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Second-line Treatment (second-line + treatment)
Selected AbstractsIfosfamide/carboplatin/etoposide (ICE) as front-line, topotecan/ cyclophosphamide as second-line and oral temozolomide as third-line treatment for advanced neuroblastoma over one year of ageACTA PAEDIATRICA, Issue 2004A Donfrancesco Children affected by advanced neuroblastoma have a discouraging prognosis, but intensive induction chemotherapy may increase the complete response rate. The combination of ifosfamide, carboplatin and etoposide (ICE) was used for the first time as front-line regimen in patients with stage 4 neuroblastoma over the age of 1 y. Similarly, second-line treatment for children with relapsed neuroblastoma, particularly after high-dose chemotherapy, has been unsatisfactory. The combination of topotecan and cyclophosphamide was studied in resistant or relapsed solid tumors. Furthermore, there is a need for effective palliative treatment in patients failing therapy. Temozolomide, a new dacarbazine analog with optimal oral bioavailability, is being used in an ongoing phase II study as an alternative to oral etoposide. Seventeen patients with stage 4 neuroblastoma have entered the ICE study; 15/16 (94%) major responses after induction were observed and 6/16 (37%) evaluable patients are disease free after a median of 51 mo. Twenty-one patients with relapsed/refractory disease (of whom 13 neuroblastomas) entered the topotecan/cyclophosphamide study: 7/21 (33%) patients responded. Forty-one patients entered the temozolomide study (of whom 16 had neuroblastomas): stable disease and symptom relief were obtained in 15/30 (50%) evaluable patients. Intensive induction with ICE resulted in a faster response with high response rate; a larger study with longer follow-up is needed to confirm a survival advantage. Second-line treatment was effective in obtaining remissions, some of them long lasting. Third-line treatment did not elicit measurable responses in neuroblastoma, but achieved prolonged freedom from disease progression and excellent palliation in several patients. [source] Nonresponse to first-line pharmacotherapy may predict relapse and recurrence of remitted geriatric depressionDEPRESSION AND ANXIETY, Issue 3 2001Alastair J. Flint MB, FRANZCP, FRCP(C) Abstract The authors examined whether nonresponse to first-line pharmacotherapy was associated with an increased probability of relapse or recurrence following remission of an episode of geriatric depression. The study group consisted of 74 elderly patients whose index episode of nonpsychotic unipolar major depression had responded to antidepressant pharmacotherapy. In 6 of these patients, the depressive episode had not responded to first-line pharmacotherapy (8 weeks of nortriptyline, including 2 weeks of adjunctive lithium) but it had responded to second-line treatment (phenelzine with or without adjunctive lithium). The 74 patients were maintained on acute doses of the medications that had led to response and were followed for 2 years or until relapse or recurrence, whichever occurred first. The cumulative probability of relapse or recurrence was 67% for patients who responded to second-line treatment compared with 18% for patients who responded to first-line treatment (P=0.0003). As expected, mean time to response was significantly longer for patients who responded to second-line treatment but this factor did not account for the difference in out-come between the two groups. These findings suggest that pharmacotherapy resistance may constitute a risk factor for relapse or recurrence of remitted geriatric depression, even when patients are maintained on the medication that they eventually respond to. Depression and Anxiety 13:125,131, 2001. © 2001 Wiley-Liss, Inc. [source] Awareness of potential valvulopathy risk with pergolide and changes in clinical practice after label change: a survey among European neurologistsEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2007A. LLedó In response to concern about the reported frequency of ergot-associated valvulopathy in patients with Parkinson's disease (PD), Eli Lilly and Company updated the Risk Minimization Program for pergolide, changing the Summary of Product Characteristics (SmPC) and distributing a Dear Doctor Letter (DDL) highlighting the new label changes. A survey was conducted subsequently to assess neurologists' awareness of the revised SmPC and their resulting changes in practice. A random sample of 20.3% of neurologists (n = 4056) from 12 eligible EU countries were invited to participate. Of the target population of 247 