Use and outcomes of dual antiplatelet therapy for acute coronary syndrome in patients with chronic kidney disease: insights from the Canadian Observational Antiplatelet Study (COAPT).

Chronic kidney disease (CKD) increases the risk of adverse outcomes in acute coronary syndrome (ACS). The optimal regimen of dual antiplatelet therapy (DAPT) post-percutaneous coronary intervention (PCI) in CKD poses a challenge due to the increased bleeding and clotting tendencies, particularly since patients with CKD were underrepresented in randomized controlled trials. We examined the practice patterns of DAPT prescription stratified by the presence of CKD. The multicentre prospective Canadian Observational Antiplatelet Study (COAPT) enrolled patients with ACS between December 2011 and May 2013. The present study is a subgroup analysis comparing type and duration of DAPT and associated outcomes among patients with and without CKD (eGFR < 60 ml/min/1.73 m2, calculated by CKD-EPI). Patients with CKD (275/1921, 14.3%) were prescribed prasugrel/ticagrelor less (18.5% vs 25.8%, p = 0.01) and had a shorter duration of DAPT therapy versus patients without CKD (median 382 vs 402 days, p = 0.003). CKD was associated with major adverse cardiovascular events (MACE) at 12 months (p < 0.001) but not bleeding when compared to patients without CKD. CKD was associated with MACE in both patients on prasugrel/ticagrelor (p = 0.017) and those on clopidogrel (p < 0.001) (p for heterogeneity = 0.70). CKD was associated with increased bleeding only among patients receiving prasugrel/ticagrelor (p = 0.007), but not among those receiving clopidogrel (p = 0.64) (p for heterogeneity = 0.036). Patients with CKD had a shorter DAPT duration and were less frequently prescribed potent P2Y12 inhibitors than patients without CKD. Overall, compared with patients without CKD, patients with CKD had higher rates of MACE and similar bleeding rates. However, among those prescribed more potent P2Y12 inhibitors, CKD was associated with more bleeding than those without CKD. Further studies are needed to better define the benefit/risk evaluation, and establish a more tailored and evidence-based DAPT regimen for this high-risk patient group.

Treatment Inertia in Patients With Familial Hypercholesterolemia.

Background We studied care gap in patients with familial hypercholesterolemia (FH) with respect to lipid-lowering therapy. Methods and Results We enrolled patients with cardiovascular disease (CVD) or FH and low-density lipoprotein-cholesterol >2.0 mmol/L despite maximally tolerated statin therapy. During follow-up physicians received online reminders of treatment recommendations of 2009 patients (median age, 63 years, 42% women), 52.4% had CVD only, 31.7% FH only, and 15.9% both CVD and FH. Patients with FH were younger and more likely to be women and non-White with significantly higher baseline low-density lipoprotein-cholesterol level (mmol/L) as compared with patients with CVD (FH 3.92±1.48 versus CVD 2.96±0.94, P<0.0001). Patients with FH received less statin (70.6% versus 79.2%, P=0.0001) at baseline but not ezetimibe (28.1% versus 20.4%, P=0.0003). Among patients with FH only, 45.3% were at low-density lipoprotein target (≥ 50% reduction from pre-treatment level or low-density lipoprotein <2.5 mmol/L) at baseline and increasing to 65.8% and 73.6% by visit 2 and 3, respectively. Among patients with CVD only, none were at recommended level (≤2.0 mmol/L) at baseline and 44.3% and 53.3% were at recommended level on second and third visit, respectively. When primary end point was analyzed as a difference between baseline and last available follow-up observation, only 22.0% of patients with FH only achieved it as compared with 45.8% with CVD only (P<0.0001) and 55.2% with both FH+CVD (P<0.0001). Conclusions There is significant treatment inertia in patients with FH including those with CVD. Education focused on patients with FH should continue to be undertaken.

Contemporary use of guideline-based higher potency P2Y12 receptor inhibitor therapy in patients with moderate-to-high risk non-ST-segment elevation myocardial infarction: Results from the Canadian ACS reflective II cross-sectional study.

