Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD‐AF and treated with vitamin K antagonists

Vitamin K antagonist (VKA) therapy for stroke prevention in atrial fibrillation (AF) requires monitoring of the international normalized ratio (INR). We evaluated the agreement between two INR audit parameters, frequency in range (FIR) and proportion of time in the therapeutic range (TTR), using data from a global population of patients with newly diagnosed non‐valvular AF, the Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD‐AF). Among 17 168 patients with 1‐year follow‐up data available at the time of the analysis, 8445 received VKA therapy (±antiplatelet therapy) at enrolment, and of these patients, 5066 with ≥3 INR readings and for whom both FIR and TTR could be calculated were included in the analysis. In total, 70 905 INRs were analysed. At the patient level, TTR showed higher values than FIR (mean, 56·0% vs 49·8%; median, 59·7% vs 50·0%). Although patient‐level FIR and TTR values were highly correlated (Pearson correlation coefficient [95% confidence interval; CI], 0·860 [0·852–0·867]), estimates from individuals showed widespread disagreement and variability (Lin's concordance coefficient [95% CI], 0·829 [0·821–0·837]). The difference between FIR and TTR explained 17·4% of the total variability of measurements. These results suggest that FIR and TTR are not equivalent and cannot be used interchangeably.     

Prognostic Significance and Prevalence of IgG Subtypes in Rh Haemolytic Disease of Fetus and Newborn

Many authors have reported poor prognostic value of anti-D antibody titer in the setting of Hemolytic Disease of Fetus and Newborn (HDFN). According to literature, HDFN cases with IgG1 and IgG3 have more severity compared to IgG2 and IgG4.Therefore, we planned this study to evaluate the prevalence and prognostic value of IgG subtypes in the setting of Rh HDFN. This was a retrospective study performed at a tertiary care center in north India from October 2015 to November 2017. Women with anti-D antibody were included in the study and categorized on the basis of presence of specific IgG subtype. “DAT IgG1/IgG3 ID” card (BIO-RAD) was used for determining the subclass of IgG. Various clinical, laboratory & interventional parameters were used to categorize fetal outcome in severe and non-severe cases. Perinatal outcome was then compared between women with different IgG subclass profile. Subclass distribution among 80 alloimmunized women was 26.2% for IgG1, 15% for IgG3, 46.2% for IgG1 + IgG3 and the rest had neither IgG1 nor IgG3. Severity of HDFN was significantly higher when IgG1 &/or IgG3 were present alone or in combination, compared to cases with absence of IgG1 or IgG3 (p value < 0.05). Risk of severe HDFN was significantly higher in the presence of IgG1 &/or IgG3 and the severity was highest when both IgG1 and IgG3 were present. We recommend that IgG subclass determination should be included in a multi—parameter protocol for more accurate prediction HDFN severity to ensure timely referral and intervention.     

Loss of Left Ventricular Torsion as the Predominant Mechanism of Left Ventricular Systolic Dysfunction in a Patient with Tubercular Cardiomyopathy

Pericarditis is the commonest form of cardiac involvement in tuberculosis whereas myocardial involvement is exceedingly rare. We hereby report a patient who presented with cardiac tuberculosis manifesting as predominantly right‐sided cardiomyopathy. In addition to being a very rare clinical presentation, this case provided an interesting insight into the left ventricular (LV) myocardial mechanics. The patient had nearly preserved contractile function of the LV myocardium (except for segmental abnormalities in circumferential strain) but had marked impairment of torsion resulting in LV systolic dysfunction. Such disproportionate loss of LV torsion leading to LV systolic dysfunction has not been previously described on echocardiography. These myocardial mechanical abnormalities almost completely recovered with adequate antitubercular treatment. Thus, this case proved to be a unique demonstration of the significant, independent role played by torsion in maintenance of normal LV systolic function.     

