Adherence: the journey of medication taking, are we there yet?

Patient adherence to medications has been an issue challenging healthcare professionals for decades. Adherence rates, causes of non-adherence, barriers and enablers to medication taking, interventions to promote adherence, and the impact of non-adherence on health outcomes, have been extensively studied. In light of this, the area of adherence research has progressed conceptually and practically. This special issue contains a range of articles which focus on different aspects of adherence, from standardising terminology and methods of measurement, to non-adherence in a broad range of patient populations, and to interventions to promote adherence.

Adhésion thérapeutique aux traitements oncologiques oraux et prise en charge interdisciplinaire [Therapeutic adherence to oral cancer therapy and interdisciplinary management].

Medication adherence is a well-known risk factor in internal medicine. However in oncology this dimension is emerging due to the increasing number of oral formulations. First results in the oral oncology literature suggest that patients' ability to cope with medical prescription decreases with time. This might preclude patients from reaching clinical outcomes. Factors impacting on medication adherence to oral oncology treatments have not been yet extensively described neither strategies to address them and support patient's needs. Oncologists and pharmacists in our University outpatient settings performed a pilot study which aimed at measuring and facilitating adherence to oral oncology treatments and at understanding determinants of patient's adherence. The ultimate purpose of such a patient-centered and interdisciplinary collaboration would be to promote patient self-management and complement the standard medical follow-up.

Chronic exercise preserves lean muscle mass in masters athletes.

Aging is commonly associated with a loss of muscle mass and strength, resulting in falls, functional decline, and the subjective feeling of weakness. Exercise modulates the morbidities of muscle aging. Most studies, however, have examined muscle-loss changes in sedentary aging adults. This leaves the question of whether the changes that are commonly associated with muscle aging reflect the true physiology of muscle aging or whether they reflect disuse atrophy. This study evaluated whether high levels of chronic exercise prevents the loss of lean muscle mass and strength experienced in sedentary aging adults. A cross-section of 40 high-level recreational athletes ("masters athletes") who were aged 40 to 81 years and trained 4 to 5 times per week underwent tests of health/activity, body composition, quadriceps peak torque (PT), and magnetic resonance imaging of bilateral quadriceps. Mid-thigh muscle area, quadriceps area (QA), subcutaneous adipose tissue, and intramuscular adipose tissue were quantified in magnetic resonance imaging using medical image processing, analysis, and visualization software. One-way analysis of variance was used to examine age group differences. Relationships were evaluated using Spearman correlations. Mid-thigh muscle area (P = 0.31) and lean mass (P = 0.15) did not increase with age and were significantly related to retention of mid-thigh muscle area (P < 0.0001). This occurred despite an increase in total body fat percentage (P = 0.003) with age. Mid-thigh muscle area (P = 0.12), QA (P = 0.17), and quadriceps PT did not decline with age. Specific strength (strength per QA) did not decline significantly with age (P = 0.06). As muscle area increased, PT increased significantly (P = 0.008). There was not a significant relationship between intramuscular adipose tissue (P = 0.71) or lean mass (P = 0.4) and PT. This study contradicts the common observation that muscle mass and strength decline as a function of aging alone. Instead, these declines may signal the effect of chronic disuse rather than muscle aging. Evaluation of masters athletes removes disuse as a confounding variable in the study of lower-extremity function and loss of lean muscle mass. This maintenance of muscle mass and strength may decrease or eliminate the falls, functional decline, and loss of independence that are commonly seen in aging adults.

Promotion de l'activité physique chez les aînés: enjeux et stratégies spécifiques. [Promotion of exercise in older people: issues and strategies].

Regular physical activity is among the most effective interventions to prevent or delay functional decline and disability, even in older persons. Despite relatively strong scientific evidence supporting these benefits, the majority of older persons remain mostly sedentary. For these persons, concerns about injury or fear of negative consequences on their chronic diseases are among the most powerful barriers to participation in regular physical activity. Promotion of physical activity among older persons has therefore become one of the five main themes of the health promotion project "Via", a project that aims at promoting good practice in prevention and health promotion directed toward older adults in Switzerland. This paper summarizes the main recommendations issued from this national project supported by the Swiss Health Promotion Foundation.

Mechanisms of skin adherence and invasion by dermatophytes.

