First-line nivolumab plus chemotherapy vs chemotherapy in patients with advanced gastric,gastroesophageal junction and esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis

First-line chemotherapy for advanced/metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric/gastroesophageal junction cancer (GC/GEJC) has poor median overall survival (OS; <1 year). We report efficacy and safety results from Chinese patients in the phase III global CheckMate 649 study of nivolumab plus chemotherapy vs chemotherapy for the first-line treatment of GC/GEJC/esophageal adenocarcinoma (EAC). Chinese patients with previously untreated advanced or metastatic GC/GEJC/EAC were randomized to receive nivolumab (360 mg Q3W or 240 mg Q2W) plus chemotherapy (XELOX [capecitabine and oxaliplatin] Q3W or FOLFOX [oxaliplatin, leucovorin and 5-fluorouracil] Q2W), nivolumab plus ipilimumab (not reported) or chemotherapy alone. OS, blinded independent central review-assessed progression-free survival (PFS), objective response rate (ORR), duration of response (DOR) and safety are reported. Of 1581 patients enrolled and randomized, 208 were Chinese. In these patients, nivolumab plus chemotherapy resulted in clinically meaningful improvement in median OS (14.3 vs 10.2 months; HR 0.61 [95% CI: 0.44-0.85]), median PFS (8.3 vs 5.6 months; HR 0.57 [95% CI: 0.40-0.80]), ORR (66% vs 45%) and median DOR (12.2 vs 5.6 months) vs chemotherapy, respectively. The safety profile was acceptable, with no new safety signals observed. Consistent with results from the global primary analysis of CheckMate 649, nivolumab plus chemotherapy demonstrated a clinically meaningful improvement in OS and PFS and higher response rate vs chemotherapy and an acceptable safety profile in Chinese patients. Nivolumab plus chemotherapy represents a new standard first-line treatment for Chinese patients with non-HER2-positive advanced GC/GEJC/EAC.     

Comparison of coronary atherosclerotic plaque progression in East Asians and Caucasians by serial coronary computed tomographic angiography: A PARADIGM substudy

ObjectivesTo investigate potential differences in plaque progression (PP) between in East Asians and Caucasians as well as to determine clinical predictors of PP in East Asians.BackgroundStudies have demonstrated differences in cardiovascular risk factors as well as plaque burden and progression across different ethnic groups.MethodsThe study comprised 955 East Asians (age 60.4 ?± ?9.3 years, 50.9% males) and 279 Caucasians (age 60.4 ?± ?8.6 years, 74.5% males) who underwent two serial coronary computed tomography angiography (CCTA) studies over a period of at least 24 months. Patients were enrolled and analyzed from the PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging) registry. After propensity-score matching, plaque composition and progression were compared between East Asian and Caucasian patients. Within East Asians, the plaque progression group (defined as plaque volume at follow-up CCTA minus plaque volume at baseline CCTA> 0) was compared to the no PP group to determine clinical predictors for PP in East Asians.ResultsIn the matched cohort, baseline volumes of total plaque as well as all plaque subtypes were comparable. There was a trend towards increased annualized plaque progression among East Asians compared to Caucasians (18.3 ?± ?24.7 ?mm³/year vs 16.6 ?mm³/year, p ?= ?0.054). Among East Asians, 736 (77%) had PP. East Asians with PP had more clinical risk factors and higher plaque burden at baseline (normalized total plaque volume of144.9 ?± ?233.3 ?mm³ vs 36.6 ?± ?84.2 ?mm³ for PP and no PP, respectively, p ?< ?0.001). Multivariate logistic regression analysis showed that baseline normalized plaque volume (OR: 1.10, CI: 1.10–1.30, p ?< ?0.001), age (OR: 1.02, CI: 1.00–1.04, p ?= ?0.023) and body mass index (OR: 2.24, CI: 1.01–1.13, p ?= ?0.024) were all predictors of PP in East Asians. Clinical events, driven mainly by percutaneous coronary intervention, were higher among the PP group with a total of 124 (16.8%) events compared to 22 (10.0%) in the no PP group (p ?= ?0.014).ConclusionEast Asians and Caucasians had comparable plaque composition and progression. Among East Asians, the PP group had a higher baseline plaque burden which was associated with greater PP and increased clinical events.     

Assessment of the knowledge,attitudes, and practices among UNRWA health staff in Jordan concerning mental health programme pre-implementation: a cross-sectional study

Background

Mental health is a major public health priority, particularly among refugees worldwide. The United Nations Relief and Works Agency for Palestine Refugees (UNRWA) started to integrate mental health and psychosocial support (MHPSS) into its primary health-care services in Jordan in late 2017. This baseline study aimed to assess the knowledge, attitudes, practices, and perceived barriers among UNRWA health staff regarding the implementation of the MHPSS programme.

Different Cosmetic Habits Can Affect the Biophysical Profile of Facial Skin: A Study of Korean and Chinese Women

BackgroundPrevious studies on the age-, climate, and skin care habit-related changes of biophysical parameters have mainly focused on Caucasians, and studies on Asians are in paucity.ObjectiveThis study was aimed to investigate the variations of cutaneous biophysical parameters in Chinese and Korean women (northeast Asians) and to assess the association between those parameters and age, climate, and cosmetic habits.MethodsA cross-sectional study included 361 healthy Chinese and Korean women between 18 and 49 years of age in 4 cities (Guangzhou, Nanjing, and Shijiazhuang in China, and Suwon in Korea). We measured skin surface temperature, hydration, transepidermal water loss (TEWL), sebum, elasticity, skin pore, wrinkle, and skin tone (brightness) using non-invasive instruments. Demographic profiles and cosmetic habits were assessed using a questionnaire.ResultsSkin elasticity and tone decreased, and pore size and wrinkle increased with age. Subjects in Suwon (Korean) showed higher hydration level, lower TEWL and lower sebum, less severe wrinkle and brighter skin than those in the 3 cities in China. After adjusting for age and region, using sunscreen everyday, wearing base makeup daily, and using moisturizers improved hydration, TEWL, and elasticity significantly.ConclusionWomen in Suwon (Korea) were found to have a better profile of biophysical parameters than women in the 3 Chinese cities, which might be attributed to cosmetic habits, besides age and climatic factors. The fact that appropriate cosmetic habits are associated with favorable skin biophysical parameters underscores the importance of daily skin care routine in preserving skin functions.     

