Improving Medication Adherence in Patients with Hypertension: A Randomized Trial

Background and Purpose

In patients with hypertension, medication adherence is often suboptimal, thereby increasing the risk of ischemic heart disease and stroke. In a randomized trial, we investigated the effectiveness of a multifaceted pharmacist intervention in a hospital setting to improve medication adherence in hypertensive patients. Motivational interviewing was a key element of the intervention.

Methods

Patients (n = 532) were recruited from 3 hospital outpatient clinics and randomized to usual care or a 6-month pharmacist intervention comprising collaborative care, medication review, and tailored adherence counseling including motivational interviewing and telephone follow-ups. The primary outcome was composite medication possession ratio (MPR) to antihypertensive and lipid-lowering agents, at 1-year follow-up, assessed by analyzing pharmacy records. Secondary outcomes at 12 months included persistence to medications, blood pressure, hospital admission, and a combined clinical endpoint of cardiovascular death, stroke, or acute myocardial infarction.

Results

At 12 months, 20.3% of the patients in the intervention group (n = 231) were nonadherent (MPR <0.80), compared with 30.2% in the control group (n = 285) (risk difference −9.8; 95% confidence interval [CI], −17.3, −2.4) and median MPR (interquartile range) was 0.93 (0.82-0.99) and 0.91 (0.76-0.98), respectively, P = .02. The combined clinical endpoint was reached by 1.3% in the intervention group and 3.1% in the control group (relative risk 0.41; 95% CI, 0.11-1.50). No significant differences were found for persistence, blood pressure, or hospital admission.

Conclusions

A multifaceted pharmacist intervention in a hospital setting led to a sustained improvement in medication adherence for patients with hypertension. The intervention had no significant impact on blood pressure and secondary clinical outcomes.     

Cell cycle progression of B-chronic lymphocytic leukemia cells induced to differentiate by TPA

The cell cycle transition and differentiation-associated surface antigen expression was studied in a clone of B cell chronic lymphocytic leukemia (B-CLL) with phenotypic properties similar to those of resting B lymphocytes. Differentiation was induced with TPA (12-O-tetradecanoyl- phorbol-13-acetate) and defined and quantitated by morphological and functional markers. Changes in the cell cycle position were determined by flow cytometry of acridine orange-stained cells. The uninduced B-CLL cells represented a homogeneous population with the same cell cycle position (GO) as resting normal peripheral blood lymphocytes. After five days of TPA stimulation, 56% of the B-CLL cells were found in G1A, 9% in G1B, and 3% in the S + G2/M phase, of which 2% was accounted to proliferating T cells. The cell cycle transition of the differentiating B-CLL cells was also examined using cell cycle-associated surface antigens as markers. HLA-DR and CD23 antigens were present already on noninduced cells. The former had a high constant expression, while the amount of CD23 increased upon induction. The 4F2 antigen was absent on noninduced cells but present on 86% of the induced cells. HH1 (CD37) was expressed by the majority of the cells before TPA treatment and decreased to almost undetectable levels within 24 hours. Two antigens related to late stages of the cell cycle, the interleukin 2 (IL 2; CD25) and the transferrin receptor, were present on about 20% of the induced cells. Experiments with enriched T cells showed that T but not B cells incorporated 3H-thymidine. Taken together these results and previous work on the induction of the protooncogene c-myc and c-fos suggest that this B-CLL clone represents GO cells that undergo differentiation without concomitant proliferation when exposed to TPA.     

Arterial plasma norepinephrine correlates to blood pressure in middle-aged men with sustained essential hypertension

Increased plasma catecholamine levels assessed from the venous blood have been found in a number of studies of younger patients with essential hypertension, but hypertensive-normotensive differences could not easily be demonstrated in subjects above 40 years of age. For several reasons, measurement of arterial plasma catecholamines may be a more sensitive tool for the detection of hypertensive-normotensive differences. The present study therefore aimed at examining both venous and arterial plasma catecholamines in a group of white men, all 50 years of age, with never-treated, established essential hypertension (n = 61, blood pressure 165 +/- 2/112 +/- 1 mm Hg, means +/- SE) and comparing them with a similar group of normotensive men (n = 51, blood pressure 128 +/- 1/85 +/- 1 mm Hg). Arterial and venous plasma epinephrine, heart rate, and body weight were significantly elevated in the hypertensive group. Plasma norepinephrine was similar between the groups in the venous blood, whereas in the arterial blood the values in hypertensive subjects were moderately, but significantly increased (p less than 0.03). However, stepwise multiple regression analysis suggested arterial plasma norepinephrine was the only significant independent explanatory variable of raised blood pressure in the hypertensive group (r = 0.51, t = 4.05, p = 0.0002). Such a relationship was not found in the normotensive group. Thus based on measurements in arterial blood, we conclude that plasma norepinephrine, representing sympathetic tone, may be an important pathogenetic factor for high blood pressure in middle-aged men with established hypertension.     

