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1.
J Cancer Surviv ; 14(6): 858-866, 2020 12.
Article in English | MEDLINE | ID: mdl-32488631

ABSTRACT

PURPOSE: Sexual health is an important quality-of-life concern for cancer patients and survivors, but a difficult discussion topic for patients and healthcare professionals. The most important barriers causing healthcare professionals to avoid the topic are lack of education and lack of knowledge. How effective education about sexual health is for oncology healthcare professionals is not clear. The aim of this review is to examine the effectiveness of interventions in improving the provision of sexual healthcare for cancer patients. METHODS: A systematic literature review was conducted according to PRISMA guidelines using the following data sources: PubMed, PsychInfo, Embase and Emcare. Quantitative research was included which contained pre-intervention and post-intervention outcomes. The assessment of the studies was conducted independently by two reviewers. A third reviewer was involved if there was no consensus. RESULTS: Seven studies were included. In total, 572 oncology healthcare professionals participated, including physicians, nurses and allied healthcare professionals. Interventions consisted of 6 face-to-face sessions and one online program. Primary objectives of the studies were the assessment of improvement in knowledge about sexual health, improvement of practice, frequency of discussing sexual health and comfort level and the decline of perceived barriers to discussing sexual health. Studies showed that interventions resulted in improved realization of the objectives. CONCLUSIONS: Although improvement in the knowledge of healthcare professionals was achieved, it was not possible to give an overall recommendation for the development of interventions due to the limited number of studies and heterogeneity of the data. IMPLICATIONS FOR CANCER SURVIVORS: Sexual health is an important area of survivorship that is often neglected. Many oncology healthcare professionals lack training and knowledge to provide such care. More evidence-based practices are needed to improve sexual healthcare for cancer survivors.


Subject(s)
Cancer Survivors/psychology , Delivery of Health Care/standards , Health Knowledge, Attitudes, Practice , Health Personnel/education , Neoplasms/psychology , Sexuality/psychology , Health Personnel/psychology , Humans
2.
J Cancer Educ ; 35(6): 1072-1088, 2020 12.
Article in English | MEDLINE | ID: mdl-31209770

ABSTRACT

Sexuality is a significant quality-of-life concern for many cancer patients. Patients may be disadvantaged if they are not informed and not offered sexual health care. We sought to reveal oncologists' current practice and opinions concerning sexual counselling. The aim of this study was to explore the knowledge, attitude and practice patterns of Dutch medical oncologists regarding treatment-related sexual dysfunction. Questionnaires were sent to 433 members of the Dutch Society of Medical Oncology. The majority (81.5%) of the 120 responding medical oncologists (response rate 30.6%) stated they discussed sexual function with fewer than half of their patients. At the same time, 75.8% of the participating oncologists agreed that addressing sexual function is their responsibility. Sexual function was discussed more often with younger patients and patients with a curative treatment intent. Barriers for avoiding discussing sexual function were lack of time (56.1%), training (49.5%) and advanced age of the patient (50.4%). More than half (64.6%) stated they had little knowledge about the subject and the majority (72.9%) wanted to acquire additional training in sexual function counselling. Medical oncologists accept that sexual function counselling falls within their profession, yet they admit to not counselling patients routinely concerning sexual function. Only in a minority of cases do medical oncologists inform their patients about sexual side effects of treatment. Whether they counsel patients is related to how they view patient's prognosis, patient's age, and self-reported knowledge. Findings indicate there is a role for developing education and practical training.


