Evolution in the management of aorta to left ventricular tunnel in a national congenital cardiology centre.

An aorto-ventricular tunnel is a rare congenital cardiac defect, where a channel connects the lumen of the ascending aorta to the left or right ventricle. Four patients presented with an aorto-left ventricular tunnel over two decades at a median age of 8 months (range 0.1-10 months). Two patients (50%) had associated cardiac anomalies including hypoplastic left heart syndrome and left ventricular noncompaction/hypertrophic cardiomyopathy with aortic/pulmonary valve dysplasia in one patient each. Although traditionally surgical treatment has addressed this problem, management has evolved to transcatheter closure with excellent outcomes in appropriately selected patients at our national centre.

Alcohol screening and brief intervention among military service members and veterans: rural-urban disparities.

BACKGROUND: Access to screening, brief intervention and referral to treatment programmes for alcohol use have been shown to be effective; however, little is known about access to these services among service members and veterans. We examined the association of service member or veteran rural-dwelling area and the following outcomes: recent general health check-up, alcohol screening and alcohol brief intervention. METHODS: Data on 5080 military service members and veterans were obtained from the 2017 Behavioural Risk Factor Surveillance System of the USA. We estimated rural-urban disparities in the receipt of a recent voluntary general health check-up, as well as the receipt of alcohol screening and brief intervention, using a mixed logit model. RESULTS: Of the 5080 participants in the study, a total of 4666 (90.49%, 95% CI 89.39% to 91.48%) reported a general health check-up in the last 2 years. Results showed 7.48% of the sample (95% CI 6.64% to 8.41%) exhibited heavy alcohol consumption patterns. Of the 414 participants who did not undergo a general health check-up, 13.80% (95% CI 9.63% to 19.41%) exhibited a pattern of heavy alcohol consumption. Rural individuals were less likely to report a recent health check-up (adjusted OR=0.82, 95% CI 0.79 to 0.87). Rurality was also independently associated with decreased likelihood of receiving an alcohol screening and brief intervention. CONCLUSION: Greater access to telehealth or other geographically flexible screening and brief intervention programmes is needed in rural areas for service members and veterans.

The role of clonal haematopoiesis in cardiovascular diseases: epidemiology and experimental studies.

Clonal haematopoiesis results from acquired mutations in haematopoietic stem and progenitor cells (HSPCs). These mutations can confer the HSPC with a competitive advantage, leading to their clonal expansion within the limiting bone marrow niche. This process is often insufficient to produce a haematologic malignancy; however, the expanding HSPC clones increasingly give rise to progeny leucocytes whose phenotypes can be altered by the somatic mutations that they harbour. Key findings from multiple human studies have shown that clonal haematopoiesis in the absence of overt haematologic alterations is common amongst the ageing population and associated with mortality and cardiovascular disease. Key findings from experimental studies have provided evidence for a causative role for clonal haematopoiesis in cardiovascular diseases, and aspects of these mechanisms have been elucidated. Whilst our understanding of the impact and biology of clonal haematopoiesis is in its infancy, analyses of some of the most commonly mutated driver genes suggest promising clinical scenarios involving the development of personalized therapies with immunomodulatory drugs that exploit the perturbation caused by the particular mutation. Herein, we review the accumulating epidemiological and experimental evidence, and summarize our current understanding of the importance of clonal haematopoiesis as a new causal risk factor for atherosclerotic cardiovascular disease and heart failure.

Leadless Micra Pacemaker Use in the Pediatric Population: Device Implantation and Short-Term Outcomes.

The development of Leadless cardiac pacemakers avoids the inherent complications that may occur secondary to lead insertion. A large number of devices have been inserted in adult patients although data in pediatric patients are lacking. We aimed to assess our experience with the Leadless device in the pediatric population. We performed a retrospective study on all pediatric patients who underwent insertion of a Leadless pacemaker in our center. Data were collected for demographic, procedural, and outcome variables. Nine patients with a median (IQR) age and weight of 13 (12-14) years and 37 (31-50) kg, respectively, were enrolled. The median (IQR) procedural time was 62 (60-65) min with insertion thresholds of 0.5 (0.35-1) Volts at 0.24 ms. All devices were successfully inserted without complication. One device was replaced with a single-lead endocardial pacemaker at 1 year for increased thresholds. Leadless pacemaker device insertion is feasible in pediatric patients. Further studies and long-term follow-up are needed to ascertain device longevity and complication rates.