neurologists who treated patients with PD, used pergolide in 2005, and were willing to participate, 244 (99%) responded. Overall awareness of the DDL and the SmPC changes was 94.2%. Over half (58.3%) of neurologists indicated that they prescribe pergolide exclusively as second-line treatment, although some (21.9%) used pergolide exclusively as first-line treatment. In response to the DDL, most neurologists perform echocardiograms before treatment (67.5%) and during treatment (76.7%), and over half (55%) avoid prescribing doses >5 mg/day. Overall, use of a DDL to communicate an SmPC change was effective in increasing the awareness of pergolide-associated valvulopathy and in modifying neurologists' clinical practice to minimize this risk. [source] A comparative study on the effects of naltrexone and loratadine on uremic pruritusEXPERIMENTAL DERMATOLOGY, Issue 9 2004E. Legroux-Crespel Two recent studies have provided opposite results on the efficacy of naltrexone on uremic pruritus. We have performed a third study. We compared efficacy and tolerance of naltrexone and loratadine on uremic pruritus. Among 296 hemodialysed patients, 65 suffered from uremic pruritus. 52 patients participated in the study. Patients were treated for 2 weeks with naltrexone (50 mg/day; 26 patients) or loratadine (10 mg/day; 26 patients), after a washout of 48 h. Pruritus intensity was scored by a visual analog scale (VAS). Adverse events were carefully searched. The two groups were statistically equivalent. There was no significant difference in the mean VAS scores after treatment, but naltrexone allowed a dramatic decrease of VAS sores (, > 3/10) in seven patients. Adverse events (mainly nausea and sleep disturbances) were observed in 10 of 26 patients. We could notice that 22% of hemodialysed patients suffered from uremic pruritus. Naltrexone was effective only in a subset of patients. Adverse events were very frequent. The differences of efficacy and tolerance between patients might be due to metabolism. Naltrexone might be considered as a second-line treatment. [source] Treatment outcomes and clinicopathologic characteristics of triple-negative breast cancer patients who received platinum-containing chemotherapyINTERNATIONAL JOURNAL OF CANCER, Issue 6 2009Ji Eun Uhm Abstract The aim of this study was to evaluate the role of platinum-containing chemotherapy for metastatic triple-negative breast cancer (TNBC) patients in terms of the response rate (RR) and progression-free survival. A second aim was to characterize the clinical behavior at the time of relapse of TNBC. We retrospectively analyzed the clinical outcomes of patients with metastatic breast cancer who received taxane,platinum chemotherapy as the first- or second-line treatment, focusing on the TN phenotype. In total, 257 patients with metastatic breast cancer received platinum-containing chemotherapy at Samsung Medical Center from 1999 to 2006. Of these patients, 106 patients with available data on estrogen (ER), progesterone (PgR) and human epidermal growth factor receptor-2 (HER2) receptor status received taxane,platinum regimen as the first- or second-line treatment. The overall RR of patients with TNBC was 39%. This rate did not differ significantly from those of patients with other phenotypes. The time to death after chemotherapy (19 vs. 50 months, p = 0.037) and overall survival (OS) (21 vs. 56 months, p = 0.030) differed significantly between patients with TNBC and non-TNBC. TNBC showed a unique locoregional infiltration pattern at relapse, which might reflect its aggressive clinical behavior. Despite the similar response to platinum-containing chemotherapy, patients with TNBC had a shorter OS than patients with non-TNBC. The implication of TN phenotype as poor prognostic factor is uncertain, because it needs to be defined whether poor outcome is related to the rapid growing characteristics of tumor itself or the resistance to drug therapy. Further prospective studies are warranted. © 2008 Wiley-Liss, Inc. [source] Long-term treatment of localized gastric marginal zone B-cell mucosa associated lymphoid tissue lymphoma including incidence of metachronous gastric cancerJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2010Shouko Ono Abstract Background and Aim:, According to a few recent reports on the long-term clinical outcome of gastric marginal zone B-cell mucosa associated lymphoid tissue lymphoma (MALT lymphoma); localized gastric MALT lymphoma generally has a favorable prognosis. However, the risk of metachronous gastric cancer has not been evaluated. In this study, we analyzed long-term outcomes of localized