Subject(s)
Counseling/methods , Neoplasms/psychology , Oncologists/psychology , Practice Patterns, Physicians'/statistics & numerical data , Quality of Life , Sexual Dysfunction, Physiological/therapy , Adult , Attitude of Health Personnel , Female , Humans , Male , Middle Aged , Sexual Health , Surveys and Questionnaires
3.
J Sex Marital Ther ; 46(3): 205-226, 2020.
Article in English | MEDLINE | ID: mdl-31762399

ABSTRACT

It is well known that breast cancer treatment can affect sexuality. This survey evaluated the needs of breast cancer patients and partners regarding sexual care. The majority of patients (80.4%) and partners (73.7%) did not receive any information regarding sexuality. Although only a quarter of all respondents reported a direct need for information regarding sexuality, most valued an opportunity to discuss sexuality. The nurse practitioner was the most preferable care provider to provide information about sexuality, supported by a brochure or website. Patients considered during treatment as most suitable timing of discussing sexuality, and partners before the start of treatment.


Subject(s)
Breast Neoplasms/psychology , Information Seeking Behavior , Sexual Health , Sexual Partners/psychology , Sexuality , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Netherlands/epidemiology , Surveys and Questionnaires
4.
Obes Rev ; 19(9): 1248-1255, 2018 09.
Article in English | MEDLINE | ID: mdl-30035359

ABSTRACT

INTRODUCTION: Uncontrolled family factors may bias the estimation of the association between maternal smoking during pregnancy and offspring body mass index (BMI). The objective was to assess if there is an association between maternal smoking during pregnancy and offspring BMI z-score independent of factors in the siblings' shared environment and if such association is linear. METHODS: We performed an individual patient data meta-analysis using five studies providing sibling data (45,299 children from 14,231 families). In a multi-level model, separating within-family and between-family effects and with random intercept for families, we analysed the dose-response association between maternal number of cigarettes per day during pregnancy and offspring's BMI z-score using B-splines to allow for non-linear associations. RESULTS: A linear within-family effect for number of cigarettes smoked in the range from 1 to 30 cigarettes per day on the offspring's BMI z-score was observed. Each additional cigarette per day between sibling pregnancies resulted in an increase in BMI z-score of 0.007 (95% CI [0.006, 0.009]). A between family-effect emerged only with doses ≥25 cigarettes per day. CONCLUSIONS: The number of cigarettes mothers smoke per day during pregnancy is positively associated with offspring BMI z-score even among siblings, suggesting that the association is not entirely explained by confounding by family factors.


Subject(s)
Body Mass Index , Prenatal Exposure Delayed Effects/physiopathology , Smoking , Female , Humans , Pregnancy
5.
Eur J Pain ; 22(2): 385-392, 2018 02.
Article in English | MEDLINE | ID: mdl-28952174

ABSTRACT

BACKGROUND: The objective was to evaluate a supposed clinical interdependency of myofascial trigger points and migraine in children. Such interdependency would support an interaction of spinal and trigeminal afferences in the trigemino-cervical complex as a contributing factor in migraine. METHODS: Children ≤18 years with the confirmed diagnosis of migraine were prospectively investigated. Comprehensive data on medical history, clinical neurological and psychological status were gathered. Trigger points in the trapezius muscle were identified by palpation and the threshold of pressure pain at these points was measured. Manual pressure was applied to the trigger points, and the occurrence and duration of induced headache were recorded. At a second consultation (4 weeks after the first), manual pressure with the detected pressure threshold was applied to non-trigger points within the same trapezius muscle (control). Headache and related parameters were again recorded and compared to the results of the first consultation. RESULTS: A total of 13 girls and 13 boys with migraine and a median age of 14.5 (Range 6.3-17.8) years took part in the study. Manual pressure to trigger points in the trapezius muscle led to lasting headache after termination of the manual pressure in 13 patients while no patient experienced headache when manual pressure was applied to non-trigger points at the control visit (p < 0.001). Headache was induced significantly more often in children ≥12 years and those with internalizing behavioural disorder. CONCLUSION: We found an association between trapezius muscle myofascial trigger points and migraine, which might underline the concept of the trigemino-cervical complex, especially in adolescents. SIGNIFICANCE: In children with migraine headache can often be induced by pressure to myofascial trigger points, but not by pressure to non-trigger points in the trapezius muscle. This supports the hypothesis of a trigemino-cervical-complex in the pathophysiology of migraine, which might have implications for innovative therapies in children with migraine.