BACKGROUND: After myocardial infarction, guidelines recommend higher-potency P2Y12 receptor inhibitors, namely ticagrelor and prasugrel, over clopidogrel. HYPOTHESIS: We aimed to determine the contemporary use of higher-potency antiplatelet therapy in Canadian patients with non-ST-elevation myocardial infarction (NSTEMI). METHODS: A total of 684 moderate-to-high risk NSTEMI patients were enrolled in the prospective Canadian ACS Reflective II registry at 12 Canadian hospitals and three clinics in five provinces between July 2016 and May 2018. Multivariable logistic regression modeling was performed to assess factors independently associated with higher-potency P2Y12 receptor inhibitor use at discharge. RESULTS: At hospital discharge, 78.3% of patients were treated with a P2Y12 receptor inhibitor. Among patients discharged on a P2Y12 receptor inhibitor, use of higher-potency P2Y12 receptor inhibitor was 61.4%. After adjustment, treatment in-hospital with PCI (OR 4.48, 95%CI 3.34-6.03, p < .0001) was most strongly associated with higher use of higher-potency P2Y12 receptor inhibitor, while oral anticoagulant use at discharge (OR 0.03, 95%CI 0.01-0.12, p < .0001), and atrial fibrillation (OR 0.40, 95%CI 0.17-0.98, p = .046) were most strongly associated with lower use of higher-potency P2Y12 receptor inhibitor. Use of higher-potency P2Y12 receptor inhibitor varied across provinces (range, 21.6%-78.9%). DISCUSSION: In contemporary Canadian practice, approximately 60% of moderate-to-high risk NSTEMI patients discharged on a P2Y12 receptor inhibitor are treated with a higher-potency P2Y12 receptor inhibitor. In addition to factors that increase risk of bleeding, interprovincial differences in practice patterns were associated with use of higher-potency P2Y12 receptor inhibitor at discharge. Opportunities remain for further optimization of evidence-based, guideline-recommended antiplatelet therapy use.

Blood Pressure Management in Adults With Type 2 Diabetes: Insights From the Diabetes Mellitus Status in Canada (DM-SCAN) Survey.

OBJECTIVES: Optimal treatment of blood pressure (BP) and other cardiovascular risk factors, including hyperglycemia, is integral to diabetes management. There are limited data from the primary care setting concerning the contemporary and comprehensive management of type 2 diabetes and other cardiovascular risk factors in relation to guideline-recommended BP target achievement. METHODS: The Diabetes Mellitus Status in Canada (DM-SCAN) survey included 5172 ambulatory patients with type 2 diabetes. Data were collected on patient demographics, medical histories, medication usage, BP levels and laboratory investigations. We stratified the study population based on their attainment of the BP target recommended by the Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada and the Canadian Hypertension Education Program (<130/80 mmHg) and compared patient clinical characteristics and treatments. RESULTS: Of the 5145 patients with available BP data, 36% achieved the BP target. Prevalence of smoking, known coronary artery disease, retinopathy, neuropathy and nephropathy were similar in the groups with BP 130/80 mmHg or higher and BP 130/80 mmHg or lower. Patients with BP 130/80 mmHg or higher were taking more antihypertensive agents and were more likely to be taking angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers, diuretics and calcium channel blockers. They also had significantly higher glycated hemoglobin and low-density lipoprotein-cholesterol levels. Overall, these patients were also less likely to achieve guideline-recommended glycemic and lipid targets. CONCLUSIONS: Only about one-third of patients with diabetes achieved the target BP of below 130/80 mmHg. Patients with BP 130/80 mmHg or higher were also less likely to achieve optimal guideline-recommended glycated hemoglobin and low-density lipoprotein-cholesterol targets. Improved comprehensive management of all risk factors in patients with diabetes is warranted.

Duration of dual antiplatelet therapy and associated outcomes following percutaneous coronary intervention for acute myocardial infarction: contemporary practice insights from the Canadian Observational Antiplatelet Study.

