Investigating the appropriateness of surgical endodontic referrals to a West Sussex regional referral unit.

Aim To audit the appropriateness, after triage, of surgical endodontic referrals to Queen Victoria Hospital, a regional referral unit in West Sussex. To discuss the current referral pathway with the aim of improving general dental practitioner (GDP) understanding of indications for surgical endodontics via the referral process.Methodology A three-year retrospective review of all surgical endodontic referrals made to Queen Victoria Hospital, East Grinstead was completed. This was inclusive of all referrals made via the National Health Service (NHS) Vantage Rego e-referral system and GDP referral letters. The quality of referrals was analysed as indicated or contraindicated in accordance with the Royal College of Surgeons guidelines for surgical endodontics and periradicular surgery.Results Out of the 34 referrals included in data analysis, 50% contained one or more contraindication for surgical intervention. The most commonly recorded contraindications to treatment were poor-quality root canal treatment, periodontal disease compromising the long-term success of treatment and a poor coronal seal deeming the tooth unrestorable post-surgical intervention.Conclusions A more efficient surgical endodontic referral system will aid resource allocation within the NHS. These results are a first step to aiding necessary modification of the primary care referral pathway to achieve a more effective service for patients, with improved acceptance rate of referrals and better surgical outcomes.

A feasibility study of transdermal buprenorphine versus transdermal fentanyl in the long-term management of persistent non-cancer pain.

OBJECTIVE: Buprenorphine and fentanyl transdermal patches are used widely for the management of persistent malignant and nonmalignant pain. Buprenorphine and fentanyl transdermal patches, both potent opioids, are considered to be equally efficacious in managing persistent pain. Various retrospective studies comparing dosage changes of buprenorphine and fentanyl patches in persistent pain patients have been completed; however, no long-term prospective, randomized, clinical study has compared the effectiveness of these patches. The objective of the present study was to satisfy this need. AIMS: This study aims to compare prospectively the long-term efficacy, acceptability, and side effects of both of these patches in patients with persistent pain. This study would examine the feasibility and lay the groundwork for a larger, multicenter study where such efficacy and safety outcomes of the two medications can be adequately assessed. DESIGN: The participants were 46 adults (range 22-80 years.) with nonmalignant persistent pain (mean = 11 years), predominantly with lower back pain. Data were obtained monthly for 12 months. Participants recruited were opioid-naïve patients, having pain for the greater part of the day and night, and appropriate for treatment with transdermal patches. After initial assessment, participants were randomly allocated to either buprenorphine or fentanyl patch treatment. Participants were then titrated to optimal doses of medication. Patients with adverse effects or unsatisfactory pain relief were treated alternatively and discontinued from the study. RESULTS: Nearly one-third of all patients, 41% (8 of 22) of the transdermal buprenorphine (TDB) group and 37.5% (8 of 24) of the transdermal fentanyl (TDF) group stopped treatment due to unacceptable side effects or inadequate pain relief. The remaining participants showed a similar trend in the improvement of pain intensity, physical activity, sleep, and mood throughout the study. Significant relief in the intensity of pain was achieved for the initial 6 months and the effects stabilized in the remainder of the study in both groups. There were no significant group differences over time. However, a higher equipotent dose of fentanyl was required for comparable pain relief. Compared with TDF group, the TDB group initially experienced relatively less side effects. However, a greater number of buprenorphine users suffered from local skin reactions. Buprenorphine users had significant improvement in mood. Thirty-one percent (5 of 16) of the buprenorphine group and 57% (8 of 14) of the fentanyl users needed additional pain relief medications by the end of 3 months. By the end of 12 months, a significant number 78% (7 of 9) of buprenorphine users but comparatively fewer 44% (4 of 9) of the fentanyl group used rescue medicines. Both had more doctor visits in the latter half of the study. CONCLUSION: Thirty percent of the total number of patients discontinued treatment because of side effects or unsatisfactory pain relief. For those continuing treatment, clinical improvements were seen in the initial 6 months in both groups. Fifty percent of the TDB and 43% of TDF groups had significant relief in 3 months, which persisted up to 6 months. Only 11% and 13% of patients, respectively, had sustained relief after 6 months. Twenty percent more patients in the TDB group benefited significantly in symptoms of depression from TDB compared with the TDF group. Interestingly, switching of patches seemed to increase acceptability by preventing adverse effects and tolerance. Confirmation of these effects should be studied in future with a multicenter study and larger sample.

