Psychological therapies for children and adolescents exposed to trauma.

BACKGROUND: Children and adolescents who have experienced trauma are at high risk of developing post-traumatic stress disorder (PTSD) and other negative emotional, behavioural and mental health outcomes, all of which are associated with high personal and health costs. A wide range of psychological treatments are used to prevent negative outcomes associated with trauma in children and adolescents. OBJECTIVES: To assess the effects of psychological therapies in preventing PTSD and associated negative emotional, behavioural and mental health outcomes in children and adolescents who have undergone a traumatic event. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Group's Specialised Register to 29 May 2015. This register contains reports of relevant randomised controlled trials from The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). We also checked reference lists of relevant studies and reviews. We did not restrict the searches by date, language or publication status. SELECTION CRITERIA: All randomised controlled trials of psychological therapies compared with a control such as treatment as usual, waiting list or no treatment, pharmacological therapy or other treatments in children or adolescents who had undergone a traumatic event. DATA COLLECTION AND ANALYSIS: Two members of the review group independently extracted data. We calculated odds ratios for binary outcomes and standardised mean differences for continuous outcomes using a random-effects model. We analysed data as short-term (up to and including one month after therapy), medium-term (one month to one year after therapy) and long-term (one year or longer). MAIN RESULTS: Investigators included 6201 participants in the 51 included trials. Twenty studies included only children, two included only preschool children and ten only adolescents; all others included both children and adolescents. Participants were exposed to sexual abuse in 12 trials, to war or community violence in ten, to physical trauma and natural disaster in six each and to interpersonal violence in three; participants had suffered a life-threatening illness and had been physically abused or maltreated in one trial each. Participants in remaining trials were exposed to a range of traumas.Most trials compared a psychological therapy with a control such as treatment as usual, wait list or no treatment. Seventeen trials used cognitive-behavioural therapy (CBT); four used family therapy; three required debriefing; two trials each used eye movement desensitisation and reprocessing (EMDR), narrative therapy, psychoeducation and supportive therapy; and one trial each provided exposure and CBT plus narrative therapy. Eight trials compared CBT with supportive therapy, two compared CBT with EMDR and one trial each compared CBT with psychodynamic therapy, exposure plus supportive therapy with supportive therapy alone and narrative therapy plus CBT versus CBT alone. Four trials compared individual delivery of psychological therapy to a group model of the same therapy, and one compared CBT for children versus CBT for both mothers and children.The likelihood of being diagnosed with PTSD in children and adolescents who received a psychological therapy was significantly reduced compared to those who received no treatment, treatment as usual or were on a waiting list for up to a month following treatment (odds ratio (OR) 0.51, 95% confidence interval (CI) 0.34 to 0.77; number needed to treat for an additional beneficial outcome (NNTB) 6.25, 95% CI 3.70 to 16.67; five studies; 874 participants). However the overall quality of evidence for the diagnosis of PTSD was rated as very low. PTSD symptoms were also significantly reduced for a month after therapy (standardised mean difference (SMD) -0.42, 95% CI -0.61 to -0.24; 15 studies; 2051 participants) and the quality of evidence was rated as low. These effects of psychological therapies were not apparent over the longer term.CBT was found to be no more or less effective than EMDR and supportive therapy in reducing diagnosis of PTSD in the short term (OR 0.74, 95% CI 0.29 to 1.91; 2 studies; 160 participants), however this was considered very low quality evidence. For reduction of PTSD symptoms in the short term, there was a small effect favouring CBT over EMDR, play therapy and supportive therapies (SMD -0.24, 95% CI -0.42 to -0.05; 7 studies; 466 participants). The quality of evidence for this outcome was rated as moderate.We did not identify any studies that compared pharmacological therapies with psychological therapies. AUTHORS' CONCLUSIONS: The meta-analyses in this review provide some evidence for the effectiveness of psychological therapies in prevention of PTSD and reduction of symptoms in children and adolescents exposed to trauma for up to a month. However, our confidence in these findings is limited by the quality of the included studies and by substantial heterogeneity between studies. Much more evidence is needed to demonstrate the relative effectiveness of different psychological therapies for children exposed to trauma, particularly over the longer term. High-quality studies should be conducted to compare these therapies.

Psychological therapies for the treatment of post-traumatic stress disorder in children and adolescents (Review).

