Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression: Assessment of Long-Term Safety in a Phase 3, Open-Label Study (SUSTAIN-2).

OBJECTIVE: To evaluate long-term safety and efficacy of esketamine nasal spray plus a new oral antidepressant (OAD) in patients with treatment-resistant depression (TRD). METHODS: This phase 3, open-label, multicenter, long-term (up to 1 year) study was conducted between October 2015 and October 2017. Patients (≥ 18 years) with TRD (DSM-5 diagnosis of major depressive disorder and nonresponse to ≥ 2 OAD treatments) were enrolled directly or transferred from a short-term study (patients aged ≥ 65 years). Esketamine nasal spray (28-mg, 56-mg, or 84-mg) plus new OAD was administered twice a week in a 4-week induction (IND) phase and weekly or every-other-week for patients who were responders and entered a 48-week optimization/maintenance (OP/MAINT) phase. RESULTS: Of 802 enrolled patients, 86.2% were direct-entry and 13.8% were transferred-entry; 580 (74.5%) of 779 patients who entered the IND phase completed the phase, and 150 (24.9%) of 603 who entered the OP/MAINT phase completed the phase. Common treatment-emergent adverse events (TEAEs) were dizziness (32.9%), dissociation (27.6%), nausea (25.1%), and headache (24.9%). Seventy-six patients (9.5%) discontinued esketamine due to TEAEs. Fifty-five patients (6.9%) experienced serious TEAEs. Most TEAEs occurred on dosing days, were mild or moderate in severity, and resolved on the same day. Two deaths were reported; neither was considered related to esketamine. Cognitive performance generally either improved or remained stable postbaseline. There was no case of interstitial cystitis or respiratory depression. Treatment-emergent dissociative symptoms were transient and generally resolved within 1.5 hours postdose. Montgomery-Åsberg Depression Rating Scale total score decreased during the IND phase, and this reduction persisted during the OP/MAINT phase (mean [SD] change from baseline of respective phase to endpoint: IND, -16.4 [8.76]; OP/MAINT, 0.3 [8.12]). CONCLUSIONS: Long-term esketamine nasal spray plus new OAD therapy had a manageable safety profile, and improvements in depression appeared to be sustained in patients with TRD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02497287.

Testosterone replacement therapy and the risk of adverse cardiovascular outcomes and mortality.

BACKGROUND: The risk of adverse cardiovascular events and mortality associated with testosterone replacement therapy is controversial. The purpose of this report was to evaluate the effect of testosterone replacement therapy (TRT) in men with secondary hypogonadism on the risk of myocardial infarction (MI), stroke (CVA) or all-cause mortality. METHODS: A retrospective cohort study was conducted using the Cleveland Clinic's electronic health record. Men ≥40 years of age, with at least two testosterone levels < 220 ng/dL, with one level obtained between 7 am and 10 am, were identified. Men with primary hypogonadism, secondary hypogonadism related to overt hypothalamic pituitary pathology, human immunodeficiency virus infection, metastatic cancer, and select contraindications to TRT, were excluded. Men exposed to TRT were matched to controls that were not exposed. A survival analysis was performed on the composite outcome of MI, CVA, or all-cause mortality. RESULTS: One hundred sixty-five patients exposed to TRT (treatment group) were matched with 210 not exposed to TRT (comparison group). The prevalence of established cardiovascular disease (CVD) was 20.0% in the treatment group vs. 17.1% in the comparison group (P = 0.478). The median [interquartile range (IQR)] age (years) and BMI (kg/m2) were 55 (49, 62) and 35.6 (32.1, 40.1) in the treatment group, and 55 (49, 61.7) and 36.3 (32.1, 40.8) in the comparison group, respectively. There were 12 (7.3%) events observed in the treatment group, and 16 (7.6%) in the comparison group. The median time (years) to the composite event was 2.1 (IQR 0.9, 4.6) and 1.8 (IQR 0.6, 3.4) for treatment and comparison groups, respectively. No difference in the risk of the combined cardiovascular endpoint was observed between the treatment group vs the comparison group, hazard ratio (HR) 0.81 (95% Confidence Interval [CI]: 0.38-1.71; P = 0.57). CONCLUSION: In hypogonadal men with a modest prevalence of established CVD, TRT was not observed to confer a protective or adverse effect on the risk of MI, CVA or all-cause mortality.