gastric MALT lymphoma including the incidence of metachronous gastric cancer. Methods:, Between April 1996 and May 2008, 60 patients (31 men and 29 women; mean age 58.1 years) with localized gastric MALT lymphoma (stage I and II1 according to Lugano classification) were analyzed retrospectively. Results:, Forty-eight patients (82.6%) achieved complete remission by eradication therapy. Radiation therapy was conducted on eight patients as second-line treatment, and all of them achieved remission. The median follow-up period was 76 months (range, 12,157 months). One patient had local relapse after remission for 5 years and three patients developed early gastric cancer without recurrence of lymphoma (5%). All of the three gastric cancers appeared in the same areas where MALT lymphoma had been eradicated. Conclusion:, Eradication therapy and radiation therapy for localized gastric MALT lymphoma have a favorable long-term outcome, though regular follow-up endoscopy should be performed for detecting metachronous early gastric cancer. [source] Lansoprazole, levofloxacin and amoxicillin triple therapy vs. quadruple therapy as second-line treatment of resistant Helicobacter pylori infectionALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2006W. M. WONG Summary Aim To test the efficacy of levofloxacin-based second-line therapy for resistant Helicobacter pylori infection. Methods One hundred and six patients who failed H. pylori eradication were randomized to receive (i) lansoprazole 30 mg, amoxicillin 1 g, levofloxacin 500 mg, all given twice daily for 7 days (LAL); or (ii) lansoprazole 30 mg twice daily, metronidazole 400 mg thrice daily, bismuth subcitrate 120 mg and tetracycline 500 mg four times daily for 7 days (quadruple). Post-treatment H. pylori status was determined by 13C-urea breath test. Results Intention-to-treat and per-protocol H. pylori eradication rates were 57/60% for the LAL group and 71/76% for the quadruple group respectively. Metronidazole, clarithromycin, amoxicillin and levofloxacin resistance were found in 76%, 71%, 0% and 18% of patients, respectively. Levofloxacin resistance led to treatment failure in the LAL group. For patients with dual resistance to metronidazole and clarithromycin, the eradication rates were 79% in the LAL group (levofloxacin-sensitive) and 65% in the quadruple group (P = 0.34). Conclusion Lansoprazole, amoxicillin plus levofloxacin second-line therapy is comparable with quadruple therapy in efficacy. Subjects, especially those with dual resistance to metronidazole and clarithromycin, may consider levofloxacin-based therapy for levofloxacin-sensitive strains. [source] EAACI/GA˛LEN/EDF/WAO guideline: management of urticariaALLERGY, Issue 10 2009T. Zuberbier This guideline, together with its sister guideline on the classification of urticaria (Zuberbier T, Asero R, Bindslev-Jensen C, Canonica GW, Church MK, Giménez-Arnau AM et al. EAACI/GA˛LEN/EDF/WAO Guideline: definition, classification and diagnosis of urticaria. Allergy 2009;64: 1417,1426), is the result of a consensus reached during a panel discussion at the Third International Consensus Meeting on Urticaria, Urticaria 2008, a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA˛LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO). As members of the panel, the authors had prepared their suggestions regarding management of urticaria before the meeting. The draft of the guideline took into account all available evidence in the literature (including Medline and Embase searches and hand searches of abstracts at international allergy congresses in 2004,2008) and was based on the existing consensus reports of the first and the second symposia in 2000 and 2004. These suggestions were then discussed in detail among the panel members and with the over 200 international specialists of the meeting to achieve a consensus using a simple voting system where appropriate. Urticaria has a profound impact on the quality of life and effective treatment is, therefore, required. The recommended first line treatment is new generation, nonsedating H1 -antihistamines. If standard dosing is not effective, increasing the dosage up to four-fold is recommended. For patients who do not respond to a four-fold increase in dosage of nonsedating H1 -antihistamines, it is recommended that second-line therapies should be added to the antihistamine treatment. In the choice of second-line treatment, both their costs and risk/benefit profiles are most important to consider. Corticosteroids are not recommended for long-term treatment due to their unavoidable severe adverse effects. