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PubMed1992

Pediatric pharmacokinetics and therapeutic drug monitoring.

Recent advances in pediatric clinical pharmacology have provided a more rational approach to using several medications in children. An increased understanding of the effect of human development, concurrent medications, organ function, and disease states on the absorption, distribution, metabolism, and excretion of drugs has provided a stronger scientific basis for determining drug dosages in children. By measuring drug concentrations and utilizing pharmacokinetic and pharmacodynamic principles, the probability of therapeutic response can be enhanced for a number of medications. Likewise, therapeutic drug monitoring can minimize the risk of adverse effects from many drugs used in children. However, it must be recognized that toxicity can occur in some patients even though plasma drug concentrations are in the therapeutic range; similarly, some patients may not experience a therapeutic effect when plasma drug concentrations are in the same target range. Therefore, achieving the desired plasma concentration of a drug can enhance both the probability of a therapeutic response and diminish the probability of a toxic response. Therapeutic ranges, however, are only intermediate endpoints that must be used in the context of additional criteria to assess the clinical efficacy of any given drug therapy.

Child↗

PubMed2004

[Long-term therapeutic effect of triple therapy consisted of omeperazole, clarithromycin and amoxycillin in children with Helicobacter pylori infection and approach to re-treatment after failure of the treatment].

OBJECTIVE: Helicobacter pylori (Hp) infection presents high prevalence in the world, but there are few pediatric assays evaluating antimicrobial treatment using a short regimen of triple therapy. To evaluate the eradication rate and long term therapeutic effect of a triple therapy consisted of omeperazole, clarithromycin (CLA) and amoxycillin (AMO) on Hp infection, the authors explored the alternative therapeutic programs and their effects after first therapeutic failure. METHODS: A total of 192 children with Hp infection were divided into two groups: 157 children were given the triple therapy for one week (CLA group); 35 children were given another triple therapy composed of omeperazole, metronidazole (MET) and AMO for two weeks (MET group). All of the children were followed up for 1 - 36 months after the therapies ended. Twenty-two children in whom Hp was eradicated with CLA triple therapy were followed up for 3 years. The children of the two groups who had therapeutic failure were given re-treatment as follows. CLA triple therapy was given for one week to the children who had failure after MET triple therapy; increased doses of CLA with longer treatment course was given to the children who had failure after CLA triple therapy. A tetra therapy consisted of omeperazole, colloidal bismuth subcitrate (CBS), furazolidone (FUR) and AMO was given to the children in whom the re-treatment failed. RESULTS: The Hp eradication and ulcer recovery rate of CLA group was 90.4% (142/157) and 96.9% (32/33), respectively; the Hp eradication rate of MET group was 77% (27/35). There was significant difference between eradication rates of the two groups (chi(2) = 4.69, P < 0.05). The recurrence rate of 22 Hp eradicated children treated with CLA triple therapy was 4.5% (1/22) during the 3-year follow-up. The eradication rate of the three re-treatment programs for 29 children was 75% (6/8), 77% (11/15) and 100% (6/6), respectively. CONCLUSION: (1) Omeperazole, CLA and AMO triple therapy for one week was the best to eradicate Hp infection with high eradication rate, few side effects, short period of treatment, good compliance and low recurrence rate. (2) Proper increase of CLA dose and longer therapeutic course may increase the eradication rate. Omeperazole, CBA, FUR and AMO tetra therapeutic program may be used as an alternative treatment in patients who develop resistance to CLA triple therapy.

Adolescent↗

PubMed2004

[Circadian rhythm variations of intraocular pressure and therapeutic decisions: interpretation of clinical trial results based on a statistical model].