Surgical management for upper urinary tract transitional cell carcinoma (UUT-TCC): a systematic review.

Surgical management of upper urinary tract transitional cell carcinoma (UUT-TCC) has significantly changed over the past two decades. Data for several new surgical techniques, including nephron-sparing surgery (NSS), is emerging. The study systematically reviewed the literature comparing (randomised and observational studies) surgical and oncological outcomes for various surgical techniques MEDLINE, EMBASE, Cochrane Library, CINAHL, British Nursing Index, AMED, LILACS, Web of Science, Scopus, Biosis, TRIP, Biomed Central, Dissertation Abstracts, ISI proceedings, and PubMed were searched to identify suitable studies. Data were extracted from each identified paper independently by two reviewers (B.R. and B.S.) and cross checked by a senior member of the team. The data analysis was performed using the Cochrane software Review manager version 5. Comparable data from each study was combined in a meta-analysis where possible. For dichotomous data, odds ratios with 95% confidence intervals (CIs) were estimated based on the fixed-effects model and according to an intention-to-treat analysis. If the data available were deemed not suitable for a meta-analysis it was described in a narrative fashion. One randomised control trial (RCT) and 19 observational studies comparing open nephroureterectomy (ONU) and laparoscopic NU (LNU) were identified. The RCT reported the LNU group to have statistically significantly less blood loss (104 vs 430 mL, P < 0.001) and mean time to discharge (2.30 vs 3.65 days, P < 0.001) than the ONU group. At a median follow-up of 44 months, the overall 5-year cancer-specific survival (CSS; 89.9 vs 79.8%) and 5-year metastasis-free survival rates (77.4 vs 72.5%) for the ONU were better than for LNU, respectively, although not statistically significant. A meta-analysis of the observational studies favoured LNU group for lower urinary recurrence (P < 0.001) and distant metastasis. The meta-analyses for local recurrence for the two groups were comparable. One retrospective study comparing ONU with a percutaneous approach for grade 2 disease reported no significant differences in CSS rates (53.8 vs 53.3 months). Three retrospective studies compared NSS and radical NU, and reported no significant differences in overall CSS and recurrence-free survival between the two approaches. Five retrospective studies compared various techniques of en bloc excision of the lower ureter. No technique was reported to be better (operative and oncological) than any other. This review concludes that there is a paucity of good quality evidence for the various surgical approaches for UUT-TCC. The techniques have been assessed and reported in many retrospective single-centre studies favouring LNU for better perioperative outcomes and comparable oncological safety. The reported observational studies data is further supported by one RCT.

Intravesical gemcitabine therapy for non-muscle invasive bladder cancer (NMIBC): a systematic review.