Aims: There is a paucity of real-world, contemporary data of practice patterns and clinical outcomes following dual-antiplatelet therapy (DAPT) in acute myocardial infarction (AMI) patients treated with percutaneous coronary intervention (PCI). Methods and results: The Canadian Observational Antiplatelet Study was a prospective, multicentre, cohort study examining adenosine diphosphate receptor antagonist use following PCI for AMI. We compared practice patterns, patient characteristics, and clinical outcomes in relation to DAPT duration (<6 weeks, 6 weeks to <6 months, 6 to <12, and ≥12 months). The primary outcome was the composite of non-fatal AMI, unplanned coronary revascularization, stent thrombosis, new or worsening heart failure, cardiogenic shock, or stroke. We identified 2034 patients with AMI treated with PCI. DAPT duration was <6 weeks in 5.2% of patients; 6 weeks to <6 months in 7.0%; 6 to <12 months in 12.6%; and ≥12 months in 75.3%. Patients who discontinued DAPT early had higher GRACE risk scores. Overall, mortality rate at 15 months was 2.5%. Compared with a duration of DAPT of ≥12 months, discontinuation of DAPT <6 weeks (P < 0.0001) and 6 weeks to <6 months (P = 0.02), but not 6 months to <12 months (P = 0.06), were independently associated with a higher incidence of the primary outcome among survivors. Conclusion: One-in-four patients with AMI treated with PCI discontinued DAPT prior to the guideline-recommended 12-month duration. Patients in whom DAPT was discontinued early were at higher baseline risk and had higher rates of non-fatal ischaemic events during follow up.

Ischemic and bleeding events in patients with myocardial infarction undergoing percutaneous coronary intervention who require oral anticoagulation: Insights from the Canadian observational AntiPlatelet sTudy.

BACKGROUND: Since the introduction of newer, more potent P2Y12 receptor inhibitors (P2Y12ris), practice patterns and associated clinical outcomes in patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI) and also requiring oral anticoagulation (OAC) have not been fully characterized. METHODS: The Canadian Observational Antiplatelet Study was a prospective, multicenter, longitudinal, observational study (26 hospitals, December 2011 to May 2013) describing P2Y12ri treatment patterns and outcomes in patients with ST-elevation and non-ST-elevation MI undergoing PCI. We describe the clinical characteristics, treatment patterns, bleeding, and ischemic outcomes over the 15-month follow-up within and between the subgroups of patients discharged on either dual-antiplatelet therapy (DAPT) (acetyl salicylic acid [ASA]+P2Y12ri) or triple therapy (ASA+P2Y12ri+OAC). RESULTS: Of the 2,034 patients at discharge, 86% (n = 1,757) were on DAPT, whereas 14% (n = 277) were on triple therapy (50% warfarin, 50% non-vitamin K OAC [NOAC]). The frequency of newer P2Y12ri use (prasugrel or ticagrelor) was similar in the DAPT and triple therapy groups (28% vs 26%, respectively). In the triple therapy group, NOAC use was higher in those receiving a new P2Y12ri compared to those receiving clopidogrel (75% vs 41%, respectively, P < .0001). The unadjusted and adjusted events of major cardiovascular event (MACE) and bleeding were higher in the triple therapy group. For patients on triple therapy, the bleeding or MACE events were not significantly different between those on clopidogrel versus those on ticagrelor or prasugrel. CONCLUSION: In this observational study of MI patients requiring PCI, 1 in 8 were discharged on triple antithrombotic therapy, of whom 26% were on newer P2Y12ris. Patients on triple therapy had higher risk at baseline, with higher unadjusted and adjusted MACE and bleeding events compared to those on DAPT alone. Among triple therapy-treated patients, there was no difference in the MACE and bleeding events regardless of the P2Y12ri used.

Evidence-based management of patients with chest tube drainage system to reduce complications in cardiothoracic vascular surgery wards.

