Evaluating cardioversion outcomes for atrial fibrillation on novel oral anticoagulants versus warfarin: experience at a tertiary referral centre.

BACKGROUND: Current guidelines recommend anticoagulation prior to cardioversion in patients with atrial fibrillation of >48 h or unknown duration to reduce thromboembolic risk. Therapeutic anticoagulation with warfarin, with INR between 2 and 3, is consistently achieved in approximately 60% of patients. AIMS: We evaluated outcomes and assessed differences in direct current cardioversion (DCCV) in patients treated with warfarin and novel oral anticoagulants (NOAC) at our institution. METHODS: A retrospective analysis of consecutive DCCV at a tertiary referral over 18 months was conducted. Analysis of cardioversion records allowed completion of a standardised dataset. Clinical variables recorded included (1) CHADSVASC score, (2) anticoagulant use, and (3) bleeding complications. RESULTS: During this period 187 DCCVs were scheduled; 119 on warfarin and 68 on NOAC. DCCV was deferred in 26% (n = 31) of the warfarin group and 4.4% (n = 3) of the NOAC group (p = 0.0002). The average time interval between referral and DCCV was 144.43 and 109.32 days for the warfarin and NOAC groups, respectively (p value = 0.023). 7.56% (n = 9) of the warfarin population had a bleeding event compared to a 2.94% total bleeding rate in NOAC group (p = 0.213). Deferral of elective DCCV and additional anticoagulant monitoring was estimated at €1160 per procedure. CONCLUSION: In elective cardioversions, the group anticoagulated with NOAC was less likely to have subtherapeutic anticoagulation and hence deferred procedures and had reduced health care consumption when compared to the group anticoagulated with warfarin.

Readmission rates among cardiology inpatients with echocardiography abnormalities associated with heart failure.

BACKGROUND: Heart failure is a condition associated with significant morbidity. It is caused by structural or functional abnormalities of the heart. Many of these abnormalities if detected and managed early would prevent the onset of heart failure. AIMS: The aim of this study was to to determine the usefulness of echocardiography as a means of predicting readmission rates. A secondary aim was to profile patients with echocardiography abnormalities. METHODS: This was a prospective cohort study that followed patients over 36 months. Data were abstracted from the medical records of 76 cardiology patients in a large urban teaching hospital between 1.6.11 and 31.8.14. The outcome of interest was the number of readmissions occurring up to 48 months after discharge. We also aimed to profile these patients in terms of their co-morbidities and their medication history. RESULTS: Of those patients who had echocardiography (n = 447), 76 were considered to have a cardiac disorder (HHD, VHD, or LVSD) (n = 29). The mean readmission rate for HHD was 0.82, LVSD 0.62, and HHD 0.98. Patients with HHD were associated with a higher readmission rate of 1.8980 and for LVSD-1.24 times more likely. Those with a cardiac disorder were 13 % more likely to have a readmission within the next 36 months than those without a cardiac disorder. CONCLUSIONS: A significant proportion of patients were found to have a cardiac disorder related to HF. Echocardiographic abnormalities were shown to be an independent risk factor for readmission.

The gap between policy and practice: a systematic review of patient-centred care interventions in chronic heart failure.

Patient-centred care (PCC) is recommended in policy documents for chronic heart failure (CHF) service provision, yet it lacks an agreed definition. A systematic review was conducted to identify PCC interventions in CHF and to describe the PCC domains and outcomes. Medline, Embase, CINAHL, PsycINFO, ASSIA, the Cochrane database, clinicaltrials.gov, key journals and citations were searched for original studies on patients with CHF staged II-IV using the New York Heart Association (NYHA) classification. Included interventions actively supported patients to play informed, active roles in decision-making about their goals of care. Search terms included 'patient-centred care', 'quality of life' and 'shared decision making'. Of 13,944 screened citations, 15 articles regarding 10 studies were included involving 2540 CHF patients. Three studies were randomised controlled trials, and seven were non-randomised studies. PCC interventions focused on collaborative goal setting between patients and healthcare professionals regarding immediate clinical choices and future care. Core domains included healthcare professional-patient collaboration, identification of patient preferences, patient-identified goals and patient motivation. While the strength of evidence is poor, PCC has been shown to reduce symptom burden, improve health-related quality of life, reduce readmission rates and enhance patient engagement for patients with CHF. There is a small but growing body of evidence, which demonstrates the benefits of a PCC approach to care for CHF patients. Research is needed to identify the key components of effective PCC interventions before being able to deliver on policy recommendations.

