In RISE, TV46000 once monthly (q1m) or once every 2 months (q2m) significantly extended time to impending schizophrenia relapse. The current study (SHINE, NCT03893825) evaluated the long-term safety, tolerability, and effect of TV46000.

Patients completing RISE without relapse (rollover) or newly recruited (de novo) were eligible. The de novo and placebo rollover cohorts were randomized 1:1 to q1m or q2m for ≤56 weeks; the TV46000 rollover cohort continued assigned regimen. Exploratory efficacy endpoints included time to impending relapse and patient centered outcomes (PCOs) including Schizophrenia Quality of Life Scale (SQLS).

334 patients were randomized and received TV46000 q1m (n=172) or q2m (n=162), for 202.3 patient-years [PY] of TV-46000 treatment. Treatment-emergent adverse events (AEs) reported for ≥5% of patients were: overall–injection site pain (event rate/100 PY, n [%]; 23.23, 16 [5%]); de novo (n=109)–injection site pain (56.10, 11 [10%]), injection site nodule (16.03, 6 [6%]), blood creatine phosphokinase increased (16.03, 8 [7%]), urinary tract infection (10.69, 7 [6%]); placebo rollover (n=53)–tremor (18.50, 5 [9%]); TV46000 rollover (n=172)–headache (7.97, n=8 [5%]). Serious AEs reported for ≥2 patients were worsening schizophrenia and hyperglycemia. Kaplan– Meier estimates for remaining relapse-free at week 56 were 0.98 (2% risk; q1m) and 0.88 (12%; q2m). SQLS improved for q1m (least-squares mean change [SE], − 2.16 [0.98]) and q2m (− 0.43 [0.98]); other PCOs (5Level EuroQoL 5Dimensions Questionnaire, Personal and Social Performance Scale, Drug Attitudes Inventory 10-item version) remained stable.

TV-46000 had a favorable long-term benefit–risk profile in patients with schizophrenia.

Teva Branded Pharmaceutical Products R&D Inc.

Study Registration Number: NCT03893825

Vasomotor symptoms (hot flashes) are the most common symptom of menopause, affecting about 75% of menopausal women and about 40% of perimenopausal women. PH80, an investigational neuroactive nasal spray, is hypothesized to be a potential treatment for moderate to severe hot flashes due to menopause given that it rapidly activates olfactory to limbic-hypothalamic neural circuits that control autonomic activity, including body temperature and sweating. The primary objective of this Phase 2A clinical study was to explore the efficacy, safety, and tolerability of intranasal administration of PH80 for the acute management of hot flashes due to menopause.

The study was a randomized, double-blind, placebo-controlled, exploratory Phase 2A clinical study. PH80 nasal spray containing epoxyestrenolone 0.8 μg per 50 μL was self-administered intranasally; two sprays in each nostril (total dose = 3.2 μg) up to four times daily as needed for 4 consecutive weeks. One additional dose was allowed at night if subjects were awakened by hot flashes. During the study period, subjects recorded the number and severity of hot flashes, disruption in function, and sweating related to hot flashes. Patient global impression of change (PGI-C) and clinician global impression of severity (CGI-S) were also assessed.

At baseline, subjects reported a daily mean of 7.7 hot flashes in the PH80 group (n = 18) and 8.0 in the placebo group (n = 18). After 1 week of treatment, the number of hot flashes dropped to 2.8 for PH80 and 6.4 for placebo (P <.001), and after 4 weeks of treatment, the number of hot flashes dropped to 1.5 for PH80 and 5.1 for placebo (P <.001). Treatment with PH80 significantly reduced the severity, disruption in function, and sweating associated with hot flashes during the treatment period as compared with subjects in the placebo group. There was a significant improvement in PGI-C for PH80 vs placebo at endpoint (P = .015) and a strong trend for improvement on CGI-S (P = .053). PH80 was well-tolerated with no serious adverse events (AEs); the AE profiles of PH80 and placebo were comparable. All 36 subjects completed 4 weeks of treatment and with no study discontinuations due to AEs.

