Left Atrial Appendage Closure for Stroke Prevention in Atrial Fibrillation.

PURPOSE OF REVIEW: Anticoagulant therapy effectively reduces the incidence of stroke in patients with atrial fibrillation (AF) but is underutilized and frequently contraindicated. The left atrial appendage (LAA) is the primary site of thrombus formation in AF patients. Surgical and percutaneous appendage closure has been evaluated as a site-specific therapy to reduce systemic thromboembolism. RECENT FINDINGS: We will review LAA closure techniques, examine recent outcome data, and discuss the indications for, and potential complications of, each approach. Randomized data examining surgical LAA closure and epicardial closure with the LARIAT device are lacking. High quality, randomized data supports the efficacy of the WATCHMAN device for stroke prevention in patients with AF.

Role of Endovascular Closure of the Left Atrial Appendage in Stroke Prevention for Atrial Fibrillation.

The pathophysiologic mechanism of thromboembolic stroke in the setting of non-valvular atrial fibrillation (AF) resides in the left atrial appendage (LAA). In this setting, approximately 90 % of all strokes originate from this structure. Percutaneous left atrial appendage occlusion (LAAO) therapy has recently emerged as an important strategy for prevention of stroke and systemic embolism in patients with non-valvular AF. Systemic anticoagulation therapy in this AF population, while effective, is associated with a significant bleeding risk, drug compliance issues, and limited reversal strategies. In this manuscript, we will review the percutaneous devices and techniques that allow endovascular closure of the LAA, including their efficacy in stroke prevention, the safety profile of these local site-specific therapies, comparison of the multiple approaches being studied, the index patient populations involved, and long-term follow-up in comparison with systemic anticoagulation therapy. The percutaneous LAAO approach indeed represents an exciting and revolutionary advance in the field of stroke prevention in AF.

Relationship of electro-mechanical remodeling to survival rates after cardiac resynchronization therapy.

Cardiac resynchronization therapy, when added to optimal medical therapy, increases longevity in symptomatic congestive heart failure patients with left ventricular ejection fractions (LVEF)≤0.35 and QRS durations>120 ms. Cardiac resynchronization therapy is also associated with electrical and mechanical reverse remodeling. We examined whether reverse remodeling predicts increased survival rates in non-trial settings. Recipients of cardiac resynchronization therapy and defibrillators (n=112; 78 men; mean age, 69±11 yr) underwent repeat echocardiography and electrocardiography at least 90 days after device implantation. Forty patients had mechanical responses of at least 0.05 improvement in absolute LVEF; 56 had electrical responses (any narrowing of biventricular-paced QRS duration compared with the electrocardiogram immediately after therapy). During a mean follow-up period of 3.1±1.7 years, 55 patients died. The average death rate per 100 person-years was lower among mechanical responders than nonresponders (9.2% vs 23.9%; P=0.009); the unadjusted hazard ratio was 0.39 (95% confidence interval [CI], 0.19-0.79). In a multivariate model adjusted for age, sex, baseline LVEF, and QRS duration, mechanical responders had 60% better survival than nonresponders (hazard ratio=0.40; 95% CI, 0.21-0.79; P=0.008). No difference in survival was observed in electrical response. In our association of absolute change in LVEF over the observed range with death (using restricted cubic splines), we observed a linear relationship with survival. In patients given cardiac resynchronization therapy, mechanical but not electrical remodeling was associated with better survival rates, suggesting that mechanical remodeling underlies this therapy's mechanism of conferring a survival benefit.

Violence and abuse faced by junior physicians in the emergency department from patients and their caretakers: a nationwide study from Pakistan.

