BMJ Journals Subject Collection: Open access

Network and satellite arrangements in liver disease [LIVER]

O'Grady, J. G. — 2013-07-01

Liver disease has evolved into a complex discipline with several tiers of service delivery. Patients' needs vary at different phases of their disease, with mobility between local hospitals and specialist centres being increasingly common. Liver transplantation requirements serve as a good illustration of this fluidity and the need for service providers to coordinate care delivery. This is facilitated by the development of networks and satellite relationships that can range in complexity and functionality.

Impact of UK Medical Eligibility Criteria implementation on prescribing of combined hormonal contraceptives [ARTICLE]

Briggs, P. E. — 2013-07-01

ObjectivesCombined hormonal contraceptives (CHCs) are the most widely prescribed contraceptive methods in the UK; however, their use is associated with significant cardiovascular risk for women with some medical conditions and risk factors. The objective of this study was to assess the potential change in CHC prescribing among higher-risk women following publication of the UK Medical Eligibility Criteria for Contraceptive Use (UKMEC) in 2006. MethodsA cross-sectional study was conducted using the General Practice Research Database to analyse UK women aged 15-49 years who were prescribed CHCs during the period 2004-2010. Of women prescribed CHCs, those at higher risk of cardiovascular events (with UKMEC Category 3 or 4 risk factors) were identified. The percentage of higher-risk CHC users, among all CHC users, in 2005 (pre-UKMEC) was compared to that in 2010 (post-UKMEC). ResultsThe percentage of higher-risk CHC users significantly decreased by 0.8% (95% CI 0.68% to 1.02%) following publication of UKMEC [8.1% (95% CI 7.98% to 8.22%) in 2005 vs 7.3% (95% CI 7.14% to 7.38%) in 2010; p<0.001]. However, an estimated 1 74 472 women in the UK were prescribed CHCs in 2010 despite having Category 3 or 4 risk factors. The most common Category 3 or 4 risk factors were body mass index [≥]35 kg/m2, hypertension and smoking in women aged [≥]35 years. ConclusionsDespite the observed reduction in prescribing of CHCs to higher-risk women after publication of UKMEC, a large number of women with Category 3 or 4 risk factors are still prescribed CHCs. The increased risk of cardiovascular events is unnecessary for many of these women given the availability of alternative contraceptive methods.

Endoscopic retrograde cholangiopancreatography: is the centre better? The case against centralisation of ERCP services [ENDOSCOPY]

Muller, A. F. — 2013-07-01

More than 48 000 endoscopic retrograde cholangiopancreatographies (ERCP) are performed in the UK per annum; the majority within district general hospitals. The proposal for centralisation of ERCP services is based on evidence that technical success, length of stay and complication rates are related to the numbers of procedures performed. Local units wishing to continue their ERCP practice, must demonstrate that they are performing sufficient numbers of procedures in a safe, timely and competent fashion.

Hemorrhagic complications after prasugrel (Effient) therapy for vascular neurointerventional procedures [HEMORRHAGIC STROKE]

Akbari, S. H. — 2013-07-01

IntroductionDual antiplatelet therapy (DAPT) with aspirin and a thienopyridine (eg, clopidogrel) prevents stent related thromboembolic events in cardiac patients and is frequently utilized during neurointerventional surgery. However, recent data suggest that many patients exhibit clopidogrel resistance. Prasugrel--a newer thienopyridine--lowers the rate of cardiac stent thromboses in clopidogrel non-responders but a paucity of data exist regarding its safety and efficacy in neurointerventional surgery. MethodsAll patients undergoing neurointerventional surgery by a single interventionalist (CJM) over a 20 month period were retrospectively identified. Charts were reviewed for pre- and post-procedural DAPT regimens, pre-procedural coagulation parameters and procedural complications. Results76 patients received pre- and post-procedural DAPT for endovascular treatment of an intracerebral aneurysm, dural arteriovenous fistula or intra/extracranial arterial stenosis. 51 patients underwent 55 total procedures and were treated with aspirin/clopidogrel; 25 patients underwent 31 total procedures and were treated with aspirin/prasugrel. Those patients who received aspirin/prasugrel DAPT were identified pre-procedurally to be clopidogrel non-responders. Both treatment groups had a similar percentage of patients undergoing aneurysm coiling, stent assisted aneurysm coiling, aneurysm Onyx embolization, aneurysm pipeline embolization device treatment, extra/intracranial carotid artery angioplasty and stenting, and dural arteriovenous fistula coil embolization. A total of eight (9.3%) hemorrhagic complications were observed, two (3.6%) in the aspirin/clopidogrel group and six (19.4%) in the aspirin/prasugrel group (p=0.02). No differences were noted in hemorrhage rates for each procedure between treatment groups, nor were there any differences in thrombotic complications between groups. ConclusionOur results suggest that DAPT with aspirin/prasugrel may predispose to a higher risk of hemorrhage during neurointerventional surgery compared with DAPT with aspirin/clopidogrel.

