Trends in overall mortality among US veterans with primary myelofibrosis

Abstract Background Primary myelofibrosis [PMF] is a myeloproliferative neoplasm associated with reduced overall survival (OS). Management strategies for PMF have evolved over the last two decades, including approval of ruxolitinib as the first Janus kinase 1 (JAK1)/JAK2 inhibitor for patients with intermediate or high-risk myelofibrosis. This study assessed changes in mortality before and after ruxolitinib approval, independent of ruxolitinib treatment. Methods This retrospective study investigated mortality trends among US veterans with PMF in 2 time periods, pre-ruxolitinib approval (01/01/2007–12/31/2010) and post-ruxolitinib approval (01/01/2015–09/30/2018). Deidentified patient-level data were extracted from US Veterans Health Administration (VHA) databases using PMF diagnosis codes; index was the first PMF diagnosis date. The analysis included adults with ≥2 PMF claims during the analysis periods who were continuously enrolled in the VHA plan 1 calendar year prior to and 6 months post-index and had ≥1 available International Prognostic Scoring System (IPSS) risk factor (available factors were age > 65, hemoglobin  25 × 109/L; each counted as one point). Patients with ≥1 MF diagnosis for 12 months before the index period were excluded. Ruxolitinib treatment was not a requirement to be included in the post-ruxolitinib approval cohort. Mortality rates and OS were estimated using the Kaplan-Meier approach; all-cause mortality hazard ratio was estimated using univariate Cox regression. Results The pre- and post-ruxolitinib approval cohorts included 193 and 974 patients, respectively, of which 80 and 197 had ≥2 IPSS risk factors. Ruxolitinib use in the post-ruxolitinib cohort was 8.5% (83/974). At end of follow-up, median (95% CI) OS was significantly shorter in the pre-ruxolitinib cohort (1.7 [1.2–2.6] years vs not reached [3.4–not reached]; P < 0.001). Overall mortality rates for the pre- versus post-ruxolitinib approval cohorts were 79.8% versus 47.3%, respectively, and overall risk of death was 53% lower in the post-ruxolitinib period (hazard ratio, 0.47; 95% CI, 0.37–0.58; P < 0.001). Mortality rates were lower among patients with < 2 vs ≥2 IPSS risk factors. Conclusions Although veterans with PMF have high overall mortality rates, and results in this population might not be generalizable to the overall population, there was a significant lowering of mortality rate in the post-ruxolitinib period

A Genome-Wide Search for Greek and Jewish Admixture in the Kashmiri Population

<div><p>The Kashmiri population is an ethno-linguistic group that resides in the Kashmir Valley in northern India. A longstanding hypothesis is that this population derives ancestry from Jewish and/or Greek sources. There is historical and archaeological evidence of ancient Greek presence in India and Kashmir. Further, some historical accounts suggest ancient Hebrew ancestry as well. To date, it has not been determined whether signatures of Greek or Jewish admixture can be detected in the Kashmiri population. Using genome-wide genotyping and admixture detection methods, we determined there are no significant or substantial signs of Greek or Jewish admixture in modern-day Kashmiris. The ancestry of Kashmiri Tibetans was also determined, which showed signs of admixture with populations from northern India and west Eurasia. These results contribute to our understanding of the existing population structure in northern India and its surrounding geographical areas.</p></div

Investigation of control region sequences of mtDNA in Naqu Tibetan population from Northwestern China

Background The sequence polymorphisms of mitochondrial DNA (mtDNA) are valuable in forensic medicine and anthropological genetics. Aim We analysed the sequences of the mtDNA control region in 207 unrelated Tibetan individuals from the Naqu region, Tibet Autonomous Region in the People's Republic of China, and investigated the population structure of the region by population comparison with other groups. Subjects and methods Genomic DNA was extracted and hypervariable regions (HVS-I and HVS-II) were amplified and sequenced. Subsequently, sequences were aligned and compared with the revised Cambridge sequence. Moreover, population comparison was performed between the Naqu Tibetan group and the other groups. Conclusion Our study provided available data for exploring the mtDNA haplotype of the Tibetan population in the Naqu region, and population comparisons found that the Naqu Tibetan population has its own unique structure

A summary of the number of significant f₃ tests per population.

<p>A summary of the number of significant f₃ tests per population.</p

An <i>ADMIXTURE</i> plot showing the proportion of ancestry each hypothetical ancestral population (K = 7) contributes to each studied population.

<p>The mean admixture proportion of each component across each given population was calculated and the sum rescaled to one. The black arrow indicates the admixture proportions of the Kashmiri population. * indicates Jewish populations. The admixture profile of the Kashmiri population is similar to other northern Indian and Pakistani populations.</p

A principal components plot of principal components 1 and 2 representing the studied genotypic data.

<p>Each population is plotted according to the mean principal component value across all individuals belonging to the respective population. The black arrow shows where the Kashmiri samples cluster. The color of the outline of each symbol corresponds to the broader population group. * indicates Jewish populations. The abbreviation S. stands for Sephardic.</p