Polypharmacy Rates among Patients over 45 years

Polypharmacy, defined as receipt of ≥5 medications in any one month, is often associated with potentially inappropriate prescribing and adverse drug interactions. High levels of polypharmacy have been observed internationally and in Ireland. The Health Service Executive Primary Care Reimbursement Services (HSE-PCRS) pharmacy claims database for the GMS eligible population was used. We conducted Chi-square tests to determine the statistical significance of perceived differences in medication use among patients aged ³ 45 years. Our results establish a national benchmark for polypharmacy in gender and various age categories in the HSE-PCRS. Of the 794,628 individuals aged ≥45 years with at least one claim in 2013, 64.3% (510,946) had polypharmacy, with higher rates among women (67.0% - 293,886 - compared to 60.8% of men - 216,444). Patients aged 45-54 years were less likely to have polypharmacy (38.6% - 69,934) compared to those aged 75 years old (82.6% - 197,565). The high levels of polypharmacy are of interest, and suggest that monitoring and evaluation of patients' medication regimes may be required to ensure appropriateness.

Transcatheter Mitral Valve-in-Ring Implantation.

Failed surgical mitral valve repair using an annuloplasty ring has traditionally been treated with surgical valve replacement or repair1. For patients at high risk for repeat open heart surgery, placement of a trans-catheter aortic valve (i.e., TAVI valve) within the mitral ring (i.e., Mitral-Valve-in-Ring, MViR) has emerged as a novel alternative treatment strategy2-5 . We describe our experience of a failed mitral valve repair that was successfully treated with a TAVI valve delivered via the trans-septal approach, and summarise the data relating to this emerging treatment strategy.

ALK immunohistochemistry is highly sensitive and specific for the detection of ALK translocated lung adenocarcinomas: lessons from an audit of lung cancer molecular testing.

Background The approval of novel targeted treatments for epidermal growth factor receptor (EGFR)-positive and anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer has led to the increased requirement for mutation testing. Results We report our experience of ALK testing with immunohistochemistry (IHC) and fluorescence in-situ hybridisation (FISH) and present the prevalence of EGFR, Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) and ALK mutations. From January 2011 to May 2014, we found mutation rates of EGFR, KRAS and ALK to be 10.4% (67/643), 35.8% (86/240) and 2.3% (7/304), respectively. ALK-rearrangements were found to be associated with never smokers (p < 0.001) and younger patients (≤ 50 years old) (p < 0.001). ALK IHC protein expression in tumour cells is 100% sensitive (7 IHC+/7 FISH+) and 96.6% specific (113 IHC-/117 FISH-) for ALK-rearrangements by FISH. ALK-rearranged tumours were wildtype for EGFR and KRAS. Conclusion Our findings support the use of ALK protein expression and KRAS mutation testing as part of the molecular diagnostic algorithm for lung adenocarcinomas.

Sub-cellular In-situ Characterization of Ferritin(iron) in a Rodent Model of Spinal Cord Injury.

Iron (Fe) is an essential metal involved in a wide spectrum of physiological functions. Sub-cellular characterization of the size, composition, and distribution of ferritin(iron) can provide valuable information on iron storage and transport in health and disease. In this study we employ magnetic force microscopy (MFM), transmission electron microscopy (TEM), and electron energy loss spectroscopy (EELS) to characterize differences in ferritin(iron) distribution and composition across injured and non-injured tissues by employing a rodent model of spinal cord injury (SCI). Our biophysical and ultrastructural analyses provide novel insights into iron distribution which are not obtained by routine biochemical stains. In particular, ferritin(iron) rich lysosomes revealed increased heterogeneity in MFM signal from tissues of SCI animals. Ultrastructural analysis using TEM elucidated that both cytosolic and lysosomal ferritin(iron) density was increased in the injured (spinal cord) and non-injured (spleen) tissues of SCI as compared to naïve animals. In-situ EELs analysis revealed that ferritin(iron) was primarily in Fe3+ oxidation state in both naïve and SCI animal tissues. The insights provided by this study and the approaches utilized here can be applied broadly to other systemic problems involving iron regulation or to understand the fate of exogenously delivered iron-oxide nanoparticles.

Buccal mucosa micronuclei counts in relation to exposure to low dose-rate radiation from the Chornobyl nuclear accident and other medical and occupational radiation exposures.

