Merck & Co.

Post-traumatic stress disorder (PTSD), a complex and chronic disorder caused by exposure to a traumatic event, is a common psychological result of current military operations. It causes substantial distress and interferes with personal and social functioning. Consequently, identifying the risk factors that make military personnel and veterans more likely to experience PTSD is of academic, clinical, and social importance. Four electronic databases (PubMed, Embase, Web of Science, and PsycINFO) were used to search for observational studies (cross-sectional, retrospective, and cohort studies) about PTSD after deployment to combat areas. The literature search, study selection, and data extraction were conducted by two of the authors independently. Thirty-two articles were included in this study. Summary estimates were obtained using random-effects models. Subgroup analyses, sensitivity analyses, and publication bias tests were performed. The prevalence of combat-related PTSD ranged from 1.09% to 34.84%. A total of 18 significant predictors of PTSD among military personnel and veterans were found. Risk factors stemming from before the trauma include female gender, ethnic minority status, low education, non-officer ranks, army service, combat specialization, high numbers of deployments, longer cumulative length of deployments, more adverse life events, prior trauma exposure, and prior psychological problems. Various aspects of the trauma period also constituted risk factors. These include increased combat exposure, discharging a weapon, witnessing someone being wounded or killed, severe trauma, and deployment-related stressors. Lastly, lack of post-deployment support during the post-trauma period also increased the risk of PTSD. The current analysis provides evidence of risk factors for combat-related PTSD in military personnel and veterans. More research is needed to determine how these variables interact and how to best protect against susceptibility to PTSD.

MK-3207 was effective and generally well tolerated in the acute treatment of migraine.

Telcagepant 140 mg taken perimenstrually for seven days was generally well tolerated, but was associated with transaminase elevations. Telcagepant did not reduce monthly headache frequency, but did reduce perimenstrual headaches.

Background: Overexpression of PD-L1 is associated with tumor invasiveness in multiple myeloma (MM) cells and may be a mechanism of immune evasion. Pembrolizumab, a highly selective, humanized IgG4 anti-PD-1 monoclonal antibody designed to block interaction of PD-1 with PD-L1 and PD-L2, may synergize with immunomodulatory drugs (IMiDs) to enhance tumor suppression. KEYNOTE-023 (NCT02036502), an open-label, phase 1, multicenter, nonrandomized, dose-escalation trial evaluated the safety, tolerability, and efficacy of pembrolizumab in combination with lenalidomide and low-dose dexamethasone in patients with RRMM. Methods: Patients with RRMM who have failed ≥2 prior therapies including a proteasome inhibitor and an IMiD were enrolled in the study. KEYNOTE-023 uses a modified 3+3 design for dose determination followed by dose confirmation and expansion arms. During the dose determination phase, cohorts of 3-6 patients were enrolled at 2 mg/kg of pembrolizumab every 2 weeks (Q2W) in combination with 10 mg or 25 mg of lenalidomide on days 1-21 and 40 mg low-dose dexamethasone weekly, to be repeated every 28 days. After preliminary MTD/MAD was identified, additional patients were to be enrolled at a fixed dose of 200 mg of pembrolizumab in combination with lenalidomide and dexamethasone in the dose confirmation and expansion arms. Study treatment is to continue for 24 months or until confirmed disease progression or unacceptable toxicity. The primary end points are safety and antitumor activity. Response is evaluated monthly, using IMWG 2006 criteria. Other end points include complete remission (CR) rate, duration of response (DOR), and exploratory biomarker analyses. Results: As of July 2015, a total of 34 patients with RRMM have been enrolled in the study. Data from 17 patients included in the dose determination and dose confirmation phase are presented in this abstract. All available data for patients currently enrolled in the study will be presented at the upcoming meeting. In the dose determination and dose confirmation phase, 4 patients were treated with pembrolizumab 2 mg/kg and lenalidomide 10 mg and 13 patients were treated with pembrolizumab 2 mg/kg or a fixed dose of 200 mg and lenalidomide 25 mg. All patients were treated with low-dose dexamethasone. The median age was 60 (46-76) years, and 59% of patients had stage (ISS) III disease. Patients were heavily pretreated: 53% had ≥3 prior therapies, 41% had IMiDs-refractory disease, and 18% had double refractory disease. Sixteen patients (94%) experienced at least 1 adverse event (AE) of any grade related to study treatment and 10 patients (58%) experienced grade 3/4 treatment-related AEs. No death or treatment discontinuation for toxicity has been observed. The most frequent treatment-related AEs were: thrombocytopenia (47%), neutropenia (41%), fatigue (29%), and anemia, hyperglycemia, and muscle spasms (23% each). No DLTs were observed in the 10-mg lenalidomide cohort. In the 25-mg lenalidomide cohort, 3 patients (3/13) experienced a dose-limiting toxicity (DLT): neutropenia (grade 3 and grade 4), infectious pneumonia (grade 3), and tumor lysis syndrome (grade 3) with hyperuricemia (grade 4). All patients recovered from the DLTs without treatment discontinuation. Based upon these data the MTD/MAD was defined as pembrolizumab 200 mg fixed dose in combination with lenalidomide 25 mg and low-dose dexamethasone 40 mg. With a median follow-up of 287 days (48-476), 13/17 patients responded to treatment. The objective response rate (ORR) was 76%, with 4 patients achieving a very good partial response and 9 patients achieving a partial response. ORR has also been observed in patients with IMiDs-refractory and double refractory disease. Updated efficacy data, including DOR, will be presented. Conclusions: The preliminary results of KEYNOTE-023 indicate that PD-1 blockade with pembrolizumab in combination with lenalidomide and dexamethasone is associated with a tolerable safety profile and promising antimyeloma activity in heavily pretreated patients with RRMM. Disclosures San Miguel: Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees. Off Label Use: The PD-1 pathway is an important mechanism of immune evasion for many tumors. Pembrolizumab is a humanized monoclonal antibody that blocks the interaction of PD-1 with its ligands PD-L1 and PD-L2 on the tumor cell surface and, based upon pembrolizumab's antitumor immune activity in several solid tumors, it may be an effective option for treating hematological malignancies.. Mateos:Onyx: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Shah:Array: Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees. Reece:BMS: Honoraria, Research Funding; Merck: Research Funding; Amgen: Consultancy, Honoraria; Novartis: Honoraria, Research Funding; Millennium: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Osuka: Honoraria, Research Funding. Ge:Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA: Employment, Equity Ownership. Balakumaran:Merck: Employment, Equity Ownership; Amgen: Equity Ownership. Marinello:Merck: Employment, Equity Ownership. Orlowski:Array Biopharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acetylon Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Millennium Pharaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Spectrum: Research Funding; Biotheryx: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees. Siegel:Celgene Corporation: Consultancy, Speakers Bureau; Amgen: Speakers Bureau; Takeda: Speakers Bureau; Novartis: Speakers Bureau; Merck: Speakers Bureau.

Combined with validation analysis and model simulation, we suggest some possible solutions. The main factors causing potential medical demand are accessibility to medical services and proportion of health insurance compensation. Thus, adjusting the number of hospitals and CHSs and increasing the proportion of health insurance compensation should decrease the actual percentage of patients not seeking medical care and accelerate the transformation of potential medical demand, which deserved being concerned in policymaking.

No abstract

Although medical school education showed little effect on attitudes, students with more individual experiences such as planning to continue clinical psychiatric training, believing psychiatry should be more valued, and having friends with mental illness had less stigmatized attitudes than others.