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). [source] Functional endoscopic sinus surgery improved asthma symptoms as well as PEFR and olfaction in patients with nasal polyposisALLERGY, Issue 5 2009A. Ehnhage Background:, Nasal polyposis is a disease known to be associated with asthma. The management is anti-inflammatory, with topical and oral corticosteroids as the first-line treatment. The effect of surgical treatment on lower airway inflammation has not been sufficiently studied. Aim:, The aim of this study is to investigate the effects of functional endoscopic sinus surgery (FESS) as well as fluticasone proprionate nasal drops (FPND) 400 ,g b.i.d. on nasal and lower airway parameters in asthmatics with nasal polyposis. Methods:, This was a prospective 21-week study of 68 patients with asthma and nasal polyposis, on the benefits of FESS on nasal ,(butanol test, subjective olfaction, peak nasal inspiratory flow, congestion, rhinorrhoea, and polyp score)', and on the lower airway parameters (dyspnea, cough, mean daily peak expiratory flow rate (PEFR), and lung function tests). It also included a randomized, double-blind, placebo-controlled 14 weeks phase on FPND. Results:, Functional endoscopic sinus surgery significantly improved mean asthma symptom scores and daily PEFR and all nasal parameters including subjective and objective olfaction tests. This is the first study that shows the benefits of FESS on butanol tests in patients with nasal polyposis. We found no significant difference between topical treatment with FPND or placebo in the nasal or lower airway variables. Conclusion:, Functional endoscopic sinus surgery improved nasal and asthma symptoms in patients with nasal polyposis. Functional endoscopic sinus surgery could be considered early in the natural course of nasal polyposis with concomitant asthma, as well as a second-line treatment in nasal polyposis patients with a reduced sense of smell. The potential benefits of FPND 400 ,g b.i.d. were probably overshadowed by FESS. [source] Efficacy of tacrolimus 0.03% ointment as second-line treatment for children with moderate-to-severe atopic dermatitis: evidence from a randomized, double-blind non-inferiority trial vs. fluticasone 0.005% ointmentPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 2p1 2010N. Doss Doss N, Kamoun M-R, Dubertret L, Cambazard F, Remitz A, Lahfa M, de Prost Y. Efficacy of tacrolimus 0.03% ointment as second-line treatment for children with moderate-to-severe atopic dermatitis: evidence from a randomized, double-blind non-inferiority trial vs. fluticasone 0.005% ointment. Pediatr Allergy Immunol 2010: 21: 321,329. © 2009 John Wiley & Sons A/S Tacrolimus 0.03% ointment is licensed for second-line treatment of children with atopic dermatitis (AD). Although data are available from clinical trials, no study has enrolled only second-line patients. This double-blind, non-inferiority study compared tacrolimus 0.03% and fluticasone 0.005% ointments in children with moderate-to-severe AD, who had responded insufficiently to conventional therapies. Children (aged 2,15 yr) were randomized to tacrolimus ointment (n = 240) or fluticasone ointment (n = 239), twice daily until clearance or for a maximum of 3 wk and, if lesions remained, once daily for up to 3 wk further. Primary end-point was week 3 response rate (improvement of ,60% in modified Eczema Area and Severity Index and not withdrawn for lack of efficacy). Secondary end-points included pruritus and sleep quality, global assessment of clinical response, incidence of new flares and safety. Response rates were 86.3% with tacrolimus ointment and 91.5% with fluticasone. Lower limit of the 95% confidence interval was ,11.8%, exceeding the non-inferiority limit of ,15% and meeting the primary end-point. Moderate or better improvement on the physicians' global assessment occurred in 93.6% and 92.4% of patients in the tacrolimus ointment and fluticasone arms, respectively, while median pruritus scores improved by 84.0% and 91.5%. Sleep quality improved by approximately 92% in both treatment arms. After day 21, new flare-up occurred in 5.5% and 11.3% of patients receiving tacrolimus ointment and fluticasone, respectively; mean times to new flares were 6.5 ± 5.0 and 8.6 ± 5.2 days. Adverse events were similar between the two arms, with the exception of application-site skin burning sensation in the tacrolimus ointment group. In conclusion, efficacy of tacrolimus 0.03% ointment as second-line treatment was not inferior to that of fluticasone 0.005% ointment, with similar benefits on global disease improvement and quality of sleep. [source] Docetaxel,ST1481 