Therapeutic decisions (treatment initiation, continuation, change, combination, etc.) based on intraocular pressure (IOP) monitoring require knowledge of both circadian IOP fluctuations and the pharmacological circadian rhythm of the active ingredients. A simple model was applied to data from two clinical trials to estimate the consequences of circadian IOP fluctuations on (1) ocular hypertension diagnosis, (2) therapeutic adjustments, and (3) the daily cumulative effect of marginally low therapeutic differences. A grid for clinical interpretation of the average IOP differences is presented. The probability of an IOP that exceeds the target value for the diagnosis or therapy varied to a large extent throughout the day. IOP was higher in the morning than in the evening. The IOP variance (measured by standard deviation) was an important factor in decision-making, regardless of the IOP value itself. Regular IOP monitoring over the entire day allowed minimization of the time spent above a target value. IOP differences that seemed low when expressed in average values in therapeutic trials could have clinically significant consequences in the practitioner's decisions. The data presented suggest that ocular hypertension diagnosis and therapeutic decisions should be made early in the morning, at least for most patients. In any case, the time of the measurement should be considered in the therapeutic approach.

Biotransformation↗

PubMed2005

Correlates of therapeutic involvement among adolescents in residential drug treatment.

The current study addresses the critical need for research on the therapeutic involvement among adolescent substance users in treatment. Although therapeutic involvement (TI) and the services that clients receive during treatment are among the best predictors of treatment retention and through retention associated with better posttreatment outcomes, there are relatively few empirical studies of therapeutic involvement among adolescents in drug treatment. Using data on N=185 adolescent clients in five adolescent residential drug-treatment programs in New Jersey, factor analyses used maximum likelihood extraction and oblique rotation. Pearson's correlation coefficients and multivariate linear regression were used to explore the utility of using existing measures of TI developed on adult populations to examine the correlates of therapeutic involvement among adolescents. The majority of subjects (85%) were between 16 and 18 years of age, with an average age of 17 years. Seventy-nine percent were male, 20% were Hispanic, 36% were African-American, and 46% were Caucasian. Working alliance, self-esteem, spirituality, deviance, and substance use problem severity were associated with therapeutic involvement and there is evidence that there may be important subgroup differences associated with gender and ethnicity. Further research on the interplay between these factors, therapeutic involvement, and recovery among adolescents can inform the development of strategies to enhance the engagement and retention of adolescents in drug treatment.

Adolescent↗

PubMed2005

[Nuclear transfer and therapeutic cloning].

Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

Animals↗

PubMed2005

[Therapeutic education for cardiac failure patients: the I-care programme].

Therapeutic education is becoming increasingly important in the management of chronic diseases including cardiac failure. The I-CARE programme consists of an evaluation of the role of therapeutic education in France, creating standardised tools and setting up training sessions for therapeutic education in the context of cardiac failure. Approximately two thirds of the French centres contacted perform therapeutic education with their available means. The lack of personnel, space, and training tools represent obstacles to the development of therapeutic education. The tools developed in the programme fall into 5 areas: diagnosis education, understanding the illness, diet, physical activity/daily life, and treatment. Training sessions were organised for the teams, consisting of at least one cardiologist and nurse. The I-CARE programme should allow the expansion of therapeutic education for cardiac failure and improve the multidisciplinary management of this disease which increasingly affects often elderly subjects.

Activities of Daily Living↗

PubMed2005

[Spanish scientific production in diagnostic and therapeutic research area of respiratory system in international journals from 1990 to 2002].

OBJECTIVE: The aim of this study were: to analyze the spanish production in diagnostic and therapeutics research area of respiratory system in international journals from 1990 to 2002. MATERIAL AND METHODS: Papers published in diagnostic and therapeutics area of respiratory system during this period of time were selected by the PUBMED system. We delimited the production with key words: respiratory system and the one that is used by the diagnostic and therapeutics research area. RESULTS: We obtain a total of 67 document published in international journals by spanish authors. The scientific production in the diagnostic and therapeutics area have stabilized in this 12 years period. The distribution of articles by the institutional affiliation and province of authors also showed a wide dispersion: Barcelona and Clinic and Provincial Hospital of Barcelona were responsible for 43.1% and 23.8% of all the production. Bronchoalveolar lavage and the use of telescopic catheter were the type of diagnostic and therapeutic procedure more productive. CONCLUSIONS: The scientific production in the diagnostic and therapeutics area of respiratory system have stabilized in this 12 years period, this evidence contrast with the high growth detected in respiratory system in general.