BACKGROUND: Post-traumatic stress disorder (PTSD) is highly prevalent in children and adolescents who have experienced trauma and has high personal and health costs. Although a wide range of psychological therapies have been used in the treatment of PTSD there are no systematic reviews of these therapies in children and adolescents. OBJECTIVES: To examine the effectiveness of psychological therapies in treating children and adolescents who have been diagnosed with PTSD. SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to December 2011. The CCDANCTR includes relevant randomised controlled trials from the following bibliographic databases: CENTRAL (the Cochrane Central Register of Controlled Trials) (all years), EMBASE (1974 -), MEDLINE (1950 -) and PsycINFO (1967 -). We also checked reference lists of relevant studies and reviews. We applied no date or language restrictions. SELECTION CRITERIA: All randomised controlled trials of psychological therapies compared to a control, pharmacological therapy or other treatments in children or adolescents exposed to a traumatic event or diagnosed with PTSD. DATA COLLECTION AND ANALYSIS: Two members of the review group independently extracted data. If differences were identified, they were resolved by consensus, or referral to the review team. We calculated the odds ratio (OR) for binary outcomes, the standardised mean difference (SMD) for continuous outcomes, and 95% confidence intervals (CI) for both, using a fixed-effect model. If heterogeneity was found we used a random-effects model. MAIN RESULTS: Fourteen studies including 758 participants were included in this review. The types of trauma participants had been exposed to included sexual abuse, civil violence, natural disaster, domestic violence and motor vehicle accidents. Most participants were clients of a trauma-related support service. The psychological therapies used in these studies were cognitive behavioural therapy (CBT), exposure-based, psychodynamic, narrative, supportive counselling, and eye movement desensitisation and reprocessing (EMDR). Most compared a psychological therapy to a control group. No study compared psychological therapies to pharmacological therapies alone or as an adjunct to a psychological therapy. Across all psychological therapies, improvement was significantly better (three studies, n = 80, OR 4.21, 95% CI 1.12 to 15.85) and symptoms of PTSD (seven studies, n = 271, SMD -0.90, 95% CI -1.24 to -0.42), anxiety (three studies, n = 91, SMD -0.57, 95% CI -1.00 to -0.13) and depression (five studies, n = 156, SMD -0.74, 95% CI -1.11 to -0.36) were significantly lower within a month of completing psychological therapy compared to a control group. The psychological therapy for which there was the best evidence of effectiveness was CBT. Improvement was significantly better for up to a year following treatment (up to one month: two studies, n = 49, OR 8.64, 95% CI 2.01 to 37.14; up to one year: one study, n = 25, OR 8.00, 95% CI 1.21 to 52.69). PTSD symptom scores were also significantly lower for up to one year (up to one month: three studies, n = 98, SMD -1.34, 95% CI -1.79 to -0.89; up to one year: one study, n = 36, SMD -0.73, 95% CI -1.44 to -0.01), and depression scores were lower for up to a month (three studies, n = 98, SMD -0.80, 95% CI -1.47 to -0.13) in the CBT group compared to a control. No adverse effects were identified. No study was rated as a high risk for selection or detection bias but a minority were rated as a high risk for attrition, reporting and other bias. Most included studies were rated as an unclear risk for selection, detection and attrition bias. AUTHORS' CONCLUSIONS: There is evidence for the effectiveness of psychological therapies, particularly CBT, for treating PTSD in children and adolescents for up to a month following treatment. At this stage, there is no clear evidence for the effectiveness of one psychological therapy compared to others. There is also not enough evidence to conclude that children and adolescents with particular types of trauma are more or less likely to respond to psychological therapies than others. The findings of this review are limited by the potential for methodological biases, and the small number and generally small size of identified studies. In addition, there was evidence of substantial heterogeneity in some analyses which could not be explained by subgroup or sensitivity analyses. More evidence is required for the effectiveness of all psychological therapies more than one month after treatment. Much more evidence is needed to demonstrate the relative effectiveness of different psychological therapies or the effectiveness of psychological therapies compared to other treatments. More details are required in future trials in regards to the types of trauma that preceded the diagnosis of PTSD and whether the traumas are single event or ongoing. Future studies should also aim to identify the most valid and reliable measures of PTSD symptoms and ensure that all scores, total and sub-scores, are consistently reported.

Psychological therapies for the treatment of post-traumatic stress disorder in children and adolescents.