Novel aneurysm neck reconstruction device: initial experience in an experimental preclinical bifurcation aneurysm model [NEW DEVICES]

Turk, A. — 2013-07-01

IntroductionTreatment of wide-necked bifurcation aneurysms often poses procedural and long-term outcome challenges. The initial preclinical experience with the Pulsar Vascular Aneurysm Neck Reconstruction Device (PVANRD) in a canine bifurcation model is described. MethodsExperimental bifurcation vein pouch aneurysms were surgically created in the carotid arteries of eight dogs. Endovascular coiling of the aneurysms with assistance of the PVANRD was performed in all cases with acute performance compared with Y-stenting. ResultsTwelve devices were deployed in the eight cases. Deployment of the devices was straightforward and successfully protected the parent artery and maintained patency of the bifurcation in all cases, despite the use of oversized coils. ConclusionThe PVANRD is a novel bifurcation stent that facilitates treatment of wide-necked bifurcation aneurysms compared with currently available adjunctive devices.

Clinical and molecular characterisation of hyperinsulinaemic hypoglycaemia in infants born small-for-gestational age [SHORT RESEARCH REPORTS]

Arya, V. B. — 2013-07-01

ObjectiveTo characterise the phenotype and genotype of neonates born small-for-gestational age (SGA; birth weight <10th centile) who developed hyperinsulinaemic hypoglycaemia (HH). MethodsClinical information was prospectively collected on 27 SGA neonates with HH, followed by sequencing of KCNJ11 and ABCC8. ResultsThere was no correlation between the maximum glucose requirement and serum insulin levels. Serum insulin level was undetectable in five infants (19%) during hypoglycaemia. Six infants (22%) required diazoxide treatment >6 months. Normoglycaemia on diazoxide <5 mg/kg/day was a safe predictor of resolved HH. Sequencing of KCNJ11/ABCC8 did not identify any mutations. ConclusionsSerum insulin levels during hypoglycaemia taken in isolation can miss the diagnosis of HH. SGA infants may continue to have hypofattyacidaemic hypoketotic HH beyond the first few weeks of life. Recognition and treatment of this group of patients are important and may have important implications for neurodevelopmental outcome of these patients.

Republished: Non-heritable genetics of human disease: spotlight on post-zygotic genetic variation acquired during lifetime [REPUBLISHED REVIEW]

Forsberg, L. A. — 2013-07-01

The heritability of most common, multifactorial diseases is rather modest and known genetic effects account for a small part of it. The remaining portion of disease aetiology has been conventionally ascribed to environmental effects, with an unknown part being stochastic. This review focuses on recent studies highlighting stochastic events of potentially great importance in human disease--the accumulation of post-zygotic structural aberrations with age in phenotypically normal humans. These findings are in agreement with a substantial mutational load predicted to occur during lifetime within the human soma. A major consequence of these results is that the genetic profile of a single tissue collected at one time point should be used with caution as a faithful portrait of other tissues from the same subject or the same tissue throughout life. Thus, the design of studies in human genetics interrogating a single sample per subject or applying lymphoblastoid cell lines may come into question. Sporadic disorders are common in medicine. We wish to stress the non-heritable genetic variation as a potentially important factor behind the development of sporadic diseases. Moreover, associations between post-zygotic mutations, clonal cell expansions and their relation to cancer predisposition are central in this context. Post-zygotic mutations are amenable to robust examination and are likely to explain a sizable part of non-heritable disease causality, which has routinely been thought of as synonymous with environmental factors. In view of the widespread accumulation of genetic aberrations with age and strong predictions of disease risk from such analyses, studies of post-zygotic mutations may be a fruitful approach for delineation of variants that are causative for common human disorders.

