Association between ORMDL3, IL1RL1 and a deletion on chromosome 17q21 with asthma risk in Australia

Genome-wide association studies followed by replication provide a powerful approach to map genetic risk factors for asthma. We sought to search for new variants associated with asthma and attempt to replicate the association with four loci reported previously (ORMDL3, PDE4D, DENND1B and IL1RL1). Genome-wide association analyses of individual single nucleotide polymorphisms (SNPs), rare copy number variants (CNVs) and overall CNV burden were carried out in 986 asthma cases and 1846 asthma-free controls from Australia. The most-associated locus in the SNP analysis was ORMDL3 (rs6503525, P=4.8 × 10⁻⁷). Five other loci were associated with P<10⁻⁵, most notably the chemokine CXC motif ligand 14 (CXCL14) gene (rs31263, P=7.8 × 10⁻⁶). We found no evidence for association with the specific risk variants reported recently for PDE4D, DENND1B and ILR1L1. However, a variant in IL1RL1 that is in low linkage disequilibrium with that reported previously was associated with asthma risk after accounting for all variants tested (rs10197862, gene wide P=0.01). This association replicated convincingly in an independent cohort (P=2.4 × 10⁻⁴). A 300-kb deletion on chromosome 17q21 was associated with asthma risk, but this did not reach experiment-wide significance. Asthma cases and controls had comparable CNV rates, length and number of genes affected by deletions or duplications. In conclusion, we confirm the association between asthma risk and variants in ORMDL3 and identify a novel risk variant in IL1RL1. Follow-up of the 17q21 deletion in larger cohorts is warranted.     

脑缺氧是影响严重颅脑创伤患者短期预后的独立危险因素(英文)

Background:Brain hypoxia(BH)can aggravate outcome after severe traumatic brain injury(TBI).Whether BH or reduced brain oxygen(Pbto2)is an independent outcome predictor or a marker of disease severity is not fully elucidated.Objective To analyze the relationship between Pbto2,intracranial pressure(ICP),and cerebral perfusion pressure(CPP)and to examine whether BH correlates with worse outcome independently of ICP and CPP.Methods We studied103patients monitored     

The observation on different effectiveness between the embedding needle therapy and medication in the preventative treatment of chronic migraine

Objective

To evaluate the therapeutic effects of the embedding needle therapy in the preventative treatment of chronic migraine.

The M-OVIN study: does switching treatment to FSH and / or IUI lead to higher pregnancy rates in a subset of women with world health organization type II anovulation not conceiving after six ovulatory cycles with clomiphene citrate – a randomised controlled trial

Background

Clomiphene citrate (CC) is first line treatment in women with World Health Organization (WHO) type II anovulation and polycystic ovary syndrome (PCOS). Whereas 60% to 85% of these women will ovulate on CC, only about one half will have conceived after six cycles. If women do not conceive, treatment can be continued with gonadotropins or intra-uterine insemination (IUI). At present, it is unclear for how many cycles ovulation induction with CC should be repeated, and when to switch to ovulation induction with gonadotropins and/or IUI.

Methods/Design

We started a multicenter randomised controlled trial in the Netherlands comparing six cycles of CC plus intercourse or six cycles of gonadotrophins plus intercourse or six cycles of CC plus IUI or six cycles of gonadotrophins plus IUI.Women with WHO type II anovulation who ovulate but did not conceive after six ovulatory cycles of CC with a maximum of 150 mg daily for five days will be included.Our primary outcome is birth of a healthy child resulting from a pregnancy that was established in the first eight months after randomisation. Secondary outcomes are clinical pregnancy, miscarriage, multiple pregnancy and treatment costs. The analysis will be performed according to the intention to treat principle. Two comparisons will be made, one in which CC is compared to gonadotrophins and one in which the addition of IUI is compared to ovulation induction only. Assuming a live birth rate of 40% after CC, 55% after addition of IUI and 55% after ovulation induction with gonadotrophins, with an alpha of 5% and a power of 80%, we need to recruit 200 women per arm (800 women in total).An independent Data and Safety Monitoring Committee has criticized the data of the first 150 women and concluded that a sample size re-estimation should be performed after including 320 patients (i.e. 80 per arm).

Discussion

The trial will provide evidence on the most effective, safest and most cost effective treatment in women with WHO type II anovulation who do not conceive after six ovulatory cycles with CC with a maximum of 150 mg daily for five days. This evidence could imply the need for changing our guidelines, which may cause a shift in large practice variation to evidence based primary treatment for these women.

Trial registration number

Netherlands Trial register NTR1449

     

Predicting serious bacterial infection in young children with fever without apparent source

The aim of this study was to design a clinical rule to predict the presence of a serious bacterial infection in children with fever without apparent source. Information was collected from the records of children aged 1-36 mo who attended the paediatric emergency department because of fever without source (temperature > or = 38 degrees C and no apparent source found after evaluation by a general practitioner or history by a paediatrician). Serious bacterial infection included bacterial meningitis, sepsis, bacteraemia, pneumonia, urinary tract infection, bacterial gastroenteritis, osteomyelitis and ethmoiditis. Using multivariate logistic regression and the area under the receiver operating characteristic curve (ROC area), the diagnostic value of predictors for serious bacterial infection was judged, resulting in a risk stratification. Twenty-five percent of the 231 patients enrolled in the study (mean age 1.1 y) had a serious bacterial infection. Independent predictors from history and examination included duration of fever, poor micturition, vomiting, age, temperature < 36.7 degrees C or > or = 40 degrees C at examination, chest-wall retractions and poor peripheral circulation (ROC area: 0.75). Independent predictors from laboratory tests were white blood cell count, serum C-reactive protein and the presence of >70 white blood cells in urinalysis (ROC area: 0.83). The risk stratification for serious bacterial infection ranged from 6% to 92%. CONCLUSION: The probability of a serious bacterial infection in the individual patient with fever without source can be estimated more precisely by using a limited number of symptoms, signs and laboratory tests.     

In situ saphenous vein bypass grafts: angiographic evaluation and interventional repair of complications

In situ saphenous vein grafts are being used with increasing frequency for bypass procedures involving the femoral and popliteal arteries. Complications of these procedures include anastomotic stenoses and persistent arteriovenous fistulae that may result in failure of the graft. Balloon angioplasty and embolotherapy with detachable balloons were employed successfully in three or four recent cases of patients with complications from in situ grafts. Tailored angiography is essential for evaluating in situ grafts, and interventional techniques are extremely useful for managing complications.     

Inpatient admissions for interventional radiology: philosophy of patient management

As an alternative to performing interventional radiology on inpatients under the care of internists and surgeons, the authors have established a cardiovascular radiology admitting service for well-screened, elective patients. The patients are admitted under the care of a cardiovascular radiology fellow and a staff physician. From April 1982 to December 1983, 133 patients were admitted to the service. Patients are cared for in a surgical ward or in an intermediate unit, as determined by the clinical situation. Advantages of this approach include a broader patient referral base, improved rapport with clinical colleagues and patients, improved follow-up data, and rapid evaluation and treatment, resulting in short hospital stays. The major disadvantages involve the commitment of time and staff necessary to provide quality care. The concept of the interventional radiologist in the role of admitting physician has important implications in terms of negotiations for additional financial compensation, commensurate with the skill and time required for performing these procedures and caring for the patient.