Dermatophytes are keratinophilic fungi that can be pathogenic for humans and animals by infecting the stratum corneum, nails, claws or hair. The first infection step consists of adherence of arthroconidia to the stratum corneum. The mechanisms and the kinetics of adherence have been investigated using different in vitro and ex vivo experimental models, most notably showing the role of a secreted serine protease from Microsporum canis in fungal adherence to feline corneocytes. After germination of the arthroconidia, dermatophytes invade keratinised structures that have to be digested into short peptides and amino acids to be assimilated. Although many proteases, including keratinolytic ones, have been characterised, the understanding of dermatophyte invasion mechanisms remains speculative. To date, research on mechanisms of dermatophyte infection focused mainly on both secreted endoproteases and exoproteases, but their precise role in both fungal adherence and skin invasion should be further explored.

Exercise prevents fructose-induced hypertriglyceridemia in healthy young subjects.

Excess fructose intake causes hypertriglyceridemia and hepatic insulin resistance in sedentary humans. Since exercise improves insulin sensitivity in insulin-resistant patients, we hypothesized that it would also prevent fructose-induced hypertriglyceridemia. This study was therefore designed to evaluate the effects of exercise on circulating lipids in healthy subjects fed a weight-maintenance, high-fructose diet. Eight healthy males were studied on three occasions after 4 days of 1) a diet low in fructose and no exercise (C), 2) a diet with 30% fructose and no exercise (HFr), or 3) a diet with 30% fructose and moderate aerobic exercise (HFrEx). On all three occasions, a 9-h oral [(13)C]-labeled fructose loading test was performed on the fifth day to measure [(13)C]palmitate in triglyceride-rich lipoprotein (TRL)-triglycerides (TG). Compared with C, HFr significantly increased fasting glucose, total TG, TRL-TG concentrations, and apolipoprotein (apo)B48 concentrations as well as postfructose glucose, total TG, TRL-TG, and [(13)C]palmitate in TRL-TG. HFrEx completely normalized fasting and postfructose TG, TRL-TG, and [(13)C]palmitate concentration in TRL-TG and apoB48 concentrations. In addition, it increased lipid oxidation and plasma nonesterified fatty acid concentrations compared with HFr. These data indicate that exercise prevents the dyslipidemia induced by high fructose intake independently of energy balance.

Exercise induces rapid interstitial lung water accumulation in patients with chronic mountain sickness.

BACKGROUND: Chronic mountain sickness (CMS) is a major public health problem in mountainous regions of the world. In its more advanced stages, exercise intolerance is often found, but the underlying mechanism is not known. Recent evidence indicates that exercise-induced pulmonary hypertension is markedly exaggerated in CMS. We speculated that this problem may cause pulmonary fluid accumulation and aggravate hypoxemia during exercise. METHODS: We assessed extravascular lung water (chest ultrasonography), pulmonary artery pressure, and left ventricular function in 15 patients with CMS and 20 control subjects at rest and during exercise at 3,600 m. RESULTS: Exercise at high altitude rapidly induced pulmonary interstitial fluid accumulation in all patients but one (14 of 15) with CMS and further aggravated the preexisting hypoxemia. In contrast, in healthy high-altitude dwellers exercise did not induce fluid accumulation in the majority of subjects (16 of 20) (P = .002 vs CMS) and did not alter arterial oxygenation. Exercise-induced pulmonary interstitial fluid accumulation and hypoxemia in patients with CMS was accompanied by a more than two times larger increase of pulmonary artery pressure than in control subjects (P < .001), but no evidence of left ventricular dysfunction. Oxygen inhalation markedly attenuated the exercise-induced pulmonary hypertension (P < .01) and interstitial fluid accumulation (P < .05) in patients with CMS but had no detectable effects in control subjects. CONCLUSIONS: To our knowledge, these findings provide the first direct evidence that exercise induces rapid interstitial lung fluid accumulation and hypoxemia in patients with CMS that appear to be related to exaggerated pulmonary hypertension. We suggest that this problem contributes to exercise intolerance in patients with CMS. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov.

