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We have performed exome-wide association studies to identify single nucleotide polymorphisms that influence serum concentrations of triglycerides, high density lipoprotein (HDL)-cholesterol, or low density lipoprotein (LDL)-cholesterol or confer susceptibility to hypertriglyceridemia, hypo-HDL-cholesterolemia, or hyper-LDL-cholesterolemia in Japanese. Exome-wide association studies for serum triglycerides (13,414 subjects), HDL-cholesterol (14,119 subjects), LDL-cholesterol (13,577 subjects), hypertriglyceridemia (4742 cases, 8672 controls), hypo-HDL-cholesterolemia (2646 cases, 11,473 controls), and hyper-LDL-cholesterolemia (4489 cases, 9088 controls) were performed with HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. Twenty-four, 69, or 32 loci were significantly (P < 1.21 × 10−6) associated with serum triglycerides, HDL-cholesterol, or LDL-cholesterol, respectively, with 13, 16, or 9 of these loci having previously been associated with triglyceride-, HDL-cholesterol-, or LDL-cholesterol-related traits, respectively. Two single nucleotide polymorphisms (rs10790162, rs7350481) were significantly related to both serum triglycerides and hypertriglyceridemia; three polymorphisms (rs146515657, rs147317864, rs12229654) were significantly related to both serum HDL-cholesterol and hypo-HDL-cholesterolemia; and six polymorphisms (rs2853969, rs7771335, rs2071653, rs2269704, rs2269703, rs2269702) were significantly related to both serum LDL-cholesterol and hyper-LDL-cholesterolemia. Among polymorphisms identified in the present study, two polymorphisms (rs146515657, rs147317864) may be novel determinants of hypo-HDL-cholesterolemia, and six polymorphisms (rs2853969, rs7771335, rs2071653, rs2269704, rs2269703, rs2269702) may be new determinants of hyper-LDL-cholesterolemia. In addition, 12, 61, 23, or 3 polymorphisms may be new determinants of the serum triglyceride, HDL-cholesterol, or LDL-cholesterol concentrations or of hyper-LDL-cholesterolemia, respectively.
triglyceride, HDL-cholesterol, LDL-cholesterol, dyslipidemia, exome-wide association study
Identification of eight genetic variants as novel determinants of dyslipidemia in Japanese by exome-wide association studies
Yoshiji Yamada,1,2 Jun Sakuma,2,3,4 Ichiro Takeuchi,2,4,5 Yoshiki Yasukochi,1,2 Kimihiko Kato,1,6 Mitsutoshi Oguri,1,7 Tetsuo Fujimaki,8 Hideki Horibe,9 Masaaki Muramatsu,10 Motoji Sawabe,11 Yoshinori Fujiwara,12 Yu Taniguchi,12 Shuichi Obuchi,13 Hisashi Kawai,13 Shoji Shinkai,14 Seijiro Mori,15 Tomio Arai,16 and Masashi Tanaka17
2017 Jun 13;
The incidence of acute otitis media (AOM) vary from country to country. Geographical variations together with differences in study designs, reporting and settings play a role. We assessed the incidence of AOM in Italian children seen by primary care paediatricians (PCPs), and described the methods used to diagnose the disease.
This secondary data analysis from the Pedianet database considered children aged 0 – 6 years between 01/2003 and 12/2007. The AOM episodes were identified and validated by means of patient diaries. Incidence rates/100 person-years (PY) were calculated for total AOM and for single or recurrent AOM.
The 92,373 children (52.1% males) were followed up for a total of 227,361 PY: 23,039 (24.9%) presented 38,241 episodes of AOM (94.6% single episodes and 5.4% recurrent episodes). The total incidence rate of AOM in the 5-year period was 16.8 episodes per 100 PY (95% CI: 16.7-16.9), including single AOM (15.9 episodes per 100 PY; 95% CI: 15.7-16.1) and recurrent AOM (0.9 episodes per 100 PY; 95% CI: 0.9-0.9). There was a slight and continuously negative trend decrease over time (annual percent change −4.6%; 95%CI: -5.3, -3.9%). The AOM incidence rate varied with age, peaking in children aged 3 to 4 years (22.2 episodes per 100 PY; 95% CI 21.8-22.7). The vast majority of the AOM episodes (36,842/38,241, 96.3%) were diagnosed using a static otoscope; a pneumatic otoscope was used in only 3.7%.
Our data fill a gap in our knowledge of the incidence of AOM in Italy, and indicate that AOM represents a considerable burden for the Italian PCP system. Educational programmes concerning the diagnosis of AOM are needed, as are further studies to monitor the incidence in relation to the introduction of wider pneumococcal conjugate vaccines.
Acute otitis media, Incidence, Primary care pediatrics
Burden of acute otitis media in primary care pediatrics in Italy: a secondary data analysis from the Pedianet database
Paola Marchisio,corresponding author1 Luigi Cantarutti,2 Miriam Sturkenboom,3,4 Silvia Girotto,2 Gino Picelli,4 Daniele Dona,5 Antonio Scamarcia,6 Marco Villa,7 and Carlo Giaquinto5, On behalf of Pedianet
The treatment of older patients with acute myeloid leukemia that is secondary to previous myelodysplastic syndrome, myeloproliferative neoplasm, or prior cytotoxic exposure remains unsatisfactory. We compared 92 and 107 patients treated, respectively, with intensive chemotherapy or azacitidine within two centres. Diagnoses were 37.5% post-myelodysplastic syndrome, 17.4% post-myeloproliferative neoplasia, and 45.1% therapy-related acute myeloid leukemia. Patients treated by chemotherapy had less adverse cytogenetics, higher white blood-cell counts, and were younger: the latter two being independent factors entered into the multivariate analyses. Median overall-survival times with chemotherapy and azacitidine were 9.6 (IQR: 3.6−22.8) and 10.8 months (IQR: 4.8−26.4), respectively (p = 0.899). Adjusted time-dependent analyses showed that, before 1.6 years post-treatment, there were no differences in survival times between chemotherapy and azacitidine treatments whereas, after this time-point, patients that received chemotherapy had a lower risk of death compared to those that received azacitidine (adjusted HR 0.61, 95%CI: 0.38−0.99 at 1.6 years). There were no interactions between treatment arms and secondary acute myeloid leukemia subtypes in all multivariate analyses, indicating that the treatments had similar effects in all three subtypes. Although a comparison between chemotherapy and azacitidine remains challenging, azacitidine represents a valuable alternative to chemotherapy in older patients that have secondary acute myeloid leukemia because it provides similar midterm outcomes with less toxicity.
therapy-related acute myeloid leukemia, secondary AML, azacitidine, intensive chemotherapy, older patients
Azacitidine or intensive chemotherapy for older patients with secondary or therapy-related acute myeloid leukemia
Pierre-Yves Dumas,1,2,3,* Sarah Bertoli,4,5,6,* Emilie Berard,7,8 Clemence Mediavilla,1 Edwige Yon,7 Suzanne Tavitian,4 Thibaut Leguay,1 Francoise Huguet,4 Edouard Forcade,1 Noël Milpied,1,2,3 Audrey Sarry,4 Mathieu Sauvezie,1 Pierre Bories,9 Arnaud Pigneux,1,2,3,** and Christian Recher4,5,6,**
2017 Oct 3;