• Intravesical immunotherapy or chemotherapy for non-muscle invasive bladder cancer is a well-established treatment for preventing or delaying tumour recurrence after tumour resection. However, up to 70% of patients may fail and new intravesical agents with improved effectiveness are needed. Gemcitabine is a relatively new anticancer drug that has shown activity against bladder cancer. • To systematically review the literature on the effectiveness and toxicity of intravesical gemcitabine for non-muscle invasive bladder cancer (NMIBC). • MEDLINE, EMBASE, CINAHL, the Cochrane database of systematic reviews, LILACS, SCOPUS, BNI, Biomed Central, Web of Science and BIOSIS were searched to identify trials of intravesical gemcitabine for the treatment of NMIBC. Also searched were meeting proceedings, international guidelines and trial registries. Data on authors, study design, patient characteristics, interventions and outcome data relating to tumour recurrence, disease progression, survival and adverse events were extracted from relevant studies. • Six relevant randomised trials were identified with the number of patients randomised in each trial varying from 30 to 341 (total 704). All trials compared gemcitabine to active controls and varied in the reporting of outcomes. • The first was a marker lesion study which reported greater tumour response rates when intravesical gemcitabine (2 g) was given as three bi-weekly doses (36%) or six weekly doses (40%) compared with a single dose (9%). • One study compared a single postoperative instillation of intravesical gemcitabine with a saline placebo in 341 patients and found no significant difference in the rates of tumour recurrence (28% vs 39%, respectively) or recurrence-free survival (hazard ratio 0.95, 95% confidence interval 0.64-1.39, P= 0.77). The rate of progression to invasive disease was greater with gemcitabine (2.4% vs 0.8%). • A further trial compared gemcitabine with intravesical mitomycin C (MMC) and reported that the rates of recurrence (28% vs 39%) and progression (11% vs 18%) were lower with gemcitabine but did not reach statistical significance. The overall incidence of adverse events was significantly less with gemcitabine (38.8% vs 72.2%, P= 0.02). • Three trials compared gemcitabine with intravesical bacille Calmette-Guérin (BCG) but a meta-analysis was not possible due to clinical heterogeneity. • In untreated patients at intermediate risk of recurrence (primary Ta-T1, no carcinoma in situ) one trial showed that gemcitabine and BCG were similar with respective recurrence rates of 25% and 30% (P= 0.92) and overall progression equal. Dysuria (12.5% vs 45%, P < 0.05) and frequency (10% vs 45%, P < 0.001) were significantly less with gemcitabine. • In a second trial of high-risk patients the recurrence rate was significantly greater with gemcitabine compared with BCG (53.1% vs 28.1%, P= 0.04%) and the time to recurrence significantly shorter with gemcitabine (25.5 vs 39.4 months, P= 0.042). • Finally, in a third trial of high-risk patients who had failed previous intravesical BCG therapy, gemcitabine was associated with significantly fewer recurrences (52.5% vs 87.5%, P= 0.002) and a longer time to recurrence (3.9 vs 3.1 months, P= 0.9) compared with BCG. Progression rates were similar in both groups (33% vs 37.5%, P= 0.12) with no significant differences in grade 2 or 3 toxicities. • The data from several observational studies confirm the pharmacology of gemcitabine as an intravesical agent whilst others report the activity of gemcitabine in terms of tumour recurrence. However, these studies are inherently biased and these data should be interpreted appropriately. • In conclusion a single study suggests that in NMIBC multiple doses of intravesical gemcitabine reduce tumour recurrences to a greater extent than a single dose. • In contrast, a single dose immediately after surgery is ineffective based on one study. Gemcitabine may be more active than MMC with a lower toxicity profile. • Compared with intravesical BCG therapy, gemcitabine had similar effects in intermediate-risk patients, less effective in high-risk patients and superior in BCG-refractory patients. However, each randomised trial identified represents a different clinical setting in NMIBC and therefore the evidence base is limited. Consequently these data should be interpreted with caution until further corroborative evidence becomes available. • Intravesical gemcitabine is a promising drug that may add to the urologist's options in treating patients with NMIBC.

Intravesical gemcitabine for non-muscle invasive bladder cancer.