Implications of acute left ventricular remodeling during squatting stress echocardiography

Background: We previously demonstrated that squatting induces left ventricular (LV) wall motion abnormalities (WMA) in areas subtended by stenotic coronary arteries. In addition, it was observed that some subjects developed acute changes in LV shape (acute left ventricular remodeling [ALVRM]) during squatting. Objective: This study tested the hypothesis that patients with ALVRM during squatting echocardiography have higher incidences of severe coronary artery disease (CAD). Methods: Echocardiography was performed in all standard views during standing and squatting. End‐systolic frames in the apical four‐chamber view were analyzed. Results: The subjects were divided into three groups. Group 1 consisted of 12 subjects who developed squatting‐induced ALVRM with apical and distal posterior septal akinesis, dilation of the apex and marked LV shape change at end‐systole. Group 2 consisted of 20 subjects with distal posterior septal and apical akinesis without ALVRM, during squatting. Group 3 consisted of 64 subjects who developed WMA in areas other than the apex (n = 49), or normal wall motion (n = 15) during squatting. Coronary angiography in group 1 revealed that 6 subjects had left main coronary artery stenosis (LMCAS ≥ 50%), two had severe three vessel disease (≥90% stenosis), and one had 100% left anterior descending coronary artery occlusion. Severe CAD was defined for purpose of this study as the presence of LMCAS, or severe three vessel disease (≥90% stenosis). Six subjects in group 2 had LMCAS and none had severe three vessel disease (P < 0.05 vs. group 1 for LMCAS and/or three vessel disease). In group 3, eight had LMCAS and none had severe three vessel disease (P < 0.0001 vs. group 1). Conclusion: Patients with ALVRM have severe CAD. Therefore, patients who develop ALVRM during squatting require urgent evaluation for revascularization therapy. (Echocardiography 2012;29:700‐705)     

Pathogen burden, cytomegalovirus infection and inflammatory markers in the risk of premature coronary artery disease in individuals of Indian origin

BACKGROUND:

Coronary artery disease (CAD) occurs at an earlier age in South Asians compared with other ethnic groups. Infection and inflammation show a positive association with the disease.

OBJECTIVE:

To investigate the association of infection and inflammatory markers with premature CAD in the Indian Atherosclerosis Research Study population.

METHODS:

Antibody titres for Chlamydia pneumoniae, cytomegalovirus (CMV), Helicobacter pylori, herpes simplex virus and levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), fibrinogen and secretory phospholipase A2, were measured in 866 individuals (433 CAD patients and matched controls). All individuals were followed-up for recurrent cardiac events for four years. ANOVA was used to study the association of infection and inflammation with CAD.

RESULTS:

The present study found that the odds of CAD occurrence was 2.42 (95% CI 1.26 to 4.64; P<0.008), with all four infections and increased in the presence of hsCRP (OR 4.67 [95% CI 1.43 to 15.25]); P=0.011). Only anti-CMV antibody levels were a significant risk factor for CAD occurrence (OR 2.23 [95% CI 1.20 to 4.15]; P=0.011) and recurrent cardiac events (OR 1.94 [95% CI 0.85 to 4.45]; P=0.015). Mean values of the inflammatory biomarkers IL-6 (P=0.035), fibrinogen (P=0.014), hsCRP (P=0.010) and secretory phospholipase A2 (P=0.002) increased with CMV antibody levels. Incorporating hsCRP and IL-6 in the risk prediction models significantly increased the OR to 2.56 (95% CI 1.16 to 5.63; P=0.019) with a c statistic of 0.826.

CONCLUSIONS:

Pathogen burden, especially CMV infection in combination with inflammatory markers, is a significant predictor of CAD risk in the young Indian population.     