AIM: This evidence-based project was to implement the best practice to provide safe and effective care to patients with chest tube drainage system in cardiothoracic wards. METHODS: Best practice recommendations on monitoring and maintenance of chest drains were retrieved from the Joanna Briggs Institute COnNECT+ database. A checklist was developed based on these recommendations. Nurses in the two cardiovascular wards were taught how to use the checklist. Two post-implementation audits on the nurses' compliance to use the checklist were conducted. Data were analysed using the Joanna Briggs Institute Practical Application of Evidence System. RESULTS: Initial post-implementation audit results showed that the compliance rates of monitoring underwater seal, suction pressure and connector were 100%, checking of dressings 90%, and swinging and/or bubbling 70%. The checklist also detected 36 near-miss events. The second post-implementation audit results showed that the compliance rate of monitoring insertion site for air infiltration was 100%, checking of dressings 78%, and swinging and/or bubbling 91%. Fifty-seven near-miss events were detected. CONCLUSION: The use of the checklist prevented adverse events during the evidence implementation period. It can thus be concluded that using a systematic guide to observe and monitor patients with chest tubes enhances the effectiveness and safety of nursing care in the hospital.

Increased uptake of guideline-recommended oral antiplatelet therapy: insights from the Canadian acute coronary syndrome reflective.

Current guideline-based recommendations for oral dual-antiplatelet therapy in an acute coronary syndrome (ACS) include the use of newer adenosine diphosphate receptor inhibitor (ADPri) regimens and agents. The Canadian ACS Reflective Program is a multicenter observational quality-enhancement project that compared the use of ADPri therapy in 2 phases (November 2011-March 2013 and April 2013-November 2013) and also compared ADPri use with previous national data from the Canadian Global Registry of Acute Coronary Events (2000-2008). Of 3099 patients with ACS, 30.6% had ST-segment elevation myocardial infarction (STEMI), 52.3% had non-STEMI, and 17% had unstable angina. There was high use of dual-antiplatelet therapy for ≤ 24 hours, with important increases noted when compared with previous national experience (P for trend, < 0.0001). Clopidogrel was the most commonly used ADPri (82.2%), with lower use of the newer agents ticagrelor (9.0%) and prasugrel (3.1%). Ticagrelor and prasugrel use was most frequent in patients with STEMI undergoing percutaneous coronary intervention PCI (34.3%). There was relatively lower use of ADPri therapy at discharge; it was given mainly to patients who did not undergo PCI (68.2%) and to those with non-ST-elevation ACS (82%). When comparing the 2 consecutive phases of data collection in the ACS Reflective, there was an approximate 3- and 2-fold increase in the early and discharge use of the newer ADPri agents, respectively. In conclusion, there has been a temporal increase in ADPri use compared with previous national experience and an increased uptake of newer ADPri agents. Additional work is needed to identify and address barriers limiting optimal implementation of these newer guideline-recommended agents into routine Canadian practice.

Comparison of the efficacy of pharmacoinvasive management for ST-segment elevation myocardial infarction in smokers versus non-smokers (from the Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction).

Compared with non-smokers, cigarette smokers with ST-segment elevation myocardial infarctions derive greater benefit from fibrinolytic therapy. However, it is not known whether the optimal treatment strategy after fibrinolysis differs on the basis of smoking status. The Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized patients with ST-segment elevation myocardial infarctions to a routine early invasive (pharmacoinvasive) versus a standard (early transfer only for rescue percutaneous coronary intervention or delayed angiography) strategy after fibrinolysis. The efficacy of these strategies was compared in 1,051 patients on the basis of their smoking status. Treatment heterogeneity was assessed between smokers and non-smokers, and multivariable analysis was performed to evaluate for an interaction between smoking status and treatment strategy after adjusting for baseline Global Registry of Acute Coronary Events (GRACE) risk score. Smokers (n=448) were younger, had fewer cardiovascular risk factors, and had lower GRACE risk scores. They had a lower rate of the primary composite end point of 30-day mortality, reinfarction, recurrent ischemia, heart failure, or cardiogenic shock and fewer deaths or reinfarctions at 6 months and 1 year. Smoking status was not a significant predictor of either primary or secondary end points in multivariable analysis. Pharmacoinvasive management reduced the primary end point compared with standard therapy in smokers (7.7% vs 13.6%, p=0.04) and non-smokers (13.1% vs 19.7%, p=0.03). Smoking status did not modify treatment effect on any measured outcomes (p>0.10 for all). In conclusion, compared with non-smokers, current smokers receiving either standard or early invasive management of ST-segment elevation myocardial infarction after fibrinolysis have more favorable outcomes, which is likely attributable to their better baseline risk profile. The beneficial treatment effect of a pharmacoinvasive strategy is consistent in smokers and non-smokers.

