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Therapeutic Goal (therapeutic + goal)
Selected AbstractsNot all roads lead to Rome,a review of quality of life measurement in adults with diabetesDIABETIC MEDICINE, Issue 4 2009J. Speight Abstract Aims Quality of life (QoL) is recognized widely as an important health outcome in diabetes, where the burden of self-management places great demands on the individual. However, the concept of QoL remains ambiguous and poorly defined. The aim of our review is to clarify the measurement of QoL in terms of conceptualization, terminology and psychometric properties, to review the instruments that have been used most frequently to assess QoL in diabetes research and make recommendations for how to select measures appropriately. Methods A systematic literature search was conducted to identify the ten measures most frequently used to assess QoL in diabetes research (including clinical trials) from 1995 to March 2008. Results Six thousand and eight-five abstracts were identified and screened for instrument names. Of the ten instruments most frequently used to assess ,QoL', only three actually do so [i.e. the generic World Health Organization Quality of Life (WHOQOL) and the diabetes-specific Diabetes Quality of Life (DQOL) and Audit of Diabetes-Dependent Quality of Life (ADDQoL)]. Seven instruments more accurately measure health status [Short-Form 36 (SF-36), EuroQoL 5-Dimension (EQ-5D)], treatment satisfaction [Diabetes Treatment Satisfaction Questionnaire (DTSQ)] and psychological well-being [Beck Depression Inventory (BDI), Hospital Anxiety and Depression Scale (HADS), Well-Being Questionnaire (W-BQ), Problem Areas in Diabetes (PAID)]. Conclusions No single measure can suit every purpose or application but, when measures are selected inappropriately and data misinterpreted, any conclusions drawn are fundamentally flawed. If we value QoL as a therapeutic goal, we must ensure that the instruments we use are both valid and reliable. QoL assessment has the proven potential to identify ways in which treatments can be tailored to reduce the burden of diabetes. With careful consideration, appropriate measures can be selected and truly robust assessments undertaken successfully. [source] Therapeutics for alcoholism: what's the future?DRUG AND ALCOHOL REVIEW, Issue 1 2007ANDREW J. LAWRENCE Abstract As with other addictions, human alcoholism is characterised as a chronically relapsing condition. Consequently, the therapeutic goal is the development of clinically effective, safe drugs that promote high adherence rates and prevent relapse. These products can then be used in conjunction with psychosocial approaches. In this review, preclinical studies are highlighted that indicate the mechanism of action of currently used anti-craving medications or demonstrate the potential of novel pharmacological agents for the treatment of alcohol use disorders. While current pharmacological strategies are far from ideal, there are a number of candidate molecules that may ultimately be developed into therapeutic agents. In addition, prescribing clinicians should also consider strategies such as combinations of various drugs to aid in the regulation of aberrant alcohol consumption. [source] Reduced intensity allogeneic stem cell transplantation for systemic primary amyloidosis refractory to high-dose melphalanEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2004Yasukazu Kawai Abstract: Complete elimination of the plasma cell dyscrasia is a rational therapeutic goal, as intercepting supply of precursor protein is a necessary condition for a major regression of amyloid deposits. High-dose melphalan with autologous stem cell transplantation has shown the ability to induce complete hematological response (HR) along with recovery of organ dysfunction. However, the rate of HR with this treatment rarely exceeds 40%. We describe here the first known case of successful reduced intensity allogeneic stem cell transplantation (RIST) for a patient with primary amyloidosis complicated with nephrotic syndrome but without cardiac disease, who had obtained only partial HR by high-dose melphalan with autologous stem cell transplantation. RIST may be feasible and be capable of achieving complete HR along with recovery from nephrotic syndrome with acceptable toxicity. [source] Reduction of stress,A new therapeutic goal in the treatment of inflammatory bowel disease?INFLAMMATORY BOWEL DISEASES, Issue 2 2000Viktor E. Eysselein M.D. No abstract is available for this article. [source] Cyclophosphamide pulse therapy followed by azathioprine or methotrexate induces long-term remission in patients with steroid-refractory Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2006C. SCHMIDT Summary Background In patients with steroid-refractory Crohn's disease, the therapeutic goal is to achieve both rapid remission and maintenance of clinical response. Aim To evaluate the long-term benefit in patients treated with cyclophosphamide pulse therapy and azathioprine or methotrexate, a combination shown to be effective in a recent pilot study. Methods Sixteen patients with acute steroid-refractory Crohn's disease participated in a prospective open-labelled uncontrolled pilot study between December 1998 and June 2003. All had a median number of 4 monthly pulses of intravenous cyclophosphamide (750 mg) and