Biomedical Research↗

PubMedDate not supplied

[Therapeutic education of the diabetic patient].

Therapeutic education is a patient centred approach focused on patients' needs, values and strategies. It allows not only to increase patients' knowledge and skills on the disease, but also on their treatments. It brings a better quality of life, an increased therapeutic compliance, and decreases complications. The most difficult part of therapeutic education occurs when patients must change their behaviour. Motivational interviewing techniques are of great support and allow to prepare and support patients in "step by step" progressive changes. It is essential to work on resistance to change. The ambivalence in the choice of a new lifestyle must be measured, discussed and negotiate. Patients become partners and health care providers become coaches. To negotiate objectives must allow patients to choose their own strategies which should cost them minimum psychological efforts and bring them maximum benefits. The efficacy of therapeutic education has not to be proved any more: 80% less of amputations at 10 years in diabetic patients, 50% of stable body weight after weight loss at 5 years, etc. In conclusion, therapeutic education is part of a humanist medicine centred on patients which allow them to take care of their own treatment, in order to improve their quality of life, therapeutic compliance and potential complications. The health care providers teach, train, negotiate, motivate and accompany their patients in the long-term follow-up of their diseases.

Diabetes Complications↗

PubMedDate not supplied

Outcome of therapeutic penetrating keratoplasty in infectious keratitis.

BACKGROUND AND OBJECTIVE: To study the outcome of therapeutic penetrating keratoplasty in eyes with microbial keratitis. PATIENTS AND METHODS: A prospective database on 134 therapeutic cornea transplants in 134 patients recorded demographic details on age and gender of the patient, indication for surgery, size of the donor and recipient bed, graft clarity, complications, and residual morbidity. Patients included in this analysis had a minimum follow-up of 1 year. All patients underwent therapeutic penetrating keratoplasty by a similar method that involved a donor button that was oversized by 0.5 mm and 16 bites of interrupted sutures. RESULTS: Most of the 134 ulcers needing therapeutic grafts were bacterial (n = 54) or fungal (n = 54). One hundred eighteen eyes had perforation at presentation. One hundred six (90%) of the therapeutic grafts achieved anatomical success. The most common complication of glaucoma occurred in 22% of eyes with presurgical perforated ulcers and 1% of nonperforated ulcers. Persistent epithelial defects were significantly more frequent in grafts of 9 mm or more (P = .05). CONCLUSIONS: Our results confirm that therapeutic penetrating keratoplasty for infections is successful in restoring anatomic integrity in most eyes.

Adolescent↗

PubMed2005

Pharmacogenetics and pharmacogenomics in oncology therapeutic antibody development.

Pharmacogenetics and pharmacogenomics are keys to the success of personalized medicine, prescribing drugs based on a patient's individual genetic and biological profile. In this review, we will focus on the application of pharmacogenetics and pharmacogenomics in developing monoclonal antibody (MAb) therapeutics in oncology. The significance of pharmacogenomics in MAb therapeutics is highlighted by the association between polymorphisms in Fc receptors and clinical response to anti-CD20 MAb rituximab (Rituxan) or anti-ganglioside GD2 MAb 3F8, as well as the potential link between polymorphisms in HER2 and cardiac toxicity in patients treated with the anti-HER2 MAb trastuzumab (Herceptin). The dependence on gene copy number or expression levels of HER2 and epidermal growth factor receptor (EGFR) for therapeutic efficacy of trastuzumab and cetuximab (Erbitux), respectively, supports the importance of selecting suitable patient populations based on their pharmacogenetic profile. In addition, a better understanding of target mutation status and biological consequences will benefit MAAb development and may guide clinical development and use of these innovative therapeutics. The application of pharmacogenetics and pharmacogenomics in developing MAb therapeutics will be largely dependent on the discovery of novel surrogate biomarkers and identification of disease- and therapeutics-relevant polymorphisms. Challenges and opportunities in biomarker discovery and validation, and in implementing clinical pharmacogenetics and pharmacogenomics in oncology MAb development and clinical practice will also be discussed.