Impact of a Simple Inexpensive Quality Assurance Effort on Physician's Choice of Thrombolytic Agents and Door-to-Needle Time: Implication for Costs of Management

The objective of this study were to assess the impact of a quality assurance effort on the door-to-needle time and the choice of thrombolytic agent for the management of acute myocardial infarction in the emergency department. The study design involved a prospective collection of data on a series of consecutive patients who received a thrombolytic agent for a presumed acute myocardial infarction. The study was carried out in the emergency department of a major university urban tertiary care center. A total of 349 patients were studied from September 1989 to March 1994. The quality assurance program began in 1989 and included chart review of all patients receiving thrombolytic therapy, with special attention to all patients with door-to-needle times >60 minutes to identify causes for delay. Feedback was directed to pharmacy, nursing, and physician staff. Biannual reports were distributed throughout the hospital and the emergency department. Nursing-specific feedback led to the development of protocols for all aspects of the delivery of thrombolytic agents. The choice of thrombolytic agent was not dictated by the protocol, but the physician staff was continuously updated on the results of the latest clinical trials comparing one thrombolytic agent with another. The mean age was 58 years for men and 67 years for women in this cohort consisting of 78% men and 22% women. Thirty-seven percent of the myocardial infarctions were in an anterior location and 56% were in an inferior location. The median duration of chest pain before presentation to the emergency department was 120 minutes. Hospital mortality was 3%. Median door-to-needle time fell from 46 (1989–1991) to 36 (1992–1994) minutes, P < 0.01. The percentage of patients with a door-to-needle time >60 minutes decreased from 35% (1989–1991) to 16% (1992–1994) minutes, P < 0.0001. Corresponding with the ISIS-3 report, there was a significant increase in the proportion of patients receiving streptokinase over the first 3 years of the study (P < 0.0001), which changed to a trend toward increased utilization of tissue plasminogen activator with the GUSTO report in the final 6 months of the study. In conclusion, a quality assurance program led to a significant reduction in the door-to-needle time, and recent megatrials were found to influence the choice of thrombolytic agent used.     

Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment

ABSTRACT: BACKGROUND: For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events. METHODS: In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. FINDINGS: A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p= 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p= 0.05). Rates of adverse events were similar. Interpretation: Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. Clinical trial registry number CTRI/2011/12/002260.     

"The group" in integrated HIV and livelihoods programming: opportunity or challenge?

HIV care and treatment providers across sub-Saharan Africa are integrating livelihood interventions to improve food security of their clientele. Many integrated HIV and livelihood programmes (IHLPs) require the formation and use of groups of HIV-infected/affected individuals as the operational target for programme interventions, indeed, virtually without exception the group is the focal point for material and intellectual inputs of IHLPs. We sought to critically examine the group approach to programming among IHLPs in Uganda, and to explore and problematise the assumptions underpinning this model. A case study approach to studying 16 IHLPs was adopted. Each IHLP was treated as a case comprising multiple in-depth interviews conducted with staff along the livelihood programme chain. Additionally, in-depth interviews were conducted with staff from The AIDS Support Organization (TASO), and with members of 71 HIV-infected TASO-registered client households. Our analysis reveals three important considerations in IHLP programming regarding the group-centred approach: (1) Group membership is widely held to confer benefits in the form of psycho-social and motivational support, particularly in empowering individuals to access HIV services and handle stigma. This is contrasted with the problem of stigma inherent in joining groups defined by HIV-status; (2) Membership in groups can bring economic benefits through the pooling of labour and resources. These benefits however need to be set against the costs of membership, when members are required to make contributions in the form of money, goods or labour; (3) Sharing of goods and labour in the context of group membership allow members to access benefits which would otherwise be inaccessible. In exchange, individual choice and control are diminished and problems of resources held in common can arise. While the group model can bring benefits to IHLP efficiency and by extension to food security, and other outcomes, its application needs to be carefully scrutinised at the individual programme level, in terms of whether it is an appropriate approach, and in terms of mitigating potentially adverse effects.     

