Modeling Recovery Housing Retention and Program Outcomes by Justice Involvement among Residents in Virginia, USA: An Observational Study.

Living in recovery housing can improve addiction recovery and desistance outcomes. This study examined whether retention in recovery housing and types of discharge outcomes (completed, "neutral," and "negative" outcomes) differed for clients with recent criminal legal system (CLS) involvement. Using data from 101 recovery residences certified by the Virginia Association of Recovery Residences based on 1,978 individuals completing the REC-CAP assessment, competing risk analyses (cumulative incidence function, restricted mean survival time, and restricted mean time lost) followed by the marginalization of effects were implemented to examine program outcomes at final discharge. Residents with recent CLS involvement were more likely to be discharged for positive reasons (successful completion of their goals) and premature/negative reasons (e.g., disciplinary releases) than for neutral reasons. Findings indicate that retention for 6-18 months is essential to establish and maintain positive discharge outcomes, and interventions should be developed to enhance retention in recovery residents with recent justice involvement.

Long-term safety and effectiveness of berotralstat for hereditary angioedema: The open-label APeX-S study.

BACKGROUND: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein recently approved for prevention of angioedema attacks in adults and adolescents with hereditary angioedema (HAE). The objective of this report is to summarize results from an interim analysis of an ongoing long-term safety study of berotralstat in patients with HAE. METHODS: APeX-S is an ongoing, phase 2, open-label study conducted in 22 countries (ClinicalTrials.gov, NCT03472040). Eligible patients with a clinical diagnosis of HAE due to C1 inhibitor deficiency (HAE-C1-INH) were centrally allocated to receive berotralstat 150 or 110 mg once daily. The primary objective was to determine long-term safety and the secondary objective was to evaluate effectiveness. RESULTS: Enrolled patients (N = 227) received berotralstat 150 mg (n = 127) or 110 mg (n = 100) once daily. The median (range) duration of exposure was 342 (11-540) and 307 (14-429) days for the 150-mg and 110-mg groups, respectively. Treatment-emergent adverse events (TEAEs) occurred in 91% (n = 206) of patients. The most common TEAEs across treatment groups were upper respiratory tract infection (n = 91, 40%), abdominal pain (n = 57, 25%), headache (n = 40, 18%), and diarrhea (n = 31, 14%) and were mostly mild to moderate. Fifty percent (n = 113) of patients had at least one drug-related adverse event (AE; 150 mg, n = 57 [45%]; 110 mg, n = 56 [56%]), and discontinuations due to AEs occurred in 19 (8%) patients (150 mg, n = 13 [10%]; 110 mg, n = 6 [6%]). Three (1.3%) patients experienced a drug-related serious TEAE. Among patients who received berotralstat through 48 weeks (150 mg, n = 73; 110 mg, n = 30), median HAE attack rates were low in month 1 (150 mg, 1.0 attacks/month; 110 mg, 0.5 attacks/month) and remained low through 12 months (0 attacks/month in both dose groups). Mean HAE attack rates followed a similar trend, and no evidence for patient tolerance to berotralstat emerged. In both dose groups, angioedema quality of life scores showed clinically meaningful changes from baseline. CONCLUSIONS: In this analysis, both berotralstat doses, 150  and 110 mg once daily, were generally well tolerated. Effectiveness results support the durability and robustness of berotralstat as prophylactic therapy in patients with HAE. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov (NCT03472040).

Patient perspectives on the treatment burden of injectable medication for hereditary angioedema.

Hereditary angioedema (HAE) is a rare, chronic disease characterized by debilitating swelling episodes in various parts of the body. Patients experience significant burdens related to the symptoms and management of HAE, which can affect their daily lives and reduce their overall quality of life. Prophylactic treatment options have expanded in the past decade to the benefit of patients; however, these therapies require scheduled injections, which can be painful, burdensome, and time consuming. We conducted an online survey of patients with HAE in the USA to better understand their experiences with available prophylactic medications and the associated treatment burdens. Our survey results suggest that most patients are satisfied with their current therapies but desire novel medications with a simpler route of administration and that, although most patients experience significant treatment-related burdens, they learn to cope with these challenges over time.

Caregivers' role in managing hereditary angioedema and perceptions of treatment-related burden.