Subject(s)
Migraine Disorders/physiopathology , Myofascial Pain Syndromes/physiopathology , Superficial Back Muscles/physiopathology , Trigger Points/physiopathology , Adolescent , Child , Female , Humans , Male , Prospective Studies
6.
Nervenarzt ; 88(12): 1402-1410, 2017 Dec.
Article in German | MEDLINE | ID: mdl-28956079

ABSTRACT

Migraine as primary headache is a life-long disease which is relevant for the quality of life and is based on complex genetics. It often starts in childhood with symptoms typical for the specific age. These show different nuances compared to the migraine symptoms in adults, for example, regarding (bilateral/unilateral) localization of the acute migraine headache. Only over the course of years-during adolescence and young adulthood-do the more specific symptoms as defined by the International Classification of Headache Disorders (ICHD 3 beta) develop. In this article we focus on the clinical specifics of children and adolescents with migraine. We elaborately refer to the trigeminocervical complex (TCC) because it forms a conceptual bridge for the understanding of migraine, for psychoeducation, and for therapeutic options. We pragmatically discuss options and limits of treatments.


Subject(s)
Migraine Disorders/diagnosis , Migraine Disorders/physiopathology , Neck Muscles/physiopathology , Analgesics/therapeutic use , Combined Modality Therapy , Craniocerebral Trauma/complications , Craniocerebral Trauma/physiopathology , Diagnosis, Differential , Humans , Migraine Disorders/genetics , Migraine Disorders/therapy , Risk Factors , Transcranial Magnetic Stimulation , Trigeminal Nerve/physiopathology
8.
Klin Padiatr ; 228(5): 251-6, 2016 Sep.
Article in German | MEDLINE | ID: mdl-27617761

ABSTRACT

BACKGROUND: Transition of care from pediatric to adult services is a complex process. Factors influencing the success of health care transition of adolescents with chronic neurological disorders are poorly understood. METHODS: Young adults with chronic neurological disorders who had been cared for in an Interdisciplinary Pediatric Center participated in this study. Using the Patient Satisfaction Questionnaire Short-form (PSQ-18) we investigated whether satisfaction of these patients with their medical care in adult services was depending on the severity and complexity of their condition. They were assigned to a group of severely disabled patients (group 1; intellectual disability or learning disability plus motor handicap or degree of disability≥80, n=11) or a group 2 of patients with milder impairment (N=39). We used descriptive and t-statistics to compare both groups. RESULTS: Patients of group 1 reported slightly lower satisfaction with their present medical care in adult services (M=3.25; 95%-KI=[2.96-3.55]) compared to patients of group 2 (M=3.59; 95%.KI=[3.37-3.81]; p=0.084). Satisfaction with transition was significantly lower in group 1 (M=2.65; 95% KI=[2.29-3.01]) than in group 2 (M=3.11; 95% KI=[2.89-3.33], p=0.045). The difference of mean values of 0.46 reflects a moderate effect size (Hedges' g=0.68). CONCLUSION: Health care transition of adolescent patients with chronic neurological disorders is significantly more successful in patients with minor impairment compared to patients with severe complex neurological conditions.


