Safety and efficacy of VB-111, an anticancer gene therapy, in patients with recurrent glioblastoma: results of a phase I/II study.

BackgroundVB-111 is a non-replicating adenovirus carrying a Fas-chimera transgene, leading to targeted apoptosis of tumor vascular endothelium and induction of a tumor-specific immune response. This phase I/II study evaluated the safety, tolerability, and efficacy of VB-111 with and without bevacizumab in recurrent glioblastoma (rGBM).MethodsPatients with rGBM (n = 72) received VB-111 in 4 treatment groups: subtherapeutic (VB-111 dose escalation), limited exposure (LE; VB-111 monotherapy until progression), primed combination (VB-111 monotherapy continued upon progression with combination of bevacizumab), and unprimed combination (upfront combination of VB-111 and bevacizumab). The primary endpoint was median overall survival (OS). Secondary endpoints were safety, overall response rate, and progression-free survival (PFS).ResultsVB-111 was well tolerated. The most common adverse event was transient mild-moderate fever. Median OS time was significantly longer in the primed combination group compared with both LE (414 vs 223 days; hazard ratio [HR], 0.48; P = 0.043) and unprimed combination (414 vs 141.5 days; HR, 0.24; P = 0.0056). Patients in the combination phase of the primed combination group had a median PFS time of 90 days compared with 60 in the LE group (HR, 0.36; P = 0.032), and 63 in the unprimed combination group (P = 0.72). Radiographic responders to VB-111 exhibited characteristic, expansive areas of necrosis in the areas of initial enhancing disease.ConclusionsPatients with rGBM who were primed with VB-111 monotherapy that continued after progression with the addition of bevacizumab showed significant survival and PFS advantage, as well as specific imaging characteristics related to VB-111 mechanism of action. These results warrant further assessment in a randomized controlled study

Health care costs during the last 12 months of life in Israel: estimation and implications for risk-adjustment

Cost, Medical care, Death, Last year of life, Risk adjustment, Risk sharing, Israel, I11, I18,

CANDIDATE GENE ANALYSIS IN ISRAELI SOLDIERS WITH STRESS FRACTURES

To investigate the association of polymorphisms within candidate genes which we hypothesized may contribute to stress fracture predisposition, a case-control, cross- sectional study design was employed. Genotyping 268 Single Nucleotide Polymorphisms- SNPs within 17 genes in 385 Israeli young male and female recruits (182 with and 203 without stress fractures). Twenty-five polymorphisms within 9 genes (NR3C1, ANKH, VDR, ROR2, CALCR, IL6, COL1A2, CBG, and LRP4) showed statistically significant differences (p < 0.05) in the distribution between stress fracture cases and non stress fracture controls. Seventeen genetic variants were associated with an increased stress fracture risk, and eight variants with a decreased stress fracture risk. None of the SNP associations remained significant after correcting for multiple comparisons (false discovery rate- FDR). Our findings suggest that genes may be involved in stress fracture pathogenesis. Specifically, the CALCR and the VDR genes are intriguing candidates. The putative involvement of these genes in stress fracture predisposition requires analysis of more cases and controls and sequencing the relevant genomic regions, in order to define the specific gene mutation

Diabetes among Ethiopian Immigrants to Israel: Exploring the Effects of Migration and Ethnicity on Diabetes Risk.