BACKGROUND: Ionizing radiation is a well-known carcinogen. Chromosome aberrations, and in particular micronuclei represent an early biological predictor of cancer risk. There are well-documented associations of micronuclei with ionizing radiation dose in some radiation-exposed groups, although not all. That associations are not seen in all radiation-exposed groups may be because cells with micronuclei will not generally pass through mitosis, so that radiation-induced micronuclei decay, generally within a few years after exposure. METHODS: Buccal samples from a group of 111 male workers in Ukraine exposed to ionizing radiation during the cleanup activities at the Chornobyl nuclear power plant were studied. Samples were taken between 12 and 18 years after their last radiation exposure from the Chornobyl cleanup. The frequency of binucleated micronuclei was analyzed in relation to estimated bone marrow dose from the cleanup activities along with a number of environmental/occupational risk factors using Poisson regression adjusted for overdispersion. RESULTS: Among the 105 persons without a previous cancer diagnosis, the mean Chornobyl-related dose was 59.5 mSv (range 0-748.4 mSv). There was a borderline significant increase in micronuclei frequency among those reporting work as an industrial radiographer compared with all others, with a relative risk of 6.19 (95% CI 0.90, 31.08, 2-sided p = 0.0729), although this was based on a single person. There was a borderline significant positive radiation dose response for micronuclei frequency with increase in micronuclei per 1000 scored cells per Gy of 3.03 (95% CI -0.78, 7.65, 2-sided p = 0.1170), and a borderline significant reduction of excess relative MN prevalence with increasing time since last exposure (p = 0.0949). There was a significant (p = 0.0388) reduction in MN prevalence associated with bone X-ray exposure, but no significant trend (p = 0.3845) of MN prevalence with numbers of bone X-ray procedures. CONCLUSIONS: There are indications of increasing trends of micronuclei prevalence with Chornobyl-cleanup-associated dose, and indications of reduction in radiation-associated excess prevalence of micronuclei with time after exposure. There are also indications of substantially increased micronuclei associated with work as an industrial radiographer. This analysis adds to the understanding of the long-term effects of low-dose radiation exposures on relevant cellular structures and methods appropriate for long-term radiation biodosimetry.

Rare case of accidental fire and burns caused by e-cigarette batteries.

E-cigarettes have become very popular among adult smokers, and many users carry e-cigarette devices and their components on their person. We present a case of a 35-year-old man who was admitted to our regional burns unit after his clothing was set-alight following the self-combustion of an e-cigarette lithium battery that was in his pocket. The patient had sustained a 1.5% mixed depth burn to the lateral aspect of his right thigh. Ward debridement under local anaesthetic was performed to remove clothing residue and reduce the risk of tattooing. Following conservative management with outpatient dressings, the burn wound healed by day 56.

Effectiveness of the STOPP/START (Screening Tool of Older Persons' potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right Treatment) criteria: systematic review and meta-analysis of randomized controlled studies.

WHAT IS KNOWN AND OBJECTIVE: STOPP/START are explicit screening tools that identify potentially inappropriate prescribing in older adults. Our objective was to update our 2013 systematic review that showed limited evidence of impact, using new evidence from randomized controlled trials (RCTs) assessing clinical, humanistic and economic outcomes in older adults. METHODS: We performed a search of PubMed, EMBASE, CINAHL, Web of Science and grey literature for RCTs published in English since the previous review through June 2014. The Cochrane Risk of Bias Tool was used. We performed a meta-analysis on the effect of STOPP on potentially inappropriate medication (PIM) rates and a narrative synthesis on other outcomes. RESULTS AND DISCUSSION: Four RCTs (n = 1925 adults) from four countries were included, reporting both acute (n = 2) and long-term care (n = 2) patients. Studies differed in implementation. Two studies were judged to have low risk, and two to have moderate-to-high risk of bias in key domains. Meta-analysis found that the STOPP criteria reduced PIM rates in all four studies, but study heterogeneity (I(2) = 86·7%) prevented the calculation of a meaningful statistical summary. We found evidence that use of the criteria reduces falls, delirium episodes, hospital length-of-stay, care visits (primary and emergency) and medication costs, but no evidence of improvements in quality of life or mortality. WHAT IS NEW AND CONCLUSION: STOPP/START may be effective in improving prescribing quality, clinical, humanistic and economic outcomes. Additional research investigating these tools is needed, especially in frail elderly and community-living patients receiving primary care.

Pattern of Change in Renal Function Following Radical Nephrectomy for Renal Cell Carcinoma.