BACKGROUND: Post-traumatic stress disorder (PTSD) is highly prevalent in children and adolescents who have experienced trauma and has high personal and health costs. Although a wide range of psychological therapies have been used in the treatment of PTSD there are no systematic reviews of these therapies in children and adolescents. OBJECTIVES: To examine the effectiveness of psychological therapies in treating children and adolescents who have been diagnosed with PTSD. SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to December 2011. The CCDANCTR includes relevant randomised controlled trials from the following bibliographic databases: CENTRAL (the Cochrane Central Register of Controlled Trials) (all years), EMBASE (1974 -), MEDLINE (1950 -) and PsycINFO (1967 -). We also checked reference lists of relevant studies and reviews. We applied no date or language restrictions. SELECTION CRITERIA: All randomised controlled trials of psychological therapies compared to a control, pharmacological therapy or other treatments in children or adolescents exposed to a traumatic event or diagnosed with PTSD. DATA COLLECTION AND ANALYSIS: Two members of the review group independently extracted data. If differences were identified, they were resolved by consensus, or referral to the review team.We calculated the odds ratio (OR) for binary outcomes, the standardised mean difference (SMD) for continuous outcomes, and 95% confidence intervals (CI) for both, using a fixed-effect model. If heterogeneity was found we used a random-effects model. MAIN RESULTS: Fourteen studies including 758 participants were included in this review. The types of trauma participants had been exposed to included sexual abuse, civil violence, natural disaster, domestic violence and motor vehicle accidents. Most participants were clients of a trauma-related support service.The psychological therapies used in these studies were cognitive behavioural therapy (CBT), exposure-based, psychodynamic, narrative, supportive counselling, and eye movement desensitisation and reprocessing (EMDR). Most compared a psychological therapy to a control group. No study compared psychological therapies to pharmacological therapies alone or as an adjunct to a psychological therapy.Across all psychological therapies, improvement was significantly better (three studies, n = 80, OR 4.21, 95% CI 1.12 to 15.85) and symptoms of PTSD (seven studies, n = 271, SMD -0.90, 95% CI -1.24 to -0.42), anxiety (three studies, n = 91, SMD -0.57, 95% CI -1.00 to -0.13) and depression (five studies, n = 156, SMD -0.74, 95% CI -1.11 to -0.36) were significantly lower within a month of completing psychological therapy compared to a control group.The psychological therapy for which there was the best evidence of effectiveness was CBT. Improvement was significantly better for up to a year following treatment (up to one month: two studies, n = 49, OR 8.64, 95% CI 2.01 to 37.14; up to one year: one study, n = 25, OR 8.00, 95% CI 1.21 to 52.69). PTSD symptom scores were also significantly lower for up to one year (up to one month: three studies, n = 98, SMD -1.34, 95% CI -1.79 to -0.89; up to one year: one study, n = 36, SMD -0.73, 95% CI -1.44 to -0.01), and depression scores were lower for up to a month (three studies, n = 98, SMD -0.80, 95% CI -1.47 to -0.13) in the CBT group compared to a control. No adverse effects were identified.No study was rated as a high risk for selection or detection bias but a minority were rated as a high risk for attrition, reporting and other bias. Most included studies were rated as an unclear risk for selection, detection and attrition bias. AUTHORS' CONCLUSIONS: There is evidence for the effectiveness of psychological therapies, particularly CBT, for treating PTSD in children and adolescents for up to a month following treatment. At this stage, there is no clear evidence for the effectiveness of one psychological therapy compared to others. There is also not enough evidence to conclude that children and adolescents with particular types of trauma are more or less likely to respond to psychological therapies than others.The findings of this review are limited by the potential for methodological biases, and the small number and generally small size of identified studies. In addition, there was evidence of substantial heterogeneity in some analyses which could not be explained by subgroup or sensitivity analyses.More evidence is required for the effectiveness of all psychological therapies more than one month after treatment. Much more evidence is needed to demonstrate the relative effectiveness of different psychological therapies or the effectiveness of psychological therapies compared to other treatments. More details are required in future trials in regards to the types of trauma that preceded the diagnosis of PTSD and whether the traumas are single event or ongoing. Future studies should also aim to identify the most valid and reliable measures of PTSD symptoms and ensure that all scores, total and sub-scores, are consistently reported.

Treatment of pancreatic and periampullary cancers at a community hospital: successful application of tertiary care treatment standards.

Background. The treatment of pancreatic cancer and other periampullary neoplasms is complex and challenging. Major high-volume cancer centers can provide excellent multidisciplinary care of these patients but almost two-thirds of pancreatic cancer patients are treated at low volume centers. There is very little published data from low volume community cancer programs in regards to the treatment of periampullary cancer. In this study, a review of comprehensive periampullary cancer care at two low volume hospitals with comparison to national standards is presented. Methods. This is a retrospective review of 70 consecutive patients with periampullary neoplasms who underwent surgery over a 5-year period (2006-2010) at two community hospitals. Results. There were 51 successful resections of 70 explorations (73%) including 34 Whipple procedures. Mortality rate was 2.9%. Comparison of these patients to national standards was made in terms of operative mortality, resectability rate, administration of adjuvant therapy, clinical trial participation and overall survival. The results in these patients were comparable to national standards. Conclusions. With adequate commitment of resources and experienced surgical and oncologic practitioners, community cancer centers can meet national tertiary care standards in terms of pancreatic and periampullary cancer care.