BACKGROUND: Intravesical immunotherapy or chemotherapy for non-muscle invasive bladder cancer is a well established treatment for preventing or delaying tumour recurrence following tumour resection. However, up to 70% of patients may fail and new intravesical agents with improved effectiveness are needed. Gemcitabine is a relatively new anticancer drug that has shown activity against bladder cancer. OBJECTIVES: To evaluate the effectiveness and toxicity of intravesical gemcitabine in preventing tumour recurrence and progression in non-muscle invasive bladder cancer (NMIBC). SEARCH METHODS: A search strategy was developed for MEDLINE to identify randomised trials of intravesical gemcitabine for the treatment of non-muscle invasive bladder cancer. The searches were from 1947 to May 2011. Other databases searched included EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials, LILACS, SCOPUS, BNI, Biomed Central, Web of Science and BIOSIS. Handsearching of meeting proceedings, international guidelines and trial registries was also carried out. SELECTION CRITERIA: The titles and abstracts of the combined electronic and handsearching were manually screened by three authors independently to determine if they met the inclusion criteria for this review. Studies were selected if they were randomised, controlled trials or quasi-randomised clinical trials that included intravesical gemcitabine in at least one arm of a comparative study. DATA COLLECTION AND ANALYSIS: Data extraction was carried out by three reviewers. The information retrieved included the author's details, the study design, the characteristics of the recruited patients, details of the interventions and data relating to the primary, and secondary outcome measures. MAIN RESULTS: Six relevant randomised trials were identified with the number of patients randomised in each trial varying from 30 to 341 (total 704). All trials compared gemcitabine to active controls and varied in the reporting of outcomes. One study compared a single post-operative instillation of intravesical gemcitabine with a saline placebo in 341 patients and found no significant difference in the rates of tumour recurrence (28% versus 39%, respectively) or recurrence-free survival (HR (hazard ratio) 0.95, 95% CI 0.64 to1.39, P = 0.77). The rate of progression to invasive disease was greater with gemcitabine (2.4% versus 0.8%). A further trial compared gemcitabine with intravesical mitomycin C and demonstrated that the rates of recurrence (28% versus 39%) and progression (11% versus 18%) were lower with gemcitabine but did not reach statistical significance. The global incidence of adverse events was significantly less with gemcitabine (38.8% versus 72.2%, P = 0.02).Three trials compared gemcitabine with intravesical BCG but a meta-analysis was not possible due to clinical heterogeneity. In untreated patients at intermediate risk of recurrence (primary Ta-T1 no CIS) one trial showed that gemcitabine and BCG were similar with respective recurrence rates of 25% and 30% (P = 0.92) and overall progression equal (P = 1.0). Dysuria (12.5% versus 45%, P < 0.05) and frequency (10% versus 45%, P < 0.001) were significantly less with gemcitabine. In a second trial of high risk patients the recurrence rate was significantly greater with gemcitabine compared to BCG (53.1% and 28.1%, P = 0.04) and the time to recurrence significantly shorter with gemcitabine (25.5 versus 39.4 months, P = 0.042). Finally in a third trial of high risk patients who had failed previous intravesical BCG therapy, gemcitabine was associated with significantly fewer recurrences (52.5% versus 87.5%, P = 0.002) and a longer time to recurrence (3.9 versus 3.1 months, P = 0.9) compared to BCG. Progression rates were similar in both groups (33% versus 37.5%, P = 0.12) with no significant differences in grade 2 or 3 toxicities.The final trial was a marker lesion study which reported greater response rates when intravesical gemcitabine (2 g) was given as three bi-weekly doses (36%) or six weekly doses (40%) compared to a single dose (9%). AUTHORS' CONCLUSIONS: A single dose immediately following surgery is ineffective based on one study. Gemcitabine may be more active than mitomycin C with a lower toxicity profile. Compared to intravesical BCG therapy, gemcitabine had similar effects in intermediate risk patients, less effective in high risk patient and superior in BCG refractory patients. However, each randomised trial identified represents a different clinical setting in NMIBC and therefore the evidence base is limited. Consequently these data should be interpreted with caution until further corroborative evidence becomes available. The aim of intravesical therapy in NMIBC is to prevent tumour recurrence and progression and to avoid the morbidity associated with cystectomy. Intravesical gemcitabine is a promising drug that may add to the urologist's options in achieving this goal.

Surgical management for upper urinary tract transitional cell carcinoma.

