. Naloxone use was 14.5% (8.4-20.6) among those who reported taking MOUD. Among people with increased risk of overdose, no significant differences in naloxone use were observed by age, race/ethnicity, education level, residential metropolitan status, or insurance status. CONCLUSIONS: Prevalence of naloxone use among people with an increased risk of overdose during pregnancy ranged from 5.0% to 17.6%. Access to naloxone, overdose prevention education, and treatment for substance use disorders may help reduce morbidity and mortality.

Occult Amyloid-ß-Related Angiitis: Neuroimaging Findings at 1.5T, 3T, and 7T MRI.

Cerebral amyloid angiopathy (CAA) is a progressive neurodegenerative small vessel disease that is associated with intracranial hemorrhage and cognitive impairment in the elderly. The clinical and radiographic presentations have many overlapping features with vascular cognitive impairment, hemorrhagic stroke, and Alzheimer disease (AD). Amyloid-ß-related angiitis (ABRA) is a form of primary CNS vasculitis linked to CAA, with the development of spontaneous autoimmune inflammation against amyloid in the vessel wall with resultant vasculitis. The diagnosis of ABRA and CAA is important. ABRA is often fatal if untreated and requires prompt immunosuppression. Important medical therapies such as anticoagulation and antiamyloid agents for AD are contraindicated in CAA. Here, we present a biopsy-proved case of ABRA with underlying occult CAA. Initial 1.5T and 3T MR imaging did not suggest CAA per the Boston Criteria 2.0. ABRA was not included in the differential diagnosis due to the lack of any CAA-related findings on conventional MR imaging. However, a follow-up 7T MR imaging revealed extensive cortical/subcortical cerebral microbleeds, cortical superficial siderosis, and intragyral hemorrhage in extensive detail throughout the supratentorial brain regions, which radiologically supported the diagnosis of ABRA in the setting of CAA. This case suggests an increased utility of high-field MR imaging to detect occult hemorrhagic neuroimaging findings with the potential to both diagnose more patients with CAA and diagnose them earlier.

Detection of P. malariae using a new rapid isothermal amplification lateral flow assay.

BACKGROUND: While Plasmodium falciparum and Plasmodium vivax cause the majority of malaria cases and deaths, infection by Plasmodium malariae and other Plasmodium species also causes morbidity and mortality. Current understanding of these infections is limited in part by existing point-of-care diagnostics that fail to differentiate them and have poor sensitivity for low-density infections. Accurate diagnosis currently requires molecular assays performed in well-resourced laboratories. This report describes the development of a P. malariae diagnostic assay that uses rapid, isothermal recombinase polymerase amplification (RPA) and lateral-flow-strip detection. METHODS: Multiple combinations of custom RPA primers and probes were designed using publicly available P. malariae genomic sequences, and by modifying published primer sets. Based on manufacturer RPA reaction conditions (TwistDx nfo kit), an isothermal assay was optimized targeting the multicopy P. malariae 18S rRNA gene with 39 °C incubation and 30-min run time. RPA product was visualized using lateral strips (FAM-labeled, biotinylated amplicon detected by a sandwich immunoassay, visualized using gold nanoparticles). Analytical sensitivity was evaluated using 18S rRNA plasmid DNA, and clinical sensitivity determined using qPCR-confirmed samples collected from Tanzania, Ethiopia, and the Democratic Republic of the Congo. RESULTS: Using 18S rRNA plasmid DNA, the assay demonstrates a detection limit of 10 copies/µL (~ 1.7 genome equivalents) and 100% analytical specificity. Testing in field samples showed 95% clinical sensitivity and 88% specificity compared to qPCR. Total assay time was less than 40 min. CONCLUSION: Combined with simplified DNA extraction methods, the assay has potential for future field-deployable, point-of-care use to detect P. malariae infection, which remains largely undiagnosed but a neglected cause of chronic malaria. The assay provides a rapid, simple readout on a lateral flow strip without the need for expensive laboratory equipment.

Detection of P. malariae using a new rapid isothermal amplification lateral flow assay.

P. malariae is found worldwide and causes chronic parasitism in its human hosts. We developed a P. malariae (Pm) diagnostic assay that uses rapid, isothermal recombinase polymerase amplification (RPA) and lateral-flow-strip detection. Using 18S rRNA plasmid DNA, the assay demonstrates a detection limit of 10 copies /µL (~1.7 genome equivalents) and 100% analytical specificity. Testing in field samples showed 95% clinical sensitivity and 88% specificity compared to qPCR. Total assay time was 35 minutes. Combined with simplified DNA extraction methods, the assay has potential for future field-deployable point-of-care use to detect a parasite species that remains largely undiagnosed.