sequence exerts a potent cytotoxic activity on hormone-resistant prostate cancer cells by reducing drug resistance-related gene expressionTHE PROSTATE, Issue 2 2010Francesco Fabbri Abstract BACKGROUND The efficacy of current therapy for hormone-refractory prostate cancer is still unsatisfactory and new agents and therapeutic modalities are needed. The aims of the present work were to examine the in vitro activity and mechanisms of action of different antitumor drug combinations in hormone-resistant prostate cancer (HRPC) cell lines. METHODS The activity of docetaxel (Doc), cisplatin (Cis), oxaliplatin (Oxa), SN-38 and ST1481, singly or in combination, was assessed in different HRPC cell lines (PC3, parental DU145 and taxane-resistant DU145-R) by SRB test. Apoptosis was evaluated by TUNEL and ANN-V assays. Extrusion pump activity was studied by Hoechst 33342 assay, while gene expression related to drug efflux mechanisms and DNA damage repair was analyzed by RT-PCR. RESULTS Doc induced a high cytocidal effect in the HRPC cells, whereas Cis, Oxa, SN-38 and ST1481 exerted prevalently cytostatic activity. Doc followed by ST1481 proved to be the most effective drug sequence among those investigated, producing an important synergistic effect (R.I. from 2.0 to 5.2) in all the tested cell lines. Moreover, this sequence induced a significant downregulation of xenobiotic extrusion pump and DNA damage repair gene expression. ST1481 synergistically increased the cytocidal effect of Doc, probably through a downregulation of extrusion pump activity and DNA damage repair-related genes. CONCLUSIONS Our results show that the Doc,,,ST1481 sequence effectively reduces the cancer cell population and restores Doc activity in taxane-resistant HRPC, indicating its potential usefulness as first- or second-line treatment of hormone-refractory prostate cancer. Prostate 70: 219,227, 2010. ©2009 Wiley-Liss, Inc. [source] Efficacy and safety of first- or second-line irinotecan, cisplatin, and mitomycin in mesotheliomaCANCER, Issue 1 2007Dean A. Fennell MD Abstract BACKGROUND. Malignant pleural mesothelioma (MPM) is a rapidly progressive lethal tumor. Treatment options remain limited and the outcome in recurrent disease is poor. METHODS. A Phase II open-label noncomparative study was conducted to assess the safety and efficacy of the triplet combination irinotecan, cisplatin, and mitomycin-C (IPM) chemotherapy in untreated patients and in those with previous exposure to chemotherapy. RESULTS. In 62 patients an objective response rate of 25% was observed. In the first-line setting progression-free survival measured 6.4 months (95% confidence interval [CI]: 4.5,7.3) and overall survival was 10.8 months (95% CI: 7.9,13.7). In the second-line setting progression-free survival was 7.3 months (95% CI: 3.4,11.2) and overall survival was also 7.3 months (95% CI: 4.8,9.8). Psychosocial well-being improved during chemotherapy and the main toxicity observed was neutropenia (40%). CONCLUSIONS. IPM appeared to have a reasonable response rate with an acceptable toxicity profile in the first- and second-line treatment of MPM. Cancer 2007. © 2006 American Cancer Society. [source] Extranodal NK,/,T-cell lymphoma, nasal type: New staging system and treatment strategiesCANCER SCIENCE, Issue 12 2009Tae Min Kim Extranodal NK/T-cell lymphoma (NTCL) is characterized by clinical heterogeneity based on clinical prognostic factors and survival outcome. NTCL subsets are classified as upper aerodigestive tract (UAT) NTCL or non-UAT NTCL; non-UAT has pathologic similarity to UAT-NTCL but is a clinically distinct subtype. Due to the clinical heterogeneity of NTCL, optimal treatment modalities and prognostic factors have been difficult to determine. Ann Arbor staging for lymphomas and the International Prognostic Index (IPI) have been used to predict prognosis for UAT-NTCL; however, local tumor invasiveness (bony invasion or perforation or invasion of the overlying skin) is the most significant factor for poor outcomes in localized UAT-NTCL. Thus, a new staging system is proposed: limited disease (stage I/II UAT-NTCL without local tumor invasiveness) and extensive disease (stage I/II with local invasiveness or stage III/IV disease of UAT NTCL, and non-UAT NTCL) based on treatment outcomes. NTCL is resistant to anthracycline-based chemotherapy, whereas non-anthracycline combination chemotherapy (such as ifosfamide, methotrexate, etoposide, and prednisolone) has an activity against NTCL as either a front-line or as a second-line treatment. The effectiveness of radiotherapy is evident in limited disease, but questionable in extensive disease. (Cancer Sci 2009; 100: 2242,2248) [source] The use of ruthenium plaque brachytherapy in retinoblastomaACTA OPHTHALMOLOGICA, Issue 2009H ABOUZEID Purpose To evaluate the efficacy of 106Ru plaque brachytherapy for the treatment of retinoblastoma. Methods We reviewed a retrospective, noncomparative case series of 39 children with retinoblastoma treated with 106Ru plaques at the Jules-Gonin Eye Hospital between October 1992 and July 2006, with 12 months of follow-up. Results A total of 63 tumors were treated with 106Ru brachytherapy in 41 eyes. The median patient age was 27 months. 