Renal Denervation as a Complementary Treatment Option for Uncontrolled Arterial Hypertension: A Situation Assessment.

Uncontrolled arterial hypertension is a major global health issue. Catheter-based renal denervation has shown to lower blood pressure in sham-controlled trials and represents a device-based, complementary treatment option for hypertension. In this situation assessment, the authors, who are practicing experts in hypertension, nephrology, general practice and cardiology in the Republic of Ireland, discuss the current evidence base for the BP-lowering efficacy and safety of catheter-based renal denervation with different modalities. Although important questions remain regarding the identification of responders, and long-term efficacy and safety of the intervention, renal denervation has the potential to provide much-needed help to address hypertension and its adverse consequences. The therapeutic approach needs to be multidisciplinary and personalised to take into account the perspective of patients and healthcare professionals in a shared decision-making process.

What do we mean by complex percutaneous coronary intervention? An assessment of agreement amongst interventional cardiologists for defining complexity.

BACKGROUND: In the last decade, percutaneous coronary intervention (PCI) has evolved toward the treatment of complex disease in patients with multiple comorbidities. Whilst there are several definitions of complexity, it is unclear whether there is agreement between cardiologists in classifying complexity of cases. Inconsistent identification of complex PCI can lead to significant variation in clinical decision-making. AIM: This study aimed to determine the inter-rater agreement in rating the complexity and risk of PCI procedures. METHOD: An online survey was designed and disseminated amongst interventional cardiologists by the European Association of Percutaneous Cardiovascular Intervention (EAPCI) board. The survey presented four patient vignettes, with study participants assessing these cases to classify their complexity. RESULTS: From 215 respondents, there was poor inter-rater agreement in classifying the complexity level (k = 0.1) and a fair agreement (k = 0.31) in classifying the risk level. The experience level of participants did not show any significant impact on the inter-rater agreement of rating the complexity level and the risk level. There was good level of agreement between participants in terms of rating 26 factors for classifying complex PCI. The top five factors were (1) impaired left ventricular function, (2) concomitant severe aortic stenosis, (3) last remaining vessel PCI, (4) requirement fort calcium modification and (5) significant renal impairment. CONCLUSION: Agreement among cardiologists in classifying complexity of PCI is poor, which may lead to suboptimal clinical decision-making, procedural planning as well as long-term management. Consensus is needed to define complex PCI, and this requires clear criteria incorporating both lesion and patient characteristics.

High rates of the SDHB p.Arg46Gln pathogenic variant predisposes New Zealand Maori to phaeochromocytoma/paraganglioma.

BACKGROUND: Phaeochromocytomas (PCC) and paragangliomas (PGL; together PPGL) are rare tumours of the adrenal medulla or extra-adrenal paraganglia. They may secrete catecholamines with significant cardiovascular effects. Management of PPGL is predominantly surgical, despite the anaesthetic risks related to potential haemodynamic instability. Meticulous pre-treatment and intra-operative management are required to improve cardiovascular outcomes. AIMS: There are limited local data regarding the incidence of PPGL and the clinical characteristics of individuals diagnosed with these tumours in New Zealand. We undertook a retrospective study investigating the local practice and patient characteristics with an additional focus on intra-operative haemodynamic stability and post-operative outcomes. METHODS: Electronic patient records were searched for individuals with a diagnosis of PPGL. Clinical records and electronic databases were interrogated for pre-operative, intra-operative and post-operative data points. Particular attention was paid to rates and types of germline mutations, intra-operative haemodynamic stability and post-operative renal and cardiovascular outcomes. RESULTS: We identified 49 individuals with PPGL, of whom 34 were from the local area. This gave a local incidence of PPGL of around five cases per million people per year. Maori were significantly over-represented in our cohort, with this being in part due to high rates of the SDHB R46Q mutation. Over 95% of our cohort met pre-specified pre-operative blood pressure parameters. Intra-operative monitoring revealed a tendency to hypotension, but this did not translate into adverse post-operative outcomes, which were infrequent. CONCLUSIONS: Maori were over-represented due to high rates of germline SDHB R46Q mutations. There were few post-operative adverse outcomes in this contemporary cohort.

Pilot study to test the safety, tolerability and feasibility of dulaglutide during a low-energy diet for weight loss and improved glycaemic control.