The epistasis between vascular homeostasis genes is apparent in essential hypertension

ObjectiveThe epistasis influence of vascular homeostasis genes is vital to multigenetic diseases. This study was designed to perceive the possible role of epistasis in the etiology of essential hypertension.MethodsWe investigated seven polymorphisms of ACE, CYP11B2 and NOS3 epistatically, and SBP, DBP, MAP, ACE activity, plasma aldosterone concentration (PAC) and NOx level in 860 age- and ethnicity-matched unrelated north-Indian subjects.ResultsThe hypertension risk in individuals with interacted-genotypes (IwIw + IwIc) + (4aa), (IcIc) + (4bb + 4ba) and IcIc + 4aa of the CYP11B2 and NOS3 was significantly higher with odds ratio 5.5 (95% CI = 2.9–10.6, P < 0.0001), 2.4 (95% CI = 1.4–4.1, P < 0.0008) and 7.5 (95% CI = 1.6–34.8, P = 0.010), respectively. The odds ratio for hypertension with interacted-haplotypes (?344T/Ic) + (?922A/?786T/4a/894G) and (?344T/Ic) + (?922G/?786C/4a/894G) of CYP11B2 and NOS3 was 5.3 (95% CI = 2.0–14.2, P = 0.005) and 3.9 (95% CI = 1.4–10.4, P = 0.04), respectively; whereas for the protective interacted-haplotypes (?344T/Iw) + (?922A/?786T/4b/894G), the odds ratio was 0.7 (95% CI = 0.5–0.9, P = 0.03). While the interacted-genotypes, IcIc + 4aa correlated with higher SBP and MAP (P = 0.006; P = 0.04), the interacted-haplotypes, (?344T/Ic) + (?922A/?786T/4a/894G) and (?344T/Ic) + (?922G/?786C/4a/894G) correlated with higher MAP and lower NOx level (P = 0.02 and P = 0.03, respectively), and the protective interacted-haplotypes (?344T/Iw) + (?922A/?786T/4b/894G) correlated with lower PAC and MAP (P = 0.024 and P = 0.018, respectively).ConclusionsThe epistasis between CYP11B2 and NOS3 and its correlation with varied clinical and biochemical parameters signify its possible contribution in the complex etiology of hypertension.     

Estrogen regulation of brain vasotocin secretion in the catfish Heteropneustes fossilis: an interaction with catecholaminergic system

Vasotocin (VT) is a basic neurohypophysial nonapeptide in non-mammalian vertebrates and is involved in diverse functions like osmoregulation, reproduction, metabolism and behavior. In this study, we report that estradiol-17β (E(2)) regulates brain and plasma VT secretion through the involvement of the catecholaminergic (CA) system. To demonstrate this, E(2) level was altered through ovariectomy (OVX, 3 weeks) and replacement study with low and high E(2) doses (0.1 and 0.5 μg/g body weight). CA activity was inhibited by treatment with α-methylparatyrosine (α-MPT; 250 μg/g body weight), a competitive inhibitor of tyrosine hydroxylase. VT was assayed by an enzyme immunoassay method. In the sham group, the low E(2) dose produced 82% and 104% increase, respectively, in brain and plasma VT levels. The high E(2) dose decreased the VT levels significantly. The low E(2) dose decreased brain E(2) but elevated plasma E(2). In the high E(2) group, the E(2) level increased further in both brain and plasma. OVX resulted in a significant inhibition (69% and 25%, respectively) of both brain and plasma VT, which was correlated with low E(2) levels. The low E(2) dose not only reversed the inhibition, but increased the VT level in both brain and plasma in comparison to the sham groups. The high E(2) replacement inhibited VT levels further low in both brain and plasma. The α-MPT treatment inhibited VT levels significantly in both sham and OVX groups. The drug treatment abolished partially the restorative effect of the low E(2) dose in the ovariectomized fish. In the high E(2) dose group, α-MPT decreased brain and plasma VT levels further low compared to the sham + 0. 5 μg E(2) group or OVX + 0.5 μg E(2) group except the brain VT level, which increased in the OVX+0.5 μg E(2) group. It is inferred that E(2) may exert biphasic effects on VT through the mediation of the CA system.