An X chromosome-wide association analysis identifies variants in GPR174 as a risk factor for Graves' disease [COMPLEX TRAITS]

Chu, X. — 2013-07-01

BackgroundGraves' disease is a female preponderant autoimmune illness and the contribution of the X chromosome to its risk has long been appreciated. However, no X-linked susceptibility loci have been indentified from recent genome-wide association studies (GWAS). MethodsWe re-examined the X chromosome data from our recent GWAS for Graves' disease by including males that were previously excluded from the X chromosome analyses. The data were analysed using logistic regression analysis including sex as a covariate, and an additive method assuming X chromosome inactivation, implemented in snpMatrix. ResultsA cluster of single nucleotide polymorphism (SNPs) at Xq21.1 was found showing association with genome-wide significance, among which rs3827440 was a non-synonymous SNP of GPR174 (Plogistic regression= 9.52x10-8; PsnpMatrix=4.60x10-9; OR=1.76, 95% CI 1.45 to 2.13). The association was reproduced in an independent sample collection set including 4564 Graves' disease cases and 3968 sex matched controls (combined Plogistic regression=5.53x10-21; combined PsnpMatrix=4.26x10-22; OR=1.69, 95% CI 1.53 to 1.86). Notably, GPR174 was widely expressed in immune related tissues and rs3827440 genotypes were associated with distinct mRNA levels (p=0.002). GPR174 did not show sex biased gene expression in our expression analysis. Resequencing study suggested the contribution of some rare variants in the GPR174 gene region to disease risk with a collapsing p value of 1.16x10-3. ConclusionsThe finding of an X-linked risk locus for Graves' disease expands our understanding of the role of the X chromosome in disease susceptibility.

Identification of doctors at risk of recurrent complaints: a national study of healthcare complaints in Australia [ORIGINAL RESEARCH]

Bismark, M. M. — 2013-07-01

Objectives(1) To determine the distribution of formal patient complaints across Australia's medical workforce and (2) to identify characteristics of doctors at high risk of incurring recurrent complaints. MethodsWe assembled a national sample of all 18 907 formal patient complaints filed against doctors with health service ombudsmen ( Commissions') in Australia over an 11-year period. We analysed the distribution of complaints among practicing doctors. We then used recurrent-event survival analysis to identify characteristics of doctors at high risk of recurrent complaints, and to estimate each individual doctor's risk of incurring future complaints. ResultsThe distribution of complaints among doctors was highly skewed: 3% of Australia's medical workforce accounted for 49% of complaints and 1% accounted for a quarter of complaints. Short-term risks of recurrence varied significantly among doctors: there was a strong dose-response relationship with number of previous complaints and significant differences by doctor specialty and sex. At the practitioner level, risks varied widely, from doctors with <10% risk of further complaints within 2 years to doctors with >80% risk. ConclusionsA small group of doctors accounts for half of all patient complaints lodged with Australian Commissions. It is feasible to predict which doctors are at high risk of incurring more complaints in the near future. Widespread use of this approach to identify high-risk doctors and target quality improvement efforts coupled with effective interventions, could help reduce adverse events and patient dissatisfaction in health systems.

Recurrent life-threatening sepsis in intestinal failure: transplantation or foster care? [CASE REPORT]

Zamvar, V. — 2013-07-01

Parenteral nutrition has transformed the outlook for patients with intestinal failure, but is associated with serious long-term complications, including catheter-related blood stream infection, liver disease and loss of venous access. Risks can be significantly reduced by strict adherence to management regimens, such as catheter-care protocols, but intestinal transplantation is indicated when complications threaten survival. The responsibility of home parenteral nutrition as an alternative to long-term hospitalisation is welcomed by many parents, but represents a huge burden of care that sometimes proves beyond their capacity. We report two children with recurrent life-threatening central venous catheter infections who were removed from the intestinal transplant list following virtual cessation of infective episodes after going into foster care. These cases raise important issues about the level of family support offered, the role of non-compliance with treatment routines in relation to risk of complications, and how this should be assessed and monitored.