The rapid onset, significant reduction in symptoms, and improved function induced by intranasal PH80 in menopausal women with hot flashes compared with placebo, observed as early as the end of week 1 of treatment, provide a strong signal for continued development of PH80 for the acute treatment of hot flashes due to menopause. The safety data further suggest that, if approved, PH80 will provide a substantial safety benefit over all currently available agents.

Vistagen Therapeutics, Inc. Editorial assistance was provided by Peloton Advantage, an OPEN Health company, funded by Vistagen Therapeutics, Inc.

Explore the relationship between water insecurity and food security and their covariates in Mexican households.

A cross-sectional study with nationally representative data from the National Health and Nutrition Survey-Continuous 2021 (in Spanish, ENSANUT-Continua 2021), collected data from 12,619 households.

Water insecurity was measured using the Household Water Insecurity Experiences (HWISE) Scale in Spanish and adapted to the Mexican context. Food security was measured using the Latin American and Caribbean Food Security Scale (ELCSA). A generalized path model was used to produce two simultaneous logistical regression equations--of water insecurity (WI, HWISE ≥12) and moderate-to-severe food insecurity (FI)—to understand key covariates as well as the contribution of WI to FI.

The head of the household, an adult of >18 years of age, consented to participate in the survey.

Households experiencing WI were more likely to experience moderate to severe FI (OR=2.35; 95%CI: 2.02-2.72). The odds of WI were lower in households with medium (OR=0.74; 95%CI: 0.61-0.9) to high (OR=0.45; 95%CI: 0.37-0.55) asset scores. Water insecurity also depended on the region of Mexico. FI is more prevalent in Indigenous people (OR=1.29; 95%CI: 1.05-1.59) and rural households (OR=0.42; 95%CI: 1.16-1.73). Notably, wealth and household size did not contribute directly to FI but did so indirectly through the mediating factor of WI.

Our study shows that there are structural factors that form part of the varied determinants of water insecurity, which in turn is closely linked to food insecurity.

Valbenazine and deutetrabenazine (vesicular monoamine transporter 2 inhibitors) are approved for tardive dyskinesia (TD) treatment in adults. To prevent potential drug-drug interactions (DDIs), valbenazine labeling recommends doses 40 mg/day when taking strong CYP3A4 or CYP2D6 inhibitors and avoidance of strong CYP3A4 inducers and monoamine oxidase inhibitors (MAOIs). Deutetrabenazine labeling recommends doses ≤36-mg/day when taking strong CYP2D6 inhibitors and avoidance of MAOIs. This study estimated proportions of patients with TD at risk of DDIs with valbenazine/deutetrabenazine in real-world practice.

Patients aged ≥18 years with TD and ≥1 antipsychotic claim(s) and no valbenazine/ deutetrabenazine claims ≥3 months prior and ≥12 months after diagnosis were identified in the Symphony Health Sciences database (US-based medical, hospital, and pharmacy claims database). Proportions of patients meeting valbenazine/deutetrabenazine concomitant medication labeling restrictions were summarized descriptively.

14,264/66,046 patients with TD met inclusion criteria. Proportions of patients at potential risk of DDIs were lower with deutetrabenazine ≤36 mg/day (0.2%) and >36 mg/day (21%) versus valbenazine 40 mg/day (4.4%; 22-times difference) and >40 mg/day (28%; 1.3-times difference). Across age groups, underlying conditions (major depressive, mood, and bipolar disorders; schizophrenia), and payer types, proportions of patients at potential risk of DDIs were lower with deutetrabenazine ≤36 mg/day (0.0%– 0.5%) and >36 mg/day (14%– 30%) versus valbenazine 40 mg/day (3%– 5%; 8.0- to >40.0times difference) and >40 mg/day (22%– 35%; 1.2- to >1.5-times difference).

Estimated proportions of patients with TD at potential risk of DDIs was lower with deutetrabenazine versus valbenazine overall and across age, underlying conditions, and payer types.

Teva Branded Pharmaceutical Products R&D, Inc.

