Clinical outcomes by race in hypertensive patients with and without the metabolic syndrome: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

BACKGROUND: Antihypertensive drugs with favorable metabolic effects are advocated for first-line therapy in hypertensive patients with metabolic/cardiometabolic syndrome (MetS). We compared outcomes by race in hypertensive individuals with and without MetS treated with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), an alpha-blocker (doxazosin mesylate), or an angiotensin-converting enzyme inhibitor (lisinopril). METHODS: A subgroup analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind hypertension treatment trial of 42 418 participants. We defined MetS as hypertension plus at least 2 of the following: fasting serum glucose level of at least 100 mg/dL, body mass index (calculated as weight in kilograms divided by height in meters squared) of at least 30, fasting triglyceride levels of at least 150 mg/dL, and high-density lipoprotein cholesterol levels of less than 40 mg/dL in men or less than 50 mg/dL in women. RESULTS: Significantly higher rates of heart failure were consistent across all treatment comparisons in those with MetS. Relative risks (RRs) were 1.50 (95% confidence interval, 1.18-1.90), 1.49 (1.17-1.90), and 1.88 (1.42-2.47) in black participants and 1.25 (1.06-1.47), 1.20 (1.01-1.41), and 1.82 (1.51-2.19) in nonblack participants for amlodipine, lisinopril, and doxazosin comparisons with chlorthalidone, respectively. Higher rates for combined cardiovascular disease were observed with lisinopril-chlorthalidone (RRs, 1.24 [1.09-1.40] and 1.10 [1.02-1.19], respectively) and doxazosin-chlorthalidone comparisons (RRs, 1.37 [1.19-1.58] and 1.18 [1.08-1.30], respectively) in black and nonblack participants with MetS. Higher rates of stroke were seen in black participants only (RR, 1.37 [1.07-1.76] for the lisinopril-chlorthalidone comparison, and RR, 1.49 [1.09-2.03] for the doxazosin-chlorthalidone comparison). Black patients with MetS also had higher rates of end-stage renal disease (RR, 1.70 [1.13-2.55]) with lisinopril compared with chlorthalidone. CONCLUSIONS: The ALLHAT findings fail to support the preference for calcium channel blockers, alpha-blockers, or angiotensin-converting enzyme inhibitors compared with thiazide-type diuretics in patients with the MetS, despite their more favorable metabolic profiles. This was particularly true for black participants.     

Assessing the validity of existing dental sealant quality measures

Background

Although sealants are highly effective in preventing caries in children, placement rates continue to be low. The authors’ goals were to implement and assess the performance of 2 existing sealant quality measures against a manual audit of charts at 4 dental institutions and to identify measurement gaps that may be filled by using data from electronic health records.

Clinical outcome of patients with venous thromboembolism and recent major bleeding: findings from a prospective registry (RIETE)

BACKGROUND: Patients who have experienced a recent major bleeding episode are usually excluded from clinical studies of venous thromboembolism (VTE) treatment. Therefore, recommendations based on evidence from clinical trials may not be suitable for these patients. The Registro Informatizado de la Enfermedad TromboEmbolica (RIETE) is a multicenter, observational registry designed to gather and analyze data on VTE treatment practices and clinical outcomes in patients with acute VTE. OBJECTIVES: The aim of this analysis was to study outcomes of patients with VTE who had experienced recent major bleeding (< 30 days prior to VTE diagnosis). METHODS: Patients with objectively confirmed symptomatic acute VTE are consecutively enrolled into the RIETE registry. Patient characteristics, details of antithrombotic therapy, and clinical outcomes at 3 months were recorded. RESULTS: Of 6361 patients enrolled up to January 2004, 170 (2.7%) had experienced recent major bleeding: 69 (40.6%) gastrointestinal tract, 60 (35.3%) intracranial, 41 (24.1%) other. The incidences of major bleeding (4.1%) and recurrent pulmonary embolism (PE) (2.4%) were significantly higher in patients with recent major bleeding. Among them, patients with cancer had an increased incidence of major bleeding [odds ratio (OR) 10.0, 95% confidence interval (CI) 2.3, 50; P < 0.001] and fatal PE (OR 4.1, 95% CI 0.98, 17; P < 0.05). CONCLUSIONS: Patients with VTE and recent major bleeding prior to VTE diagnosis (2.7% of total enrolled patients) had poorer clinical outcomes compared with those who had not experienced recent major bleeding. In patients who had recent major bleeding prior to enrollment, those with cancer had a poorer clinical outcome than those without cancer.     