Introduction: Diabetes and obesity are significant public health concerns. Previous studies have demonstrated that low energy diets are effective in promoting weight loss and inducing diabetes remission. However, hunger is a potential barrier to adherence for such diets.Dulaglutide is a glucagon-like peptide receptor agonist used in diabetes treatment. Its use is associated with weight loss, partly through increased satiety. The use of dulaglutide may improve adherence to a low energy diet through a reduction in hunger. We undertook a pilot study to assess the safety, tolerability and feasibility of this combination in individuals with obesity and type 2 diabetes. Research design and methods: We enrolled individuals with type 2 diabetes and obesity from a tertiary diabetes service in Auckland, New Zealand. Owing to their higher rates of diabetes and poorer diabetes-related health outcomes, we preferentially enrolled Maori and Pacific individuals.Participants underwent 2 weeks of dulaglutide run-in followed by 12 weeks of the combination of dulaglutide and low energy diet. The primary endpoints were the proportion of people successfully completing the dietary intervention and the rates and types of adverse events. Secondary outcomes were changes in weight, glycaemic control, quality of life and biochemical parameters. Results: The intervention was well tolerated. Mild side effects were common during the first 2 weeks of the intervention but generally improved over the study period. Eighty-nine per cent of participants completed the 12-week dietary intervention. Participants achieved an average weight loss of 9.5 kg and a mean reduction in haemoglobin A1c of 15.8 mmol/mol. Quality of life metrics were unchanged. Conclusions: We conclude that the combination of dulaglutide and a low energy diet is a feasible and well-tolerated intervention for individuals with diabetes and increased body weight. Future studies could be performed assessing this combination against a low energy diet alone. Trial registration number: This study was registered with the Australia New Zealand Clinical Trials Registry (ACTRN1262200015279p).

Tumour-induced osteomalacia due to a durally-based intracranial phosphaturic mesenchymal tumour.

A man in his 40s was referred with persistent hypophosphataemia and bony pain. A serum fibroblast growth factor 23 level was markedly elevated and a diagnosis of tumour-induced osteomalacia was considered. Whole body imaging revealed multiple insufficiency fractures but no osseus tumours. There was, however, a durally-based intracranial lesion whose imaging characteristics were consistent with a meningioma. The tumour was removed, leading to rapid normalisation of the patient's symptoms and serum markers. Histology confirmed a phosphaturic mesenchymal tumour. We review the literature regarding this rare clinical situation.

Mortality after discharge from hospital following an episode of diabetic ketoacidosis.

AIMS: The rate of inpatient mortality associated with diabetic ketoacidosis (DKA) has steadily decreased in recent decades. However, there remains a significantly increased outpatient death rate following an episode of survived DKA. We undertook this study to investigate the observed increase in mortality following an episode of DKA. METHODS: We completed a retrospective cohort study to investigate rates and causes of death in people admitted to our hospital with DKA between 2013 and 2018. DKA was confirmed by pre-defined biochemical parameters and cause of death data was extracted from multiple sources. Follow-up was for two years after discharge for all participants with one-year mortality being the main time point for analysis. RESULTS: We identified 818 admissions to hospital with DKA, affecting 284 people. Twenty people died as inpatients and a further 40 people died during the two-year follow-up. Of these 60 participants, cause of death was able to be determined for 41 (68%), with most deaths occurring due to infection or macrovascular disease. Risk factors for death within a year of hospital discharge included older age, vascular complications of diabetes, intellectual impairment and residential care living. Those who survived an episode of DKA had a one-year age-corrected mortality rate 13 times higher than the general population. This was more marked in the younger cohort with those aged 15-39 years being 49 times more likely to die in the year after surviving a DKA admission compared to their general population counterparts. CONCLUSION: An episode of diabetic ketoacidosis is associated with a significant outpatient mortality risk with most deaths due to infectious or macrovascular causes. This study should prompt investigation of predictive scoring tools to identify those at increased mortality risk after DKA and encourage the development of targeted interventions to reduce mortality.

Human-Computer Agreement of Electrocardiogram Interpretation for Patients Referred to and Declined for Primary Percutaneous Coronary Intervention: Retrospective Data Analysis Study.