Subject(s)
Nervous System Diseases/therapy , Transition to Adult Care , Adolescent , Chronic Disease , Comorbidity , Disabled Persons , Humans , Intellectual Disability/diagnosis , Intellectual Disability/therapy , Interdisciplinary Communication , Intersectoral Collaboration , Learning Disabilities/diagnosis , Learning Disabilities/therapy , Motor Disorders/diagnosis , Motor Disorders/therapy , Nervous System Diseases/diagnosis , Nervous System Diseases/psychology , Patient Satisfaction , Surveys and Questionnaires , Young Adult
9.
Clin Genet ; 89(2): 258-66, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26084449

ABSTRACT

Recent progress in genetic testing has facilitated obtaining an etiologic diagnosis in children with developmental delay/intellectual disability (DD/ID) or multiple congenital anomalies (MCA) or both. Little is known about the benefits of diagnostic elucidation for affected families. We studied the impact of a genetic diagnosis on parental quality of life (QoL) using a validated semiquantitative questionnaire in families with a disabled child investigated by array-based comparative genomic hybridization (aCGH). We received completed questionnaires from 95 mothers and 76 fathers of 99 families. We used multivariate analysis for adjustment of potential confounders. Taken all 99 families together, maternal QoL score (percentile rank scale 51.05) was significantly lower than fathers' QoL (61.83, p = 0.01). Maternal QoL score was 20.17 [95% CI (5.49; 34.82)] percentile rank scales higher in mothers of children with diagnostic (n = 34) aCGH as opposed to mothers of children with inconclusive (n = 65) aCGH (Hedges' g = 0.71). Comparison of these QoL scores with retrospectively recalled QoL before aCGH revealed an increase of maternal QoL after diagnostic clarification. Our results indicate a benefit for maternal QoL if a genetic test, here aCGH, succeeds to clarify the etiologic diagnosis in a disabled child.


Subject(s)
Developmental Disabilities/diagnosis , Developmental Disabilities/genetics , Parents , Quality of Life , Adult , Child , Comparative Genomic Hybridization , Confounding Factors, Epidemiologic , Demography , Female , Humans , Male
10.
Eur J Neurol ; 22(2): 270-6, e22, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25244562

ABSTRACT

BACKGROUND AND PURPOSE: Headache is a common health problem in adolescents. There are a number of risk factors for headache in adolescents that are amenable to intervention. The aim of the study was to assess the effectiveness of a low-level headache prevention programme in the classroom setting to prevent these risk factors. METHODS: In all, 1674 students in 8th-10th grade at 12 grammar schools in greater Munich, Germany, were cluster randomized into intervention and control groups. A standardized 60-min prevention lesson focusing on preventable risk factors for headache (physical inactivity, coffee consumption, alcohol consumption and smoking) and providing instructions on stress management and neck and shoulder muscle relaxation exercises was given in a classroom setting. Seven months later, students were reassessed. The main outcome parameter was headache cessation. Logistic regression models with random effects for cluster and adjustment for baseline risk factors were calculated. RESULTS: Nine hundred students (intervention group N = 450, control group N = 450) with headache at baseline and complete data for headache and confounders were included in the analysis. Headache cessation was observed in 9.78% of the control group compared with 16.22% in the intervention group (number needed to treat = 16). Accounting for cluster effects and confounders, the probability of headache cessation in the intervention group was 1.77 (95% confidence interval = [1.08; 2.90]) higher than in the control group. The effect was most pronounced in adolescents with tension-type headache: odds ratio = 2.11 (95% confidence interval = [1.15; 3.80]). CONCLUSION: Our study demonstrates the effectiveness of a one-time, classroom-based headache prevention programme.


Subject(s)
Headache/therapy , Health Education/methods , Adolescent , Female , Germany , Headache/prevention & control , Humans , Male , Treatment Outcome
11.
Article in German | MEDLINE | ID: mdl-25002234

