Multiple endocrine neoplasia type 1 (MEN1) gene mutations in a subset of patients with sporadic and familial primary hyperparathyroidism target the coding sequence but spare the promoter region

Germ line mutations of the multiple endocrine neoplasia type 1 (MEN1) tumour suppressor gene cause MEN1, a rare familial tumour syndrome associated with parathyroid hyperplasia, adenoma and hyperparathyroidism (HP). Here we investigated the role of the MEN1 gene in isolated sporadic and familial HP. Using RT-PCR single-strand conformational polymorphism screening, somatic (but not germ line) mutations of the MEN1 coding sequence were identified in 6 of 31 (19.3%) adenomas from patients with sporadic primary HP, but none in patients (n=16) with secondary HP due to chronic renal failure. MEN1 mutations were accompanied by a loss of heterozygosity (LOH) for the MEN1 locus on chromosome 11q13 in the adenomas as detected by microsatellite analysis. No DNA sequence divergence within the 5' region of the MEN1 gene, containing the putative MEN1 promoter, was detectable in HP adenomas. Clinical characteristics were not different in HP patients with or without MEN1 mutation. Heterozygous MEN1 gene polymorphisms were identified in 9.6% and 25% of patients with primary and secondary HP respectively. In a large kindred with familial isolated familial HP, MEN1 germ line mutation 249 del4 and LOH was associated with the HP phenotype and a predisposition to non-endocrine malignancies. We suggest that the bi-allelic somatic loss of MEN1 wild-type gene expression is involved in the pathogenesis of a clinically yet undefined subset of sporadic primary HP adenomas. MEN1 genotyping may further help define the familial hyperparathyroidism-MEN1 disease complex, but it seems dispensable in sporadic primary HP.     

Implementation of healthcare accreditation in Danish general practice: a questionnaire study exploring general practitioners’ perspectives on external support

ObjectiveTo describe the use and perceived usefulness of implementation support provided to general practice during an accreditation process and to explore potential variations across clinic characteristics.DesignCross-sectional questionnaire study.Setting and subjectsAll Danish general practice clinics undergoing an accreditation survey from 27 September 2016 to 15 December 2017 (n = 608).Main outcome measuresUse and perceived usefulness of seven types of implementation support as reported by general practitioners (GPs). Clinic characteristics included practice type, number of GP partners and staff and employment of GP trainees.ResultsThe total response rate was 74% (n = 447). Most clinics (99.5%) used some type of implementation support (average: 4.8 different types). The most used types of support were peer support (80–92%) and various accreditation documents (85–92%). Support tailored to the individual clinic was most often considered useful (91–97%). However, this type of support was used relatively infrequently (16–40%). In most cases, clinic characteristics were neither significantly associated with the use of support nor with the perceived usefulness of the available support.ConclusionDuring the accreditation processes, each clinic used a broad variety of implementation support. Support tailored to the individual clinic was highly appreciated and should be promoted in future quality interventions in general practice. Discussions with peers were widely used, and it should be investigated further how peer discussions are best facilitated. The study calls for a multifactorial approach to future quality interventions in general practice to target the needs and capacities of the individual clinics.     

Escherichia coli clonal group A causing bacteraemia of urinary tract origin

Escherichia coli clonal group A (CgA) causes disease in humans. This is the first study investigating the prevalence of CgA among E. coli from non-urine, extraintestinal infections in a northern European country. E. coli blood (n = 196) and paired urine (n = 195) isolates from the same patients with bacteraemia of urinary tract origin were analysed. The isolates were collected from January 2003 through May 2005 at four hospitals in Copenhagen, Denmark. Pulsed-field gel electrophoresis (PFGE) patterns, antimicrobial resistance and patient characteristics were determined for all CgA isolates; presence of virulence-associated genes (VAGs) and serotypes were determined for the blood CgA isolates. Thirty blood isolates (15%) belonged to CgA. CgA blood isolates were associated with female patients and sulfamethoxazole-trimethoprim resistance and they harboured a distinctive VAG profile. The blood and urine isolates from each pair were found to be related in 26 of 27 CgA blood/urine pairs, confirming a urinary tract origin of infection. Furthermore, a relationship between the PFGE patterns of CgA blood/urine isolates and CgA isolates from UTI patients in general practice and a CgA isolate from a community-dwelling human reported previously, was found, suggesting a community origin of CgA. The finding of CgA strains in 15% of the E. coli bloodstream infections with a urinary tract origin in Denmark suggests that CgA constitutes an important clonal lineage among extraintestinal pathogenic E. coli. A reservoir of this pathogenic E. coli group in the community causing not only UTI but also more severe infections such as bacteraemia has implications for public health.     