BACKGROUND: Upper tract transitional cell carcinomas (TCC) are uncommon and aggressive tumours. There are a number of surgical approaches to manage this condition including open radical nephroureterectomy and laparoscopic procedures. OBJECTIVES: To determine the best surgical management option for upper tract transitional cell carcinoma. SEARCH STRATEGY: A sensitive search strategy was developed to identify relevant studies for inclusion in this review. The following databases were searched for randomised trials evaluating surgical approaches to the management of upper tract TCC: Medline EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, British Nursing Index, AMED, LILACS, Web of Science®, Scopus, Biosis, TRIP, Biomed Central, Dissertation Abstracts, and ISI Proceedings. SELECTION CRITERIA: The following criteria that were considered for this review.Types of studies - All randomised or quasi-randomised controlled trials comparing the various surgical methods and approaches for the management of localised upper tract transitional cell carcinoma. Types of participants - All adult patients with localised transitional cell carcinoma. Localised disease was defined as limited to the kidney or ureter with no gross regional lymph nodal enlargement on imaging. Types of interventions - Any surgical method or approach for managing localised upper tract transitional cell carcinoma. Types of outcome measures - Overall and cancer-specific survival were primary outcomes. Surgery-related morbidity. Quality of life and health economics outcomes were secondary outcomes. DATA COLLECTION AND ANALYSIS: Two review authors examined the search results independently to identify trials for inclusion. MAIN RESULTS: We identified one randomised controlled trial that met our inclusion criteria. The trial showed that the laparoscopic approach had superior peri-operative outcomes compared to open approach. Laparoscopic was superior and statistically significant for blood loss (104 mL (millilitres) versus 430 mL, P < 0.001) and mean time to discharge (2.3 days versus 3.7, P < 0.001). Oncological outcomes (bladder tumour-free survival, metastasis-free survival, cancer-specific survival curves), at a median follow up of 44 months and in organ-confined disease, were comparable for both groups. AUTHORS' CONCLUSIONS: There is no high quality evidence available from adequately controlled trials to determine the best surgical management of upper tract transitional cell carcinoma. However, one small randomised trial and observational data suggests that laparoscopic approach is associated with less blood loss and early recovery from surgery with similar cancer outcomes when compared to open approach.

Gemcitabine for unresectable, locally advanced or metastatic bladder cancer.

BACKGROUND: The prognosis for unresectable, locally advanced or metastatic transitional cell carcinoma of the bladder is poor with most patients succumbing to their disease within 2 to 3 years. Clinical management at this stage of the disease is palliative with systemic chemotherapy the main treatment of choice. A number of cytotoxic agents have shown activity in metastatic disease including cisplatin, methotrexate, doxorubicin and vinblastine. However, response rates still need improving and toxicities may sometimes be severe, and so the search for newer agents with improved benefit-to-risk ratios is constantly being pursued. One such agent that shows promise is gemcitabine. OBJECTIVES: Evaluate the effectiveness and toxicity of gemcitabine for the management of unresectable, locally advanced or metastatic bladder cancer. SEARCH STRATEGY: A search strategy was developed for MEDLINE to identify randomised trials of gemcitabine for the treatment of unresectable, locally advanced or metastatic bladder cancer. The searches were from 1966 to July 2010.  Other databases searched included EMBASE, CINAHL, the Cochrane Database of Systematic Reviews, LILACS, and the Web of Science®. There were no language or location restrictions. SELECTION CRITERIA: The titles and abstracts of the combined electronic and hand searching searches were manually screened by two authors to determine if they met the inclusion criteria of this review. Studies were selected if they were randomised, controlled trials or quasi-randomised clinical trials that included gemcitabine in at least one arm of a comparative study. DATA COLLECTION AND ANALYSIS: Data extraction was carried out in duplicate by two authors. The information retrieved included the author's details, the study design, the characteristics of the recruited patients, details of the interventions and data relating to the primary and secondary outcomes measures. MAIN RESULTS: Three randomised trials used gemcitabine plus cisplatin (GCis) as one of the arms in each trial. The first randomised trial compared GCis with MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) and showed no significant difference in overall survival (hazard ratio1.09, 95% CI 0.88 to 1.34, P = 0.443) however the GCis regime had fewer incidences of neutropenic sepsis (1% versus 12%, P = 0.001) and mucositis (1% versus 22%, P = 0.001). A second randomised trial compared GCis to gemcitabine plus carboplatin (GCarbo) and reported an improved, but non-significant 1-year survival rate with GCis (64% versus 37%). A third randomised trial compared GCis with gemcitabine plus cisplatin plus paclitaxel (GCisPac) and again found no significant difference in overall survival (respective medians 49 weeks versus 61 weeks).One randomised trial evaluated GCarbo against methotrexate plus carboplatin plus vinblastine (MCarboV) in patients "unfit" for cisplatin-based chemotherapy. There were more overall responses (38% versus 20%) and less severe acute toxicities (14% versus 23%) with GCarbo.In one randomised study evaluating 3-weekly gemcitabine plus paclitaxel (GPac3) versus a 2-weekly regimen overall survival was not significantly different (respective medians 13 and 9 months) however toxicities were worse with GPac3 especially alopecia (76% versus 32%).A larger trial compared gemcitabine (1 g/m(2)) (grams per metre squared) plus paclitaxel (175 mg/m(2)) (milligrams per metre squared) as a 3-weekly schedule for 6 cycles with a 2-weekly maintenance schedule. There was no significant difference in response rates, progression-free survival, disease-specific survival, and overall survival. AUTHORS' CONCLUSIONS: A review of the published evidence found that one trial reported gemcitabine plus cisplatin had a better safety profile than MVAC and may be considered the first choice for treatment of metastatic bladder cancer. However, the data are limited to one trial only. Patients unable to tolerate cisplatin may benefit from gemcitabine plus carboplatin.