ABSTRACT

BACKGROUND: Strategies to prevent primary headaches could be very beneficial, especially given that primary headaches can lead to the development of chronic headache. In order to establish headache prevention strategies, the modifiable risk factors for primary headaches need to be identified. MATERIAL AND METHODS: A systematic literature search on the risk factors for primary headaches was conducted independently by two persons using the databases MEDLINE and Embase. Further inclusion criteria were observational studies in adult general populations or case-control studies, where the effect sizes were reported as odds ratios or where the odds ratios could be calculated from the given data. RESULTS: In all, 24 studies were included in the analysis. There was a large amount of heterogeneity among the studies concerning headache acquisition, headache classification, and risk factors for headache development. Independent of headache trigger and definition of headache, the association between headache and the risk factor "stress" was very high: The meta-analysis shows an overall effect of 2.26 (odds ratio; 95 %-CI = [1.79; 2.85]). Studies evaluating neck and shoulder pain also report a strong association with headache; however, these results could not be summarized in a meta-analysis. Equally, the overall effects of smoking and coffee consumption on headaches could not be verified because the effect sizes were rather small and predominantly noticeable only at higher doses. CONCLUSION: A strong association between headache and the risk factors stress and neck and shoulder pain was confirmed. The effect sizes of smoking and coffee consumption on headaches were rather small.


Subject(s)
Headache Disorders, Primary/epidemiology , Headache/epidemiology , Mental Disorders/epidemiology , Neck Pain/epidemiology , Shoulder Pain/epidemiology , Stress, Psychological/epidemiology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Comorbidity , Female , Humans , Male , Middle Aged , Prevalence , Risk Factors , Smoking/epidemiology , Young Adult
12.
BJOG ; 121(9): 1145-53; discussion 1154, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24548705

ABSTRACT

OBJECTIVE: Maternal expulsive efforts are thought to damage the pelvic floor. We aimed to compare pelvic floor function and anatomy between women who delivered vaginally (VB) versus those with caesarean delivery (CD) prior to the second stage of labour. DESIGN: Prospective cohort. SETTING: University Hospital Midwifery practice. POPULATION: Nulliparas. METHODS: Pregnant nulliparas were recruited during pregnancy and women who underwent CD prior to the 2nd stage of labour at birth were recruited immediately postpartum. Both groups were followed prospectively to 6 months postpartum. MAIN OUTCOME MEASURES: POPQ, perineal ultrasound (U/S) and Paper Towel Test (PTT), an objective measure of stress incontinence; Incontinence Severity Index (ISI), Pelvic Floor Impact Questionnaire (PFIQ-7), Wexner Fecal Incontinence Scale (W) and Female Sexual Function Index (FSFI). RESULTS: 336/448 (75%) VB and 138/224 (62%) CD followed up. The VB group was younger (23.9 ± 4.9 versus 26.6 ± 6.1 years, P < 0.001) and less overweight/obese (38 versus 56%, P < 0.001); baseline functional measures were similar (all P > 0.05). At follow-up, urinary incontinence (UI) (55 versus 46% ISI > 0, P = 0.10), fecal incontinence (FI) (8 versus 13% FI on W, P = 0.12), sexual activity rates (88 versus 92%, P = 0.18) and PFIQ-seven scores were similar. Positive PTT tests (17 versus 6%, P = 0.002) and ≥ Stage 2 prolapse (22 versus 15%, P = 0.03) were higher with VB; differences were limited to points Aa and Ba. U/S findings were not different between groups. Stepwise multivariate analyses controlling for age, body mass index, and non-Hispanic White race for prolapse of points Aa and Ba did not alter conclusions (all P < 0.004). CONCLUSIONS: VB resulted in prolapse changes and objective UI but not in increased self-report pelvic floor dysfunction at 6 months postpartum compared with women who delivered by CD prior to the second stage of labour. The second stage of labour had a modest effect on postpartum pelvic floor function.