BACKGROUND: Across the globe, physicians in the emergency department (ED) are subject to violence by patients and visitors. This has been shown to have negative effects on patient care and physician performance. STUDY OBJECTIVES: This study was conducted to determine the magnitude of the problem in a developing country, to examine the effects of ED violence on physician satisfaction and performance, and to identify underlying etiologies and potential solutions. METHODS AND SETTING: This nationwide cross-sectional study examined physicians-in-training (n = 675) in the EDs of nine major tertiary care hospitals in Pakistan. RESULTS: The study reveals a significant problem, with 76.9% of physicians facing verbal (65.0%) or physical (11.9%) abuse from patients or their caretakers in the previous 2 months. Male physicians were more likely than female physicians to be victims of such episodes (p < 0.05), as were physicians who had spent more than 60 h in the ED in the past 2 months (p < 0.0001). Reduced job satisfaction and a decline in the quality of job performance were reported by 40.7% and 44.3% of physicians, respectively. Junior trainee physicians were more likely to report impairment in job performance when compared to their senior colleagues (p = 0.014). Patients' lack of education, overcrowding in the ED, and lack of coverage by security staff were identified as the major areas that need attention to address the problem. CONCLUSION: This study provides further evidence of the global prevalence of the problem, with the first nationwide epidemiological study performed in a developing country.

Coping styles in patients with anxiety and depression.

Different individuals use different coping styles to cope with their problems. In patients with anxiety and/or depression, these have important implications. The primary objective of our study was to estimate the frequency of different coping mechanisms used by patients with symptoms of anxiety and depression. A descriptive, cross-sectional survey was conducted and patients with symptoms of anxiety and depression were identified using the Aga Khan University's Anxiety and Depression Scale (AKUADS). Coping styles were determined by using the 28-item Brief COPE inventory. We were able to recruit 162 people. The prevalence of anxiety and depression was found to be 34%. Females were more than 2 times likely to have anxiety and depression (P value = 0.024, OR = 2.62). In patients screening positive for AKUADS, "religion" was the most common coping mechanism identified. "Acceptance", "Use of instrumental support", and "Active coping" were other commonly used coping styles. Our findings suggest that religious coping is a common behavior in patients presenting with symptoms anxiety and depression in Pakistan. Knowledge of these coping styles is important in the care of such patients, as these coping methods can be identified and to some extent modified by the treating clinician/psychiatrist.

Right ventricular function with standard and speckle-tracking echocardiography and clinical events in adults with D-transposition of the great arteries post atrial switch.

BACKGROUND: The prognostic value of deformation parameters of the systemic right ventricle in adults with D-transposition of the great arteries and prior atrial switch has not been reported. METHODS: Sixty-four adults with D-transposition of the great arteries and prior atrial switch (mean age, 29 ± 6 years; 22 women; mean right ventricular [RV] fractional area change, 22.9 ± 7.5%; 31 with pacemakers at baseline) and no histories of heart failure or ventricular tachycardia were prospectively evaluated. Global longitudinal strain (GS), global systolic strain rate (GSRs), and global early diastolic strain rate (GSRe) of the right ventricle were measured using speckle tracking from apical views and compared with standard parameters of RV function (fractional area change, tricuspid annular plane systolic excursion, tissue Doppler velocities, and isovolumic acceleration) for association with and potential prediction of clinical events, defined as incident stage C heart failure or ventricular tachycardia. RESULTS: Baseline RV GS, GSRs, and GSRe were -12.5 ± 3.0%, -0.59 ± 0.14 sec(-1), and 0.68 ± 0.22 sec(-1), respectively. After a median of 2.4 years (interquartile range, 1.5-4.1 years), 12 patients (19%) presented with clinical events (heart failure in 11 patients, ventricular tachycardia in one patient). In Cox models, RV GS had the strongest association with clinical events (hazard ratio [HR] per 1%, 1.35; 95% confidence interval [CI], 1.14-1.58; P < .001), followed by GSRs (HR per 0.01 sec(-1), 1.06; 95% CI, 1.02-1.11; P = .006), GSRe (HR per -0.01 sec(-1), 1.04; 95% CI, 1.00-1.07; P = .031), and fractional area change (HR per -1%, 1.08; 95% CI, 1.00-1.17; P = .047). Other measures of RV function were not significantly associated with risk for events. In receiver operating characteristic analysis, RV GS ≥ -10% optimally predicted future events (C = 0.83; 95% CI, 0.71-0.91; P < .001). CONCLUSIONS: Reduced longitudinal GS of the systemic right ventricle is associated with increased risk for clinical events among patients with D-transposition of the great arteries and prior atrial switch.

Chemical composition and mechanisms underlying the spasmolytic and bronchodilatory properties of the essential oil of Nepeta cataria L.