were followed until relapse of the disease. Results Thirteen of 16 patients (81%) achieved remission within 8 weeks after two pulses of cyclophosphamide in combination with azathioprine or methotrexate, with a Crohn's Disease Activity Index decrease from 294 to 111 (median). Remission sustained for 19 months (median, range: 1,45). Moreover, eight patients with pyoderma gangrenosum and erythema nodosum who responded to cyclophosphamide have maintained their remission for up to 30 months. Conclusions In steroid refractory patients with Crohn's disease, cyclophosphamide is highly effective to induce remission. This uncontrolled study indicates that cyclophosphamide-induced remission is long-lasting under standard immunosuppressive therapy. [source] Is clinical remission the optimum therapeutic goal in the treatment of Crohn's disease?ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2002I. D. R. Arnott Currently, the therapeutic end-point in the treatment of Crohn's disease is the remission of symptoms, but recent data confirm that mucosal inflammation may continue in the absence of symptoms. Furthermore, emerging evidence indicates that such subtle, sub-clinical mucosal inflammation leads to clinical relapse. The assessment of mucosal inflammation has become easier with the availability of faecal calprotectin assay. Current anti-inflammatory therapy often leaves low-grade mucosal inflammation untreated, and therefore recurrent relapses occur. We need to investigate whether the therapeutic end-point of anti-inflammatory medications needs to be more rigorous and to aim at complete mucosal healing, confirmed by the normalization of mucosal inflammatory markers such as faecal calprotectin concentrations. Immunosuppressive therapy with azathioprine/ 6-mercaptopurine currently offers the best mucosal healing treatment with reduction of relapses, but newer biological agents might offer less toxic therapy. Clinical trials to test the feasibility and efficacy of such a paradigm shift in the medical management of Crohn's disease are now warranted. [source] General principles to enhance practice patterns in gastrointestinal endoscopyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2002A. Sonnenberg To develop general rules on how to pursue a therapeutic goal of interventional endoscopy without getting lost in abundant details. Methods: The influences of various medical interventions on the survival of a patient with gastrointestinal haemorrhage are modelled by an influence diagram. Survival is the focal point of multiple influences affecting its overall strength. Any downstream influence can represent the focal point of other preceding upstream influences. The mathematics underlying the influence diagram are similar to those of a decision tree with some notable exceptions. Its formalism allows one to consider inhibitory and additive influences and to include in the same analysis non-commensurable qualities, such as correct diagnosis, haemostasis or survival. Results: The analysis reveals five general rules. First, the large number of factors involved in successful endoscopy render the influence of each individual factor less important. Second, a single factor that exerts its influence on many subsequent factors tends to be associated with an overall greater relevance. Third, remote influences are of lesser relevance than those directly linked to the final outcome. Fourth, factors multiplied by several consecutive probabilities lose their influence. Fifth, endoscopists need to assess the relevance of individual factors with respect to the immediate goals of endoscopy, as well as the general goals of patient well-being. Conclusions: The influence model of endoscopic haemostasis reveals several general principles that can be utilized as tools in endoscopy training. [source] Research Review: Cholinergic mechanisms, early brain development, and risk for schizophreniaTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 5 2010Randal G. Ross The onset of diagnostic symptomology for neuropsychiatric diseases is often the end result of a decades-long process of aberrant brain development. Identification of novel treatment strategies aimed at normalizing early brain development and preventing mental illness should be a major therapeutic goal. However, there are few models for how this goal might be achieved. This review uses the development of a psychophysiological correlate of attentional deficits in schizophrenia to propose a developmental model with translational primary prevention implications. Review of genetic and neurobiological studies suggests that an early interaction between ,7 nicotinic receptor density and choline availability may contribute to the development of schizophrenia-associated attentional deficits. Therapeutic implications, including perinatal dietary choline supplementation, are discussed. [source] Overexpression of human fibroblast growth factor 2 stimulates cell proliferation in an ex vivo model of articular chondrocyte transplantation,THE JOURNAL OF GENE MEDICINE, Issue 2 2004Henning Madry Abstract Background Genetically engineered chondrocytes could be used to enhance cartilage repair. Fibroblast growth factor 2 (FGF-2) is a mitogen for chondrocytes and may be a candidate for gene transfer approaches to stimulate chondrocyte proliferation. In the present study, we tested