Hereditary angioedema (HAE) is a rare genetic disease that results in recurrent, debilitating, and potentially life-threatening swelling episodes in the extremities, genitals, gastrointestinal tract, and upper airway. Patients can experience significant burdens related to their disease. Informal or familial caregivers often support patients with HAE and likely share in the disease-related burdens, although there are limited HAE caregiver-focused reports in the scientific literature. In the United States, we conducted an online survey of adults caring for an individual with HAE to better understand their experiences with the disease and identify psychosocial impacts of providing care for a patient with HAE. Thirty caregivers provided responses to the survey. Most caregivers were family members of the care recipient and many had HAE themselves. Caregivers reported participating in a number of medical-related tasks and experiencing some burdens as a result of caring for a person with HAE.

Physician and patient perspectives on the management of hereditary angioedema: a survey on treatment burden and needs.

Hereditary angioedema (HAE) is a rare disorder caused by genetic mutations that lead to recurrent episodes of swelling in various parts of the body. Prophylactic treatment is common for patients with HAE, and the therapeutic options have expanded in recent years. The current standard of care for prophylactic HAE therapies is subcutaneous treatment, which can be self-administered at home, greatly improving patient quality of life. As new therapies emerge, it is important for patients and physicians to discuss the risks and benefits associated with each treatment to develop an individualized approach to HAE management. We conducted surveys of patients with HAE and physicians who treat patients with HAE to identify prescribing trends for prophylactic HAE treatments and the impact that such treatments has on patients. Our results confirmed that newer, subcutaneous therapies are prescribed for HAE prophylaxis more frequently than other therapies in the United States and that treatment burdens still exist for patients with HAE. We found that physicians and patients were not always aligned on how treatment choices affect patients' lives, which may mean that there are opportunities for enhanced patient-physician dialog and shared decision-making in HAE management in the United States.

Randomized Trial of the Efficacy and Safety of Berotralstat (BCX7353) as an Oral Prophylactic Therapy for Hereditary Angioedema: Results of APeX-2 Through 48 Weeks (Part 2).

BACKGROUND: Berotralstat (BCX7353) is a recently approved, oral, once-daily kallikrein inhibitor for hereditary angioedema (HAE) prophylaxis. In the APeX-2 trial, berotralstat reduced HAE attack rates over 24 weeks, with a favorable safety and tolerability profile. OBJECTIVE: Evaluate berotralstat safety, tolerability, and effectiveness over 48 weeks. METHODS: APeX-2 is a phase 3, parallel-group, multicenter trial (NCT03485911) in patients with HAE due to C1 esterase inhibitor deficiency. Part 1 was double-blind and placebo-controlled, with patients randomized to 24 weeks of berotralstat 150 mg, 110 mg, or placebo. In part 2, patients continued berotralstat the same dose or, if initially randomized to placebo, were rerandomized to berotralstat 150 mg or 110 mg through weeks 24 to 48. The primary end point was safety and tolerability. RESULTS: One hundred eight patients received 1 or more doses of berotralstat in part 2. Treatment-emergent adverse events (TEAEs) occurred in 30 of 39 patients (77%) in the placebo group during part 1, and 25 of 34 patients (74%) re-randomized from placebo to berotralstat 110 mg or 150 mg in part 2, with drug-related TEAEs in 13 of 39 (33%), and 11 of 34 (32%) in the same groups. Most TEAEs were mild or moderate, with no serious drug-related TEAEs. The most common TEAEs were upper respiratory tract infections, abdominal pain, diarrhea, and vomiting. Mean (±standard error of the mean) monthly attack rates at baseline and week 48 were 3.06 (±0.25) and 1.06 (±0.25) in the berotralstat 150mg 48-week group and 2.97 (±0.21) and 1.35 (±0.33) in the berotralstat 110mg 48-week group. CONCLUSIONS: The safety, tolerability, and effectiveness of berotralstat were maintained over 48 weeks of treatment.

Oral berotralstat for the prophylaxis of hereditary angioedema attacks in patients in Japan: A phase 3 randomized trial.

