Biomedical subjects

Constant P van Schayck

Publications and source records attributed to Constant P van Schayck.

At least 19 recordsLinked to original sources

PubMed2006

Long-term efficacy of cognitive-behavioral therapy by general practitioners for fatigue: a 4-year follow-up study.

OBJECTIVE: In an earlier study, we found that cognitive-behavioral therapy (CBT) delivered by general practitioners (GPs) for fatigue among employees on sick leave was not effective after 12 months. In this study we aim to assess the long-term efficacy of CBT by GPs for fatigue. It was hypothesized that the intervention could prevent deterioration as well as relapse of fatigue complaints and relapse into absenteeism in the long term. METHODS: Patients who participated in the original randomized controlled trial were followed up 4 years later. Fatigue and absenteeism were the main outcomes. RESULTS: Fatigue and absenteeism were high in the intervention and control groups at the 4-year follow-up. There was no significant difference between the intervention group and the control group on fatigue and absenteeism. The intervention group however tended toward less-favorable outcomes as compared with the control group. CONCLUSIONS: Like that of chronic fatigue syndrome, the prognosis of less-advanced fatigue is rather poor. CBT delivered by GPs is not effective in the long term.

Absenteeism↗

PubMed2006

Relationship between radical generation by urban ambient particulate matter and pulmonary function of school children.

The mechanisms by which particulate matter (PM) produces adverse effects on the respiratory system, such as pulmonary dysfunction in children, are largely unknown. However, oxidative stress is thought to play an important role. Various chemical compounds in ambient particulate matter, including transition metals and aromatic organic compounds, may contribute to adverse effects through intrinsic generation of reactive oxygen species (ROS). It was hypothesized that ROS generation by PM, as determined through electron spin resonance (ESR) spectroscopy, may be negatively associated with pulmonary function in school children. PM(2.5), PM(10), and total suspended particulates (TSP) were sampled at the playgrounds of six elementary schools in the city of Maastricht, the Netherlands. All children (8-13 yr) from the six schools were asked to undergo spirometry. Multivariate linear regression models were constructed to evaluate associations between oxygen radical formation by PM and lung function. The radical-generating capacity per microgram PM correlated negatively to forced expiratory volume in 1 s (FEV(1)) and forced expiratory flow at 50% (FEF(50%)) of forced vital capacity (FVC). The data indicate that chemical features that contribute to intrinsic generation of ROS may be relevant for PM risk assessment.

Adolescent↗

PubMed2006

Encouraging smokers to quit: the cost effectiveness of reimbursing the costs of smoking cessation treatment.

BACKGROUND: Smoking cessation should be encouraged in order to increase life expectancy and reduce smoking-related healthcare costs. Results of a randomised trial suggested that reimbursing the costs of smoking cessation treatment (SCT) may lead to an increased use of SCT and an increased number of quitters versus no reimbursement. OBJECTIVE: To assess whether reimbursement for SCT is a cost-effective intervention (from the Dutch societal perspective), we calculated the incremental costs per quitter and extrapolated this outcome to incremental costs per QALY saved versus no reimbursement. METHODS: In the reimbursement trial, 1266 Dutch smokers were randomly assigned to the intervention or control group using a randomised double consent design. Reimbursement for SCT was offered to the intervention group for a period of 6 months. No reimbursement was offered to the control group. Prolonged abstinence from smoking was determined 6 months after the end of the reimbursement period. The QALYs gained from quitting were calculated until 80 years of age using data from the US. Costs (year 2002 values) were determined from the societal perspective during the reimbursement period (May-November 2002). Benefits were discounted at 4% per annum. The uncertainty of the incremental cost-effectiveness ratios was estimated using non-parametric bootstrapping. RESULTS: Eighteen participants in the control group (2.8%) and 35 participants in the intervention group (5.5%) successfully quit smoking. The costs per participant were 291 euro and 322 euro, respectively. If society is willing to pay 1000 euro or 10,000 euro for an additional 12-month quitter, the probability that reimbursement for SCT would be cost effective was 50% or 95%, respectively. If society is willing to pay 18,000 euro for a QALY, the probability that reimbursement for SCT would be cost effective was 95%. However, the external validity of the extrapolation from quitters to QALYs is uncertain and several assumptions had to be made. CONCLUSION: Reimbursement for SCT may be cost effective if Dutch society is willing to pay 10,000 euro for an additional quitter or 18,000 euro for a QALY.