CONTEXTE: Le risque d'événements cardiovasculaires indésirables et de mortalité associé au traitement de substitution de la testostérone est controversé. Le but du présent article est d'évaluer chez les hommes qui présentent un hypogonadisme secondaire l'effet du traitement de substitution de la testostérone (TST) sur le risque d'infarctus du myocarde (IM), d'accident cérébrovasculaire (ACV) ou de mortalité toutes causes confondues. PATIENTS ET MÉTHODES: Une étude de cohorte rétrospective a été menée en utilisant les dossiers de santé électroniques de la Clinique Cleveland. Ont été identifiés les hommes âgés de plus de 40 ans qui avaient au moins deux dosages de testostérone inférieurs à 220ng/dl, dont l'un obtenu le matin entre 7 et 10 heures. Ont été exclus les hommes qui présentaient un hypogonadisme primaire, un hypogonadisme secondaire lié à une pathologie hypothalamo-hypophysaire évidente, une infection par le virus de l'immunodéficience humaine, un cancer métastatique, et ceux qui présentaient des contrindications déterminées au TST. Les hommes exposés au TST ont été appariés à des témoins non exposés au TST. Une analyse de survie a été réalisée sur le paramètre composite incluant l'IM, l'AVC et la mortalité toutes causes confondues. RÉSULTATS: 165 patients exposés au TST (groupe traité) ont été appariés à 210 hommes non exposés au TST (groupe de référence). La prévalence de maladie cardiovasculaire (MCV) établie était de 20.0% dans le groupe traité versus 17.1% dans le groupe de référence (P=0.478). La médiane (écart interquartile (EI)) de l'âge et de l'indice de masse corporelle (IMC) était respectivement de 55 (49, 62) ans et de 35.6 (32.1, 40.1) kg/m2 dans le groupe traité, et respectivement de 55 (49, 61.7) ans et 36.3 (32.1, 40.8) kg/m2 dans le groupe de référence. Il y eut 12 événements indésirables (7.3%) dans le groupe traité, et 16 (7.6%) dans le groupe de référence. La médiane du temps (en années) des événements composites était de 2.1 (EI 0.9, 4.6) et de 1.8 (EI 0.6, 3.4) respectivement pour les groupes traité et de référence. Aucune différence n'a été observée en ce qui concerne le risque cardiovasculaire entre le groupe traité et le groupe de référence, rapport de risque (RR) 0.81 (Intervalle de Confiance à 95% [IC]: 0.38-1.71; P = 0.57). CONCLUSION: Chez les hommes qui présentent un hypogonadisme et une faible prévalence de maladie cardiovasculaire (MCV) établie, le TST n'apparait pas conférer un effet protecteur ou défavorable sur le risque de d'infarctus du myocarde (IM), d'accident cérébrovasculaire (ACV) ou de mortalité toutes causes confondues. MOTS-CLÉS: Traitement de substitution de la testostérone, Hypogonadisme masculin, Risque cardiovasculaire, Mortalité.

Tulsa health care challenge: a compilation of issues and possible solutions.

The delivery of adequate health care to "all of the people" has become an increasing challenge in the United States. The problem of timely access to affordable health care is even more serious in Oklahoma. The University of Oklahoma-Tulsa Health Science Center, the OU College of Medicine-Tulsa, and Community HealthNET, Inc. have taken leadership roles in convening two Oklahoma Health Care Challenge summit meetings this past year. Tulsa community leaders are now addressing the seriousness of the local problem and, more importantly, are coming up with ways to alleviate it. The focus of the summits has centered on providing indigent care, which will provide relief to the Tulsa hospitals and physicians from the growing burden of charity care costs. The most beneficial results of these meetings have been a clearer definition of the problem specific to Tulsa, the recognition that the solution will require coalitions of multidisciplinary groups, and the realization that cooperation, as well as collaboration, is the key to success.

The effect of early geriatric exposure upon career development and subspecialty selection among physician assistant students.

PURPOSE: The elderly population is increasing. So too is the demand for geriatric medical care. Currently, there are too few practitioners to meet the expanding need for geriatric health services. Physician assistants (PAs) can help bridge this gap. METHODS: A descriptive, quantitative study assessing PA students of five Pennsylvania programs and their level of geriatric training and subsequent career specialty selection was conducted. The study consisted of a 10-question survey regarding student exposure to geriatric patients, type of exposure, and career plans. RESULTS: The study concluded that although the majority indicated both geriatric coursework (61.9%) and clinical exposure (54.2%) to geriatric patients in the first year of training, Pennsylvania PA students expressed little interest in specializing in geriatric medicine. CONCLUSION: Present findings indicate current geriatric curricula and exposure of PA students to the elderly may be inadequate to influence PA students in northeastern Pennsylvania to choose to specialize in geriatric medicine. Further research and findings from this study indicate using a multifaceted approach to geriatric education including more frequent positive interactions with elderly patients, and enhancing geriatric clinical exposure may result in increased interest of PA students in geriatric medicine. Additionally, the provision of a financial incentive may influence current PA students to more strongly consider a practice in geriatrics. These changes could potentially help increase the number of PAs interested in geriatrics as a career choice and facilitate PAs filling the anticipated gap between elderly medical needs and available health care providers.

Age-adjustment and related epidemiology rates in education and research.

A quick review of introductory textbooks reveals that while gerontology authors and instructors introduce some aspect of demography and epidemiology data, there is limited focus on age adjustment or other important epidemiology rates. The goal of this paper is to reintroduce a variety of basic epidemiology strategies such as incidence, prevalence, crude, age-specific and age-adjustment rates into the gerontology classroom. Background information and formulas for each rate, as well as examples of how they can be applied are provided. A recent change, encouraged by the U.S. Department of Health and Human Services, from a 1940 to a 2000 "standard million population" for ageadjusted rates, is reviewed. Finally, a teaching module with answers is provided for use in the gerontology classroom.