Impact of medical practice guidelines on the assessment of patients with acute coronary syndrome without persistent ST segment elevation.

OBJECTIVE: To assess the impact of introducing clinical practice guidelines on acute coronary syndrome without persistent ST segment elevation (ACS) on patient initial assessment. DESIGN: Prospective before-after evaluation over a 3-month period. SETTING: The emergency ward of a tertiary teaching hospital. PATIENTS: All consecutive patients with ACS evaluated in the emergency ward over the two 3-month periods. INTERVENTION: Implementation of the practice guidelines, and the addition of a cardiology consultant to the emergency team. MAIN OUTCOME MEASURES: Diagnosis, electrocardiogram interpretation, and risk stratification after the initial evaluation. RESULTS: The clinical characteristics of the 328 and 364 patients evaluated in the emergency ward for suspicion of ACS before and after guideline implementation were similar. Significantly more patients were classified as suffering from atypical chest pain (39.6% versus 47.0%; P = 0.006) after guideline implementation. Guidelines availability was associated with significantly more formal diagnoses (79.9% versus 92.9%; P < 0.0001) and risk stratification (53.7% versus 65.4%, P < 0.0001) at the end of initial assessment. CONCLUSION: Guidelines implementation, along with availability of a cardiology consultant in the emergency room had a positive impact on initial assessment of patients evaluated for suspicion of ACS. It led to increased confidence in diagnosis and stratification by risk, which are the first steps in initiating effective treatment for this common condition.     

Prevalence of methicillin-resistant Staphylococcus aureus nasal carriage among patients with femoral neck fractures: implication for antibiotic prophylaxis.

Fifteen (8.4%) of 179 patients admitted with femoral neck fractures carried MRSA. Among 96 patients admitted from their homes, only 2 (2%) were carriers, whereas 13 (15.6%) of 83 patients from nursing or residential homes or long-term-care facilities were colonized (P = .001). Routine prophylaxis with vancomycin is recommended in the latter group.     

Phase I combining a P-glycoprotein inhibitor, MS209, in combination with docetaxel in patients with advanced malignancies.

PURPOSE: The purpose of this study was to investigate the safety and tolerability of MS209, a potent inhibitor of P-glycoprotein, when given in combination with docetaxel and to determine whether MS209 affects docetaxel pharmacokinetics. EXPERIMENTAL DESIGN: Patients with advanced solid malignancies were eligible for this phase I trial. Docetaxel as 1-hour infusion was given alone during the first cycle. MS209 was introduced as of cycle 2 and given orally 30 minutes after docetaxel infusion. The dose escalation scheme followed a modified Fibonacci model with six steps (docetaxel, 60-100 mg/m2 and MS209, 300-1,200 mg per body). RESULTS: A total of 30 patients were treated at five dose levels. Dose-limiting toxicities were febrile neutropenia, infection, stomatitis, dysphagia, and fatigue. The maximum tolerated dose was reached at level 5 (docetaxel, 80-MS: 1,200). Pharmacokinetic analysis failed to show a strong pharmacokinetic interaction between the two compounds, but at the highest dose levels, there is a trend to an increase of docetaxel AUC when this agent is given in combination with MS209. CONCLUSION: MS209 can be given in combination with docetaxel, with limited effect on docetaxel toxicity or pharmacokinetics.     

The NHS England 100,000 Genomes Project: feasibility and utility of centralised genome sequencing for children with cancer

Background Whole-genome sequencing (WGS) of cancers is becoming an accepted component of oncological care, and NHS England is currently rolling out WGS for all children with cancer. This approach was piloted during the 100,000 genomes (100 K) project. Here we share the experience of the East of England Genomic Medicine Centre (East-GMC), reporting the feasibility and clinical utility of centralised WGS for individual children locally.Methods Non-consecutive children with solid tumours were recruited into the pilot 100 K project at our Genomic Medicine Centre. Variant catalogues were returned for local scrutiny and appraisal at dedicated genomic tumour advisory boards with an emphasis on a detailed exploration of potential clinical value.Results Thirty-six children, representing one-sixth of the national 100 K cohort, were recruited through our Genomic Medicine Centre. The diagnoses encompassed 23 different solid tumour types and WGS provided clinical utility, beyond standard-of-care assays, by refining (2/36) or changing (4/36) diagnoses, providing prognostic information (8/36), defining pathogenic germline mutations (1/36) or revealing novel therapeutic opportunities (8/36).Conclusion Our findings demonstrate the feasibility and clinical value of centralised WGS for children with cancer. WGS offered additional clinical value, especially in diagnostic terms. However, our experience highlights the need for local expertise in scrutinising and clinically interpreting centrally derived variant calls for individual children.Subject terms: Cancer genomics, Cancer genomics     

Preliminary study on the role of the human IZUMO gene in oocyte-spermatozoa fusion failure

We studied the IZUMO gene 9 coding exons sequence in four groups of patients including those with fertilization failure by conventional IVF. We observed in our populations two combinations of four polymorphisms that appeared to be preferentially linked (CGG-CG and TAA-TT) without any significant difference between different genotype repartitions.     

Hypophosphatasia: molecular testing of 19 prenatal cases and discussion about genetic counseling

OBJECTIVE: We studied hypophosphatasia (HP) mutations in 19 cases prenatally detected by ultrasonography without familial history of HP. We correlated the mutations with the reported ultrasound signs, and discussed genetic counseling with regard to the particular dominantly inherited prenatal benign form of HP. METHOD: The coding sequence of the tissue nonspecific alkaline phosphatase (TNSALP) gene was analyzed by DNA sequencing, and 3D modeling was used to locate the mutated amino acids with regard to the functional domains of TNSALP. RESULTS: Although reported ultrasound signs were heterogeneous, two mutated alleles were found in 18 of the 19 cases studied, indicating recessive transmission of the disease. Functional domains of TNSALP were affected by 74% of missense mutations. In all the cases, including one with only a heterozygous mutation, molecular, biological, and familial data do not corroborate the hypothesis of prenatal benign HP. The mutation c.1133A>T observed in the prenatal benign form of HP and common in USA was not found in this series. CONCLUSION: The results point out the prenatally detectable allelic heterogeneity of HP. The nature of the detected mutations and the evidence of recessive inheritance do not support these cases being affected with prenatal benign HP.     

Duration of labor induction in nulliparous women at term: how long is long enough?

We evaluated the relationship between duration of labor induction and successful vaginal delivery (VD) in nulliparous women at term. Nulliparous women with singleton pregnancies > or = 37 weeks who underwent labor induction at a single institution were studied. Exclusion criteria were nonvertex presentation, stillbirth, fetal chromosomal/structural abnormalities, spontaneous labor, and spontaneous rupture of membranes. VD rates and maternal/neonatal outcomes were evaluated and compared with respect to the duration from induction to delivery. Over the 1-year study period, 340 women met all criteria. Seventy-five percent achieved VD (n = 255), 40.6% of whom had rate of cervical dilation in active labor < 1.0 cm/hour. Women requiring cesarean delivery were more likely to have fetal acidemia, admission to the neonatal intensive care unit, chorioamnionitis, and endometritis. There was no association with prolonged induction to delivery intervals and adverse maternal/neonatal outcomes. In our population, only 5.7% of nulliparous women undergoing labor induction at term remain undelivered at 48 hours. Of women achieving VD, > 40% had rate of cervical dilation in active labor < 1.0 cm/hour.