Adolescent↗

PubMed2005

Symptom-based questionnaire for differentiating COPD and asthma.

BACKGROUND: Many patients with obstructive lung disease (OLD) carry an inaccurate diagnostic label. Symptom-based questionnaires could identify persons likely to need spirometry. OBJECTIVES: We prospectively tested questions derived from a comprehensive literature review and an international Delphi panel to help identify chronic OLD (COPD) in persons with prior evidence of OLD. METHODS: Subjects were recruited via random mailing to primary-care practices in Aberdeen, Scotland, and Denver, Colorado. Persons aged 40 and older reporting any prior diagnosis of OLD or any respiratory medications in the past year were enrolled. Participants answered 54 questions covering demographics and symptoms and underwent spirometry with reversibility testing. A study diagnosis of COPD was defined by fixed airway obstruction as measured by post-bronchodilator FEV(1)/FVC <0.70. We examined ability of individual questions in a multivariate framework to discriminate between persons with and without the study diagnosis of COPD. RESULTS: 597 persons completed all investigations and proceeded to analysis. The list of 54 questions yielded 52 items for analyses, which was reduced to 19 items for entry into a multivariate regression model. Nine items had significant relationships with the study diagnosis of COPD, including increased age, pack-years, worsening cough, breathing-related disability or hospitalization, worsening dyspnea, phlegm quantity, cold going to the chest, and receipt of treatment for breathing. Individual items yielded odds ratios ranging from 0.33 to 20.7. This questionnaire demonstrated a sensitivity of 72.0 and a specificity of 82.7. CONCLUSIONS: A short, symptom-based questionnaire identifies persons more likely to have COPD among persons with prior evidence of OLD.

Adult↗

PubMed2005

Symptom-based questionnaire for identifying COPD in smokers.

BACKGROUND: Symptom-based questionnaires may enhance chronic obstructive pulmonary disease (COPD) screening in primary care. OBJECTIVES: We prospectively tested questions to help identify COPD among smokers without prior history of lung disease. METHODS: Subjects were recruited via random mailing to primary care practices in Aberdeen, UK, and Denver, Colo., USA. Current and former smokers aged 40 or older with no prior respiratory diagnosis and no respiratory medications in the past year were enrolled. Participants answered questions covering demographics and symptoms and then underwent spirometry with reversibility testing. A study diagnosis of COPD was defined as fixed airway obstruction as measured by post-bronchodilator FEV(1)/FVC <0.70. We examined the ability of individual questions in a multivariate framework to correctly discriminate between persons with and without COPD. RESULTS: 818 subjects completed all investigations and proceeded to analysis. The list of 54 questions yielded 52 items for analysis, which was reduced to 17 items for entry into multivariate regression. Eight items had significant relationships with the study diagnosis of COPD, including age, pack-years, body mass index, weather-affected cough, phlegm without a cold, morning phlegm, wheeze frequency, and history of any allergies. Individual items yielded odds ratios ranging from 0.23 to 12. This questionnaire demonstrated a sensitivity of 80.4 and specificity of 72.0. CONCLUSIONS: A simple patient self-administered questionnaire can be used to identify patients with a high likelihood of having COPD, for whom spirometric testing is particularly important. Implementation of this questionnaire could enhance the efficiency and diagnostic accuracy of current screening efforts.

Adult↗

PubMed2005

Factors influencing breastfeeding practices and postponement of solid food to prevent allergic disease in high-risk children: results from an explorative study.

This paper presents results of seven focus group interviews conducted to gain insight into the feelings, opinions and perceived barriers of parents with a history of asthma who have recently delivered a child. The parents participated in an educational program regarding breastfeeding and postponement of solid food to prevent their child from developing allergic symptoms. Breastfeeding exclusively for 6 months seemed an advice difficult to follow. The most important influencing factors regarding initiation and continuation of breastfeeding were health advantages for the baby, bonding, social support, modelling, knowledge about all the aspects of breastfeeding and breastfeeding confidence. In general, parents adhered to the advice to postpone solid food until the child had reached the age of 6 years. The few obstacles revealed were social pressure, hungry babies and eagerness of parents to give solid food.

Age Factors↗

PubMed2005

The primary prevention of asthma in children study: design of a multifaceted prevention program.