The Postpartum Period: An Opportunity for Alcohol Screening and Counseling to Reduce Adverse Health Impacts.

OBJECTIVES: The postpartum period presents an opportunity to engage in discussions about alcohol consumption and related health harms. This study examined the prevalence of alcohol consumption among a sample of postpartum persons with a recent live birth and screening and brief intervention (alcohol SBI) or counseling by their providers. METHODS: We analyzed 2019 data from a telephone survey conducted 9 to 10 months postpartum among individuals who responded to the standard Pregnancy Risk Assessment Monitoring System survey in 6 states. Weighted prevalence estimates were calculated for alcohol consumption and alcohol SBI after birth through up to 10 months postpartum. RESULTS: Among 1790 respondents, 53.1% reported consuming alcohol postpartum. Among those who drank postpartum, 70.8% reported being asked about alcohol use by a healthcare provider. Slightly more than half of respondents who drank postpartum and were trying to get pregnant (52.4%) or were not using birth control at the time of the survey (59.8%) reported being asked about alcohol use. Approximately 25% of respondents who drank alcohol postpartum were advised about risky alcohol levels by a healthcare provider. Small proportions of individuals who drank alcohol postpartum and were pregnant or trying to get pregnant at the time of the survey were advised to reduce or stop drinking alcohol (10.6% and 2.3%, respectively). CONCLUSIONS: These findings suggest missed opportunities to promote health and prevent adverse alcohol-related health outcomes during the postpartum period through evidence-based tools such as alcohol SBI.

Federal legal and regulatory aspects of contingency management incentives.

OBJECTIVE: Incentives are an integral part of Contingency Management (CM) Programs for substance use disorder treatment, primarily for the treatment stimulant use disorders, but because stimulant use often co-occurs with opioid use, the Substance Abuse and Mental Health Services Administration (SAMHSA) permits the use of CM incentives as a part of its State Opioid Response grant program. However, incentives implicate federal laws and could result in either financial penalties or criminal sanctions against programs that use them. METHODS: The U.S. Department of Health and Human Services Office of Inspector General (OIG) is tasked with enforcing key federal laws that address the issues of kick-backs, inducements, and false claims. By looking at these laws and regulations, this paper seeks to create a clearer understanding of the the barriers providers face when utilizing CM, as well as the guardrails that can be put in place to alleviate those barriers. RESULTS: This paper distills key concerns raised by the OIG and suggests critical guardrails that militate against fraud, waste and abuse. CONCLUSION: Following the recommended guardrails should allow providers to employ CM strategies to help their patients by making clear that the intent is to help patients without engaging in kickbacks, illegal inducements or false claims.

Recovery incentives program: California's contingency management benefit.

OBJECTIVE: The role of methamphetamine and cocaine use in California's drug poisoning (overdose) crisis has dramatically increased in the past five (5) years and has disproportionately affected American Indian, Alaska Native, and Black Californians. No FDA-approved medications currently exist for the treatment of individuals with stimulant use disorder (StimUD). Outside the Veteran's Administration, the Recovery Incentives Program: California's Contingency Management Benefit is the first large scale implementation of contingency management (CM). CM is the behavioral treatment with the most evidence and largest effect sizes for StimUD. METHODS: The Program uses a CM protocol where participants can receive a maximum of $599 over a six-month period, contingent upon 36 stimulant-negative urine test results. Urine tests are conducted using a set of approved, CLIA-waived, point-of-care urine drug tests (UDTs). To ensure fidelity to the CM protocol and to prevent fraud, waste, and abuse, all aspects of incentive accounting and distribution are managed electronically via a custom-developed software system. Incentive distribution utilizes electronic gift cards. A significant innovation of the project is the conceptualization of the CM Coordinator, a designated and highly trained and supervised individual responsible for all aspects of CM operation in a specific site. RESULTS AND CONCLUSIONS: The California Department of Health Care Services contracted with UCLA to develop and implement a robust evaluation of the Program; goals include evaluating the effectiveness of real-world implementation and facilitating quality improvement. The project will likely significantly impact the use of CM for StimUD nationally and may well reduce stimulant-related drug poisoning deaths.