To glue or not to glue? Reassembling broken otoliths for population discrimination.

Twenty-five Atlantic cod Gadus morhua otoliths were examined using eight shape measurements along with Fourier analysis of their outlines to test whether discrimination using otolith shape is affected by gluing broken otoliths. Small differences in seven of the eight shape measurements were found between unbroken otoliths and the same otoliths after breaking and subsequently gluing together; however, none of the Fourier descriptors differed. Cluster analyses indicated that resultant morphological differences will have no impact when applying discriminant analysis.

Identification of stock components using morphological markers.

This study investigated the development of a quantitative method for distinguishing stock components of Icelandic cod Gadus morhua based on visual examination of morphology. The stock is known to be structured into genetically distinct geographic components (north and south of Iceland) and behavioural types that spawn sympatrically. Differences in morphology were tested between locations, genotypes (a proxy for behaviour) and sexes. Results show morphological markers on the head, fins and body of G. morhua that are correlated with the sex, genotype of the fish at the pantophysin (pan-I) locus and the location at which the fish were caught. Females were found to have relatively deep bodies, and the pan-I(BB) genotype (associated with deep-water feeding behaviour) have greater gaps between their fins. Overall, morphology is more useful for distinguishing sympatric genotypes but less powerful at identifying genetically distinct geographic sub-populations, perhaps because counter-gradient evolution reduces phenotypic differences even with an underlying genetic cause.

Prevalence of dyslipidaemia in statin-treated patients in Ireland: Irish results of the DYSlipidaemia International Study (DYSIS).

BACKGROUND: Statins are proven to reduce cardiovascular risk; however, substantial risk remains in patients on statin therapy. Persisting dyslipidaemia is likely to play a contributory role. AIM: To assess the prevalence of persisting lipid abnormalities in patients treated with statins. METHODS: DYSIS was a cross-sectional study of 22,063 patients in Europe and Canada. 900 Irish patients participated. All patients were ≥ 45 years and treated with statins for ≥ 3 months. Data were collected from the patients' records. ESC guidelines were used to classify risk and to define lipid levels. RESULTS: Mean age was 66.1 years with women representing 40.7%. 78.6% were high-risk patients; that is 53.9% with cardiovascular disease (CVD), 20.1% with diabetes and 15.9% with a SCORE risk ≥ 5%. Total cholesterol was not at goal in 34.4% of all patients. LDL-C was elevated in 30.8% of all patients and in 30% at high risk. Low HDL-C was found in 34.7% of high-risk patients compared to 16.9% of patients with an ESC score <5%. In diabetics without CVD, low HDL-C and elevated TGs were found in 46 and 44.3%, respectively. CONCLUSIONS: Despite statin therapy, a significant number of patients have persistent dyslipidaemia. While LDL-C targets are suboptimal in three out of ten patients, the prevalence of low HDL-C and high TGs in high-risk patients is greater than one in three. A more integrated approach to the treatment of patients with dyslipidaemia is warranted. Clinical trials are needed to assess the impact of therapies that raise HDL-C and lower elevated TGs.

Effect of regulated expression of human cyclooxygenase isoforms on eicosanoid and isoeicosanoid production in inflammation.

To examine the role of cyclooxygenase (COX) isozymes in prostaglandin formation and oxidant stress in inflammation, we administered to volunteer subjects placebo or bolus injections of lipopolysaccharide (LPS), which caused a dose-dependent increase in temperature, heart rate, and plasma cortisol. LPS caused also dose-dependent elevations in urinary excretion of 2,3-dinor 6-keto PGF(1alpha) (PGI-M) and 11-dehydro thromboxane B(2) (Tx-M). Platelet COX-1 inhibition by chronic administration of low-dose aspirin before LPS did not alter the symptomatic and febrile responses to LPS, but the increment in urinary PGI-M and Tx-M were both partially depressed. Pretreatment with ibuprofen, a nonspecific COX inhibitor, attenuated the febrile and systemic response to LPS and inhibited prostanoid biosynthesis. Both celecoxib, a selective COX-2 inhibitor, and ibuprofen attenuated the pyrexial, but not the chronotropic, response to LPS. Experimental endotoxemia caused differential expression of the COX isozymes in monocytes and polymorphonuclear leucocytes ex vivo. LPS also increased urinary iPF(2alpha)-III, iPF(2alpha)-VI, and 8,12-iso-iPF(2alpha)-VI, isoprostane (iP) indices of lipid peroxidation, and none of the drugs blunted this response. These studies indicate that (a) although COX-2 predominates, both COX isozymes are induced and contribute to the prostaglandin response to LPS in humans; (b) COX activation contributes undetectably to lipid peroxidation induced by LPS; and (c) COX-2, but not COX-1, contributes to the constitutional response to LPS in humans.