Antibodies, Monoclonal↗

PubMed2005

Therapeutic drug monitoring and the inhibitory quotient of antiretroviral drugs: can they be applied to the current situation?

Therapeutic drug monitoring is attracting growing interest as a means of increasing the effectiveness of antiretroviral therapy and of decreasing its toxicity, although data supporting this strategy are still scarce. Currently, nucleoside analog reverse-transcriptase inhibitors (NARTI) are not candidates because their effect depends on their active intracellular form and not on plasma concentration. Protease inhibitors (PI) and non-nucleoside analogue reverse-transcriptase inhibitors (NNARTI) meet the criteria for therapeutic drug monitoring. The main limitations are that the parameters to be monitored in order to measure exposure to the drug and the effective concentration of the drug have not been well defined. The few studies performed in treatment-naive patients have demonstrated that monitoring improves therapeutic efficacy. This strategy will be particularly useful when the risk of subtherapeutic or toxic concentrations is especially high (pharmacokinetic interactions, intestinal malabsorption, adverse effects, virological failure without obvious cause, pregnancy, children). Although it remains to be standardized, the inhibitory quotient integrates pharmacological and virological parameters and is useful in patients with prior virological failure. Any therapeutic drug monitoring program should be accompanied by measures to monitor and improve treatment adherence. There are good reasons to believe that therapeutic drug monitoring can be useful to improve treatment in specific circumstances. However, before its widespread use as a routine method can be recommended, the parameters to be used should be standardized and studies with appropriate methodology should be performed to define the role of therapeutic drug monitoring in distinct clinical situations.

Algorithms↗

PubMed2006

[Observation on therapeutic effect of aponeurotic system penetration needling on peripheral facial paralysis].

OBJECTIVE: To observe therapeutic effect of aponeurotic system penetration needling on peripheral facial paralysis. METHODS: One hundred and ten cases of peripheral facial paralysis were randomly divided into a Jingjin group (n=68) and a control group (n=42). The therapeutic effects of acute stage, resting stage and sequela stage, and the relation between the facial nerve lesion degree and the therapeutic effect were investigated. RESULTS: The effective rates of the two needling methods were respectively 98.5% and 90.5%, the Jing1in group being better than the control group (P < 0.05); at the acute stage, the therapeutic effect of acupuncture was obvious, and the therapeutic effect at the sequela stage and for the patient of nerve faulty type in the Jingjin group were better than that of the control group (P < 0.05). CONCLUSION: Acupuncture and moxibustion has definite therapeutic effect on facial paralysis at the acute stage and in the patient of nerve active type, and aponeurotic system penetration needling can be used for the patient of facial paralysis at the sequela stage or with nerve faulty type.

Acupuncture Points↗

PubMed2006

Effect of therapeutic exercise on gait speed in community-dwelling elderly people: a meta-analysis.

BACKGROUND AND PURPOSE: Inconsistent research findings make it unclear whether therapeutic exercise improves gait speed in community-dwelling elderly people. Using meta-analytical procedures, we examined the effect of therapeutic exercise on changing gait speed in community-dwelling older adults and the effect of type, intensity, and dose of therapeutic exercise on gait speed. METHOD: Studies were retrieved using a comprehensive database search. Two independent reviewers determined study eligibility based on inclusion criteria, rated study quality, and extracted information on study methods, design, intervention, and results. Data were combined to obtain an overall effect size, its 95% confidence interval, and a measure of significance. In addition, analyses to characterize the clinical relevance of the findings were performed. RESULTS: One hundred seventeen studies were evaluated, with 24 studies (n=1,302 subjects) meeting the inclusion criteria for habitual gait speed and 18 studies (n=752 subjects) meeting the inclusion criteria for fast gait speed. Therapeutic exercise--or, more specifically, strength training and combination training (aerobic plus other exercise)--had significant effects (r=.145, P=.017; r=.176, P=.002, respectively) on habitual gait speed. High-intensity (effort expended by subjects) exercise and high-dosage (frequency and duration of exercise sessions) intervention also had a significant effect (r=.184, P=.001; r=.190, P=.001, respectively) on gait speed, whereas there was no effect for moderate- and low-intensity exercise or for low-dosage exercise. No exercise intervention affected fast gait speed in this analysis. DISCUSSION AND CONCLUSION: The results provide support for the belief that therapeutic exercise can improve gait speed in community-dwelling elderly people and that intensity and dosage are important contributing factors. The relatively weak correlation found between therapeutic exercise and gait speed merits further study.