Surgical management of localised renal cell carcinoma.

BACKGROUND: Surgical excision remains the core to the management of localised renal cancer and several studies have evaluated the safety and clinical effectiveness of laparoscopic surgery and other recently introduced interventions for the localised disease. OBJECTIVES: To identify and review the evidence from randomised trials comparing different surgical interventions in localised renal cell carcinoma. SEARCH STRATEGY: Randomised or quasi randomised trials comparing various surgical interventions in the management of adults with surgically resectable localised renal cancer. RCTs were identified by searching The Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2009), MEDLINE (Silver Platter, from 1966 to August 2009), EMBASE via Ovid (from 1980 to August 2009), and a number of other data bases. SELECTION CRITERIA: Studies were assessed for eligibility and quality, and data from published trials were extracted by two reviewers. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: No randomised trials were identified meeting the inclusion criteria reporting on the comparison between open radical nephrectomy with laparoscopic approach or new modalities of treatment such as radiofrequency or cryoablation. Three randomised controlled trials compared the different laparoscopic approaches to nephrectomy (transperitoneal versus retroperitoneal) and found no statistical difference in operative or perioperative outcomes between the two treatment groups. There were several non-randomised and retrospective case series reporting various advantages of laparoscopic renal cancer surgery such as less blood loss, early recovery and shorter hospital stay AUTHORS' CONCLUSIONS: The main source of evidence for the current practice of laparoscopic excision of renal cancer is drawn from case series, small retrospective studies and very few small randomised controlled trials. The results and conclusions of these studies must therefore be interpreted with caution.

Intravesical therapy for superficial bladder cancer: a systematic review of randomised trials and meta-analyses.

BACKGROUND: In 2002 there were estimated to be 357,000 new cases of bladder cancer worldwide and 145,000 deaths making bladder cancer the 9th most common malignancy globally. At diagnosis, 60-80% of tumours are superficial and endoscopic resection is the initial treatment for this disease. In patients with low, medium or high risk disease, about 20%, 40% and 90%, respectively, will develop tumour recurrence. To delay or prevent recurrence, intravesical therapy is routinely used. Commonly used intravesical agents include immunotherapy with BCG and chemotherapy with cytotoxics such as Mitomycin C, Adriamycin, Epirubicin and Gemcitabine. However, controversy exists as to which agent and schedule should be used. METHODS: An overarching search of the literature was used to identify relevant studies to assess the clinical benefit of intravesical therapy and provide clinical guidance in a comprehensive systematic review of randomised trials and meta-analyses of intravesical therapy for superficial bladder cancer. Findings and interpretation the search identified over 80 randomised trials and 11 meta-analyses. The extensive evidence suggests that an immediate post-operative instillation of a chemotherapeutic agent, such as Mitomycin C or Epirubicin, is effective in reducing tumour recurrence. In intermediate or high risk patients, further intravesical induction and maintenance therapy with BCG is recommended. CONCLUSION: Intravesical chemotherapy with either Mitomycin C or Epirubicin would be an option for those patients failing or who are unsuitable for BCG therapy. Intravesical BCG is superior to chemotherapy in terms of complete response and disease-free survival. However, there is no conclusive evidence that one agent is superior in terms of overall survival.

Disclosure of traumatic experiences, dissociation, and anxiety in group therapy for posttraumatic stress.