BACKGROUND: When a patient is suspected of having an acute myocardial infarction, they are accepted or declined for primary percutaneous coronary intervention partly based on clinical assessment of their 12-lead electrocardiogram (ECG) and ST-elevation myocardial infarction criteria. OBJECTIVE: We retrospectively determined the agreement rate between human (specialists called activator nurses) and computer interpretations of ECGs of patients who were declined for primary percutaneous coronary intervention. METHODS: Various features of patients who were referred for primary percutaneous coronary intervention were analyzed. Both the human and computer ECG interpretations were simplified to either "suggesting" or "not suggesting" acute myocardial infarction to avoid analysis of complex heterogeneous and synonymous diagnostic terms. Analyses, to measure agreement, and logistic regression, to determine if these ECG interpretations (and other variables such as patient age, chest pain) could predict patient mortality, were carried out. RESULTS: Of a total of 1464 patients referred to and declined for primary percutaneous coronary intervention, 722 (49.3%) computer diagnoses suggested acute myocardial infarction, whereas 634 (43.3%) of the human interpretations suggested acute myocardial infarction (P<.001). The human and computer agreed that there was a possible acute myocardial infarction for 342 out of 1464 (23.3%) patients. However, there was a higher rate of human-computer agreement for patients not having acute myocardial infarctions (450/1464, 30.7%). The overall agreement rate was 54.1% (792/1464). Cohen κ showed poor agreement (κ=0.08, P=.001). Only the age (odds ratio [OR] 1.07, 95% CI 1.05-1.09) and chest pain (OR 0.59, 95% CI 0.39-0.89) independent variables were statistically significant (P=.008) in predicting mortality after 30 days and 1 year. The odds for mortality within 1 year of referral were lower in patients with chest pain compared to those patients without chest pain. A referral being out of hours was a trending variable (OR 1.41, 95% CI 0.95-2.11, P=.09) for predicting the odds of 1-year mortality. CONCLUSIONS: Mortality in patients who were declined for primary percutaneous coronary intervention was higher than the reported mortality for ST-elevation myocardial infarction patients at 1 year. Agreement between computerized and human ECG interpretation is poor, perhaps leading to a high rate of inappropriate referrals. Work is needed to improve computer and human decision making when reading ECGs to ensure that patients are referred to the correct treatment facility for time-critical therapy.

Increased Peripheral Blood Heteroplasmy of the mt.3243A>G Mutation Is Associated with Earlier End-Stage Kidney Disease: A Case Report and Review of the Literature.

The mitochondrial DNA mutation mt.3243A>G is most commonly associated with maternally inherited diabetes and deafness (MIM 52,000), but it has protean phenotypes including renal disease due to focal segmental glomerulosclerosis. We describe monozygotic twins who both harboured this mutation and developed ESRD. Although otherwise genetically identical, the twins differed in their peripheral blood leucocyte levels of circulating mt.3243A>G heteroplasmy: 20 versus 10%, when assessed at 42 years of age. The twin with the higher heteroplasmy load developed end-stage kidney disease 15 years earlier than her sister. A review of the published literature supports a relationship between heteroplasmy level and the age at the development of the end stage of renal failure in patients with mt.3243A>G-related kidney disease.

The Fentanyl Patch Boil-Up - A Novel Method of Opioid Abuse.

Fentanyl is a potent opioid analgesic used in the treatment of pain. Transdermal fentanyl patches are now widely utilized as an acceptable and efficacious method of medication delivery. Unfortunately, the potential for their abuse is well recognized. Previous case reports have documented deaths after intravenous (IV) misuse of fentanyl which had been extracted from Duragesic (liquid reservoir type) patches. We present a case of IV fentanyl abuse after the extraction from a Mylan (matrix type) patch. This method of abuse has not previously been described in the literature.

A prospective intravascular ultrasound investigation of the necessity for and efficacy of postdilation beyond nominal diameter of 3 current generation DES platforms for the percutaneous treatment of the left main coronary artery.