Typical and atypical antipsychotics (AAPs) are the main treatment options among patients with schizophrenia. However, AAPs have been associated with several side effects and comorbid conditions. To manage side effects, often patients are prescribed concomitant medications to manage their condition, increasing polypharmacy. Though common in practice, the prevalence of concomitant medication use in patients with schizophrenia is not well established. This study evaluated the annual prevalence of concomitant medications among patients with schizophrenia who were prescribed AAPs.

This retrospective study was conducted using the PharMetrics database (01/2019 – 12/2021). Patients were included in the analyses if they had a diagnosis of schizophrenia, were continuously enrolled in pharmacy and medical claims for the full year and were prescribed AAPs. A sensitivity analysis was also conducted among patients who demonstrated ≥50% adherence to their prescribed AAPs (with a grace period of 30 days). For both the main and sensitivity analyses patient populations, the concomitant drugs prescribed were labeled at the drug class (GPI2) and generic drug level. Prevalence for drug class and each drug was calculated as a percentage of patients who were prescribed ≥1 of the agent among those who met the inclusion and exclusion criteria within the given year.

For the year 2019, 2020 and 2021, 12,360; 13,242 and 14,780 patients met the inclusion and exclusion criteria, respectively. The mean age of the cohort ranged from 43.5 - 45.4 years. Patients were predominantly male and commercially insured. Antidepressants were the most prevalent concomitant medication prescribed (2019: 61.2%, 2020: 61.2%, 2021: 62.0%). Other highly prevalent drug classes identified were - anticonvulsants (2019: 44.2%, 2020: 44.5%, 2021: 45.0%), antianxiety agents (2019: 36.3%, 2020: 37.6%, 2021: 38.9%), antihyperlipidemics (2019: 26.3%, 2020: 28.1%, 2021: 30.7%), antihypertensives (2019: 25.7%, 2020: 27.2%, 2021: 28.1%), antiparkinson agents (2019: 61.2%, 2020: 61.2%, 2021: 62.0%), anticholinergics (2019: 61.2%, 2020: 61.2%, 2021: 62.0%) and analgesics (2019: 61.2%, 2020: 61.2%, 2021: 62.0%). At the individual drug level, benzotropine mesylate (2019: 19.5%, 2020: 18.7%, 2021: 18.8%), atorvastatin (2019: 14.5%, 2020: 16.7%, 2021: 18.4%), lorazepam (2019: 14.1%, 2020: 14.7%, 2021: 14.3%), gabapentin (2019: 13.7%, 2020: 13.9%, 2021: 14.8%), and metformin (2019: 13.2%, 2020: 13.7%, 2021: 15.4%) were the most prevalent prescribed concomitant medications. There was no difference when similar analyses were conducted in the adherent patient population.

These results indicate a high prevalence of concomitant antidepressants, antihyperlipidemics, antihypertensives and anticholinergics among patients with schizophrenia who are prescribed AAPs.

Sumitomo Pharma America Inc.

To compare the per-patient direct and indirect costs associated with achieving remission with esketamine nasal spray plus oral antidepressants (ESK NS+OAD) versus quetiapine extended release plus oral antidepressants (QTP XR+OAD) among patients with treatment-resistant depression (TRD). This comparison was based on a subanalysis of results from the ESCAPE-TRD Phase 3b trial (ex-US) comparing response and remission rates for ESK NS+OAD vs QTP XR+OAD in TRD patients over 32 weeks.

An Excel-based model was developed to estimate the cost-per-remitter for ESK NS+OAD and QTP XR+OAD from the perspective of a commercial insurance plan in the US. Remission rates, response rates, and relapse rates (among patients remitting or responding during the first 8 weeks of treatment) were estimated in 4-week intervals over 32 weeks using data from the ESCAPE-TRD Phase 3b clinical trial comparing ESK NS+OAD versus QTP XR+OAD in patients with TRD. Patients not remitting/responding (non-responders) or experiencing a relapse either stayed on current treatment (i.e., ESK NS+OAD or QTP XR+OAD) or discontinued current treatment and initiated either augmented therapy with antipsychotics (APS) or recurring transcranial magnetic stimulation (rTMS). For basecase analysis, equal proportions of non-responders off-treatment initiated rTMS or augmented therapy with APS. In a scenario analysis, all non-responders off-treatment initiated rTMS. Direct costs, including medical and drug costs, were derived from health economic literature and the RED BOOK® drug pricing database. Indirect costs attributed to work productivity loss from presenteeism and absenteeism were derived from a separate analysis of ESCAPE-TRD patients using the Work Productivity and Activity Impairment: Depression (WPAI:D) questionnaire and US Bureau of Labor Statistics survey results.