BACKGROUND: With no approved treatments in Japan for the prevention of hereditary angioedema (HAE) attacks, there is a significant unmet need for long-term prophylactic therapies for Japanese patients with HAE. Berotralstat (BCX7353) is an oral, once-daily, highly selective inhibitor of plasma kallikrein in development for prophylaxis of angioedema attacks in HAE patients. METHODS: APeX-J is a phase 3, randomized, double-blind, placebo-controlled, parallel-group, 3-part trial conducted in Japan (University Hospital Medical Information Network identifier, UMIN000034869; ClinicalTrials.gov identifier, NCT03873116). Patients with a clinical diagnosis of type 1 or 2 HAE underwent a prospective run-in period of 56 days to determine eligibility, allowing enrollment of those with ≥2 expert-confirmed angioedema attacks. Patients were randomly assigned (1:1:1) and stratified by baseline attack rate (≥2 vs. <2 expert-confirmed attacks/month between screening and randomization) to receive once-daily berotralstat 110 mg, berotralstat 150 mg, or placebo. The primary endpoint was the rate of expert-confirmed angioedema attacks during dosing in the 24-week treatment period. RESULTS: Nineteen patients were randomized to receive once-daily berotralstat 110 mg (n = 6), berotralstat 150 mg (n = 7), or placebo (n = 6). Treatment with berotralstat 150 mg significantly reduced HAE attacks relative to placebo (1.11 vs. 2.18 attacks/month, p = .003). The most frequently reported treatment-emergent adverse events (TEAEs) in berotralstat-treated patients (n = 13) were nasopharyngitis (n = 4, 31%), abdominal pain, cough, diarrhea, and pyrexia (n = 2 each, 15%). CONCLUSIONS: Orally administered, once-daily berotralstat 150 mg significantly reduced the frequency of HAE attacks and was safe and well tolerated, supporting its use as a prophylactic therapy in patients with type 1 or 2 HAE in Japan.

Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks. OBJECTIVE: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial). METHODS: APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 investigator-confirmed HAE attacks in the first 56 days of a prospective run-in period were eligible. The primary efficacy end point was the rate of investigator-confirmed HAE attacks during the 24-week treatment period. RESULTS: A total of 121 patients were randomized; 120 of them received at least 1 dose of the study drug (n = 41, 40, and 39 in the 110-mg dose of berotralstat, 150-mg of dose berotralstat, and placebo groups, respectively). Berotralstat demonstrated a significant reduction in attack rate at both 110 mg (1.65 attacks per month; P = .024) and 150 mg (1.31 attacks per month; P < .001) relative to placebo (2.35 attacks per month). The most frequent treatment-emergent adverse events that occurred more with berotralstat than with placebo were abdominal pain, vomiting, diarrhea, and back pain. No drug-related serious treatment-emergent adverse events occurred. CONCLUSION: Both the 110-mg and 150-mg doses of berotralstat reduced HAE attack rates compared with placebo and were safe and generally well tolerated. The most favorable benefit-to-risk profile was observed at a dose of 150 mg per day.

Multiple spawning run contingents and population consequences in migratory striped bass Morone saxatilis.

Multiple spawning run contingents within the same population can experience varying demographic fates that stabilize populations through the portfolio effect. Multiple spawning run contingents (aka run timing groups) are reported here for the first time for striped bass, an economically important coastal species, which is well known for plastic estuarine and shelf migration behaviors. Adult Hudson River Estuary striped bass (n = 66) were tagged and tracked with acoustic transmitters from two known spawning reaches separated by 90 km. Biotelemetry recaptures for two years demonstrated that each river reach was associated with separate contingents. Time series of individual spawning phenologies were examined via nonparametric dynamic time warping and revealed two dominant time series centroids, each associated with a separate spawning reach. The lower spawning reach contingent occurred earlier than the higher reach contingent in 2017 but not in 2018. The majority (89%) of returning adults in 2018 showed the same contingent behaviors exhibited in 2017. Spawning contingents may have been cued differently by temperatures, where warming lagged 1-week at the higher reach in comparison to the lower reach. The two contingents exhibited similar Atlantic shelf migration patterns with strong summer fidelity to Massachusetts Bay and winter migrations to the southern US Mid-Atlantic Bight. Still, in 2017, differing times of departure into nearby shelf waters likely caused the early lower reach contingent to experience substantially higher mortality than the later upper reach contingent. Anecdotal evidence suggests that higher fishing effort is exerted on the early-departing individuals as they first enter shelf fisheries. Thus, as in salmon, multiple spawning units can lead to differential demographic outcomes, potentially stabilizing overall population dynamics.