The PREVASC study addresses the primary prevention of asthma in infants and small children. The objective of this study is to investigate whether a multifaceted prenatally started intervention strategy in high-risk infants leads to a decrease in the occurrence of (severe) asthma and whether a refinement of the prevention strategy leads to an increase in the adherence to the prevention program. The primary prevention program includes house dust mite impermeable bed coverings, education on breast feeding, hypoallergenic feeding, timing of introduction of solid food and smoking cessation. A total of 888 infants were prenatally included. By the time of inclusion the mothers were 3-7 months pregnant. About 27 infants were excluded from the study and 18 dropped out. Of the remaining 843 infants 535 had a first-degree familial predisposition of asthma (high-risk group), whereas a reference group of 308 (162 boys) infants was not predisposed for asthma in the first-degree (low-risk group). To evaluate the (cost-)effectiveness of the preventive intervention, 222 (118 boys) infants of the high-risk group allocated to the intervention group and 221 (112 boys) allocated to a control group are followed up. The low-risk infants served as controls to evaluate the predictive value of high risk (first-degree familial predisposition of asthma). The infants are followed from the prenatal stage until they reach the age of 6 yr. The remaining 92 high-risk infants were included in an optimized randomized-clinical adherence trial (RCAT). Of these 92 infants, 45 (20 boys) were allocated to an intervention group and 47 (24 boys) to a control group. Until now all infants have been followed for at least 1 yr.

Allergens↗

PubMed2005

Comparison of existing symptom-based questionnaires for identifying COPD in the general practice setting.

OBJECTIVE: Underdiagnosis of COPD is widespread, at least in part due to underuse of spirometry. Symptom-based questionnaires may be helpful as an adjunct to spirometry. The aim of this study was to determine which types of questions might aid in identifying COPD. METHODOLOGY: Questionnaires were identified by literature review and input from a multinational advisory board of primary care providers. Questions were placed into groups and evaluated with respect to their ability to perform in two scenarios: (i) to identify persons with COPD from a general population (Case-finding scenario); and (ii) to distinguish persons with COPD from those with asthma (Differential Diagnosis scenario). Questions were retrospectively validated using the Third National Health and Nutrition Examination Survey data. Potential predictive ability was examined in bivariate and multivariate frameworks. RESULTS: Four published question sets and six additional documents were included. There was agreement in the use of smoking and symptom-based questions, but important differences in the use of demographic, personal history and other information. Most question types had significant bivariate relationships with airway obstruction. In multivariate analysis, age, BMI, smoking status and pack-years, symptoms (cough, phlegm, dyspnoea, wheeze), and prior diagnosis consistent with asthma or COPD all showed significant ability to discriminate between persons with and without obstruction in a general population. CONCLUSION: Simple self-administered questionnaires can be used to identify persons for whom spirometric testing may be especially appropriate. Development of such questionnaires will require additional study, including prospective validation of items in an appropriate clinical setting and policy recommendations on the use of these tools.

Diagnosis, Differential↗

PubMed2005

Assessment of readiness to change in patients with osteoarthritis. development and application of a new questionnaire.

OBJECTIVE: To develop a self-report measure for assessment of the stage of change in patients with osteoarthritis, in order to identify patients who would benefit from a self-management programme. METHODS: According to the 'stages of change' model a questionnaire was developed with three groups of items corresponding to the precontemplation stage (Pre), the contemplation (Cont) and the action (Act) stage. Internal consistency and factor structure of this questionnaire were investigated by assessing Cronbach's alphas and by performing factor analysis. SUBJECTS AND SETTING: The questionnaire was offered to 273 patients who entered a randomized clinical trial on self-management in a general health care setting. RESULTS: Factor analysis revealed that most items corresponded to the a priori described groups, while some items were not loading on the presumed factor. In each subgroup some items were deleted, resulting in a 15-item questionnaire. After this item reduction Cronbach's alphas were 0.72 (Pre), 0.76 (Cont) and 0.79 (Act) and all factor loadings were satisfactory (above 0.35). Classification revealed some differences between parts of the total group, for example in the proportion of patients in the preparation stage (recruited by general practitioner = 33.6%; advertisement = 49.2%). CONCLUSIONS: The Stages of Change Questionnaire in Osteoarthritis, a 15-item questionnaire to assess the 'stage of change' of a patient with osteoarthritis showed good internal consistency and adequate factor structure. These findings warrant further studies on validity and applicability in a clinical context.