Treatment-resistant depression in primary care across Canada.

OBJECTIVE: Treatment-resistant depression (TRD) represents a considerable global health concern. The goal of the InSight study was to investigate the prevalence of TRD and to evaluate its clinical characterization and management, compared with nonresistant depression, in primary care centres. METHODS: Physicians completed a case report on a consecutive series of patients with major depressive disorder (n = 1212), which captured patient demographics and comorbidity, as well as current and past medication. RESULTS: Using failure to respond to at least 2 antidepressants (ADs) from different classes as the definition of TRD, the overall prevalence was 21.7%. There were no differences in prevalence between men and women or among ethnicities. Patients with TRD had longer episode duration, were more likely to receive polypharmacy (for example, psychotropic, lipid-lowering, and antiinflammatory agents), and reported more AD related side effects. Higher rates of disability and comorbidity (axes I to III) were associated with treatment resistance. Obesity and being overweight were also associated with treatment resistance. While the selection and sequencing of pharmacotherapy by family physicians in this sample was in line with recommendations from evidence-based treatment guidelines, the wait time to make a change in treatment was 6 to 8 weeks in both groups, which exceeds guideline recommendations. CONCLUSIONS: These real-world data demonstrate the high prevalence of TRD in primary care settings, and underscore the substantial burden of illness associated with TRD.

Bone marrow cytogenetics workup: Application of lean management system to determine if additional cell workup is helpful and necessary to analysis.

INTRODUCTION: High workload volumes in a Cytogenetics laboratory can lead to long result turn-around times (TAT). This study aimed to improve laboratory efficiency by adopting Lean Management System initiatives to increase productivity through the elimination of wastes. This study examined if the prerequisite 20-cell analysis was sufficient for a conclusive result or if additional cell workup was necessary to ascertain the presence of a previous chromosome abnormality among cases on follow-up, or when a single abnormal cell was encountered during the analysis to determine the presence of a clone. MATERIALS AND METHODS: The karyotype results of cases that had additional workup were retrieved from among 8040 bone marrow cases of various haematological disorders performed between June 2003 and June 2008. RESULTS: Of 8040 cases analysed, 2915 cases (36.3%) had additional cell workup. Only 49 cases (1.7%) led to the establishment of a clone. The majority of these cases could have been resolved without the additional workup, especially if fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR)-based assays had been utilised. CONCLUSION: This study shows that the additional workup procedure is redundant. The time saved by discontinuing the workup procedure can be used to analyse other cases, leading to increased laboratory efficiency and a faster TAT without compromise to patient care. The practice of additional workup over and above the 20- cell analysis should be dispensed with as little benefit was derived for the amount of additional manpower expended. FISH or PCR-based assays should be utilised to elucidate a case further.

Outcome of patients with acute coronary syndromes enrolled in clinical trials.

The objective of this study was to evaluate in-hospital and 1-year outcomes of patients with acute coronary syndrome (ACS) enrolled in clinical studies. Among patients included in the Canadian ACS Registries, patients enrolled in clinical studies (n = 883, 13.4%) were compared with patients who were not enrolled. Enrolled patients were younger, more likely to be smokers, had less diabetes, less hypertension, less previous myocardial infarction, and less previous percutaneous coronary intervention and coronary artery bypass grafting. Enrollment in clinical studies was higher in patients with ST-elevation and ST-depression ACS. Furthermore, patients enrolled had more coronary interventions (percutaneous coronary intervention and coronary artery bypass grafting) and received more evidence-based therapies such as aspirin and statins. Unadjusted event rates were significantly higher in patients not enrolled in clinical studies: in-hospital death 2.4 versus 1.1% (P = 0.02), and 1-year death 9.2 versus 6.1% (P = 0.003), and death or myocardial infarction 16.1 versus 13.8% (P = 0.09). After multivariable analysis, enrollment in clinical studies showed a trend towards decreased in-hospital and 1-year death. Patients with ACS in Canada who participate in clinical studies are more likely to receive evidence-based therapies and interventions throughout hospitalization. After multivariable analysis, enrollment in a clinical trial may also contribute to better in-hospital and 1-year outcome.