Effects of specific inhibition of cyclooxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoids.

Conventional nonsteroidal anti-inflammatory drugs inhibit both cyclooxygenase (Cox) isoforms (Cox-1 and Cox-2) and may be associated with nephrotoxicity. The present study was undertaken to assess the renal effects of the specific Cox-2 inhibitor, MK-966. Healthy older adults (n = 36) were admitted to a clinical research unit, placed on a fixed sodium intake, and randomized under double-blind conditions to receive the specific Cox-2 inhibitor, MK-966 (50 mg every day), a nonspecific Cox-1/Cox-2 inhibitor, indomethacin (50 mg t.i.d.), or placebo for 2 weeks. All treatments were well tolerated. Both active regimens were associated with a transient but significant decline in urinary sodium excretion during the first 72 h of treatment. Blood pressure and body weight did not change significantly in any group. The glomerular filtration rate (GFR) was decreased by indomethacin but was not changed significantly by MK-966 treatment. Thromboxane biosynthesis by platelets was inhibited by indomethacin only. The urinary excretion of the prostacyclin metabolite 2,3-dinor-6-keto prostaglandin F1alpha was decreased by both MK-966 and indomethacin and was unchanged by placebo. Cox-2 may play a role in the systemic biosynthesis of prostacyclin in healthy humans. Selective inhibition of Cox-2 by MK-966 caused a clinically insignificant and transient retention of sodium, but no depression of GFR. Inhibition of both Cox isoforms by indomethacin caused transient sodium retention and a decline in GFR. Our data suggest that acute sodium retention by nonsteroidal anti-inflammatory drugs in healthy elderly subjects is mediated by the inhibition of Cox-2, whereas depression of GFR is due to inhibition of Cox-1.

Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2.

Prostaglandins (PG) are synthesized by two isoforms of the enzyme PG G/H synthase [cyclooxygenase (COX)]. To examine selectivity of tolerated doses of an inhibitor of the inducible COX-2 in humans, we examined the effects of celecoxib on indices of COX-1-dependent platelet thromboxane (Tx) A2 and on systemic biosynthesis of prostacyclin in vivo. Volunteers received doses of 100, 400, or 800 mg of celecoxib or 800 mg of a nonselective inhibitor, ibuprofen. Ibuprofen, but not celecoxib, significantly inhibited TxA2-dependent aggregation, induced ex vivo by arachidonic acid (83 +/- 11% vs. 11. 9 +/- 2.2%; P < 0.005) and by collagen. Neither agent altered aggregation induced by thromboxane mimetic, U46619. Ibuprofen reduced serum TxB2 (-95 +/- 2% vs. -6.9 +/- 4.2%; P < 0.001) and urinary excretion of the major Tx metabolite, 11-dehydro TxB2 (-70 +/- 9.9% vs. -20.3 +/- 5.3%; P < 0.05) when compared with placebo. Despite a failure to suppress TxA2-dependant platelet aggregation, celecoxib had a modest but significant inhibitory effect on serum TxB2 4 hr after dosing. By contrast, both ibuprofen and celecoxib suppressed a biochemical index of COX-2 activity (endotoxin induced PGE2 in whole blood ex vivo) to a comparable degree (-93.3 +/- 2% vs. -83 +/- 6.1%). There was no significant difference between the doses of celecoxib on COX-2 inhibition. Celecoxib and ibuprofen suppressed urinary excretion of the prostacyclin metabolite 2,3 dinor 6-keto PGF1alpha. These data suggest that (i) platelet COX-1-dependent aggregation is not inhibited by up to 800 mg of celecoxib; (ii) comparable COX-2 inhibition is attained by celecoxib (100-800 mg) and ibuprofen (800 mg) after acute dosing; and (iii) COX-2 is a major source of systemic prostacyclin biosynthesis in healthy humans.

Reduced fetal exposure to aspirin using a novel controlled-release preparation in normotensive and hypertensive pregnancies.