The urgent need for contingency management among Tribal communities in the United States: Considerations for implementation, policy, and sovereignty.

In two randomized controlled trials, culturally adapted contingency management (i.e., incentives provided for substance-negative urine samples) was associated with reduced alcohol and drug use among geographically diverse American Indian and Alaska Native (AI/AN) adults. In response to interest in contingency management from other Tribal and AI/AN communities, our research team in collaboration with AI/AN behavioral health experts, translated the research into practice with new AI/AN community partners. Tenets of community-based participatory research were applied to develop, pilot, and refine contingency management training and implementation tools, and identify implementation challenges. In partnership with the AI/AN communities, four members of the university team developed tools and identified implementation and policy strategies to increase the successful uptake of contingency management in each location. Through our collaborative work, we identified policy barriers including inadequate federal funding of contingency management incentives and a need for further clarity regarding federal anti-kickback regulations. Adoption of contingency management is feasible and can strengthen Tribal communities' capacity to deliver evidence-based substance use disorder treatments to AI/AN people. Unfortunately, non-evidence-based limits to the use of federal funding for contingency management incentives discriminate against AI/AN communities. We recommend specific federal policy reforms, as well as other practical solutions for Tribal communities interested in contingency management.

The fourth wave of the overdose crisis: Examining the prominent role of psychomotor stimulants with and without fentanyl.

The current overdose and broader public health crisis involving illicit drug use is often referred to as the "opioid" or "fentanyl" crisis. Clearly there is extensive data on the profound damage done by opioids over the past 20 years and specifically by fentanyl in the past 5 years. However, there is an extensive array of data that suggests there is more to the current crisis than opioids/fentanyl. Much recent evidence indicates that methamphetamine and cocaine are playing a substantial and increasing role in the illicit drug crisis in the US-the 4th wave. This paper reviews data that illustrate the role of psychomotor stimulants in fatal overdoses, nonfatal overdoses, and emergency department visits. Despite the major detrimental role that stimulants are having on the public health in the US in 2023, there is virtually no evidence-based treatment available in practice for people with stimulant use disorder (StimUD). Although there are no medications with FDA-approval for the treatment of StimUD, there is a behavioral treatment, contingency management (CM), with over 3 decades of robust research supporting its efficacy for individuals with StimUD. Despite the overwhelming evidence supporting CM, it is not being widely used in routine treatment outside the VA healthcare system. This paper reviews some of the (a) evidence for CM, (b) CM protocol design elements that require consideration, (c) current obstacles to the widespread implementation of CM, and (d) strategies for addressing these obstacles. Overcoming these obstacles is a priority to allow routine use of CM as a treatment for StimUD.

Polysubstance use during pregnancy: The importance of screening, patient education, and integrating a harm reduction perspective.

BACKGROUND: Substance use during pregnancy is associated with poor health outcomes. This study assessed substance use, polysubstance use, and use of select prescription medications during pregnancy. METHODS: We analyzed 2019 data from the Pregnancy Risk Assessment Monitoring System in 25 United States jurisdictions that included questions on prescription medications, tobacco, and illicit substance use during pregnancy. Alcohol and electronic cigarette use were assessed during the last three months of pregnancy, and all other substances and medications were assessed throughout pregnancy. Weighted prevalence estimates and 95% confidence intervals (CIs) were calculated. RESULTS: Nearly one-fifth of respondents who reported use of any substance reported use of at least one other substance during pregnancy. Cigarettes (8.1%; 95% CI 7.6-8.7%) and alcohol (7.4%; 95% CI 6.7-8.1%) were the most frequently reported substances, followed by cannabis (4.3%; 95% CI 3.9-4.7%). Substance use was higher among individuals who reported having depression or using antidepressants during pregnancy compared with those who did not report depression or antidepressant use. Illicit drug use prevalence was low (0.5%, 95% CI 0.4-0.7%); however, respondents reporting heroin use also frequently reported use of illicit stimulants (amphetamines: 51.7%, 95% CI 32.1-71.3% or cocaine: 26.5%, 95% CI 11.9-41.1%). Although prenatal clinician screening for alcohol and cigarette use was approximately 95%, fewer respondents (82.1%) reported being screened for cannabis or illicit substance use during pregnancy. CONCLUSIONS: One in five individuals who reported use of any substance during pregnancy engaged in polysubstance use, highlighting the importance of comprehensive screening and evidence-based interventions including harm reduction.