Subject(s)
Fecal Incontinence/etiology , Pelvic Floor Disorders/etiology , Pelvic Floor/physiopathology , Sexual Dysfunction, Physiological/etiology , Urinary Incontinence/etiology , Adult , Cesarean Section/adverse effects , Female , Humans , Labor Stage, Second/physiology , New Mexico , Parity , Pregnancy , Prospective Studies , Risk Factors , Surveys and Questionnaires , Young Adult
13.
BJOG ; 119(12): 1483-92, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22830446

ABSTRACT

OBJECTIVE: To determine whether primary midwife care (caseload midwifery) decreases the caesarean section rate compared with standard maternity care. DESIGN: Randomised controlled trial. SETTING: Tertiary-care women's hospital in Melbourne, Australia. POPULATION: A total of 2314 low-risk pregnant women. METHODS: Women randomised to caseload received antenatal, intrapartum and postpartum care from a primary midwife with some care by 'back-up' midwives. Women randomised to standard care received either midwifery or obstetric-trainee care with varying levels of continuity, or community-based general practitioner care. PRIMARY OUTCOME: caesarean birth. Secondary outcomes included instrumental vaginal births, analgesia, perineal trauma, induction of labour, infant admission to special/neonatal intensive care, gestational age, Apgar scores and birthweight. RESULTS: In total 2314 women were randomised-1156 to caseload and 1158 to standard care. Women allocated to caseload were less likely to have a caesarean section (19.4% versus 24.9%; risk ratio [RR] 0.78; 95% CI 0.67-0.91; P = 0.001); more likely to have a spontaneous vaginal birth (63.0% versus 55.7%; RR 1.13; 95% CI 1.06-1.21; P < 0.001); less likely to have epidural analgesia (30.5% versus 34.6%; RR 0.88; 95% CI 0.79-0.996; P = 0.04) and less likely to have an episiotomy (23.1% versus 29.4%; RR 0.79; 95% CI 0.67-0.92; P = 0.003). Infants of women allocated to caseload were less likely to be admitted to special or neonatal intensive care (4.0% versus 6.4%; RR 0.63; 95% CI 0.44-0.90; P = 0.01). No infant outcomes favoured standard care. CONCLUSION: In settings with a relatively high baseline caesarean section rate, caseload midwifery for women at low obstetric risk in early pregnancy shows promise for reducing caesarean births.


Subject(s)
Cesarean Section/statistics & numerical data , Continuity of Patient Care/organization & administration , Midwifery/organization & administration , Postnatal Care/organization & administration , Prenatal Care/organization & administration , Adult , Episiotomy/statistics & numerical data , Extraction, Obstetrical/statistics & numerical data , Female , Humans , Infant, Newborn , Pregnancy , Risk , Victoria
14.
Biomacromolecules ; 2(3): 851-5, 2001.
Article in English | MEDLINE | ID: mdl-11710041

ABSTRACT

The cytotoxicity of a unimolecular polymeric micelle (1) and its degradation products was assessed by cell proliferation and viability with L929 mouse areolar/adipose fibroblasts. Polymer 1 and poly(ethylene glycol) (PEG) were diluted to concentrations from 10(-4) to 10(-6) M in culture media, whereas the degradation products were diluted to concentrations (10(-4) to 10(-6) M) that would theoretically occur upon degradation of polymer 1. The polymer degradation products that were evaluated included mucic acid, hexanoic acid, 1,1,1-tris(4-hydroxyphenyl)ethane (THPE),2,3,4,5-tetrakis-hexanoyloxy-hexanedioic acid or MA(hex), Core(hex), and PEG5, which is PEG of molecular weight 5000. Cells exposed to polymer 1 proliferated at the same rate as cells grown in polymer-free or PEG5-containing solutions up to 36 h. In both the polymer 1 and PEG5 solutions, cytotoxicity was not observed at any concentration (up to 10(-4) M) as indicated by cell attachment, growth, and morphology. Fibroblasts exposed to the degradation products fared as well as fibroblasts in contact with polymer 1 and PEG5, except for cells exposed to the highest concentration (10(-4) M) of THPE.