A practical guide to the management of menopausal symptoms in breast cancer patients

Breast cancer is the most frequently diagnosed cancer in Canadian women. As a result of increased screening and improved treatment, more women are becoming long-term breast cancer survivors. However, due to either their treatment or prolonged survival, many of these women now have to face the consequences of premature menopause and prolonged estrogen deprivation. Hormone replacement therapy/estrogen replacement therapy (HRT/ERT) has, in the past, been recommended to healthy women at menopause not only for relief of short-term menopausal changes, particularly hot flashes, but also for its benefits on bone density, fracture reduction, and genitourinary symptoms. Recent studies have demonstrated that not only is HRT associated with an increased risk of developing breast cancer, but it also has been shown to increase the risk of recurrence in those with a breast cancer history. Until the safety of HRT/ERT in breast cancer patients can be more fully clarified, it would be wise to develop alternative strategies for the management of menopausal symptoms in these patients. This paper will discuss nonestrogen-based therapies for hot flashes, osteoporosis, and genitourinary symptoms, with emphasis on efficacy and safety in breast cancer survivors.     

Effects of bile salt and phospholipid hydrophobicity on lithogenicity of human gallbladder bile

Abstract Increased biliary bile salt and phospholipid hydrophobicity may promote nucleation of cholesterol crystals and gallstone formation. We therefore compared bile salt composition (determined by gas-liquid chromatography) in patients with cholesterol ( n = 35) and pigment ( n = 16) gallstones (group A). Bile salt composition and cumulative bile salt hydrophobicity index were not different between both stone types. Hydrophobicity index or % of individual bile salts did not correlate with cholesterol saturation index or nucleation time. In an additional 21 cholesterol stone patients (group B) biliary bile salt and phospholipid hydrophobicity as determined by high-pressure liquid chromatography did not correlate with cholesterol saturation index or nucleation time. In both group A and group B, cholesterol stone patients with cholesterol crystals in their fresh biles had a higher % deoxycholic acid, a lower % cholic acid and a higher bile salt hydrophobicity index than crystal-negative patients. This study indicates the need for further research on the role of bile salt hydrophobicity in the pathogenesis of gallstones.     

In Vivo Ventricular Lesion Growth in Radiofrequency Catheter Ablation

While radiofrequency catheter ablation has proved highly effective in the treafment of various supravenfricular tQchyarrhythmias, resulls in the trentment of ventricular tachycardia invite improvement. Knowledge of lesion growth in vivo might improve understanding of this discrepancy. So far only information from in vitro and in vivo studies using a small 2 mm tip eiectrode is available. Growlh of ventricular radiofrequency lesions created with a 4 mm ahlalion electrode was studied in 11 closed-chest dogs. Endocardia] ablations were performed at 31 left and 35 right ventricuiar sites at a power setting of 25 Watts and 5, 10, 20, 30 or 60 seconds pulse duration. Macroscopic and histopathologic lesion examination were performed after one week survival. Mean lesion volume increased from 52 mm³ after 5 seconds pulse duration to a maximum 388 mm³ and approximately 7 mm depth after 30 seconds. Lesions were prolate spheroid in form, with a sparing of subendocardial myocardium and maximum lesion diameter at some millimeters depth. Results indicate that catheter positioning at no more tlian 7 mm from the target is required for successful ablation. Due to lesion geometry, subendocardial targets demand even more exact catheter positioning, while subepicardial substrates may not be ammenable to ablation if ventricular wall thickness exceeds 7 mm at the ablation site. Repeated pulses at adjacent sites may be required for ablation of extended arrhytbmogenic areas. Volume at 5 seconds was only approximately 15% of mature lesions. Therefore, the use of a short'test pulse after careful mapping may be useful to pinpoint the most appropriate site for ablation in discrete pathways.     