Adult↗

PubMed2005

Fatigue and job stress as predictors for sickness absence during common infections.

The objective of this study was to investigate the effect of health and work-related factors as predictors of subsequent sickness absence when experiencing common infections (common cold, flu-like illness, and gastroenteritis). Self-administered questionnaire data were used (baseline n = 12,140). To perform the analysis, employees reporting common infections in the final questionnaire were selected. Employees reporting sickness absence due to common infections were compared with a group who stayed at work during an infection. Multivariate survival analysis revealed no significant effects of job demands, decision latitude, or job strain on absence in workers experiencing common infections. Low levels of commitment (risk [RR] 1.22; confidence interval [CI] 1.03-1.44) and low job satisfaction (RR 1.36; CI 1.13-1.164) increased the chance of being absent during a common cold. Also, having a long-standing disease (RR 1.22; CI 1.05-1.41) and fatigue (RR 1.20; CI 1.05-1.37) increased the chance of being absent during a common infection. Having an executive function decreased the chance of being absent. We conclude that absence during a common cold is partly influenced by motivational factors in work, in contrast to more severe common infections which are more health related. Insight in factors related to absenteeism are important as a start for preventive measures to reduce sickness absence.

Adult↗

PubMed2004

Childhood infections and risk of wheezing and allergic sensitisation at age 7-8 years.

BACKGROUND: Childhood atopic disease has been associated with exposure to infections early in life. There is however considerable controversy on this issue, since evidence exists for both protective and adverse effects of infections. Aim of this study was to investigate the association between childhood infections and the occurrence of wheeze and allergic sensitisation in 7-8-year-old Dutch and German children. METHODS: A nested case-control study was conducted among German and Dutch children participating in a large longitudinal study on respiratory health. Parents of 510 7-8-year-old children with respiratory complaints and an equal number of children without respiratory complaints were asked to complete a questionnaire. Blood samples were collected for specific serum Immunoglobulin E (IgE) analysis. Data on childhood infections were collected through records of the participating Municipal Health Services. RESULTS: No association was found between recent wheeze and any of the childhood infections investigated. For scarlet fever infection an increased risk of allergic sensitisation (OR: 2.82; 95% CI: 1.40-5.72) and sensitisation against grasses (OR: 3.00; 95% CI: 1.35-6.69) at the age of 7-8 years was found. Varicella infection tended towards increased risk of sensitisation against grasses (OR: 1.88; 95% CI: 0.99-3.58). For allergic sensitisation and sensitisation against grasses the odds ratios increased with increasing number of infections. CONCLUSIONS: The results do not lend support to the suggestion that childhood infection protects against wheezing or allergic sensitisation at age 7-8 years. Scarlet fever or varicella infection presented an increased risk of allergic sensitisation.

Case-Control Studies↗

PubMed2004

Clinical effectiveness of a mite allergen-impermeable bed-covering system in asthmatic mite-sensitive patients.

BACKGROUND: Exposure to allergens plays a role in the development of bronchial hyperresponsiveness and in the chronic inflammatory response seen in asthmatic patients. House dust mites (HDMs) are an important source of allergen. Reduction of these allergens might lead to better lung function and reduction of asthma symptoms. OBJECTIVE: The effect of HDM-impermeable covers on HDM allergen levels, peak flow values, and asthma symptoms were measured. Therefore a randomized clinical trial was carried out. METHODS: Fifty-two allergic asthmatic patients were randomly allocated to use the HDM-impermeable or placebo covers. During the study period, daily peak flow and asthma symptom scores were recorded. Dust samples were taken from the mattresses. RESULTS: We observed a significant reduction in HDM allergen levels on the mattresses after encasing them with HDM-impermeable covers (reduction of 87% of Der p 1 in micrograms per gram of dust; P <.001). Baseline symptoms were so low that no improvement could be established. Morning peak expiratory flow is significantly higher in the intervention group compared with that seen in the placebo group during the study period (beta=20.2; P <.01). CONCLUSIONS: HDM-impermeable covers significantly decreased the level of HDM allergens. Furthermore, morning peak flow was significantly increased during the intervention period. This study indicates that HDM allergen-avoidance measures might have beneficial effects on allergen reduction and asthma outcome.