Optimal medical therapy at discharge in patients with acute coronary syndromes: temporal changes, characteristics, and 1-year outcome.

BACKGROUND: There are limited data on the recent trend in the use of optimal evidence-based medical therapies after acute coronary syndromes (ACSs). We sought to evaluate (1) the temporal changes in medical management of patients discharged after an ACS; (2) patient and practice characteristics associated with optimal medical therapy at discharge; and (3) the association between discharge medication use and 1-year outcome. METHODS: The Canadian ACS I (September 1999-June 2001) and ACS II (October 2002-December 2003) Registries were prospective, multicenter, observational studies of 6853 patients admitted for ACS. We examined the discharge use of medications among 5833 hospital survivors who did not have any contraindications to antiplatelet/anticoagulant, beta-blocker, angiotensin-converting enzyme inhibitor, or lipid-modifying therapies. Optimal medical therapy was defined as the use of all indicated medications. Follow-up data at 1 year were collected by telephone interview. We performed hierarchical logistic regression to identify patient characteristics and care patterns associated with optimal medical treatment and to examine its relationship with 1-year mortality. RESULTS: There were significant increases in the discharge use of all 4 classes of medications over time; 28.9% and 51.8% of patients in ACS I and ACS II Registries, respectively, were prescribed optimal medical therapy (P < .001). Advanced age, female sex, prior heart failure, renal dysfunction, and coronary bypass surgery during hospitalization were negative independent predictors of optimal medical therapy. Conversely, enrollment in ACS II Registry, history of dyslipidemia, presence of ST elevation and abnormal cardiac biomarker, previous myocardial infarction, and previous coronary revascularization were independently associated with the use of combination therapy. After adjusting for other validated prognosticators, patients receiving optimal medical therapy had significantly lower 1-year mortality (adjusted odds ratio 0.54, 95% confidence interval 0.36-0.81, P = .003) compared with those given 0 or 1 drug at discharge. Over the 1-year follow-up period, substantial numbers of patients discontinued therapies, whereas others were initiated on treatment. CONCLUSIONS: Despite the temporal increases in the combined use of evidence-based pharmacologic therapies, which is associated with improved outcome, medical management of ACS remains suboptimal. Quality improvement strategies are needed to enhance the appropriate use of effective therapies, targeting specifically the high-risk but undertreated patients who may derive the greatest therapeutic benefit.

Contemporary management of dyslipidemia in high-risk patients: targets still not met.

PURPOSE: Our objective was to evaluate treatment patterns and the attainment of current National Cholesterol Education Program (NCEP)-recommended lipid targets in unselected high-risk ambulatory patients. METHODS: Between December 2001 and December 2004, the prospective Vascular Protection and Guidelines Oriented Approach to Lipid Lowering Registries recruited 8056 outpatients with diabetes, established cardiovascular disease (CVD), or both, who had a complete lipid profile measured within 6 months before enrollment. The primary outcome measure was treatment success, defined as the achievement of LDL-cholesterol<2.6 mmol/L (100 mg/dL) according to NCEP guidelines. We examined patient characteristics and use of lipid-modifying therapy in relation to treatment outcome, which included the recently proposed optional LDL-cholesterol target (<1.8 mmol/L [70 mg/dL]) for very high-risk patients. RESULTS: Overall, 78.2% of patients were treated with a statin and 51.2% had achieved the recommended LDL-cholesterol target. Treatment success rate was highest in diabetic patients with CVD (59.6%), followed by nondiabetic patients with CVD (51.8%), and lowest (44.8%) in diabetic patients without CVD (P<.0001). Compared with untreated patients, those on statins were more likely to achieve target (34.4% vs 55.9%, P<.0001). Of the patients who failed to meet target, only 9.9% were taking high-dose statin, while 29.3% were not prescribed any statin therapy. Among very high-risk patients, 20.8% attained the optional LDL-cholesterol goal. In multivariable analysis, advanced age, male sex, diabetes, coronary artery disease, coronary revascularization, and use of statin were associated with treatment success (all P<.0001). CONCLUSION: Despite the well-established benefits of available lipid-modifying drugs, current management of dyslipidemia continues to be suboptimal, with a substantial proportion of patients failing to achieve guideline-recommended lipid targets. There remains an important opportunity to improve the quality of care for these high-risk patients.