OBJECTIVES: To examine the fetal effects of a novel controlled-release, low dose aspirin preparation in normal and hypertensive pregnancies. DESIGN: Random double-blind study. Participants assigned to receive conventional formulation aspirin (75 mg), controlled-release low dose aspirin (75 mg), or a matching placebo. SETTING: National Maternity Hospital, Dublin. PARTICIPANTS: Eighteen women with an uncomplicated pregnancy and 18 women with preeclampsia. MAIN OUTCOME MEASURES: Urine was analysed for metabolites of thromboxane and prostacyclin by gas chromatography, mass spectrometry. Serum thromboxane B2 was determined in maternal and cord blood. RESULTS: Both aspirin preparations reduced maternal serum thromboxane B2 by 95% and induced similar reductions in the urinary 11-dehydro-thromboxane B2, a major metabolite of thromboxane A2 in vivo. In contrast, neither preparation altered urinary 2,3-dinor-6-keto PGF1alpha, the major metabolite of prostacyclin. Despite their similar effects in the mothers, the two aspirin preparations differed in their effects on the fetus. While both suppressed cord fetal thromboxane B2, this was significantly (P < 0.005) less for the controlled-release preparation (210+/-42 ng/ml for placebo vs 109+/-22 ng/ml for controlled-release aspirin and 44+/-9 ng/ml for regular oral aspirin). CONCLUSIONS: At equivalent maternal suppression of serum thromboxane B2, a controlled aspirin release preparation results in lower fetal exposure than regular oral aspirin.

Lateral and anterior reciprocal electrocardiographic changes: relationship to ST segment elevation and underlying coronary artery disease in inferior myocardial infarction.

The electrocardiogram in patients with acute inferior myocardial infarction frequently displays ST depression in non-infarct leads. The significance of this finding is uncertain. The relationship between ST depression, ST elevation and arteriographic severity of coronary artery disease was explored. 22 patients with acute inferior myocardial infarction, receiving thrombolysis and undergoing acute (within seven hours of the onset of chest pain) coronary angiography were studied prospectively. The electrocardiographic ST segment elevation in the inferior leads and ST segment depression in the lateral and in the anterior precordial leads were measured. In each group of leads, the maximum value of ST deviation in any lead as well as the sum of the values for ST deviation in the individual leads was determined. Gensini scores of total coronary artery disease and component scores for the major coronary arteries were determined from the coronary arteriogram. There was a strong correlation of maximum inferior ST elevation with both maximum lateral ST depression (r = 0.96, p < 0.001) and with maximum anterior precordial ST depression (r = 0.78, p < 0.001). The corresponding correlations for sum of ST deviations were r = 0.91, p < 0.001 and r = 0.79, p < 0.001 respectively. There was no relationship between Gensini scores of coronary artery disease and measures of electrocardiographic ST segment depression or elevation. Electrocardiographic ST depression in non-infarct leads in patients with inferior myocardial infarction, does not provide information regarding the degree of coronary artery disease. The ST depression in both lateral and anterior precordial leads correlates with and is a reflection of inferior ST elevation.

Health care focus documentation--more efficient charting.

A revised nursing documentation system is now user-friendly, multi-disciplinary and computer adaptable. Sixteen health care focus topics replaced nursing diagnoses and served as a common thread to coordinate documentation of patient care.

Transdermal modification of platelet function: an aspirin patch system results in marked suppression of platelet cyclooxygenase.

Aspirin inhibits platelet cyclooxygenase and prevents thromboxane A2 (TXA2) production. Although it is an effective antithrombotic, even at a low doses aspirin may induce gastrointestinal toxicity. We examined the feasibility of delivering aspirin transdermally using two patch systems, one without (type A) and one with (type B) the permeation enhancer limonene. Daily application of two type A patches that had a total surface area of 100 cm2 and contained 84 mg/patch resulted in 85% +/- 6% reduction in serum TXB2 in six male subjects by day 14. Suppression of serum TXB2 was less marked in females (32% +/- 16%). Analysis of the residual drug in the patch showed that each patch delivered 18 +/- 3 mg on day 1 and 17 +/- 4 mg on day 14, with no difference between males and females. Daily application of a single patch B that had a surface area of 50 cm2 and contained 120 mg aspirin resulted in 60% +/- 11% suppression of serum TXB2 by day 14 in nine male subjects and 84% +/- 9% suppression by day 21. Analysis of the applied patches showed that patch B delivered 33 +/- 3 mg of aspirin daily. Plasma aspirin and salicylate were determined by gas chromatography, mass spectrometry. No aspirin was detected, whereas plasma salicylate was 157 +/- 38 ng/ml and 133 +/- 20 ng/ml by day 14 with patch A and patch B, respectively. Analysis of aspirin applied by patch to the skin in three subjects showed marked hydrolysis to the inactive product, salicylic acid. Aspirin can be delivered transdermally by patch in a dose that suppresses platelet cyclooxygenase. The delivery rate is low reflecting hydrolysis of the drug in the skin. Delivery is improved by the permeation enhancer limonene. This novel route of delivery may be applicable to other antithrombotics and may limit the risk of gastrointestinal toxicity.