Relationship Between Ligament Forces and Contact Forces in Balancing at Total Knee Surgery

BackgroundSpacer blocks, tensors, or instrumented tibial trials are current methods of balancing the knee during surgery but there are no current techniques for measuring ligament forces. Our goal was to study the relationship between the collateral ligament forces and the condylar contact forces to determine whether there was equivalence.MethodsA test rig was constructed modeling an artificial knee joint with collateral ligaments. The ligament forces as well as the lateral and medial tibial contact forces were measured during flexion for different positions of the femoral component on the femur, producing a set of forces for the simulated conditions. A regression analysis was used to study the correlation between the ligament and contact forces.ResultsThe combined medial and lateral ligament and contact forces showed a linear relation with a correlation coefficient of 0.98. For the medial and lateral sides separately, the correlations were 0.85 and 0.88, respectively, with more than 80% of points within a ±25% deviation from the linear relations. This deviation from the linear correlation is linked to differences in medial-lateral femoral-tibial contact point locations at different flexion angles.ConclusionWithin balancing accuracies generally achieved at surgery, the collateral ligament forces were linearly correlated to the condylar contact forces. These forces can also be equally correlated to the distraction forces as well as the moments at which condylar liftoff would occur from varus-valgus moments. This indicated a unification of the different balancing parameters, and hence such quantitative methods can be used interchangeably.     

Induction Type and Outcomes in HLA-DR Mismatch Kidney Transplantation

BackgroundIn kidney transplantation, donor recipient human leukocyte antigen (HLA)-DR mismatch signals high immunologic risk and portends inferior outcomes. We compared the impacts of depleting vs non-depleting antibody induction on the outcomes in kidney transplant recipients (KTRs) at different levels of HLA-DR mismatches.MethodsUsing the Organ Procurement and Transplantation Network/United Network for Organ Sharing database, we identified adult KTRs from 2001 to 2015 who received induction therapy with either depleting (thymoglobulin/alemtuzumab) or non-depleting (basiliximab/daclizumab) antibody and were discharged on calcineurin inhibitor/mycophenolic acid maintenance. Patients were then stratified by the number of donor-recipient HLA-DR mismatches (0, 1, 2) in both living donor (LD) and deceased donor (DD) KTRs. Under each HLA-DR mismatch category, long-term outcomes were compared for depleting vs non-depleting induction using a Cox model.ResultsA total of 63,821 LD (HLA-DR mismatches: 0, n = 6945 [depleting = 4409, non-depleting = 2536]; 1, n = 19,557 [depleting = 13,558, non-depleting = 6019]; and 2, n = 10,727 [depleting = 7694, non-depleting = 3033]) and 64,922 DD (HLA-DR mismatches: 0, n = 13,915 [depleting = 10,124, non-depleting = 3791]; 1, n = 27,994 [depleting = 20,454, non-depleting = 7540]; and 2, n = 23,013 [depleting = 16,908, non-depleting = 6105]) KTRs were included in the analysis. Adjusted patient death risk was significantly lower in the depleting vs non-depleting antibody induction group among DD kidney recipients (hazard ratio 0.90, 95% CI 0.85–0.96, P = .001) and trended lower among LD kidney recipients (HR 0.88, 95% 0.79–1.01, P = .05) with 2 HLA-DR mismatches.DiscussionOur study found a patient survival benefit associated with the use of perioperative induction with depleting when compared to non-depleting antibody in KTRs with 2 HLA-DR mismatches and maintained on a calcineurin inhibitor/mycophenolic acid regimen.     

MERS coronavirus outbreak: Implications for emerging viral infections

In September 2012, a novel coronavirus was isolated from a patient who died in Saudi Arabia after presenting with acute respiratory distress and acute kidney injury. Analysis revealed the disease to be due to a novel virus which was named Middle East Respiratory Coronavirus (MERS-CoV). There have been several MERS-CoV hospital outbreaks in KSA, continuing to the present day, and the disease has a mortality rate in excess of 35%. Since 2012, the World Health Organization has been informed of 2220 laboratory-confirmed cases resulting in at least 790 deaths. Cases have since arisen in 27 countries, including an outbreak in the Republic of Korea in 2015 in which 36 people died, but more than 80% of cases have occurred in Saudi Arabia.. Human-to-human transmission of MERS-CoV, particularly in healthcare settings, initially caused a ‘media panic’, however human-to-human transmission appears to require close contact and thus far the virus has not achieved epidemic potential. Zoonotic transmission is of significant importance and evidence is growing implicating the dromedary camel as the major animal host in spread of disease to humans. MERS-CoV is now included on the WHO list of priority blueprint diseases for which there which is an urgent need for accelerated research and development as they have the potential to cause a public health emergency while there is an absence of efficacious drugs and/or vaccines. In this review we highlight epidemiological, clinical, and infection control aspects of MERS-CoV as informed by the Saudi experience. Attention is given to recommended treatments and progress towards vaccine development.