To test or not: A registry-based observational study of an online decision support for prostate-specific antigen tests

BackgroundWatchful waiting is an essential part in the handling of patients with prostate cancer (PC). More effective disease management may be achieved by this strategy. Correct use of prostate-specific antigen (PSA) test is crucial and the general practitioner (GP) may therefore benefit from access to a clinical decision support system (CDSS) that focuses on this challenge. There are many barriers to the use of CDSSs. The aim of the present paper is to study if such barriers may be overcome by granting GPs easier access to a web-based CDSS via a hyperlink in the GPs’ electronic medical record system (EMR).MethodsIn the present population-based observational registry study with an intervention and control group, we created a web-based CDSS that was made accessible to GPs via hyperlink inserted into the EMR medical chart contents. The intervention was introduced 1 January 2011. Our outcome measure was the number of age-standardised PSA test rates per 1000 men per practice during three equally sized periods of 6 months within the study period from 1 January 2010 to 30 June 2011.ResultsWe found that none of the differences between intervention and control groups were statistically significant.ConclusionsProviding GPs with access to a CDSS to aid their decision to use the PSA, had no measurable effect on the GPs’ PSA testing behaviour.     

Implementation of a Cross-specialty Training Program in Basic Laparoscopy

Background and Objectives:

Several surgical specialties use laparoscopy and share many of the same techniques and challenges, such as entry approaches, equipment, and complications. However, most basic training programs focus on a single specialty. The objective of this study was to describe the implementation of a regional cross-specialty training program for basic laparoscopy, to increase the flexibility of educational courses, and to provide a more efficient use of simulation equipment.

Methods:

Using a regional training program in basic laparoscopy for gynecology as a model, we developed a cross-specialty training program for residents in surgery, gynecology, urology, and thoracic surgery. We reviewed data on training for the first year of the program and evaluated the program by using a scoring system for quality criteria for laparoscopic curricula and skills.

Results:

We held 6 full-day theoretical courses involving 67 residents between September 1, 2013, and August 31, 2014. In the weeks following each course, residents practiced in a self-directed, distributed, and proficiency-based manner at a simulation center and in local hospital departments. A total of 57 residents completed the self-practice and a subsequent practical animal laboratory–based course. The structure of the training program was evaluated according to identified quality criteria for a skills laboratory, and the program scored 38 of a maximum 62 points.

Discussion:

Implementation of a regional cross-specialty training program in basic laparoscopy is feasible. There are several logistic benefits of using a cross-specialty approach; however, it is important that local departments include specialty-specific components, together with clinical departmental follow-up.     

Dabigatran and Warfarin for Secondary Prevention of Stroke in Atrial Fibrillation Patients: A Nationwide Cohort Study

Background

This register-based observational study compares dabigatran to warfarin for secondary stroke prevention in atrial fibrillation patients among both “new starters” on dabigatran and “switchers” to dabigatran from warfarin.

Methods

We identified, in nationwide Danish registries, 2398 patients with atrial fibrillation and a history of stroke/transient ischemic attack, making a first-time purchase of dabigatran 110 mg twice a day (bid; D110) and 150 mg bid (D150). Patients were categorized as either vitamin K antagonist (VKA) naive or experienced. Warfarin controls were identified using a complete (for VKA-naive dabigatran patients) or matched sampling approach (for VKA-experienced dabigatran patients). Subjects were followed for an average of 12.6 months for stroke and transient ischemic attacks. Confounder-adjusted Cox regression models were used to compare event rates between treatments.

Results

Among patients with a history of stroke/transient ischemic attack and prior VKA experience, switching to dabigatran was associated with an increased stroke/transient ischemic attack rate for both dabigatran doses compared with continuing on warfarin (D110 hazard ratio [HR] 1.99; 95% confidence interval [CI], 1.42-2.78; D150 HR 2.34; 95% CI, 1.60-3.41). Among prior stroke/transient ischemic attack patients who were new starters on dabigatran or warfarin, the rate of stroke/transient ischemic attack for both doses of dabigatran was similar to or lower than warfarin (D110 HR 0.64; 95% CI, 0.50-0.80; D150 HR 0.92l; 95% CI, 0.73-1.15).

Conclusions

In this register-based study, VKA-experienced patients with a history of stroke or transient ischemic attack who switched to dabigatran therapy had an increased rate of stroke compared with patients persisting with warfarin therapy.