Screening and Brief Interventions for Alcohol Use During Pregnancy: Practices Among US Primary Care Clinicians, DocStyles 2019.

INTRODUCTION: Alcohol use during pregnancy can cause birth defects and developmental disabilities. From 2018 through 2020, 13.5% of pregnant women reported current drinking. The US Preventive Services Task Force recommends evidence-based tools (eg, AUDIT-C and SASQ) for implementing screening and brief interventions to reduce excessive alcohol use among adults, including pregnant people, for whom any alcohol use is considered excessive. METHODS: We used DocStyles 2019 data to conduct a cross-sectional analysis to examine current screening and brief intervention practices that primary care clinicians conduct among pregnant patients; clinicians' confidence levels in conducting screening, brief interventions, and referral to treatment; and the documentation of brief interventions in the medical record. RESULTS: A total of 1,500 US adult medicine clinicians completed the entire survey. Among the respondents who conduct screening (N = 1,373) and brief interventions (N = 1,357) in their practice, nearly all reported implementing screening (94.6%) and brief interventions (94.9%) with their pregnant patients for alcohol use, but fewer than half felt confident about conducting their screening practices (46.5%). Two-thirds (64%) reported using a tool that met the criteria recommended by the US Preventive Services Task Force (USPSTF). Over half documented brief interventions in electronic health record notes (51.7%) or designated space (50.7%). CONCLUSION: Pregnancy presents a unique opportunity for clinicians to incorporate screening into routine obstetric care and encourage behavior change among patients. Most providers reported always screening their pregnant patients for alcohol use, but fewer used evidence-based USPSTF-recommended screening tools. Increased clinician confidence in screening and brief intervention, the use of standardized screening tools tailored to pregnant people, and maximal use of electronic health record technology may enhance the benefits of their application to alcohol use, which ultimately can reduce adverse outcomes associated with alcohol use during pregnancy.

A rare case of isolated IgG4-related hypophysitis with Rathke's cleft cyst presenting as panhypopituitarism.

Summary: We report a rare case of biopsy-proven isolated immunoglobulin G4 (IgG4)-related hypophysitis and Rathke's cleft cyst (RCC) presenting as panhypopituitarism. A 54-year-old Caucasian female presented with symptoms of slurred speech, altered mental status, polyuria and polydipsia and was found to have panhypopituitarism. Brain MRI showed a suprasellar mass with suspected intralesional hemorrhage. She underwent trans-sphenoidal resection due to MRI evidence of compression of the optic chiasm and left optic nerve. Preoperatively, she was started on hydrocortisone, levothyroxine and desmopressin. Histopathology demonstrated a RCC with adjacent lymphoplasmacytic hypophysitis with numerous IgG4-immunoreactive plasma cells. Hydrocortisone was stopped at 10 months after confirming hypothalamic-pituitary-adrenal (HPA)-axis recovery and desmopressin was stopped at 1 year. There was recurrence of a cystic mass at 1 year follow-up. Over 4 years of follow-up, she continued to require levothyroxine, and the mass remained stable in size. In order to begin to understand how this case's unique histopathological presentation influences clinical presentation, pituitary imaging and prognosis, we present an accompanying literature review. Learning points: Isolated IgG4 hypophysitis and coexisting Rathke's cleft cyst is a rare condition, which presents a diagnostic challenge. Recognizing its characteristic features can assist with early recognition and initiation of therapy to promote optimal outcomes. Further studies investigating the mechanisms promoting co-occurrence of these entities and their effect on prognosis are needed.

Systematic Review: Polysubstance Prevalence Estimates Reported during Pregnancy, US, 2009-2020.

INTRODUCTION: The objective of this systematic review is to describe polysubstance studies and their prevalence estimates among pregnant people in the US. METHODS: This review was not subject to protocol preparation or registration with the International Prospective Register of Systematic Reviews (PROSPERO) because outcome data were not reported. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Checklist was followed. Four scientific literature databases were used to identify articles published from January 1, 2009 to June 3, 2020 reporting prenatal exposure to two or more substances in the US. A standardized process of title and abstract screening followed by a two-phase full-text review was used to assess study eligibility. RESULTS: A total of 119 studies were included: 7 case-control studies, 7 clinical trials, 76 cohort studies, and 29 cross-sectional studies. Studies varied with respect to study design, time period, region, sampling and participant selection, substances assessed, and method of exposure ascertainment. Commonly reported polysubstance prevalence estimates among studies of pregnant people included combinations with alcohol, marijuana, and/or tobacco/nicotine. The range of prevalence estimates was wide (alcohol 1-99%; marijuana 3-95%; tobacco/nicotine 2-95%). DISCUSSION: Polysubstance use during pregnancy is common, especially with alcohol, marijuana, and/or tobacco/nicotine. Future research to assess polysubstance use during pregnancy could help better describe patterns and ultimately help mitigate its effects on maternal and infant health outcomes.

