Osteoporosis in Primary Biliary Cirrhosis: A Randomized Trial of the Efficacy and Feasibility of Estrogen/Progestin

The optimal therapy for the prevention and treatment of osteoporosis in primary biliary cirrhosis (PBC) is unknown. Hormone replacement therapy (HRT) prevents osteoporosis, but may promote cholestasis. We performed a double-blind, randomized, placebo-controlled trial of transdermal estrogen/progestin in postmenopausal women with PBC. The 24-month study enrolled 31 patients, but trial uptake was limited and treatment arm dropout was significant. Placebo-treated patients had a higher percentage loss in femoral neck bone mineral density than actively treated patients (−3.76 ± 1.37% versus 0.21 ± 1.01%, respectively, P = .058). New fractures occurred in 2 patients on placebo, and in no patients on treatment. The mean monthly increase in bilirubin was not significantly different between groups, but individual data suggest HRT may worsen cholestasis. In conclusion, women with PBC have strong feelings about HRT, and recruitment for this intervention is difficult. Transdermal estrogen/progestin likely provides protection against bone loss in PBC patients, but may worsen cholestasis. Supported by Canadian Institute of Health Research Grant PA-12412. Transdermal estrogen/progestin and placebo supplied by Novartis.     

Inhibitory effect of adenosine on electrically evoked contractions in the rat vas deferens: pharmacological characterization

The inhibitory effects of adenosine as well as its related analogues on the contractile response of the rat vas deferens to field stimulation were compared in the absence and in the presence of nitrobenzylthioguanosine (NBTGR), a potent adenosine uptake inhibitor. In the presence of NBTGR, the order of potency was N6-cyclohexyladenosine (CHA) greater than or equal to L-N6-phenylisopropyladenosine (L-PIA) greater than 2-chloroadenosine greater than D-N6-phenylisopropyladenosine (D-PIA) greater than or equal to adenosine greater than 2'-deoxyadenosine. The inhibitory effect of adenosine but not that of clonidine, beta-endorphin and somatostatin was blocked by 1,3-diethyl-8-phenylxanthine (DPX, pA2 = 7.2), a potent P1-purinergic antagonist. The results suggest that adenosine inhibited the electrically evoked contractions of the rat vas deferens via the activation of the A1 subtype of P1-purinergic receptors.     

The meaning of pain relief in a clinical trial.

Data from 207 subjects in the early postoperative period in a controlled clinical trial were used to examine the factors that contribute to global ratings of satisfaction with pain relief. Prerecovery to postrecovery period change scores in pain intensity were not significantly associated with level of satisfaction with pain relief. However, endpoint pain intensity, average pain intensity, recall rating of maximum pain, and actual maximum pain during the immediate postoperative period all predicted relief satisfaction. Of these predictors, average pain and change in pain were associated with relief satisfaction when controlling for all the predictors. The average pain levels reported by patients who rated themselves as being "very satisfied" and "somewhat satisfied" with the level of pain relief were 32.86 (on a 0 to 100 visual analogue scale [VAS]) and 40.00, respectively. Patients who were "slightly satisfied," "neither satisfied nor dissatisfied," and "slightly," "somewhat," and "very dissatisfied" reported similar levels of average pain during the recovery period (range = 51.37-56.32). The findings indicate that the primary variable related to relief satisfaction following surgery during the immediate postoperative period is an average of the pain intensity experienced during this time period. PERSPECTIVE: In order to be "very satisfied" with pain relief during the postoperative period, patients are not required to experience no pain. Rather, the study findings suggest that mild pain averaging less than 40 on a 0 to 100 VAS is adequate. However, moderate pain during the early recovery period averaging about 50 or more on a 0 to 100 VAS appears to be associated with dissatisfaction with pain relief.     

Advantages of blood pressure optimization

Lowering blood pressure (BP) reduces cardiovascular events, but aggressive BP management may not be advantageous. Optimal BP control (target: < 120/ 80 mm Hg) and conventional BP control (target: < 140/90 mm Hg) were compared in patients with hypertension in terms of target-organ damage and tolerability. A total of 23 patients with hypertension were randomly assigned to optimal versus conventional therapy for 6 months. Therapy was initiated with lercanidipine 10 mg/day. For BP control, the dose could be doubled or other drugs added. Three indices of target-organ damage were studied: left ventricular mass (LVM) index, flow-mediated dilatation (FMD) of the brachial artery, and 24-hour urinary albumin excretion. The BP decreased markedly by 21.3±3.4/13.2±1.7 mm Hg in the conventional therapy group and by 26.6±3.6/17.9±1.5 mm Hg in the optimal therapy group. Diastolic BP was significantly lower, by 4.7±2.3 mm Hg, in the optimal therapy group (P < .05). Ambulatory BP was also decreased in both groups. There was no significant change in LVM or FMD in either group. Baseline LVM index and FMD values were correlated with systolic BP (r=0.51, P=.02; r=0.54, P=.009). In the optimal therapy group, urinary albumin excretion increased significantly (P=.04). Plasma levels of B-type natriuretic peptide (BNP) decreased with antihypertensive therapy (P=.03). Treatment was well tolerated, and none of the patients withdrew from the study. There was no significant difference in adverse events between the 2 groups. Optimization of BP is feasible, safe, and well tolerated; however, a larger study of longer duration may be needed to demonstrate improvements in LVM and endothelial function with conventional versus optimal therapy.     