AIM OF THE STUDY: The study was aimed to investigate the chemical composition and pharmacological basis for traditional use of essential oil of Nepeta cataria L. (Limiaceae) (Nc.Oil) in gastrointestinal and respiratory disorders. MATERIALS AND METHODS: Chemical analysis was carried out through GC-EIMS, 13C NMR and Kovats Retention Indices while pharmacological study was carried out in isolated tissues preparations. RESULTS: Four major components; 1,8-cineol (21.00%), alpha-humulene (14.44%), alpha-pinene (10.43%) and geranyl acetate (8.21%) were identified among the 27 compounds in Nc.Oil. In isolated rabbit jejunum, Nc.Oil, papaverine and verapamil inhibited spontaneous and high K+(80 mM) precontractions, as well as shifted the Ca++ concentration-response curves (CRCs) to right, indicating calcium channel blocking activity. In isolated guinea-pig trachea, Nc.Oil and papaverine inhibited carbachol (1 microM) and K+ precontractions with similar potency, while verapamil was more potent against K+. Nc.Oil also potentiated isoprenaline inhibitory CRCs, similar to papaverine, indicating papaverine-like PDE inhibitor activity. In isolated guinea-pig atria, Nc.Oil caused cardiodepression at around 25-80 times higher concentrations, similar to papaverine. CONCLUSIONS: These data indicate that Nepeta cataria possesses spasmolytic and myorelaxant activities mediated possibly through dual inhibition of calcium channels and PDE, which may explain its traditional use in colic, diarrhea, cough and asthma.

Medicinal importance of grapefruit juice and its interaction with various drugs.

Grapefruit juice is consumed widely in today's health conscious world as a protector against cardiovascular diseases and cancers. It has however, been found to be an inhibitor of the intestinal cytochrome P - 450 3A4 system, which is responsible for the first pass metabolism of many drugs. The P - glycoprotein pump, found in the brush border of the intestinal wall which transports many of these cytochrome P - 450 3A4 substrates, has also been implicated to be inhibited by grapefruit juice. By inhibiting these enzyme systems, grapefruit juice alters the pharmacokinetics of a variety of medications, leading to elevation of their serum concentrations. Most notable are its effects on the calcium channel antagonist and the statin group of drugs. In the case of many drugs, the increased serum concentration has been found to be associated with increased frequency of dose dependent adverse effects. In this review, we have discussed the phytochemistry of grapefruit juice, the various drugs involved in the drug - grapefruit juice reaction with their mechanisms of action and have presented the clinical implications of these interactions.

Outcomes of primary percutaneous coronary intervention at a joint commission international accredited hospital in a developing country -- can good results, possibly similar to the west, be achieved?

BACKGROUND: Primary percutaneous coronary intervention (PCI) is the treatment of choice following ST-elevation myocardial infarction (STEMI). There is limited adoption and a paucity of data on outcomes following primary PCI in developing countries. The objective of this study was to describe the procedural and clinical outcomes of patients undergoing PCI for STEMI at a Joint Commission International Accreditation (JCIA) certified hospital in Pakistan and make a comparison with outcomes from the West. METHODS: We conducted a retrospective cohort study at a tertiary care university hospital in Karachi, Pakistan. A total of 277 consecutive patients undergoing primary PCI between January 2001 and December 2005 were reviewed. Exclusion criteria included preceding fibrinolytic therapy and STEMI due to stent thrombosis. Cox proportional hazards models were constructed. The primary outcome was mortality. RESULTS: Procedural success was 97.1%. Inhospital mortality was 8.3% (43.9% in cardiogenic shock, 2.1% in non-shock patients), comparing very favorably with the published literature from developed countries. Multivariate predictors of death included (hazards ratio, 95% confidence interval) age (1.42 [1.14-1.76]), mechanical ventilation (8.35 [2.82-24.73]), cardiogenic shock (2.80 [1.04-7.55]), prior CABG (9.78 [1.15-83.13]) and ejection fraction (0.96 [0.92-0.99]). CONCLUSIONS: We conclude that excellent outcomes for a critical illness like STEMI can be achieved in a developing country at a JCIA-certified hospital, possibly similar to those seen in the West. There is a strong need for making the practice of primary PCI more widespread in developing nations. More outcomes data are needed from similar hospitals in the region to determine whether our results are generalizable.

Studying the association between postgraduate trainees' work hours, stress and the use of maladaptive coping strategies.