Contingency Management for Stimulant Use Disorder: Progress, Challenges, and Recommendations.

The United States is currently in the fourth wave of the overdose crisis wherein stimulants together with fentanyl are the major drivers of overdose deaths. To date, there has been limited effort outside the US Veterans Administration Health System health system to disseminate evidence-based treatment for people with stimulant use disorder. Contingency management, a behavioral intervention in which positive reinforcement is provided for a target behavior indicating treatment progress, has decades of empirical support but limited implementation in real-world, non-US Veterans Administration Health System settings. The purpose of the report is to provide an overview of contingency management, the barriers to adoption, and recommendations for overcoming these barriers.

Rate adaptive pacing in people with chronic heart failure increases peak heart rate but not peak exercise capacity: a systematic review.

Rate adaptive cardiac pacing (RAP) allows increased heart rate (HR) in response to metabolic demand in people with implantable electronic cardiac devices (IECD). The aim of this work was to conduct a systematic review to determine if RAP increases peak exercise capacity (peak VO2) in line with peak HR in people with chronic heart failure. We conducted a systematic literature search from 1980, when IECD and RAP were first introduced, until 31 July 2021. Databases searched include PubMed, Medline, EMBASE, EBSCO, and the Clinical Trials Register. A comprehensive search of the literature produced a total of 246 possible studies; of these, 14 studies were included. Studies and subsequent analyses were segregated according to comparison, specifically standard RAP (RAPON) vs fixed rate pacing (RAPOFF), and tailored RAP (TLD RAPON) vs standard RAP (RAPON). Pooled analyses were conducted for peak VO2 and peak HR for RAPON vs RAPOFF. Peak HR significantly increased by 15 bpm with RAPON compared to RAPOFF (95%CI, 7.98-21.97, P < 0.0001). There was no significant difference between pacing mode for peak VO2 0.45 ml kg-1 min-1 (95%CI, - 0.55-1.47, P = 0.38). This systematic review revealed RAP increased peak HR in people with CHF; however, there was no concomitant improvement in peak VO2. Rather RAP may provide benefits at submaximal intensities by controlling the rise in HR to optimise cardiac output at lower workloads. HR may be an important outcome of CHF management, reflecting myocardial efficiency.

The Obligate Intracellular Bacterial Pathogen Anaplasma phagocytophilum Exploits Host Cell Multivesicular Body Biogenesis for Proliferation and Dissemination.

Anaplasma phagocytophilum is the etiologic agent of the emerging infection, granulocytic anaplasmosis. This obligate intracellular bacterium lives in a host cell-derived vacuole that receives membrane traffic from multiple organelles to fuel its proliferation and from which it must ultimately exit to disseminate infection. Understanding of these essential pathogenic mechanisms has remained poor. Multivesicular bodies (MVBs) are late endosomal compartments that receive biomolecules from other organelles and encapsulate them into intralumenal vesicles (ILVs) using endosomal sorting complexes required for transport (ESCRT) machinery and ESCRT-independent machinery. Association of the ESCRT-independent protein, ALIX, directs MVBs to the plasma membrane where they release ILVs as exosomes. We report that the A. phagocytophilum vacuole (ApV) is acidified and enriched in lysobisphosphatidic acid, a lipid that is abundant in MVBs. ESCRT-0 and ESCRT-III components along with ALIX localize to the ApV membrane. siRNA-mediated inactivation of ESCRT-0 and ALIX together impairs A. phagocytophilum proliferation and infectious progeny production. RNA silencing of ESCRT-III, which regulates ILV scission, pronouncedly reduces ILV formation in ApVs and halts infection by arresting bacterial growth. Rab27a and its effector Munc13-4, which drive MVB trafficking to the plasma membrane and subsequent exosome release, localize to the ApV. Treatment with Nexinhib20, a small molecule inhibitor that specifically targets Rab27a to block MVB exocytosis, abrogates A. phagocytophilum infectious progeny release. Thus, A. phagocytophilum exploits MVB biogenesis and exosome release to benefit each major stage of its intracellular infection cycle: intravacuolar growth, conversion to the infectious form, and exit from the host cell. IMPORTANCE Anaplasma phagocytophilum causes granulocytic anaplasmosis, a globally emerging zoonosis that can be severe, even fatal, and for which antibiotic treatment options are limited. A. phagocytophilum lives in an endosomal-like compartment that interfaces with multiple organelles and from which it must ultimately exit to spread within the host. How the bacterium accomplishes these tasks is poorly understood. Multivesicular bodies (MVBs) are intermediates in the endolysosomal pathway that package biomolecular cargo from other organelles as intralumenal vesicles for release at the plasma membrane as exosomes. We discovered that A. phagocytophilum exploits MVB biogenesis and trafficking to benefit all aspects of its intracellular infection cycle: proliferation, conversion to its infectious form, and release of infectious progeny. The ability of a small molecule inhibitor of MVB exocytosis to impede A. phagocytophilum dissemination indicates the potential of this pathway as a novel host-directed therapeutic target for granulocytic anaplasmosis.