The cumulative relapse-free remission rate at 32 weeks was 50% for patients receiving ESK NS+OAD and 33% for patients receiving QTP XR+OAD. In the basecase analysis, the cost-per-remitter (including direct and indirect costs) for ESK NS+OAD was $3,102.17 lower than that of QTP XR+OAD. In the scenario where 100% of non-responders off-treatment were assumed to initiate rTMS, the cost-per-remitter (including direct and indirect costs) for ESK NS+OAD was $15,133.66 lower than that of QTP XR+OAD.

These findings suggest that esketamine nasal spray in conjunction with oral antidepressants is a cost-efficient alternative compared with quetiapine extended release for treatment of TRD for commercial insurance plans. The comparative benefits associated with ESK NS+OAD treatment are driven primarily by better short- and long-term efficacy observed in the trial and particularly pronounced when considering the costs associated with lost productivity.

Janssen Scientific Affairs, LLC

Crowd crush disasters result in psychological risks such as anxiety, depression, and post-traumatic stress disorder (PTSD). This descriptive research study identified the mental health status of Koreans after the Itaewon crowd crush disaster and explored related factors.

Data were collected May 2-9, 2023 using an online survey. Participants included 205 adults aged 19-69 years recruited through South Korean local and online university communities. Their mental health and related factors were measured at 6 months post-disaster. Data were analyzed using IBM® SPSS® Statistics 26.0. and R 3.4.2.

Significant differences in anxiety, depression, and PTSD among participants who experienced the disaster as victims; changes in drinking frequency and alcohol consumption; and differences in anxiety and PTSD according to family type were observed. Comparing the 3 and 6 month surveys, there were no significant changes in anxiety, depression, PTSD, general mental health, or mental well-being. When mental health severity was divided according to victimization, a significant difference in the severity of anxiety, depression, and PTSD was observed.

Participants’ levels of anxiety, depression, and PTSD varied according to their direct and indirect experience of the disaster, with higher levels of PTSD even without direct experience with the disaster.

Patients with chronic kidney disease suffer from immune dysfunction, increasing susceptibility to infections. The aim of the study was to investigate air contamination with respiratory viruses in a dialysis unit at a quaternary hospital using molecular detection techniques and to analyze airflow dynamics through computational fluid dynamics (CFD) simulations for a comprehensive assessment of air transmission risks.

We conducted dialysis unit air sampling using AerosolSense™ samplers. Air and clinical sampling occurred during three periods in 2022: winter, early, and late fall. A technical team maintained the dialysis unit’s ventilation system during mid fall. Ventilation system capacity and airflow rates were measured. CFD simulations were used to evaluate airflow dynamics.

The investigation collected 144 air samples, revealing heterogeneous virus detection rates across locations and study periods. Virus positivity correlated with the presence of patients and the effectiveness of the ventilation system. The ratio of virus air positivity to virus patient positivity was 1.84 and 3.35 during the first and the second periods, respectively, and collapsed to 0.64 after maintenance. Airflow rate measurements highlighted a ninefold discrepancy between actual and theoretical airflow (393 m3/h vs. 3530 m3/h), which was rectified by maintenance actions. Airflow dynamics and particle dispersion visualization through CFD simulations contributed to a better understanding of transmission risks.

Detection of viruses in the air, combined with CFD, revealed deficiencies in air renewal. Maintenance interventions significantly improved airflow dynamics and particle dispersion, reducing airborne virus spread.