Radical nephrectomy (RN) is an independent risk factor for the development of chronic kidney disease (CKD) in those with renal cell carcinoma (RCC). We aimed to examine the pattern of change in post-operative renal function in patients who underwent RN for RCC over a 3 year period at our institution. We performed a retrospective review of histological and biochemical findings in patients undergoing RN for RCC over a 38 month period. Estimated glomerular filtration rate (eGFR) was recorded pre- and post-operatively and at follow-up. We analysed data on 131 patients (median follow-up 24 months). The proportion of patients with advanced CKD increased significantly at follow-up with 48 (85.7%) patients, classified as having stage 2 CKD pre-operatively, being re-classified as stage 3-5. Mean eGFR was significantly lower pre-operatively (76.6 mL/min/1.73 m2) compared to hospital discharge (61 mL/min/1.73 m2, p < 0.001) and follow-up (55.5 mL/min/1.73 m2, p < 0.001). Those with pT1 tumours sustained a significantly greater decline in eGFR compared to other stages. In conclusion, patients with pT1 a and pT1 b tumours sustain a disproportionate decline in renal function and may benefit the most from NSS.

Late outcomes in adults with coarctation of the aorta.

AIMS: Previous cohort studies of patients with coarctation of the aorta (CoA) demonstrate reduced long-term survival. Improved surgical outcomes in children and evolution of adult congenital heart disease (ACHD) services have resulted in improved survival in patients with other CHDs. We hypothesise that for young adult patients with CoA long-term outcomes have improved in the contemporary era. METHODS: 151 patients (58% men) with simple CoA followed up at a tertiary ACHD service in Sydney, Australia, from 1993 to 2013 were included. We documented mortality and major morbidity such as the need for re-intervention for re-coarctation or aneurysms. RESULTS: 140 patients (mean age 35±15 years) underwent CoA repair at median age of 5 (IQR 0-10) years. Initial surgical strategy included end-to-end repair in 43, subclavian flap aortoplasty in 28 and patch aortoplasty in 31 patients (and was not documented in 28 cases). 6 patients had endovascular repair, 4 had interposition tube grafts and 11 were unrepaired. There were a total of seven deaths at a median age of 60 years. Actuarial survival was 98% at 40, 98% at 50 and 89% at 60 years of age. Re-coarctation occurred in 34% and descending aortic aneurysms were noted in 18%. Patients with end-to-end repair had lower rates of significant re-coarctation or descending aortic aneurysms (p=0.026 and <0.001, respectively). 66% had bicuspid aortic valve and 44% were hypertensive. CONCLUSIONS: Patients with CoA who reach adolescence demonstrate very good long-term survival up to age 60 years. Long-term morbidity is common, however, related largely to aortic complications and late hypertension.

Prostate cancer risk assessment tools in an unscreened population.

OBJECTIVE: To compare the prostate cancer prevention trial risk calculator (PCPT-RC) and European randomized study of screening for prostate cancer risk calculator (ERSPC-RC) in a unique unscreened population from the West of Ireland. PATIENTS AND METHODS: Data was prospectively recorded for all 556 consecutive men who underwent prostate biopsy at our institution as part of the Rapid Access Prostate Assessment Clinic program in Ireland. The estimated probabilities of detecting prostate cancer and high-grade disease were calculated using the PCPT and ERSPC risk calculators. For each calculator the discriminative ability, calibration and clinical utility was assessed. RESULTS: Prostate cancer was detected in 49% and high-grade prostate cancer in 34% of men. Receiver operating characteristic curve analysis demonstrated that the PCPT-RCs outperformed the ERSPC-RCs for the prediction of prostate cancer areas underneath the ROC curve (AUC 0.628 vs. 0.588, p = 0.0034) and for the prediction of high-grade prostate cancer (AUC 0.792 vs. 0.690, p = 0.0029). Both risk calculators generally over-predicted the risk of prostate cancer and high-grade disease across a wide range of predicted probabilities. Decision curve analysis suggested greater net benefit using the PCPT-RCs in this population. CONCLUSIONS: Multivariable nomograms can further aid patient counselling for early prostate cancer detection. In unscreened men from Western Ireland, the PCPT-RCs provided better discrimination for overall prostate cancer and high-grade disease compared to the ERSPC-RC. However, both tools overpredicted the risk of cancer detection on biopsy, and it is possible that a different set of predictive variables may be more useful in this population.

Cost and value in medical education--what we can learn from the past.