A hyperthyroid patient with measurable thyroid-stimulating hormone concentration - a trap for the unwary.

INTRODUCTION: In a patient with hyperthyroidism, the detection of elevated thyroid hormone concentration with measurable thyroid-stimulating hormone (TSH) value poses considerable diagnostic difficulties. CLINICAL PICTURE: This 38-year-old lady presented with clinical features of thyrotoxicosis. Her serum free thyroxine concentrations were unequivocally elevated [45 to 82 pmol/L (reference interval, 10 to 20 pmol/L)] but the serum TSH values were persistently within the reference interval [0.49 to 2.48 mIU/L (reference interval, 0.45 to 4.5 mIU/L)]. TREATMENT: Investigations excluded a TSH-secreting pituitary adenoma and a thyroid hormone resistance state and confirmed false elevation in serum TSH concentration due to assay interference from heterophile antibodies. The patient was treated with carbimazole for 18 months. OUTCOME: The heterophile antibody-mediated assay interference disappeared 10 months following the initiation of treatment with carbimazole, but returned when the patient relapsed. It disappeared again 2 months after the initiation of treatment. CONCLUSIONS: Clinicians should be aware of the potential for interference in immunoassays, and suspect it whenever the test results seem inappropriate to the patient's clinical state. Misinterpretation of test values, arising as a result of assay interference, may lead to misdiagnosis, unnecessary and at times expensive investigations, delay in initiation of treatment and worst of all, the initiation of inappropriate treatment.

Supporting a call to action for peripheral artery disease: insights from two prospective clinical registries.

BACKGROUND: Patients affected by peripheral arterial disease (PAD) incur a heightened risk of adverse cardiovascular events, including stroke, myocardial infarction, and vascular mortality. We examined risk factors, medications, and prognosis of outpatients with PAD enrolled in two national, prospective, practice-based Canadian registries that encompassed 484 physician practices: the Vascular Protection and Guideline Oriented Approach in Lipid Lowering registries. METHODS: The 2 registries were combined to analyze 9810 patients with vascular disease, diabetes mellitus, or age 65 years or older plus at least 2 additional cardiovascular risk factors. Risk factors, medications, and major cardiovascular events were recorded at baseline and again at 6 months' follow-up. RESULTS: Compared with patients without PAD (n = 8303), those with PAD (n = 1507) had substantially worse risk factor profiles and were more likely to have coexisting coronary or cerebrovascular disease. Both groups received high rates of treatment with evidence-based therapies, including antiplatelet drugs, statins, and angiotensin-converting enzyme inhibitors. Despite this, patients with PAD had a nearly twofold higher risk of major cardiovascular events at 6 months than non-PAD patients (7.3% vs 4.1%; P < .0001). After adjustment for multiple confounding factors, the presence of PAD at baseline continued to predict a heightened risk of adverse vascular sequelae (odds ratio, 1.54; 95% confidence interval, 1.18-2.01; P < .0001). CONCLUSIONS: These data support a strong relationship between PAD and worsened vascular prognosis that is independent of both conventional vascular risk factors and concomitant cardiovascular disease. The presence of PAD should therefore provide a clear impetus for intensive risk factor modification and use of preventive medical therapy in affected patients.

Comparison of potential chemotherapeutic agents, 5-fluoruracil, green tea, and thymoquinone on colon cancer cells.