National mutation study among Danish patients with hereditary haemorrhagic telangiectasia

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominantly inherited vascular disease characterized by the presence of mucocutaneous telangiectasia and visceral arteriovenous malformations (AVM). The clinical diagnosis of HHT is based on the Curaçao criteria. About 85% of HHT patients carry mutations in the ENG, ACVRL1 or SMAD4 genes. Here, we report on the genetic heterogeneity in the Danish national HHT population and address the prevalence of pulmonary arteriovenous malformations (PAVM). Probands of 107 apparently unrelated families received genetic testing, including sequencing and multiplex ligation‐dependent probe amplification (MLPA) analyses of ENG, ACVRL1 and SMAD4. These 107 families included 320 patients confirmed to have HHT either clinically or genetically. In 89% of the probands (n = 95), a mutation was identified. We detected 64 unique mutations of which 27 (41%) were novel. Large deletions were identified in ENG and ACVRL1. The prevalence of PAVM was 52.3% in patients with an ENG mutation and 12.9% in the ACVRL1 mutation carriers. We diagnosed 80% of the patients clinically, fulfilling the Curaçao criteria, and those remaining were diagnosed by genetic testing. It is discussed when to assign pathogenicity to missense and splice site mutations. The adding of an extra criterion to the Curaçao criteria is suggested.     

MRI findings in people with epilepsy and nodding syndrome in an area endemic for onchocerciasis: an observational study

Background

Onchocerciasis has been implicated in the pathogenesis of epilepsy. The debate on a potential causal relationship between Onchocerca volvulus and epilepsy has taken a new direction in the light of the most recent epidemic of nodding syndrome.

Objective

To document MRI changes in people with different types of epilepsy and investigate whether there is an association with O. volvulus infection.

Methods

In a prospective study in southern Tanzania, an area endemic for O. volvulus with a high prevalence of epilepsy and nodding syndrome, we performed MRI on 32 people with epilepsy, 12 of which suffered from nodding syndrome. Polymerase chain reaction (PCR) of O. volvulus was performed in skin and CSF.

Results

The most frequent abnormalities seen on MRI was atrophy (twelve patients (37.5%)) followed by intraparenchymal pathologies such as changes in the hippocampus (nine patients (28.1%)), gliotic lesions (six patients (18.8%)) and subcortical signal abnormalities (three patients (9.4%)). There was an overall trend towards an association of intraparenchymal cerebral pathologies and infection with O. volvulus based on skin PCR (Fisher''s Exact Test p=0.067) which was most pronounced in children and adolescents with nodding syndrome compared to those with other types of epilepsy (Fisher''s Exact Test, p=0.083). Contrary to skin PCR results, PCR of CSF was negative in all patients.

Conclusion

The observed trend towards an association of intraparenchymal cerebral pathological results on MRI and a positive skin PCR for O. volvulus despite negative PCR of CSF is intriguing and deserves further attention.     

Effects of anthocyanins on blood pressure and stress reactivity: a double-blind randomized placebo-controlled crossover study

High intakes of flavonoids are associated with reduced cardiovascular risk, and flavonoids such as cocoa and soy protein isolate have shown beneficial effects on blood pressure (BP). Anthocyanins constitute a flavonoid subgroup consumed in regular diets, but few studies have assessed the antihypertensive potential of anthocyanins. We aimed to assess whether high concentrations of relatively pure anthocyanins reduce BP and alter cardiovascular and catecholamine reactivity to stress. A total of 31 healthy men between 35-51 years of age with screening BP >140/90 mm Hg, not on antihypertensive or lipid-lowering medication, were randomised in a double-blind crossover study to placebo versus 320-mg anthoycanins twice daily. Treatment duration was 4 weeks, with a 4-week washout. Sitting and supine BP measurements, ambulatory BP recording and stress reactivity were assessed and analyzed by a paired sample t-test. In all, 27 patients completed all visits. Sitting systolic BP (primary endpoint) was 133 mm Hg after placebo versus 135 mm Hg after anthocyanin treatment (P=0.25). Anthocyanins did neither affect semiautomatic oscillometric BP measurements in the sitting or supine position nor 24-h ambulatory BP. No significant differences in stress reactivity were found across treatment periods. Overall, we conclude that high concentrations of these relatively pure anthocyanins do not reduce BP in healthy men with a high normal BP.