Mechanism of immediate recurrences of atrial fibrillation after restoration of sinus rhythm

An immediate recurrence of AF may occur after restoration of sinus rhythm. Although pulmonary vein (PV) isolation has been shown to prevent immediate recurrence of AF, the specific trigger for immediate recurrence of AF has not been described. In 89 consecutive patients (mean age 53 +/- 11 years) who had sinus rhythm restored by spontaneous or transthoracic cardioversion in the course of a PV isolation procedure, electrograms recorded within a PV and in the adjacent left atrium were analyzed to determine the mechanism of initiation of immediate recurrence of AF. Immediate recurrence of AF was defined as a recurrence of AF within 90 seconds after restoration of sinus rhythm. There were 124 episodes of immediate recurrence of AF at a mean of 18 +/- 23 seconds after cardioversion. Recordings within the PV that triggered the immediate recurrence of AF were available in 23 (19%) of the 124 immediate recurrence of AF episodes. Among these 23 episodes of immediate recurrence of AF, all (100%) were triggered by a burst of PV tachycardia (P < 0.001). The coupling interval and prematurity index (coupling interval/preceding sinus cycle length) of the premature depolarizations that did and did not trigger immediate recurrence of AF were 246 +/- 67 ms and 0.30 +/- 0.11 vs 378 +/- 117 ms and 0.49 +/- 0.16, respectively (P < 0.01). Immediate recurrence of AF was abolished by PV isolation. The mechanism of immediate recurrence of AF is a burst of PV tachycardia, not a single premature depolarization. Immediate recurrence of AF identifies patients with AF in whom the PVs may play a major role in the initiation of AF.     

Chinese translation and validation of the Nowicki-Strickland Locus of Control Scale for Children

The objective of this study is to evaluate the psychometric properties of the Chinese version of the Nowicki-Strickland Locus of Control Scale for Children for its utility in clinical research and nursing practice. The scale was translated from the original English language into the Chinese language and the reliability and validity of the translated scale were tested. Results showed that there was high test re-test reliability, acceptable internal consistency reliability, appropriate content validity, concurrent validity and construct validity. It is concluded that the psychometric properties of the Chinese version of the Nowicki-Strickland Locus of Control Scale for Children presented in this paper supports its feasibility as a research instrument to measure children's locus of control objectively and appropriately in the Chinese population.     

Psychometric evaluation of the Chinese version of the State Anxiety Scale for Children

The assessment of anxiety in children undergoing surgery must be addressed before any intervention can be appropriately planned, provided, and evaluated. The purpose of this study was to evaluate the psychometric properties of the Chinese version of the State Anxiety Scale for Children. Two hundred and thirty-seven children from a primary school and 112 children admitted for day surgery were recruited for this study. The instrument demonstrated adequate internal-consistency reliability, appropriate concurrent validity, and construct validity. Factor analyses further confirmed the construct validity of the scale, with a good fit between the factor structure of the scale and the observed data. Results suggest that the Chinese version of the State Anxiety Scale for Children can be used as a self-report assessment tool in measuring the anxiety level of Chinese children ages 7-12 years.     

Incremental value of isolating the right inferior pulmonary vein during pulmonary vein isolation procedures in patients with paroxysmal atrial fibrillation

Electrical isolation of the left superior, left inferior, and right superior pulmonary veins (PVs) is often, but not always, effective in eliminating paroxysmal atrial fibrillation (PAF). The incremental clinical value of also isolating the right inferior PV has not been well defined. PV isolation by ostial applications of radiofrequency energy guided by PV potentials was performed in 176 consecutive patients (mean age 52 +/- 11 years) with PAF. The left superior, left inferior, and right superior PVs were targeted in 106 patients, and all four PVs were targeted 70 patients. Successful isolation was achieved in 96% of targeted PVs. The mean duration of follow-up was 15 +/- 7 months. At 1-year follow-up, 58% of patients in whom three PVs were isolated were free of recurrent PAF in the absence of antiarrhythmic drug therapy, compared to 73% of patients in whom all four PVs were isolated (P = 0.07). There is a trend towards a better outcome when all four PVs are isolated than when only the three major PVs are isolated. Whenever feasible, the right inferior PV should be isolated along with the other three PVs during the first ablation procedure in patients with PAF.