Comparative migration ecology of striped bass and Atlantic sturgeon in the US Southern mid-Atlantic bight flyway.

Seasonal migrations are key to the production and persistence of marine fish populations but movements within shelf migration corridors or, "flyways", are poorly known. Atlantic sturgeon and striped bass, two critical anadromous species, are known for their extensive migrations along the US Mid-Atlantic Bight. Seasonal patterns of habitat selection have been described within spawning rivers, estuaries,and shelf foraging habitats, but information on the location and timing of key coastal migrations is limited. Using a gradient-based array of acoustic telemetry receivers, we compared the seasonal incidence and movement behavior of these species in the near-shelf region of Maryland, USA. Atlantic sturgeon incidence was highest in the spring and fall and tended to be biased toward shallow regions, while striped bass had increased presence during spring and winter months and selected deeper waters. Incidence was transient (mean = ~2 d) for both species with a pattern of increased residency (>2 d) during autumn and winter, particularly for striped bass, with many individuals exhibiting prolonged presence on the outer shelf during winter. Flyways also differed spatially between northern and southern migrations for both species and were related to temperature: striped bass were more likely to occur in cool conditions while Atlantic sturgeon preferred warmer temperatures. Observed timing and spatial distribution within the Mid-Atlantic flyway were dynamic between years and sensitive to climate variables. As shelf ecosystems come under increasing maritime development, gridded telemetry designs represent a feasible approach to provide impact responses within key marine flyways like those that occur within the US Mid-Atlantic Bight.

Wrist acupressure for post-operative nausea and vomiting (WrAP): A pilot study.

Post-operative nausea and vomiting are undesirable complications following anaesthesia and surgery. It is thought that acupressure might prevent nausea and vomiting through an alteration in endorphins and serotonin levels. In this two-group, parallel, superiority, randomised control pilot trial we aimed to test pre-defined feasibility outcomes and provide preliminary evidence for the efficacy of PC 6 acupoint stimulation vs. placebo for reducing post-operative nausea and vomiting in cardiac surgery patients. Eighty patients were randomly assigned to either an intervention PC 6 acupoint stimulation via beaded intervention wristbands group (n=38) or placebo sham wristband group (n=42). The main outcome was assessment of pre-defined feasibility criteria with secondary outcomes for nausea, vomiting, rescue anti-emetic therapy, quality of recovery and adverse events. Findings suggest that a large placebo-controlled randomised controlled trial to test the efficacy of PC 6 stimulation on PONV in the post-cardiac surgery population is feasible and justified given the preliminary clinically significant reduction in vomiting in the intervention group in this pilot. The intervention was tolerated well by participants and if wrist acupressure of PC 6 acupoint is proven effective in a large trial it is a simple non-invasive intervention that could easily be incorporated into practice.

Diagnosis and management of urinary tract infections in the emergency department.

Urinary tract infections are a heterogeneous group of disorders, involving infection of all or part of the urinary tract, and are defined by bacteria in the urine with clinical symptoms that may be acute or chronic. Approximately 1 million urinary tract infections are treated every year in United States emergency departments. The female-to-male ratio is 6:1. Urinary tract infections are categorized as upper versus lower tract involvement and as uncomplicated versus complicated. The emergency clinician must carefully categorize the infection and take into account patient host factors to optimally treat and disposition patients. A working knowledge of local or at least national susceptibility patterns of the most likely pathogens is essential. A variety of special populations exist that require special management, including pregnant females, patients with anatomic abnormalities, and instrumented patients.

Single dose oral dexibuprofen [S(+)-ibuprofen] for acute postoperative pain in adults.