Adult↗

PubMed2004

Predictors of outcome in fatigued employees on sick leave: results from a randomised trial.

OBJECTIVE: The main objective of this study was to identify predictors of fatigue caseness, work resumption and chronic fatigue syndrome (CFS)-like caseness in a sample of fatigued employees on sick leave. METHODS: For 12 months, 151 fatigued employees on sick leave, 44% of whom met research criteria for CFS at baseline, were followed. Measures included fatigue, health aspects, psychological problems, burnout, causal attributions and self-efficacy. Logistic regression analysis was used to determine associations between predictor variables at baseline and outcome at follow-up. RESULTS: After 12 months, 43% of the patients were no longer fatigue cases, and 62% had resumed work. Recovery from fatigue caseness was predicted by stronger psychological attributions and other perception-related factors, whereas work resumption was predicted by lower age, male sex, CFS-like caseness and less cognitive difficulties. Lower physical functioning scores were predictive of (the development of) CFS-like caseness. CONCLUSION: Recovering from persistent fatigue and work resumption seem to result from different underlying processes and do not necessarily fall together. As many factors associated with outcome in fatigue reflect illness perception, the prevention of persistent fatigue and CFS may partly be achieved by the modification of perception.

Adult↗

PubMed2004

Psychological distress and depressed mood in employees with asthma, chronic bronchitis or emphysema: a population-based observational study on prevalence and the relationship with smoking cigarettes.

OBJECTIVES: To evaluate if employees with asthma, chronic bronchitis or emphysema can be characterized as a population of patients with a high prevalence of psychological distress and/or depressed mood. Above all, we wanted to examine the influence of smoking status on the relationship between chronic disease and psychological distress/depressed mood. METHODS: A postal survey was conducted among 12,103 employees participating in the Maastricht Cohort Study. RESULTS: Smoking employees, who reported having asthma, chronic bronchitis or emphysema were more likely to report suffering from depressed mood compared to smokers with no long-lasting disease (prevalence rate, PR: 29.3 and 9.0%, respectively; OR for depressed mood = 4.04; 95% CI: 2.56-6.39) and when compared to smoking employees with a history of heart disease, hypertension or myocardial infarction (PR: 18.1%; OR: 1.99; 95% CI: 1.07-3.68), or rheumatoid arthritis (PR: 20.1%; OR: 1.73; 95% CI: 0.96-3.11). CONCLUSION: These findings provide health care professionals with additional evidence regarding the importance for including the assessment of psychological distress and depressed mood in the routine evaluation of the patient with asthma, chronic bronchitis or emphysema, especially with regard to smoking cessation.

Age Distribution↗

PubMed2004

An alternative trial design to overcome validity and recruitment problems in primary care research.

BACKGROUND: Although the randomized controlled trial is widely accepted as the best design to investigate new interventions, conducting a trial in primary care may present researchers with many methodological problems. OBJECTIVE: Our aim was to present an alternative trial design to overcome internal validity and recruitment problems. METHODS: In a randomized controlled trial, fatigued employees absent from work were selected among the population of an occupational health service in the South of The Netherlands. Patients randomly assigned to the experimental condition received cognitive behavioural therapy by a research GP near their home address, whereas patients in the control group received no intervention. We describe our considerations for building an alternative design. Research GPs and patients were recruited separately for the study. The pre-randomization design was applied. RESULTS: Nine research GPs performed all the interventions. Seventy-six experimental patients and 75 control patients were selected for study participation. Of these, only six patients in the experimental group and seven patients in the control group withdrew from the study at some point during follow-up. CONCLUSION: Results suggest that recruitment and randomization procedures in the alternative design served their purpose well. The alternative design proposed here might have several advantages compared with conventional trial procedures. However, our design is not widely applicable and there are ethical aspects involved that should be considered. Researchers should address their creativity when trying to minimize the problems they may encounter in designing a study.

Absenteeism↗

PubMed2004

Predicting the two-year course of unexplained fatigue and the onset of long-term sickness absence in fatigued employees: results from the Maastricht Cohort Study.