BACKGROUND: The growing debate regarding long working hours of postgraduate trainees has been receiving considerable attention recently. This greater workload contributes to increasing stress. Our objective was to specifically study the association between long working hours, stress and the greater use of 'maladaptive' coping strategies. METHODS: A cross-sectional descriptive study was carried out on all interns and residents at the Aga Khan University Hospital during February to May, 2005. Level of stress was measured by use of General Health Questionnaire (GHQ-12) and the use of maladaptive coping mechanisms through Brief Cope-28. RESULTS: 55.1% scored over the threshold for mild stress i.e. GHQ > 3, while more than 46% of the trainees scored over the threshold of more than 4 for morbid stress. Trainees under stress reported more working hours on average as compared to those not under stress, 83.8 and 74.7 hours respectively. At the same time, those working for longer hours were more likely to have used these negative coping mechanisms, which would further contribute to more stress rather than relieving it. CONCLUSIONS: Significant levels of stress have been identified. Along with this, those working for longer hours were more likely to have used these negative coping mechanisms. Reduction of working hours is important. Simultaneously, interventions need to be planned at imparting knowledge, awareness and skills to cope with various kinds of stressors encountered by a trainee during his/her training. Additionally, limits need to be devised for the working hours of the trainees.

Estrogen receptor alpha-negative and progesterone receptor-positive breast cancer: lab error or real entity?

Aretrospective study comparing the estrogen receptor (ER) alpha subtype and progesterone receptor (PR) profile of breast carcinomas amongst 1625 cases over 2.5 years was carried out. Strictly speaking it is generally believed that breast carcinomas can biochemically express PR only if they are ER-positive. However, a few ERalpha-PR+ cases do exist paradoxically. This class of tumors was the focus of our study in which we looked at the possible reasons for such an immunophenotype and compared it with a group of ERalpha+PR+ breast carcinomas. An internationally recognized immunohistochemical method employing monoclonal antibodies against estrogen and progesterone receptors was used. Correlations with established risk factors i.e. menopausal status, grade, tumor size and lymph node status were analyzed for our study group (ERalpha-PR+) and compared with a control (ERalpha+PR+). Out of the total 1625 cases, 29.91% (486) were ERalpha+PR+, 5.11% (83) were ERalpha+PR-, 56.86% (924) were ERalpha-PR- and 8.12% (132) were ERalpha-PR+. Patients' age was significantly lower in the ERalpha-PR+ group (P=0.002). Statistical analysis of the grading between the two study groups revealed no significant difference (P=0.091), although the ERalpha-PR+ group contained significantly more poorly differentiated tumors than the ERalpha+PR+ one (P=0.032). Tumor size was also significantly larger in the ERalpha-PR+ than in the ERalpha+PR+ group (P=0.046). The frequency of lymph node metastases was independent of receptor profile. In conclusion, our study group does exhibit characteristics which are suggestive of a distinct breast cancer phenotype (ERalpha-PR+) with a different etiology and prognosis.

Association of G-protein beta-3 subunit gene (GNB3) T825 allele with Type II diabetes.

To date, the human G-protein beta 3 subunit (GNB3) gene and some of its variants represent some of the best examples of genetic influences that are involved in the determination of hypertension and obesity, which make it a sensible candidate gene for type 2 diabetes. To assess the influence of GNB3 in type II diabetes mellitus (NIDDM), we carried out a retrospective, case-control study of variant GNB3 825C>T for putative correlations with NIDDM amongst nationals from the United Arab Emirates (Emirati) - an ethnic group characterized by no alcohol intake and no cigarette smoking. We investigated a sample population of 510 Emirati (257 men, 253 women) comprising two groups - 254 controls and 256 patients with clinical diagnoses of type 2 diabetes (cases). The GNB3 C825T dimorphism showed an association with NIDDM Chi2 =22.5, 2 df, P<0.001). Further analysis revealed that the GNB3 T/T 825 genotype was positively associated with NIDDM (Yates corrected Chi2=20.6, 2 df, P<0.001; odds ratio of 2.44 with a 95% confidence interval of 1.64 - 3.63) compared to pooled CC/CT genotypes. Our data shows that GNB3 T825 allele may be involved in the pathogenesis of DM through a pathway that is different from the one implicated in obesity.