Effects of flecainide on exercise-induced ventricular arrhythmias and recurrences in genotype-negative patients with catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND: Conventional therapy with beta-blockers is incompletely effective in preventing arrhythmic events in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). We have previously discovered that flecainide in addition to conventional drug therapy prevents ventricular arrhythmias in patients with genotype-positive CPVT. OBJECTIVE: To study the efficacy of flecainide in patients with genotype-negative CPVT. METHODS: We studied the efficacy of flecainide for reducing ventricular arrhythmias during exercise testing and preventing arrhythmia events during long-term follow-up. RESULTS: Twelve patients with genotype-negative CPVT were treated with flecainide. Conventional therapy failed to control ventricular arrhythmias in all patients. Flecainide was initiated because of significant ventricular arrhythmias (n = 8), syncope (n = 3), or cardiac arrest (n = 1). At the baseline exercise test before flecainide, 6 patients had ventricular tachycardia and 5 patients had bigeminal or frequent ventricular premature beats. Flecainide reduced ventricular arrhythmias at the exercise test in 8 patients compared to conventional therapy, similar to that in patients with genotype-positive CPVT in our previous report. Notably, flecainide completely prevented ventricular arrhythmias in 7 patients. Flecainide was continued in all patients except for one who had ventricular tachycardia at the exercise test on flecainide. During a follow-up of 48±94 months, arrhythmia events (sudden cardiac death and aborted cardiac arrest) associated with noncompliance occurred in 2 patients. Flecainide was not discontinued owing to side effects in any of the patients. CONCLUSIONS: Flecainide was effective in patients with genotype-negative CPVT, suggesting that spontaneous Ca(2+) release from ryanodine channels plays a role in arrhythmia susceptibility, similar to that in patients with genotype-positive CPVT.

Suivi de l'adhésion thérapeutique des patients hypertendus ou dyslipi- démiques par les cercles de qualité médecins-pharmaciens [Monitoring drug adherence for hypertensive and dyslipidemic patients in networks of community-based pharmacists and physicians].

Patient adherence is often poor for hypertension and dyslipidaemia. A monitoring of drug adherence might improve these risk factors control, but little is known in ambulatory care. We conducted a randomised controlled study in networks of community-based pharmacists and physicians in the canton of Fribourg to examine whether monitoring drug adherence with an electronic monitor (MEMS) would improve risk factor control among treated, but uncontrolled hypertensive and dyslipidemic patients. The results indicate that MEMS achieve a better blood pressure control and lipid profile, although its implementation requires considerable resources. The study also shows the value of collaboration between physicians and pharmacists in the field of patient adherence to improve ambulatory care of patients with cardiovascular risk factors.

Clinical benefits of an adherence monitoring program in the management of secondary hyperparathyroidism with cinacalcet: results of a prospective randomized controlled study.

BACKGROUND/AIMS: One of the causes of uncontrolled secondary hyperparathyroidism (sHPT) is patient's poor drug adherence. We evaluated the clinical benefits of an integrated care approach on the control of sHPT by cinacalcet. METHODS: Prospective, randomized, controlled, multicenter, open-label study. Fifty hemodialysis patients on a stable dose of cinacalcet were randomized to an integrated care approach (IC) or usual care approach (UC). In the IC group, cinacalcet adherence was monitored using an electronic system. Results were discussed with the patients in motivational interviews, and drug prescription adapted accordingly. In the UC group, drug adherence was monitored, but results were not available. RESULTS: At six months, 84% of patients in the IC group achieved recommended iPTH targets versus 55% in the UC group (P = 0.04). The mean cinacalcet taking adherence improved by 10.8% in the IC group and declined by 5.3% in the UC group (P = 0.02). Concomitantly, the mean dose of cinacalcet was reduced by 7.2 mg/day in the IC group and increased by 6.4 mg/day in the UC group (P = 0.03). CONCLUSIONS: The use of a drug adherence monitoring program in the management of sHPT in hemodialysis patients receiving cinacalcet improves drug adherence and iPTH control and allows a reduction in the dose of cinacalcet.

Health impact of sport and exercise in emerging adult men: a prospective study.

PURPOSE: Health benefits of sport and exercise are well documented in children, adolescents and adults, but little is known about emerging adulthood-a period of life characterized by significant demographic and developmental changes. The present study aimed to assess the health impact of changes in sport and exercise levels during that specific period of life. METHODS: The analysis used baseline and 15-month follow-up data (N = 4,846) from the cohort study on substance use risk factors. Associations between baseline exercise levels or changes in exercise levels and health indicators (i.e., health-related quality of life, depression, body mass index, alcohol dependence, nicotine dependence and cannabis use disorder) were measured using chi-squared tests and ANOVA. Direction of effects was tested using cross-lagged analysis. RESULTS: At baseline, all health indicator scores were observed to be better for regular exercisers than for other exercise levels. At follow-up, participants who had maintained regular exercise over time had better scores than those who had remained irregular exercisers or had discontinued, but their scores for health-related quality of life and depression were close to those of participants who had adopted regular exercise after the baseline questionnaire. Cross-lagged analysis indicated that regular exercise at baseline was a significant predictor of health-related quality of life and substance use dependence at follow-up, but was itself predicted only by health-related quality of life. CONCLUSIONS: From a health promotion perspective, this study emphasizes how important it is for emerging adult men to maintain, or adopt, regular sport and exercise.