Subject(s)
Polymers/toxicity , Animals , Biodegradation, Environmental , Cell Division/drug effects , Cell Line , Drug Carriers , Drug Stability , Fibroblasts/cytology , Fibroblasts/drug effects , Macromolecular Substances , Mice , Micelles , Molecular Structure , Polyethylene Glycols , Polymers/chemistry
16.
J Midwifery Womens Health ; 46(3): 130-6, 2001.
Article in English | MEDLINE | ID: mdl-11480744

ABSTRACT

Evidence-based care has become the new standard in the clinical disciplines. It represents a paradigm shift for clinicians, toward greater inclusion of research findings in patient care decisions. Randomized trials are the "gold standard" in clinical research and provide the strongest evidence for a treatment or intervention. But, randomized trials have limitations and cannot address all important clinical questions. Research using observational, descriptive, and qualitative methods also has a place in generating evidence for practice. Balancing the needs of individual women against what is learned from research with groups or populations is a challenge for midwives.


Subject(s)
Evidence-Based Medicine , Midwifery , Female , Humans , Pregnancy , Randomized Controlled Trials as Topic
17.
J Clin Psychopharmacol ; 21(4): 398-407, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11476124

ABSTRACT

Clozapine is an atypical antipsychotic drug and displays efficacy in 30% to 60% of patients with schizophrenia who do not respond to traditional antipsychotics. A clozapine concentration greater than 1,150 nmol/L increases the probability of antipsychotic efficacy. However, plasma clozapine concentration can vary more than 45-fold during long-term treatment. The aim of this study was to assess the contribution of CYP1A2 to variability in steady-state concentration of clozapine and its active metabolite norclozapine. Patients with schizophrenia or schizoaffective disorder were prospectively monitored during clozapine treatment (N = 18). The in vivo CYP1A2 activity was measured using the caffeine metabolic ratio (CMR) in overnight urine. Trough plasma samples were drawn after at least 5 days of treatment with a constant regimen of clozapine. A significant negative association was found between the CMR and the dose-corrected clozapine (r(s) = -0.87,p < 0.01) and norclozapine (r(s) = -0.76,p < 0.01) concentrations. Nonsmokers displayed a higher clozapine (3.2-fold) and norclozapine (2.3-fold) concentration than smokers (p < 0.05). Furthermore, there was marked person-to-person variation in CYP1A2 activity during multiple-dose clozapine treatment (coefficient of variation = 60%). Age, weight, serum creatinine, and grapefruit juice consumption did not significantly contribute to variability in clozapine and norclozapine concentration (p > 0.05). In conclusion, CYP1A2 is one of the important contributors to disposition of clozapine during multiple-dose treatment. Although further in vitro experiments are necessary, the precise metabolic pathways catalyzed by CYP1A2 seem to be subsequent to the formation of norclozapine, hitherto less recognized quantitatively important alternate disposition routes, or both. From a clinical perspective, an environmentally induced or constitutively high CYP1A2 expression can lead to a decrease in steady-state concentration of clozapine as well as its active metabolite norclozapine. Thus, interindividual variability in CYP1A2 activity may potentially explain treatment resistance to clozapine in some patients. CYP1A2 phenotyping with a simple caffeine test may contribute to individualization of clozapine dosage and differentiate between treat ment noncompliance and high CYP1A2 activity.


Subject(s)
Antipsychotic Agents/pharmacokinetics , Caffeine , Clozapine/analogs & derivatives , Clozapine/blood , Clozapine/pharmacokinetics , Cytochrome P-450 CYP1A2/metabolism , Phosphodiesterase Inhibitors , Schizophrenia/metabolism , Adult , Aged , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/blood , Clozapine/administration & dosage , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Psychotic Disorders/metabolism , Reference Values , Smoking/metabolism
18.
J Midwifery Womens Health ; 46(6): 366-73, 2001.
Article in English | MEDLINE | ID: mdl-11783684

ABSTRACT

Electronic fetal monitoring (EFM) was implemented across the United States in the 1970s. By 1998, it was used in 84% of all U.S. births, regardless of whether the primary caregiver was a physician or a midwife. Numerous randomized trials have agreed that continuous EFM in labor increases the operative delivery rate, without clear benefit to the baby. Intermittent auscultation (IA) is safe and effective in low-risk pregnancies and may play a role in helping birth remain normal. Clinicians and educators are encouraged to reconsider the use of IA in the care of healthy childbearing women.