OBJECTIVE:Diabetes prevalence among ethnic minorities and immigrants often differs from the majority indigenous population. We compared diabetes prevalence, incidence and risk among Ethiopian and non-Ethiopian Jews. Within these main groups, we controlled for the effect of migration on diabetes risk by comparing the subgroups of Ethiopian and former Soviet Union (FSU) immigrants, and compared both with Israeli-born non-Ethiopian Jews. METHODS:The study cohort included adult Ethiopian (n = 8,398) and age-matched non-Ethiopian Jews (n = 15,977) and subgroups: Ethiopian immigrants (n = 7,994), FSU immigrants (n = 1,541) and Israeli-born non-Ethiopian Jews (n = 10,828). Diabetes prevalence, annual incidence, and hazard ratios (HRs) adjusted for sex and metabolic syndrome (MetS)-components, were determined in three age groups (<50yrs, 50-59yrs, and ≥60yrs). Comparisons of body mass index (BMI) at diabetes incidence were made. RESULTS:Younger (<50yrs) Ethiopians had higher prevalence rates, 3.6% (95%CI: 3.1-4.1) and annual incidence, 0.9% (95%CI: 0.8-1.0) than non-Ethiopians, 2.7% (95%CI: 2.3-3.0) and 0.5% (95%CI: 0.4-0.6), respectively. These differences were particularly pronounced among Ethiopian women. Diabetes risk among Ethiopians was higher and adjustment for MetS-components was important only for BMI, which further increased hazard ratio (HR) estimates associated with Ethiopian ethnicity from 1.81 (95% CI:1.50-2.17) to 2.31 (95% CI:1.91-2.79). The same differences were seen when comparing Ethiopian to FSU immigrants. BMI before incident diabetes was lower among younger Ethiopian immigrants than younger FSU immigrants and Israeli-born. CONCLUSIONS:Ethiopian ethnicity is associated with increased diabetes risk, which is age and BMI dependent. Young Ethiopians<50yrs, particularly women, had the greatest increase in risk. Lower BMI cut-offs should be defined to reflect diabetes risk among Ethiopians

Adult Arabs have higher risk for diabetes mellitus than Jews in Israel

<div><p>Objective</p><p>Diabetes mellitus is an emerging epidemic in the Arab world. Although high diabetes prevalence is documented in Israeli Arabs, information from cohort studies is scant.</p><p>Methods</p><p>This is a population study, based on information derived between 2007–2011, from the electronic database of the largest health fund in Israel, among Arabs and Jews. Prevalence, 4-year-incidence and diabetes hazard ratios [HRs], adjusted for sex and the metabolic-syndrome [MetS]-components, were determined in 3 age groups (<50 years, 50–59 years, and ≥60 years).</p><p>Results</p><p>The study cohort included 17,044 Arabs (males: 49%, age: 39.4±17.3) and 16,012 Jews (males: 50%, age: 40.5 ±17.6). The overall age and sex-adjusted diabetes prevalence rates were much higher among Arabs 18.4% (95%CI: 17.6–19.1); and 10.3% (95%CI: 9.7–10.9) among Jews. Arab females had higher prevalence rates 20.0% (95%CI: 19–21) than Arab males 16.7% (95%CI: 15.7–17.8). Annual incidence rates were also significantly higher among Arabs 2.9% (95%CI: 2.7–3.1) than among Jews 1.7% (95%CI: 1.6–1.8). This held true across all age and sex subgroups. Adjustment for body mass index [BMI] attenuated HR estimates associated with Arab ethnicity across all age subgroups, mainly in the <50yrs age group from HR 2.04 (95%CI: 1.74–2.40) to 1.64 (95%CI: 1.40–1.92). BMI at incident diabetes among females was higher in Arabs than Jews. Males, however, did not differ by ethnicity.</p><p>Conclusion</p><p>Arabs, mainly female, have high incidence and prevalence of diabetes. This excess risk is only partially explained by the high prevalence of obesity. Effective culturally-congruent diabetes prevention and treatment and an effective engagement partnership with the Arab community are of paramount need.</p></div

Baseline characteristics of the study cohort.

<p>Baseline characteristics of the study cohort.</p

Standardized and age-specific prevalence and weighted cumulative 4-yr incidence per 100 persons of diabetes (95% confidence interval)^*.

<p>Standardized and age-specific prevalence and weighted cumulative 4-yr incidence per 100 persons of diabetes (95% confidence interval)^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0176661#t002fn002" target="_blank">*</a>}.</p

Baseline characteristics of the study cohort.

<p>Baseline characteristics of the study cohort.</p

Standardized and age-specific prevalence and weighted average annual incidence per 100 persons of diabetes (95% confidence interval)^* over the period of 2008–11.

<p>Standardized and age-specific prevalence and weighted average annual incidence per 100 persons of diabetes (95% confidence interval)^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0157354#t002fn002" target="_blank">*</a>} over the period of 2008–11.</p