Aged↗

PubMedDate not supplied

[Evaluation of the therapeutic benefits in relation to the extent of surgery in patients with differentiated thyroid carcinoma].

INTRODUCTION: Evaluation of the therapeutic benefits in relation to the stage of thyroid cancer and to the extent of surgery and the risk of postoperative complications. MATERIAL AND METHODS: Retrospective analysis of differentiated thyroid carcinoma (DTC) patients staged T1M0 versus T2-T4M0 was performed. All of them were treated or diagnosed in Institute of Oncology in Gliwice between 1986-1998. Previously they were operated in various surgical centers all-over Poland. The risk of death, local relapse and postoperative complications were analyzed using the decisiontree model to evaluate the therapeutic benefits. RESULTS: The recurrent laryngeal nerve injury (transient or permanent) was observed in retrospective analysis in 21% of patients, while postoperative hyperparathyroidism in 15.8%. The analysis of the therapeutic benefit index showed no advantage of total thyroidectomy in the T1M0 group (0.96 vs. 0.98 in patients treated by less than total thyroidectomy). The advantage of radical surgery was confirmed in T2-T4M0 group. The therapeutic benefit index was 0.92 in patients treated by total thyroidectomy and 0.69 in those who received less extensive operation. CONCLUSIONS: The analysis of therapeutic benefits confirmed the limit of 1 cm tumor diameter between less extensive surgery and total thyroidectomy. It showed that total thyroidectomy brings a significant therapeutic benefits in patients in > T1M0 stage. The improvement of overall survival and decrease of local relapse far outweigh the disadvantages related to postoperative complications.

Adenocarcinoma, Follicular↗

PubMed2006

What is the best pre-therapeutic dosimetry for successful radioiodine therapy of multifocal autonomy?

PURPOSE: Dose calculation for radioiodine therapy (RIT) of multifocal autonomies (MFA) is a problem as therapeutic outcome may be worse than in other kinds of autonomies. We compared different dosimetric concepts in our patients. PATIENTS, METHODS: Data from 187 patients who had undergone RIT for MFA (Marinelli algorithm, volumetric compromise) were included in the study. For calculation, either a standard or a measured half-life had been used and the dosimetric compromise (150 Gy, total thyroid volume). Therapeutic activities were calculated by 2 alternative concepts and compared to therapeutic success achieved (concept of TcTUs-based calculation of autonomous volume with 300 Gy and TcTUs-based adaptation of target dose on total thyroid volume). RESULTS: If a standard half-life is used, therapeutic success was achieved in 90.2% (hypothyroidism 23,1%, n = 143). If a measured half-life was used the success rate was 93.1% (13,6% hypothyroidism, n = 44). These differences were statistically not significant, neither for all patients together nor for subgroups eu-, hypo-, or hyperthyroid after therapy (ANOVA, all p > 0.05). The alternative dosimetric concepts would have resulted either in significantly lower organ doses (TcTUs-based calculation of autonomous volume; 80.76 +/- 80.6 Gy versus 125.6 +/- 46.3 Gy; p < 0.0001) or in systematic over-treatment with significantly higher doses (TcTUs-adapted concept; 164.2 +/- 101.7 Gy versus 125.6 +/- 46.3 Gy; p = 0.0097). CONCLUSIONS: TcTUsbased determination of the autonomous volume should not be performed, the TcTUs-based adaptation of the target dose will only increase the rate of hypothyroidism. A standard half-life may be used in pre-therapeutic dosimetry for RIT of MFA. If so, individual therapeutic activities may be calculated based on thyroid size corrected to the 24h ITUs without using Marinelli's algorithm.