BACKGROUND: This review is an update of a previously published review in The Cochrane Database of Systematic Reviews Issue 3, 2009 on single dose oral dexibuprofen (S(+)-ibuprofen) for acute postoperative pain in adults.Dexibuprofen is a non-steroidal anti-inflammatory drug (NSAID) licensed for use in rheumatic disease and other musculoskeletal disorders in the UK, and widely available in other countries worldwide. It is an active isomer of ibuprofen. This review sought to evaluate the efficacy and safety of oral dexibuprofen in acute postoperative pain, using clinical studies in patients with established pain, and with outcomes measured primarily over four to six hours, using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties. OBJECTIVES: To assess the efficacy and adverse effects of single dose oral dexibuprofen for acute postoperative pain using methods that permit comparison with other analgesics evaluated in standardised studies using almost identical methods and outcomes. SEARCH METHODS: Searches were run for the original review in 2009 and subsequent searches have been run in August 2013. We did not find any new published studies as a result of the updated search.We searched for randomised studies of dexibuprofen in acute postoperative pain in MEDLINE, EMBASE, and CENTRAL (The Cochrane LIbrary), and for clinical trial reports and synopses of published and unpublished studies from Internet sources. SELECTION CRITERIA: Randomised, double blind, placebo-controlled clinical studies of oral dexibuprofen for relief of acute postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study quality and extracted data. We extracted pain relief or pain intensity data and converted it into the dichotomous outcome of number of participants with at least 50% pain relief over four to six hours, from which relative risk and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. We collected information on adverse events and withdrawals. MAIN RESULTS: New data were identified for this update in one unpublished trial synopsis (BR1160 1995) in addition to the single study (Dionne 1998) that was included in the original review. In both studies dexibuprofen gave high levels of response, with 51/96 (53%) participants experiencing at least 50% pain relief with dexibuprofen 200 mg and 35/50 (70%) with dexibuprofen 400 mg, compared with 75/147 (51%) with racemic ibuprofen 400 mg, and 12/62 (13%) with placebo. The numbers of participants was too small to calculate NNTs with any meaning. The median time to additional analgesic use was greater than four hours for all active therapies, but about two hours for placebo.Adverse events were generally of mild or moderate intensity and consistent with events normally associated with anaesthesia and surgery. There were no serious adverse events or deaths.Additional data did not alter the conclusions from the earlier review. AUTHORS' CONCLUSIONS: The information from these two studies in acute postoperative pain suggested that dexibuprofen may be a useful analgesic, but at doses not very different from racemic ibuprofen, for which considerably more evidence exists.

Central scotoma without prodromal illness caused by Bartonella henselae neuroretinitis.

This case report describes Bartonella henselae neuroretinitis in a 26-year-old woman who presented to the emergency department with unilateral central scotoma and no prodromal symptoms, a unique presentation of this disease. B henselae, a gram-negative bacteria, is the cause of cat scratch disease. Cat scratch disease (CSD) is a self-limiting illness, which typically presents with regional lymphadenopathy, fever, and small skin lesions in associationwith a cat scratch or bite. The mostcommon ocular manifestations of cat scratch disease are Parinaud oculoglandular syndrome and neuroretinitis. All prior reported cases of CSD neuroretinitis presented with prodromal symptoms, not vision loss alone.

Stabilizing formulations for inhalable powders of live-attenuated measles virus vaccine.

Carbon dioxide Assisted Nebulization with a Bubble Dryer((R)) (CAN-BD) processing allows particles to be made in the 3-5 mum size range, which is desirable for lung delivery, without destroying biological activity. In response to the Grand Challenge in Global Health Initiative #3, we have been developing an inhalable needle-free live-attenuated measles virus vaccine for use in developing countries. Measles was chosen because it is the number one vaccine preventable killer of children worldwide. Powders were processed by CAN-BD, where a solution containing excipients and live-attenuated measles virus in water was mixed intimately with supercritical or near superctitical carbon dioxide to form an emulsion. The emulsion was expanded to atmospheric pressure through a flow restrictor. The resulting plume was dried by heated nitrogen and the powders collected on a filter at the bottom of the drying chamber. Powders were analyzed using varying techniques including X-ray diffraction, scanning electron microscopy, Andersen cascade impaction, differential scanning calorimetery, Karl Fischer titration, and viral plaque assay. CAN-BD has been used to produce powders of live-attenuated measles virus vaccine with characteristics desirable for lung delivery. The powders retain viral activity through forming and drying the microparticles by CAN-BD, and have passed the WHO stability test for 1 week at 37 degrees C. The powders have an amorphous character and a glass transition temperature of around 60 degrees C. Lyophilization, the present standard commercial method of processing measles vaccine makes solids with a water content of less than 1%. By substituting myo-inositol for sorbitol and using the CAN-BD drying technique the water content can be lowered to 0.5%. The most successful formulations to date have been based conceptually on the current lyophilized formulation, but with modifications to the type and amounts of sugar. Of current interest are formulations containing myo-inositol, as they retain high viral activity and have low initial water content.