What lessons can be learned from the history of cost and value in medical education? First, the issue of cost and value in medical education has been around for a long time. Rising costs and an economic recession have made us focus on the subject more, but the issue has been just below the surface for over 200 years. A problem like this will not go away by itself - we must tackle it now. Second, the history of cost and value in medical education makes us look critically at who should pay. Should it be students, institutions or governments? We can see from the past that several different models have been tried; that all have their advantages and disadvantages; and that none are perfect. Third, looking at the past should make us realise that the issue of cost in medical education cannot be viewed in isolation. Medical educators throughout history have looked at how cost can affect selection for medical school, how costs can be related to benefits, and the effect of rising costs on career choices. Cost in medical education has always had far reaching consequences and implications. It probably always will. Looking at issues in medical education from the perspective of cost often makes them more stark and explicit - this in turn may help us to start to find solutions. In the future our solutions must be evidence based and must take account of cost.

Differences in parent and teacher rating of everyday executive function in pediatric brain tumor survivors.

We aimed to compare executive function (EF) outcomes in pediatric brain tumor (BT) survivors compared with healthy children (HC) across multiple settings. This retrospective cross-sectional study of BT survivors and age- and gender-matched HC analyzed scale patterns of parent and teacher ratings of EF (Behavior Ratings of Executive Function; BRIEF). We also analyzed relationships between groups and raters (parent/teacher) and clinical elevations across EF domains on the BRIEF. Group differences in aspects of EF emerged from parent ratings in working memory (WM), while significant interactions from teacher ratings emerged on nearly all EF scales. Parents reported impaired cognitive/behavioral flexibility in the BT group four times more than parents of HC. Teachers rated survivors significantly more poorly as a group on the majority of EF domains, and indicated clinical impairment in cognitive/behavioral flexibility, emotional regulation, self-starting/initiation, WM, and planning and organization (P/O) four to ten times more often than the teachers of HC. Overall, teacher ratings of EF impairment in pediatric BT survivors were significantly greater than parent ratings, who reported far fewer EF problems. Possible explanations for inter-rater discrepancies include potential reporting bias/response shift in parents and/or differences in EF demands across settings.

A cautionary lesson on the use of targeted methods for EGFR mutation analysis: a case report.

Epidermal growth factor receptor (EGFR) mutation analysis is recommended for lung cancer patients prior to the prescription of first-line EGFR tyrosine kinase inhibitors in order to predict response to treatment. There are many methods available to identify mutations in the EGFR gene; a large number of clinical laboratories use the therascreen EGFR RGQ PCR kit (Qiagen). We report a case where this kit detected an exon 19 deletion, predicting sensitivity to tyrosine kinase inhibitors (TKIs), which on further analysis was found to be a 2 bp indel (c.2239_2240delinsCC, p.(Leu747Pro)). Two of four published cases with this mutation were found to be associated with resistance to EGFR TKI. The sample was also tested using two other commercial kits, one of which indicated a deletion. This is a rare mutation making the erroneous detection of a deletion unlikely; however, it is important that clinical laboratories are aware of the potential failings of two commercial kits for EGFR mutation analysis.

Audit of rapid access introduction reveals high prevalence of prostate cancer in Western Region.

INTRODUCTION: Men with symptoms suggestive of prostate cancer are now directly referred by their general practitioners to rapid access prostate assessment clinics (RAPACs). This service implements recommendations outlined by the National Cancer Control Programme. The RAPAC was introduced at Galway University Hospital, Galway, Ireland in June 2009, aiming to structure GP referral of patients with suspected prostate cancer to a urology service. AIMS: The aims of this study are to assess our initial experience with particular emphasis on access times, patient demographics, detection rates and treatment outcomes. METHODS: Data on all patients presenting to the RAPAC during the preliminary 2-year period have been gathered prospectively and analysed using standard parametric analysis methods. RESULTS: A total of 1,106 patients were reviewed at 278 clinic sessions during the initial 2-year period. The average waiting time to first clinic visit was 18 days (12-39 days). The mean age of referral to the clinic is 65 years (44-88 years). The mean PSA is 16.31 g/dL (0.4-845 g/dL). Of the 1106 patients undergoing TRUS biopsies, 503 (45.5 %) patients were diagnosed with prostate cancer. Further analysis patient demographics and cancer grading is presented in the article. Seventy-one patients (14.1 %) underwent radical retropubic prostatectomy. Sixty-seven patients (13.3 %) are being followed on an active monitoring programme, whilst 235 (56.7 %) received primary treatment with external beam radiotherapy and 68 (13.5 %) received brachytherapy. CONCLUSION: This data highlight the necessity of a RAPAC to streamline the provision of prostate cancer services in the west of Ireland.