Dose-Response Relationship, Radiation↗

PubMed2006

[Therapeutic effect of deoxyribonucleotidum on acute viral myocarditis].

OBJECTIVE: To evaluate the therapeutic efficacy of deoxyribonucleotidum in treatment of acute viral myocarditis. METHODS: Eighty-eight patients with acute viral myocarditis were randomized equally into therapeutic group and control group. Patients in the control group were treated with routine treatment and those in the therapeutic group were given deoxyribonucleotidum in addition to routine treatment. After 4 weeks, the total efficacy rate and median time of symptom disappearance were compared between the two groups. RESULTS: The total efficacy rate in the control and therapeutic groups was 79.54% and 95.45% (P=0.049), and the median time of symptom disappearance was 9.5 days and 6.5 days, respectively (P=0.035). Hypotension and mild dizziness were found in 2 patients in the therapeutic group without other severe side effects. CONCLUSION: Deoxyribonucleotidum can improve the therapeutic effect for acute viral myocarditis.

Adolescent↗

PubMed2006

A model to explain the therapeutic effects of serotonin reuptake inhibitors: the role of 5-HT2 receptors.

In this article, it is posited that major depression involves an underfunctioning dopamine system resulting from hypersensitive inhibitory 5-HT2 receptors located on dopaminergic neurons. After a few weeks, treatment with most antidepressant drugs leads to a downregulation of the 5-HT2 receptors that allows for increased dopaminergic firing, which is proposed to be decisive for the antidepressant effect. However, serotonin reuptake inhibitors (SRIs) therapeutic mechanisms probably differ between different therapeutic outcomes. It is hypothesized, that in women, the use of female sex steroids leads to a downregulation of 5-HT2C receptors that contributes to atypical depressive symptoms and premenstrual dysphoria. Consequently, these conditions can be assumed to benefit from the acute increase of serotonergic neurotransmission following ingestion of an SRI rather than the secondary receptor changes, which would explain why there is a therapeutic lag time when SRIs are used to treat depression but not premenstrual dysphoric disorder. The clinical predictions derived from this hypothesis are that 5-HT2 antagonists would be an effective treatment in melancholic depression, have a fast onset of action, speed the onset of SRIs, and can be an effective augmentation for SRI-refractory patients. In contrast, in atypical depression and premenstrual dysphoria a 5-HT2 antagonist would counteract the therapeutic effect of an SRI, while 5-HT2 agonists have a therapeutic potential. It is suggested that therapeutic response to 5-HT2 antagonists/agonists may be used as a diagnostic tool to dissect subgroups of depression.

Brain↗

PubMed2006

[Evaluation of the therapeutic response: role of isotopic imaging].

In comparison with conventional imaging, nuclear medicine offers an original metabolic approach for the assessment of the therapeutic response. Gallium 67, thallium 201, technetium 99m-labeled sestamibi and diphosphonates can be performed for therapeutic response assessment in lymphoma, brain and breast tumours, sarcoma, or bone metastasis. PET-CT facilities are now easily available in France and are ready to provide a new and accurate tool in oncology, specially for therapeutic evaluation. The procedure consists in the injection of fluor-18-fluoro-déoxyglucose (18FDG), an analogue of glucose, followed by a PET then a CT acquisition for FDG uptake abnormalities location. Therapeutic response is assessed by a decrease of 18FDG tumoral uptake between two consecutive studies. Methodology and interpretation criteria have been recently defined in international guidelines. 18FDG-PET-CT seems to be a valuable tool for therapeutic response assessment of patients with Hodgkin or non Hodgkin malignant lymphoma. Promising preliminary results have been recently published for lung, gastro-intestinal and head and neck cancers. PET-CT could also be able to predict the therapeutic response after the first courses of chemotherapy, allowing an early treatment optimization. Finally, new PET agents pave the way for molecular imaging with promising results in gene therapy and targeted treatment in oncology.

Diphosphonates↗