Seasonal trends and maternal characteristics as predictors of maternal undernutrition and low birthweight in Eastern Maharashtra,India

Few studies have assessed whether women and infants in rural and peri‐urban communities in South Asia experience seasonal fluctuations in nutritional status; however, a handful of studies have documented seasonal variability in risk factors for undernutrition including food availability, physical activity and infections. We used data from the Maternal and Newborn Health (MNH) registry, a population‐based pregnancy and birth registry in Eastern Maharashtra, India, to analyse seasonal trends in birthweight and maternal nutritional status—body mass index (BMI) and haemoglobin—in the first trimester of pregnancy. We plotted monthly and seasonal trends in birthweight, and maternal BMI and haemoglobin, and used multivariable regression models to identify seasonal and maternal characteristics that predicted each outcome. Between October 2014 and January 2018, MNH included 29,253 livebirths with recorded birthweight. BMI was assessed in 15,252 women less than 12 weeks of gestation and haemoglobin in 18,278 women less than 13 weeks of gestation. Maternal characteristics (age, education, parity and height) were significantly associated with nutritional status; however, there were minimal seasonal fluctuations in birthweight or maternal nutrition. There were significant secular trends in maternal haemoglobin; between 2014 and 2018, the prevalence of maternal anaemia decreased from 91% to 79% and moderate or severe anaemia from 53% to 37%. The prevalence of maternal underweight (45.3%) and overweight (9.8%) and low birthweight (19.1%) remained relatively constant over the study period. Our findings highlight that in some rural and peri‐urban areas in South Asia, tackling systemic drivers of malnutrition may be more effective than targeted interventions based on season.     

Monocyte antigen CD14 is a phospholipid anchored membrane protein

A cDNA clone encoding the human monocyte antigen CD14 was isolated by transient expression in COS cells of a cDNA library prepared from phorbol diester-treated HL60 cells. RNA blot analysis showed abundant expression of a single mRNA species in mature monocytes and an increased expression of the mRNA following induction of differentiation in leukemic cell lines. The DNA blot hybridization pattern was consistent with a single-copy gene. The predicted amino acid sequence lacks the characteristic transmembrane domain and stop transfer motif of conventionally anchored membrane proteins. COS cells transfected with the CD14 cDNA released virtually all CD14 protein in soluble form following treatment with glycosyl phosphatidylinositol-specific phospholipase C, and CD14 immunoreactivity was absent from the affected monocytes of a patient with paroxysmal nocturnal hemoglobinuria (PNH). The data show that, to the limit of experimental sensitivity, all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid.     

Initial Experience with the High-Density Mesh Ablation Catheter for Pulmonary Vein Isolation

Background: Pulmonary vein isolation (PVI) is usually performed with multiple point-by-point radiofrequency ablation with a second multielectrode circular mapping catheter to validate isolation. We evaluated a 30-mm high-density mesh electrode (HDMA) for mapping and PVI in patients with recurrent atrial fibrillation (AF).
Methods: In 13 patients (validation group) up to three pulmonary veins (PVs) were targeted with the HDMA. A circular mapping catheter was used to validate PVI. PVI was completed with a CARTO-guided approach (Biosense Webster, Diamond Bar, CA, USA) followed by a voltage remap. In 11 patients (feasibility group) the HDMA catheter was evaluated as a stand-alone mapping and ablation tool.
Results: The diagnostic accuracy of the HDMA catheter to evaluate PVI was 100%. The encircled low-voltage area (<0.15 mV) after HDMA-guided PVI was smaller compared to CARTO-guided PVI. In the feasibility group 76% of the PVs could be isolated. Complete isolation of all PVs was feasible in five patients (45%) with a mean procedure and fluoroscopy time of respectively 180 ± 39 minutes and 40 ± 14 minutes. After 1 year 64% of the patients were free of symptomatic AF.
Conclusions: The HDMA electrode is a reliable mapping tool to validate PVI. The majority of PVs can be isolated, but on a patient basis touch-up ablations are necessary in more than 50% of the cases. Therefore, modifications in catheter design are required. The small area of voltage abatement points to an ostial left atrium-pulmonary vein disconnection. Initial clinical results in a small number of patients are promising.