Subject(s)
Fetal Distress/diagnosis , Fetal Monitoring/methods , Adult , Asphyxia Neonatorum/diagnosis , Asphyxia Neonatorum/prevention & control , Auscultation/methods , Cerebral Palsy/physiopathology , Cerebral Palsy/prevention & control , Female , Fetal Monitoring/adverse effects , Heart Rate, Fetal/physiology , Humans , Infant, Newborn , Labor, Obstetric , Midwifery , Obstetrics , Pregnancy , Randomized Controlled Trials as Topic , Reproducibility of Results , Sensitivity and Specificity , Technology Assessment, Biomedical , United States
19.
J Clin Psychopharmacol ; 21(6): 603-7, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11763009

ABSTRACT

Antipsychotic response to clozapine varies markedly among patients with schizophrenia. The disposition of clozapine is dependent, in part, on the cytochrome P-450 (CYP) 1A2 enzyme in vivo. In theory, a very high CYP1A2 activity may lead to subtherapeutic concentrations and treatment resistance to clozapine. This prospective case study evaluates the clinical significance of ultrarapid CYP1A2 activity and a recently discovered single nucleotide (C --> A) polymorphism in intron 1 of the CYP1A2 gene (CYP1A2*F) for treatment resistance to clozapine. In addition, we describe the effect of grapefruit juice or low-dose fluvoxamine (25-50 mg/d) coadministration on clozapine and active metabolite norclozapine steady-state plasma concentration and antipsychotic response.


Subject(s)
Beverages , Citrus , Clozapine/therapeutic use , Cytochrome P-450 CYP1A2/genetics , Cytochrome P-450 CYP1A2/metabolism , Fluvoxamine/administration & dosage , Introns/genetics , Polymorphism, Genetic/genetics , Adult , Antidepressive Agents, Second-Generation/administration & dosage , Antipsychotic Agents/blood , Antipsychotic Agents/therapeutic use , Citrus/enzymology , Clozapine/blood , Humans , Male , Prospective Studies , Treatment Outcome
20.
Psychiatry Res ; 96(3): 235-43, 2000 Nov 20.
Article in English | MEDLINE | ID: mdl-11084219

ABSTRACT

The present study was designed to determine the effect of venlafaxine on imipramine metabolism in an attempt to elucidate the potential for cytochrome P450 drug-drug interactions with venlafaxine. We examined the metabolism of a single 100-mg dose of imipramine before and after treatment with venlafaxine, 50 mg three times a day. Eight male subjects were phenotyped for CYP2D6 activity. Two subjects were poor metabolizers of dextromethophan, and data from the remaining six subjects (mean age=45.3+/-15) were analyzed. Venlafaxine increased imipramine C(max) and elevated AUC by 40%. Desipramine clearance and volume of distribution were reduced by 20% and 25%, respectively. These findings are consistent with a statistically significant, but clinically modest impact of venlafaxine on CYP2D6-metabolized substrates.


Subject(s)
Antidepressive Agents, Second-Generation/pharmacology , Antidepressive Agents, Tricyclic/pharmacokinetics , Cyclohexanols/pharmacology , Cytochrome P-450 CYP2D6/metabolism , Imipramine/pharmacokinetics , Adult , Antidepressive Agents, Second-Generation/blood , Antidepressive Agents, Tricyclic/blood , Cross-Over Studies , Cyclohexanols/blood , Cytochrome P-450 CYP2D6/genetics , Desipramine/pharmacokinetics , Drug Interactions , Humans , Imipramine/blood , Male , Middle Aged , Phenotype , Venlafaxine Hydrochloride
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