An interprofessional clinic for adults with Turner syndrome: the patient perspective.

OBJECTIVES: This qualitative study assessed the value of a primary care-based interprofessional clinical team for adults with Turner syndrome (TS) utilizing patient perspectives. METHODS: Ten patients within one institution's interprofessional adult TS clinic participated in one of two semi-structured focus groups. Content analysis was used to classify content provided by participants into themes and sub-themes using Dedoose software. RESULTS: Participants found that their quality of care and life were both improved due to the presence of the interprofessional Adults with TS Clinic. Specifically, participants reported that the clinic helped address problems with finding knowledgeable providers and care gaps, made appointments more convenient and improved interprofessional communication. Participants also reported that the clinic helped them find a sense of community and increased personal confidence. Study participants suggested improvements to the clinic by expanding the scope of practice further, simplifying processes to schedule appointments, and potentially creating interprofessional clinics for other rare diseases as well. CONCLUSION: Pursuing avenues to create interprofessional clinics for adults with rare diseases has value from the patient perspective. This value can translate to improved patient outcomes through improvements in patient knowledge of their diagnosis, adherence to evidence-based care and quality of life.

Eye Movement Abnormalities in Glaucoma Patients: A Review.

Glaucoma is a common condition that relies on careful clinical assessment to diagnose and determine disease progression. There is growing evidence that glaucoma is associated not only with loss of retinal ganglion cells but also with degeneration of cortical and subcortical brain structures associated with vision and eye movements. The effect of glaucoma pathophysiology on eye movements is not well understood. In this review, we examine the evidence surrounding altered eye movements in glaucoma patients compared to healthy controls, with a focus on quantitative eye tracking studies measuring saccades, fixation, and optokinetic nystagmus in a range of visual tasks. The evidence suggests that glaucoma patients have alterations in several eye movement domains. Patients exhibit longer saccade latencies, which worsen with increasing glaucoma severity. Other saccadic abnormalities include lower saccade amplitude and velocity, and difficulty inhibiting reflexive saccades. Fixation is pathologically altered in glaucoma with reduced stability. Optokinetic nystagmus measures have also been shown to be abnormal. Complex visual tasks (eg reading, driving, and navigating obstacles), integrate these eye movements and result in behavioral adaptations. The review concludes with a summary of the evidence and recommendations for future research in this emerging field.

A suite of PCR-LwCas13a assays for detection and genotyping of Treponema pallidum in clinical samples.

The performance of commonly used assays for diagnosis of syphilis varies considerably depending on stage of infection and sample type. In response to the need for improved syphilis diagnostics, we develop assays that pair PCR pre-amplification of the tpp47 gene of Treponema pallidum subsp. pallidum with CRISPR-LwCas13a. The PCR-LwCas13a assay achieves an order of magnitude better analytical sensitivity than real-time PCR with equivalent specificity. When applied to a panel of 216 biological specimens, including 135 clinically confirmed primary and secondary syphilis samples, the PCR-LwCas13a assay demonstrates 93.3% clinical sensitivity and 100% specificity, outperforming tpp47 real-time PCR and rabbit-infectivity testing. We further adapt this approach to distinguish Treponema pallidum subsp. pallidum lineages and identify genetic markers of macrolide resistance. Our study demonstrates the potential of CRISPR-based approaches to improve diagnosis and epidemiological surveillance of syphilis.