the hypothesis that human FGF-2 (hFGF-2) gene transfer into articular chondrocytes modulates cell proliferation in an ex vivo model of chondrocyte transplantation. Methods Transfection of articular chondrocytes with an expression plasmid vector carrying the cDNA for hFGF-2 under the control of the cytomegalovirus promoter/enhancer mediated transgene expression and synthesis of biologically relevant amounts of the recombinant hFGF-2 protein. Articular chondrocytes transfected with the Escherichia coli ,-galactosidase (lacZ) gene or a hFGF-2 cDNA were transplanted onto the surface of articular cartilage explants. Results The tissue formed by the chondrocytes expressing hFGF-2 was thicker and contained more cells than control cultures. Quantitative analysis of [3H]thymidine and [35S]sulfate incorporation in composite cultures revealed that hFGF-2 transfection stimulated mitogenic activity in the new tissue but did not augment matrix glycosaminoglycan synthesis. Conclusions These data support the concept that chondrocytes overexpressing a hFGF-2 cDNA selectively modulate cell proliferation in an ex vivo model of chondrocyte transplantation. These results suggest that therapeutic hFGF-2 gene transfer may be applicable for the treatment of articular cartilage disorders, such as traumatic defects in which cellular repopulation is a therapeutic goal. Copyright © 2004 John Wiley & Sons, Ltd. [source] New prospects for immunotherapy at diagnosis of type 1 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2009Paolo Pozzilli Immune intervention at diagnosis of type 1 diabetes (T1D) aims to prevent or reverse the disease by blocking autoimmunity, thereby preserving/restoring ,-cell mass and function. Recent clinical trials of non-specific and of antigen-specific immune therapies have demonstrated the feasibility of modulation of islet-specific autoimmunity in patients with partial prevention of loss of insulin secretion. In a series of review articles published in this issue of the journal, some of the most promising approaches of immune intervention in T1D are presented. Here we outline the rationale of such interventions and future prospects in this area. Copyright © 2009 John Wiley & Sons, Ltd. Insulin therapy in type 1 diabetes (T1D) rescues the patient from a certain death but not cure the disease. The goal of any therapeutic intervention in T1D is the preservation of insulin-secreting cells; this is achieved by the abrogation of pathogenic reactivity to beta cell autoantigens while preserving full capacity to generate a normal immune response against foreign antigens. Although several therapeutic candidates have been investigated in experimental models of T1D many of which showed promising results, a successful extrapolation of these findings to human T1D has proved to be difficult. In part, this failure results from the considerable disease heterogeneity associated with diverse genetic and non-genetic disease determinants and the spectrum of clinical phenotype at diagnosis. Thus, a younger age at onset is associated with stronger genetic susceptibility, more intense immune response to ,-cell antigens, shorter duration of symptoms, more severe metabolic derangement at diagnosis and a more rapid rate of ,-cell-destruction 1,3. Therefore, designing therapies that would be effective in all clinical settings is definitely challenging. In this issue five different approaches are discussed ranging from antigen-specific therapies [DiaPep277 and glutamic acid decarboxylase(GAD)], to non-antigen-specific immunoregulation (anti-CD3) and to anti-inflammatory (anti-IL1 receptor antagonist). These approaches are currently being tested in large international multicenter trials, and all of them use very similar outcome in terms of a beneficial effect (C-peptide secretion as evidence of a therapeutic effect on restoration of ,-cell function). The authors have been asked to follow a similar format in presenting their approaches so that the reader can easily compare them in terms of rationale and therapeutic goals. [source] Evaluation of a holistic treatment and teaching programme for patients with Type 1 diabetes who failed to achieve their therapeutic goals under intensified insulin therapyDIABETIC MEDICINE, Issue 9 2000U. Bott SUMMARY Aims To evaluate a treatment and teaching programme including psychosocial modules for patients with Type 1 diabetes mellitus on intensified insulin therapy who failed to achieve their treatment goals despite participation in standard programmes. Methods The 5-day inpatient programme comprises small groups of 4,6 patients, focusing on individual needs and problems. Beyond the teaching lessons (most topics are deliberately chosen by the patients), the programme provides intensive group discussions and offers individual counselling concerning motivational aspects, psychosocial problems and coping strategies. Of the first consecutive 83 participants, 76 were re-examined after 17.5 ± 5.5 months (range 9,31 months). Results At follow-up, HbA1c was not improved compared to baseline (8.0 ± 1.3% vs. 8.1 ± 1.5%). However, the incidence of severe hypoglycaemia per patient/year (glucose i.v., glucagon injection) was substantially decreased: 0.62 ± 1.5 episodes at baseline compared to 0.16 ± 0.9 at follow-up (P < 0.001). Twenty-six per cent of the patients at baseline, and 4% at re-examination