Antioxidants have been found to be quite successful in deterring certain disease processes for years, especially cancer. Antioxidants protect the body by neutralizing the free radicals and donating one of their own electrons, thus ending the scavenger reaction. Epigallocatechin-3-gallate (EGCG), the most abundant catechin found in green tea, is a valuable scavenger of reactive oxygen species in vitro as well as in vivo. Thymoquinone (TQ), a major active component of black seed (Nigella sativa), is also known for its powerful scavenger abilities as an inhibitor of oxidative stress and has been utilized in the Middle East for centuries for healing properties. These two potent antioxidants when compared to the chemotherapeutic drug of choice, 5-fluorouracil (5-FU), have demonstrated incredible chemotherapeutic responses to the SW-626 cell line. The objective of this study was to evaluate and compare the effects of SW-626 colon cancer cells after a 24, 48, and 72 hour incubation periods with low, medium, and high doses of EGCG, TQ, and 5-FU. Cell viability, cell number, cellular morphology, and cellular metabolism were compared for the control and treatment groups. The results of this study evidenced a similar significant decrease in cell number as early as 24 hours in the groups treated with TQ and EGCG compared to 5-FU. Increases in cellular damage were evident after 24, 48, and 72 hours and in all treated groups compared with the control. Reduced cell numbers in the treated groups suggests the possibility that TQ and EGCG may have similar chemotherapeutic effects on cancer cells as 5-FU.

Effects of (-)epigallocatechin gallate and thymoquinone on proliferation of a PANC-1 cell line in culture.

The limited ability of current treatments for pancreatic cancer prompted us to examine the effects of antioxidants on proliferation of pancreatic cancer cells. Antioxidants have been reported to possess antioxidant activity in vitro. The specific aim of this study was to investigate the role of epigallocatechin gallate (EGCG), a major component of green tea and thymoquinone on the proliferation and viability of PANC-1 cell line using a standard method of treatment. The PANC-1 cells were treated with three predetermined doses of thymoquinone and EGCG (5, 25, and 50 ug/dL) for 24, 48, and 72 hours in culture medium. Determination of viability and morphology was examined microscopically after each 24 hour interval. Data collected from this study indicated a dose dependent relationship with direct administration of EGCG alone or in combination with thymoquinone. However, a rebound effect was observed after 48 and 72 hours during direct administration of both antioxidants. These results indicate that direct administration of EGCG alone or in combination with thymoquinone can limit PANC-1 cell proliferation (p < 0.05). EGCG and thymoquinone may be a potent biologic inhibitor of human pancreatic carcinomas, reducing their propagation activities.

Randomized evaluation of the efficacy of enoxaparin versus unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes receiving the glycoprotein IIb/IIIa inhibitor eptifibatide. Long-term results of the Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment (INTERACT) trial.

BACKGROUND: Patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE ACS) benefit from the early administration of aspirin, a small molecule glycoprotein IIb/IIIa inhibitor such as eptifibatide, and heparin. The INTERACT trial demonstrated that in high-risk patients with ACS receiving aspirin and eptifibatide, the use of enoxaparin compared with unfractionated heparin (UFH) was associated with less bleeding, less early myocardial ischemia, and improved 30-day outcomes. OBJECTIVE: The aim of our study was to determine whether the short-term benefits of enoxaparin compared with UFH observed in high-risk patients with NSTE ACS are maintained over a prolonged period of follow-up. METHODS: Six hundred thirty-nine patients that were representative of the total population of subjects in the INTERACT trial were followed up for a median period of 2.5 years. RESULTS: In this group, the early benefit of enoxaparin was maintained. The incidence of death or myocardial infarction at the time of long-term follow-up was 39% lower in patients receiving enoxaparin compared with those who received UFH (8.9% vs 14.7%, P = .024). There was no difference in the frequency of cardiac catheterization in the groups receiving either enoxaparin or UFH. CONCLUSIONS: The early treatment of high-risk patients with NSTE ACS receiving aspirin and eptifibatide with enoxaparin is associated with early outcome benefits that are sustained over a prolonged follow-up period. This trial supports the concept that early treatment directed against platelet and thrombin formation is associated with better short- and long-term outcomes.