Trastuzumab plus docetaxel in HER-2/neu-positive prostate carcinoma: final results from the California Cancer Consortium Screening and Phase II Trial.

BACKGROUND: Overexpression of the HER-2/neu oncoprotein has been reported to occur in 2) were initially randomized to receive either single-agent trastuzumab or docetaxel. After two treatment cycles, nonresponding patients received the trastuzumab/docetaxel combination. Treatment was comprised of 30 mg/m(2) of docetaxel weekly for 6 weeks followed by a 2-week break and 4 mg/kg of trastuzumab intravenously during Week 1 then 2 mg/kg per week thereafter. The cycle length was 8 weeks. RESULTS: One hundred patients with HPRC were screened. IHC results were as follows: 3+ (n = 1), 2+ (n = 6), 1+ (n = 26), 0 (n = 39), and insufficient tissue specimen/not tested (n = 28). Only 3 of 37 patients had elevated shed HER-2 by ELISA (> 15 mg/mL). None overexpressed HER-2 by IHC. FISH amplification was found in 0 of 34 tissue samples. Of seven patients with IHC 3+ or 2+, four were tested by ELISA and two by FISH. None were abnormal. Age and Gleason score did not correlate with IHC status. Of the seven patients eligible for the Phase II study, only four agreed to participate. The trial was thus closed for nonfeasibility (the overall HER-2 positivity rate was < 20%). No patient responded to trastuzumab alone. The median survival was not reached and the median progression-free survival was 7 months. CONCLUSIONS: HER-2 overexpression by IHC in archival prostate carcinoma specimens was infrequent. There was no apparent correlation among IHC, ELISA, and FISH, although the sample size was limited. Conclusions regarding the predictive value of HER-2 status on outcome after trastuzumab-based therapy were not reached and were only drawn after larger-scale screening efforts. The authors estimated that 1000 patients need to be screened to complete accrual to a 40-patient efficacy trial.

HER-2/neu is overexpressed infrequently in patients with prostate carcinoma. Results from the California Cancer Consortium Screening Trial.

BACKGROUND: The overexpression of HER-2/neu is found in 20-30% of patients with breast carcinoma and is an adverse prognostic factor. HER-2 overexpression also has been reported in up to 60% of patients with hormone-refractory prostate carcinoma (HRPC) and was correlated with shortened survival. Trastuzumab (Herceptin) is a humanized monoclonal antibody that binds to the HER-2 receptor and has antitumor activity in patients with HER-2-overexpressing breast carcinoma. The authors report the results of HER-2 screening from a Phase II trial of chemotherapy with trastuzumab and docetaxel in patients with HER-2-overexpressing prostate carcinoma. METHODS: Archival paraffin embedded tumor tissue was obtained from potentially eligible patients and was screened for HER-2 expression by immunohistochemistry (IHC) using a specialized test kit. Shed HER-2 antigen in serum also was determined using an enzyme-linked immunosorbent assay (ELISA). HER-2 gene amplification was assessed by fluorescent in situ hybridization (FISH). Patients with IHC scores of 2+ or 3+ were considered to have HER-2 overexpression and were eligible for the trial. To date, 62 patients with HRPC have been screened. RESULTS: The median patient age was 72 years, and Gleason scores were < 5 in 1 patients, 5-7 in 24 patients, > 7 in 23 patients, and not specified in 14 patients. IHC HER-2 expression was 0 in 28 patients, 1+ in 14 patients, 2+ in 4 patients, and 3+ in 1 patients. Fifteen patients had either suboptimal tissue (13 patients) for interpretation or had pending results (2 patients). Therefore, 8% of all patients screened (5 of 62 patients) had HER-2 overexpression by IHC. Quantitative ELISA for shed HER-2 was available in 32 patients; this level was elevated (> 15 ng/mL) in only 2 patients, and neither had HER-2 expression by IHC. Of the 5 patients with 2+ or 3+ HER-2 expression by IHC, none had elevated shed HER-2 antigen levels by ELISA. FISH for HER-2 amplification was performed on 12 specimens; 5 of these specimens were uninterpretable due to specimen artifact, and none of the remaining 7 specimens had HER-2 amplification, defined as a ratio > 1. Patient age and Gleason score were not correlated with HER-2 status. CONCLUSIONS: Unlike breast carcinoma and contrary to prior reports, HER-2 overexpression by IHC in archival prostate tissue from patients who eventually developed hormone-refractory disease was infrequent. There did not appear to be any correlation between HER-2 overexpression by IHC and shed HER-2 antigen levels in serum by ELISA in this tumor type. Whether trastuzumab possesses single-agent activity or modulates chemotherapy response in tumor types other than breast carcinoma remains to be determined.