had experienced at least one episode of severe hypoglycaemia during the preceding year (P < 0.001). Sick leave days per patient/year decreased from 17.0 ± 38.5,7.7 ± 13.6 days (P < 0.05). Patients improved their perceptions of self-efficacy, their relationship to doctors and felt less externally controlled (P < 0.001). The majority of patients perceived an improved competence regarding diet (80.6%) and adaptation of insulin dosage (82.4%), an improved knowledge (82.2%), and a renewed motivation for the treatment (84.5%). Treatment success was significantly associated with baseline HbA1c, stability of motivation, frequency of blood glucose self-monitoring, control beliefs and change in subsequent outpatient care. Conclusions The programme improved glycaemic control mainly as a result of a substantial reduction in the incidence of severe hypoglycaemia. Patients with persistent poor glycaemic control may benefit from structured follow-up care focusing on motivational aspects of self-management and psychosocial support. [source] Population pharmacokinetic modelling of carbamazepine in epileptic elderly patients: implications for dosageJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2006I. B. Bondareva PhD Summary Background:, Proper use of antiepileptic drugs in the elderly involves knowledge of their pharmacokinetics to ensure a patient-specific balance between efficacy and toxicity. However, populations of epileptic patients on chronic carbamazepine (CBZ) therapy which have been studied have included data of relatively few elderly patients. Aims:, The aim of the present study was to evaluate the population pharmacokinetics of CBZ in elderly patients on chronic monotherapy. Methods:, We have used the non-parametric expectation maximization (NPEM) program in the USC*PACK collection of PC programs to estimate individual and population post-induction pharmacokinetics of CBZ in epileptic elderly patients who received chronic CBZ monotherapy. Age-related changes of CBZ population pharmacokinetics were evaluated from routine therapeutic drug monitoring (TDM) data of 37 elderly and 35 younger patients with epilepsy. As a ,historical control' we used previously published population modelling results from 99 young epileptic patients on chronic CBZ monotherapy. In that control group, TDM was performed in the same pharmacokinetic (PK) laboratory, using the same sampling strategy as in the present study, and the same PK population modelling software was used for data analysis. Results and conclusions:, A poor correlation was found between daily CBZ dose and serum concentrations in the elderly patients (r = 0·2, P = 0·25). Probably statistically significant difference in the median values of the CBZ metabolic rate constant (P < 0·001) between elderly and relatively young epileptic patients was found. Our results showed that age-related influences in CBZ pharmacokinetics in elderly patients should be considered in the optimal planning of CBZ dosage regimens. Most elderly patients with epilepsy will usually need CBZ dosages lower than those based on the median population PK parameter values obtained from younger patients. The present population model is also uniquely well suited for the new ,multiple model' design of dosage regimens to hit target therapeutic goals with maximum precision. [source] Paramethoxyamphetamine (PMA) poisoning; a ,party drug' with lethal effectsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2003S. Refstad Among young people in Norway the recreational use of amphetamine derivatives seems to be increasing. Methylenedioxymethamphetamine (MDMA), known as ecstasy, is the dominant substance, having both stimulant and psychedelic properties. Depending on the illegal source of these so-called ,party drugs' the content and purity can vary. This case report describes the first lethal case of paramethoxyamphetamine (PMA) and paramethoxymethamphetamine (PMMA) intoxication reported in Norway. A 16-year-old male was admitted to a local hospital in a coma with seizures and hyperthermia after he had been found undressed and barefooted in a local forest (temperature 2°C). He was intubated and given supportive care. Blood chemistry revealed hypoglycaemia, hypocalcaemia and hyperkalaemia. Shortly after transfer to the central hospital he developed bradycardia with continuous seizures and asystole. Adverse effects of MDMA are well described and include serotonergic and sympathomimetic symptoms with hyperthermia, coagulopathy, rhabdomyolysis and acute kidney and liver failure. Case reports of PMA deaths collectively suggest PMA to be more toxic than MDMA. A delayed effect after intake of PMA compared with MDMA can lead to increased intake. Hypoglycaemia and hyperkalaemia may be specific to PMA poisoning. Increased thermo genesis will result in a search for cooling, which explains the attempt to undress and a desire to submerge in water. In a cool climate this behaviour itself can be lethal. Measures to treat seizures, hypoglycaemia, electrolyte anomalies and hyperthermia are the therapeutic goals. No specific treatment is available. [source] Nonadherence as a predictor of antidiabetic drug therapy intensification (augmentation),PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 9 2004Dr Stephen J. Kogut MBA Abstract Purpose To determine if nonadherence with antidiabetic drug