OBJECTIVES: To define the size of the left mainstem coronary artery (LMS) in the Northern Irish population and investigate the clinical feasibility, safety, and efficacy of post dilation beyond nominal diameter of current generation Drug eluting stent (DES) when treating the LMS. BACKGROUND: There is no prospective data examining the need, feasibility, and safety of over-expansion of current generation DES beyond nominal diameter. METHODS: Patients with flow-limiting coronary atheroma requiring IVUS assessment of the LMS were recruited. Standardized measurements of the distal LMS were made. Subsequently, patients requiring post dilation of current generation DES within the LMS were entered into a PCI registry. RESULTS: Overall, 125 patients were recruited into the initial study. Mean cross-sectional area (CSA) of the distal LMS was 22.6 mm(2) (SD ± 5.4 mm(2) ). Mean maximal vessel diameter was 5.7 mm (SD ± 0.7 mm). Increasing plaque burden was associated with reduced CSA (P < 0.001). In 31 consecutive patients undergoing IVUS guided PCI of the LMS with 5.5 and 6.0 mm balloon catheters, mean maximal stent diameters were >5.0 mm with the Biomatrix Flex 9 crown and Promus Element Large vessel platforms. No intraprocedural complications occurred. Mean follow up was 13.4 months. Clinical restenosis rate was 3.2%, with 2 deaths unrelated to index procedure. CONCLUSIONS: The majority of patients with angiographic coronary atheroma have a mean LMS diameter of >4 mm indicating the requirement for post dilation beyond nominal diameter all of current generation DES in almost all patients when treating the LMS. This is achievable with current DES platforms with no intraprocedural complication. Clinical follow up indicates excellent short-term efficacy.

An audit of outcomes after same-day discharge post-PCI in acute coronary syndrome and elective patients.

OBJECTIVES: To investigate the outcomes of a cohort of acute and elective percutaneous coronary intervention (PCI) patients who were discharged home 6 hours postprocedure. BACKGROUND: Contemporary PCI is safe with a low rate of acute complications. It is well established as a day procedure in elective cases; however, data are lacking in acute cases. METHODS: We describe a prospective observational audit of routine clinical practice in the 3 PCI centers in Northern Ireland. Patients were selected for same-day discharge after 6 hours of post-PCI observation. Both elective and acute coronary syndrome (ACS) cases were included. Criteria for same-day discharge were based on the technical result of the procedure rather than lesion complexity or clinical presentation. Radial access was preferred but not mandatory. Patients were contacted directly to assess for 30-day major adverse cardiovascular events (MACE). Reported events were corroborated with the general practitioner or hospital notes. RESULTS: A total of 1,059 patients were selected for same-day discharge with 30-day follow-up available for all cases. Of these, 766 (72.3%) were elective and 293 (27.7%) were ACS patients. Radial access was almost universal (98%). A total of 1,224 lesions were stented, of which 432 (40.8%) were high risk (highest risk lesion in each case by AHA/ACC classification). MACE rate at 30 days was 0.85% with a sub-acute stent thrombosis rate of 0.4%. There were no MACE events from discharge to 24 hours. CONCLUSIONS: Selected acute and elective patients with a range of lesion complexity and risk can be discharged safely home early after PCI.

Reducing magnocellular processing of various motion trajectories tests single process theories of visual position perception.

Spatial projection and temporal integration are two prominent theories of visual localization for moving stimuli which gain most of their explanatory power from a single process. Spatial projection theories posit that a moving stimulus' perceived position is projected forwards in order to compensate for processing delays (Eagleman & Sejnowski, 2007; Nijhawan, 2008). Temporal integration theories (Krekelberg & Lappe, 2000) suggest that an averaging over positions occupied by the moving stimulus for a period of time is the dominant process underlying perception of position. We found that when magnocellular (M) pathway processing was reduced, there were opposite effects on localization judgments when a smooth, continuous trajectory was used, compared to when the moving object suddenly appeared, or suddenly reversed direction. The flash-lag illusion was decreased for the continuous trajectory, but increased for the onset and reversal trajectories. This cross-over interaction necessitates processes additional to those proposed by either the spatial projection or temporal integration theories in order to explain the perception of the position of moving stimuli across all our conditions. Differentiating our onset trajectory conditions from a Fröhlich illusion, in a second experiment, we found a null Fröhlich illusion under normal luminance-defined conditions, significantly smaller than the corresponding flash-lag illusion, but significantly increased when M processing was reduced. Our data are most readily accounted for by Kirschfeld and Kammer's (1999) backward-inhibition and focal attention theory.