106Ru brachytherapy was the first-line treatment for 3 tumors (4.8%), second-line treatment for 13 (20.6%), and salvage treatment for 47 tumors (74.6%) resistant to other treatment modalities. Overall tumor control was achieved in 73% at 1 year. Tumor recurrence at 12 months was observed in 2 (12.5%) of 16 tumors for which 106Ru brachytherapy was used as the first- or second-line treatment and in 15 (31.9%) of 47 tumors for which 106Ru brachytherapy was used as salvage treatment. Eye retention was achieved in 76% of cases (31 of 41 eyes). Univariate and multivariate analyses revealed no statistically significant risk factors for tumor recurrence. Radiation complications included retinal detachment in 7 (17.1%), proliferative retinopathy in 1 (2.4%), and subcapsular cataract in 4 (9.7%) of 41 eyes. Conclusion 106Ru brachytherapy is an effective treatment for retinoblastoma, with few secondary complications.Local vitreous seeding can be successfully treated with 106Ru brachytherapy. [source] Boosted protease inhibitors as a therapeutic option in the treatment of HIV-infected childrenHIV MEDICINE, Issue 9 2009JT Ramos Objective Paediatric HIV treatment must address various special considerations. Administration of pharmacokinetically enhanced protease inhibitors (PIs) can improve paediatric therapeutic outcomes. The objective of this study was to review the use of boosted PI regimens in children. Methods Systematic literature searches of published manuscripts and conference databases using generic drug names and specific keywords were performed to ensure thorough and balanced reporting of available data. Results Boosted PI regimens offer multiple options across a range of ages and are efficacious in naďve and experienced children; safety and tolerability are similar to those observed in adults. Novel boosted PI simplification approaches may foster adherence and diminish resistance. Conclusions Boosted PIs are key components of first- and second-line treatments in children. Identifying factors associated with the response to highly active antiretroviral therapy in children may ultimately permit individualized therapies. [source] Practitioner Review: The effectiveness of systemic family therapy for children and adolescentsTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 5 2002David Cottrell Background: Systemic family therapy has become a widely used intervention in child and adolescent mental health services over the last twenty years. Methods: This paper reviews the development of systemic family therapy, briefly describes the theory and techniques associated with the most prominent contemporary strands of systemic practice, and examines the empirical justification for using systemic family therapies with children and adolescents. Results: There is a paucity of well-designed randomised controlled trials of systemic therapies with children and adolescents and those trials that do exist evaluate older structural and strategic therapies. Methodological limitations of existing research include the use of unrepresentative participants, small sample sizes and wide age ranges. There is a lack of credible no-treatment or alternative treatment controls, tests of clinical as opposed to statistical significance, and conceptually relevant outcome measures that examine underlying interactional mechanisms. The term `family therapy' encompasses a wide range of interventions and it is not always clear what treatment intervention has been delivered. Nevertheless, there is good evidence for the effectiveness of systemic family therapies in the treatment of conduct disorders, substance misuse and eating disorders, and some support for their use as second-line treatments in depression and chronic illness. Conclusions: Systemic family therapy is an effective intervention for children and adolescents but further well-designed outcome studies are needed using clearly specified, manualised forms of treatment and conceptually relevant outcome measures. [source] | ||||||||||||||||||||||