Because of the serious adverse consequences of unexplained fatigue, it is important to identify factors that determine the prognosis of unexplained fatigue and the onset of long-term sickness absence in fatigued employees. Analyses were based on the Maastricht Cohort Study, a prospective population-based cohort study among more than 12,000 employees. Severely fatigued employees who were not on sick leave (n = 2108) were selected at baseline and followed up at six time points during the course of 2 years. Point prevalences of severe fatigue (59% to 63%) and long-term sickness absence (1.8% to 3.1%) among participants were fairly stable at all consecutive time points. Lower levels of fatigue severity, work-related exhaustion and anxious mood, absence of conflicts with colleagues, and good self-rated health at baseline were predictors of the onset of recovery from fatigue in survival analyses. Older age, low decision authority, female sex, working in nightshift, a physical attribution of fatigue, and a history of absenteeism were predictors of the onset of long-term absenteeism. The course of unexplained fatigue in employees is characterized by remission and relapse in time while the absolute risk of long-term absenteeism is small. Given the broad range of predictors, it appears that fatigue and long-term sickness absence entangle different underlying processes. Our findings underscore the notion that prevention and treatment of fatigue should be aimed at health perception and emotional well-being.

Adult↗

PubMed2003

Undiagnosed patients and patients at risk for COPD in primary health care: early detection with the support of non-physicians.

Given the increasingly heavy workload in the primary health care sector, the option of allocating activities involving the management of chronic diseases to non-physicians has recently come under scrutiny. The purpose of this study was to assess the feasibility of the support provided by non-physicians to general practitioners (GPs) in the early detection of chronic obstructive pulmonary disease (COPD). A convenience sample consisting of 231 patients [40-70 years; >10 pack years (number of packs of cigarettes smoked per day multiplied by the number of years the individual has smoked)] from eight general practices in the Maastricht region in the southern Netherlands, who consulted their GP for reasons unrelated to respiratory diseases, were assessed for their respiratory function. Prior to the first assessment, patients were interviewed about their medical history and symptoms. By taking the results of the lung function measurement as the starting point, the predictive value of medical history and symptoms in the identification of patients at risk for airflow obstruction or of COPD was assessed and compared with findings in the literature. Seventeen patients (7.4%) were diagnosed with COPD, 11 patients (4.8%) with asthma. In addition to age and moderate smoking history, breathlessness and a history of heavy smoking were identified as risk factors for airflow limitation and COPD. Early detection of COPD in primary health care by non-physicians is feasible and should be considered for middle aged, moderate and heavy smokers experiencing breathlessness.

Adult↗

PubMed2003

Benefits and risks of pharmacological smoking cessation therapies in chronic obstructive pulmonary disease.

Smoking cessation is the most effective way to reduce the risk of developing chronic obstructive pulmonary disease (COPD) or to reduce its progression. However, little is known about the efficacy and safety of different pharmacological smoking cessation therapies used for the treatment of patients with COPD who smoke. The aim of this review was to evaluate the benefits and risks of pharmacological smoking cessation therapies in COPD. We conducted an extensive computer-aided literature search which resulted in the identification of four papers that met the inclusion criteria and contributed to this review. In two studies the efficacy of nicotine polacrilex (nicotine gum) was assessed. In one study, which did not have a control group, the efficacy of nicotine nasal spray was evaluated. The fourth study, a placebo-controlled trial, evaluated the efficacy of bupropion sustained release. The results of these studies indicated that nicotine gum, nicotine nasal spray and bupropion have a good safety profile and seem to increase abstinence rates in smokers with COPD. The incidence and nature of specific adverse effects occurring in patients with COPD seem to be comparable with the adverse effects reported by healthy smokers. However, the efficacy seems to depend on the follow-up period used to define success (i.e. abstinence rates decline with longer follow-up), as well as the intensity and duration of the concomitant psychosocial intervention. This review indicates that for a continuation of the effect of pharmacological smoking cessation therapies, the combination of pharmacotherapy (to reduce craving and withdrawal) and a relapse-prevention programme, in which attention is focused on the behavioural aspects of smoking and smoking cessation, seems to increase abstinence, especially when the psychosocial intervention is prolonged for a longer period. Also, the characteristics of the smokers who are motivated to quit must be taken into account in order to increase the number of successful attempts to quit smoking and prevent relapses. We therefore recommend using a holistic approach in which the possible coexistence of multiple problems (which are known to affect the success of smoking cessation strategies) is integrated.

Administration, Buccal↗