therapy is predictive of subsequent antidiabetic drug therapy intensification. Methods We conducted a retrospective cohort study examining retail pharmacy dispensings of sulfonylureas or metformin to 1067 patients having diabetes. Patients that did not receive a sufficient quantity of medication to cover at least 80% of days during the evaluation period were classified as nonadherent. Outcomes identified were increase in the dose of antidiabetic medication utilized, the addition of a second antidiabetic agent to the regimen or either. Results Among users of sulfonylurea monotherapy, those classified as nonadherent were 45% more likely to intensify therapy in subsequent months as compared with those classified as adherent (age-adjusted odds ratio (OR) 1.45; 95% confidence interval (CI) 1.06,2.00). This finding was largely driven by observed increases in dosage, which were more likely among patients classified as nonadherent (age-adjusted OR 1.48, 95%CI 1.07,2.05). Nonadherence was not found to be predictive of the subsequent addition of a second antidiabetic agent (OR 1.02; 95%CI 0.64,1.63). Overall findings were similar for the smaller sample of patients receiving metformin monotherapy, though observed differences did not achieve statistical significance. Conclusions Patients who were poorly adherent to oral antidiabetic drug therapy more frequently experienced an increase in the dose of medication prescribed, as compared to patients that were classified as adherent. This finding underscores the need for prescribers to consider nonadherence as a root cause when patients fail to achieve therapeutic goals. Copyright © 2004 John Wiley & Sons, Ltd. [source] Novel role of plasmacytoid dendritic cells in humans: Induction of interleukin-10,producing treg cells by plasmacytoid dendritic cells in patients with rheumatoid arthritis responding to therapyARTHRITIS & RHEUMATISM, Issue 1 2010Melina Kavousanaki Objective Reestablishing immune tolerance and long-term suppression of disease represent major therapeutic goals in rheumatoid arthritis (RA). Dendritic cells (DCs) likely play a central role in such regulation via the expansion and/or induction of Treg cells. The present study was undertaken to explore the contribution of DCs to the development of Treg cells in a human autoimmune disease setting. Methods DC subsets were characterized by flow cytometry in the peripheral blood and synovial fluid of patients with RA. Proliferation of and cytokine release by naive CD4+CD25, T cells were measured in cocultures of these cells with DCs from patients with RA and healthy controls. The suppressive capacity of DC-polarized T cells was explored in vitro by a standard suppression assay. Results Only very low numbers of both plasmacytoid DCs (CD303+) and myeloid DCs (CD1c+) were present in the peripheral blood of patients with active RA. In contrast, patients with therapy-induced remission of RA exhibited higher numbers of circulating plasmacytoid DCs. Mature plasmacytoid DCs from RA patients with low disease activity, but not those from healthy controls, expressed high levels of indoleamine 2,3-dioxygenase and promoted the differentiation of allogeneic naive CD4+CD25, T cells into interleukin-10,secreting Treg cells, or Tr1 cells, that showed poor proliferation in vitro. Importantly, these plasmacytoid DC,primed Treg cells potently suppressed the proliferation of autologous naive CD4+ T cells, in a dose-dependent manner. Conclusion These results demonstrate, for the first time, that human plasmacytoid DCs may be educated within the rheumatoid microenvironment to acquire a tolerogenic phenotype. Modulation of the immune response by plasmacytoid DCs might provide novel immune-based therapies in autoimmunity and transplantation. [source] Kangaroo Mother Care: 25 years afterACTA PAEDIATRICA, Issue 5 2005Nathalie Charpak Abstract The components of the Kangaroo Mother Care (KMC) intervention, their rational bases, and their current uses in low-, middle-, and high-income countries are described. KMC was started in 1978 in Bogotá (Colombia) in response to overcrowding and insufficient resources in neonatal intensive care units associated with high morbidity and mortality among low-birthweight infants. The intervention consists of continuous skin-to-skin contact between the mother and the infant, exclusive breastfeeding, and early home discharge in the kangaroo position. In studies of the physiological effects of KMC, the results for most variables were within clinically acceptable ranges or the same as those for premature infants under other forms of care. Body temperature and weight gain are significantly increased, and a meta-analysis showed that the kangaroo position increases the uptake and duration of breastfeeding. Investigations of the behavioral effects of KMC show rapid quiescence. The psychosocial effects of KMC include reduced stress, enhancement of mother,infant bonding, and positive effects on the family environment and the infant's cognitive development. Conclusion: Past and current research has clarified some of the rational bases of KMC and has provided evidence for its effectiveness and safety, although more research is needed to clearly define the effectiveness of the various components of the intervention in different settings and for different therapeutic goals. [source] | |||||||||||||||||||||||||