Immediate and follow-up results of coronary angioplasty--lessons for the future.

In a series of 129 patients having coronary angioplasties in St. James's Hospital in 1989, the average age was 54.8 (30-77 years). There were 102 (79%) men and 27 (21%) females. Clinical indications were unstable angina 62, stable angina 26, post myocardial infarction 39 and asymptomatic ischaemia 2. The distribution of coronary disease was single vessel 62%, double vessel 28%, triple vessel 7% and previous coronary bypass surgery 3%. Only 10 patients had more than one vessel dilated. Primary success was achieved in 119 (92%), there were no deaths, 3 patients had abrupt closure of the vessel during angioplasty and sustained a nonfatal myocardial infarction, 1 patient required urgent bypass surgery and 2 patients had peripheral vascular complications requiring surgery. There were 6 failed angioplasties, 4 of which had chronic total occlusion. At a mean follow-up of 5.3 months, 85 patients had no symptoms, 34 had angina, 2 developed myocardial infarction and 1 died suddenly at 5 months. Repeat angiography was performed in 96 (79%) patients. At follow-up, no symptoms were present in 69% of those with single vessel disease and 70% of multivessel disease. Of those who had more than one vessel dilated in multivessel disease, 80% were asymptomatic (P = NS). There were 11 patients with initial total occlusion at presentation, 4 had failed angioplasties, 5 recurrent angina of which 4 reoccluded and 1 restenosed and only 2 were asymptomatic and without restenosis. Angioplasty was performed with primary success (92%) and follow up results (70% asymptomatic). Those with single or multivessel disease had similar clinical outcome, favouring the use of target vessel angioplasty. Long term results following angioplasty of chronic total occlusions were poor and suggests the need for additional treatment.

Percutaneous endoscopic gastrostomy--results of an Irish single unit series.

The technique of percutaneous endoscopic gastrostomy (PEG) was first described in 1980, as an alternative to traditional surgical methods. The main indication for PEG is the need for longterm nutritional support. It is reported to have many advantages over surgical gastrostomy, being safer and cheaper. We reviewed our experience with the first 44 patients referred to our unit for PEG. The most common indications for referral were stroke, head injury and post brain surgery. There was a success rate of 97.6% and a complication rate of 13.8%. One patient (2.3%) suffered major complications as a result of early tube displacement. There were no procedure related deaths in our series and no deaths as a result of an underlying disease process within 30 days, reflecting appropriate patient selection. All patients benefited nutritionally from PEG placement. Two patients recovered sufficiently to no longer require a gastrostomy and the tube was easily removed in both cases.

Lactate dehydrogenase levels during MACOP-B chemotherapy for non-Hodgkin's lymphoma.

Lactate dehydrogenase (LD) levels rose consistently during MACOP-B chemotherapy for intermediate and high-grade non-Hodgkin's lymphoma (NHL). Levels peaked at week nine and fell to normal within six weeks of completion of therapy. Isoenzyme patterns, studied prospectively in seven patients, showed a parallel rise in LD1 and LD2 suggesting a source other than tumour tissue for the rise in total LD. In the absence of evidence of myocardial or renal damage, haematopoietic tissue was the most likely source. With no evidence of haemolysis, normal serum levels of vitamin B12 and folate and normal red cell folate, dyserythropoiesis was considered to be the underlying mechanism. A rising mean corpuscular volume further reinforced this suggestion. Intensive use of methotrexate along with co-trimoxazole as prophylaxis against pneumoycystis carinii is considered the most likely cause of marrow dysfunction. Failure to recognise that rising LD levels during such therapy is treatment-related, rather than of tumour origin, may lead to inappropriate change or abandonment of therapy.