This study examined the relationships among the symptoms of posttraumatic stress disorder (PTSD), anxiety, dissociation with self-disclosure among 72 male military veterans with PTSD who were attending an eight-week group therapy treatment program. At intake to the program, participants were administered a baseline demographics questionnaire, the Clinicians Administered PTSD Scale, a dissociation measure, and the Hospital Anxiety and Depression Scale (HADS). Participants completed the dissociation measure and the HADS again at discharge from the program and at a follow-up three months later. We found that the frequency and severity of dissociation reported by participants decreased over time. It was also found that high self-disclosers had higher levels of dissociation when compared to low self-disclosers at baseline and program end, but showed a greater decline in levels of dissociation at three-month follow-up. It was also found that, regardless of the level of disclosure, anxiety levels at follow-up were significantly lower than baseline levels of anxiety.

Management of venous thromboembolism in patients with advanced cancer: a systematic review and meta-analysis.

Venous thromboembolism is common in patients with cancer. However, no management guidelines exist for venous thromboembolism specific to patients with advanced progressive cancer. To help develop recommendations for practice, we have done a comprehensive review of anticoagulation treatment in patients with cancer, with particular focus on studies that included patients with advanced disease. Data from 19 publications, including randomised, prospective, and retrospective studies suggest that: long-term full-dose low-molecular-weight heparin (LMWH) is more effective than warfarin in the secondary prophylaxis of venous thromboembolism in patients with cancer of any stage, performance status, or prognosis; warfarin should not be used in patients with advancing progressive disease; and in patients at high risk of bleeding, full-dose LMWH for 7 days followed by a long-term decreased fixed dose long term can be considered. The optimum treatment duration is unclear, but because the prothrombotic tendency will persist in patients with advanced cancer, indefinite treatment is generally recommended. For patients with contraindications to anticoagulation, inferior-vena-caval filters can be considered, but their use needs careful patient selection. Ultimately, the decision to initiate, continue, and stop anticoagulation will need to be made on an individual basis, guided by the available evidence, the patient's circumstances, and their informed preferences.

Should the Gleason grading system for prostate cancer be modified to account for high-grade tertiary components? A systematic review and meta-analysis.

The Gleason system for grading prostate cancer assigns a score on the basis of the most prevalent and second most prevalent grade. Several studies have investigated the clinical significance of a tertiary grade in radical prostatectomy samples. A systematic search of the published work identified seven studies that reported the prognostic value of a tertiary Gleason grade. Three studies correlated the presence of a tertiary grade with pathological stage, and six with prostate-specific antigen recurrence or clinical progression. In the small number of studies available, the frequency of a tertiary grade was consistently higher in samples characterised with pathological variables of poor outcome, such as extra-prostatic extension and positive surgical margins, but not lymph-node metastases. In five studies the presence of a tertiary grade increased the risk of prostate-specific antigen recurrence after radical prostatectomy by a factor of 2.5. However, modification of the Gleason score to include a tertiary grade in Gleason 4+3 tumours might overestimate the risk of seminal-vesicle or lymph-node invasion. This systematic review has established the association of a tertiary grade with poorer outcome than that associated with no tertiary grade. A tertiary grade should, therefore, be included in the pathological reporting of prostate cancer and be considered in the interpretation and design of clinical trials. However, all studies assessed for this review were retrospective, potentially affected by selection bias, and based on radical prostatectomy samples or transurethral resections rather than biopsy samples. Therefore, more evidence is needed to warrant the adaptation of the Gleason system to account for the presence of a tertiary grade, especially when scoring prostatic biopsies and applying predictive algorithms.

The effects of preoperative preparation on postoperative outcomes: the moderating role of control appraisals.

OBJECTIVE: To test the proposal that external health locus of control and self-efficacy would moderate the effects of a psychological preparation for surgery on outcomes for surgical heart patients. MAIN OUTCOME MEASURES: Psychological distress, pain, serum cortisol, and tumor necrosis factor alpha. DESIGN: A total of 80 coronary artery bypass graft patients were given standard care plus a psychological preparation or standard care alone using a single-blind methodology with random assignment. Data on psychological and biological functioning were collected at admission (baseline) and discharge. RESULTS: As predicted, external health locus of control and self-efficacy moderated the effect of the preparation on all outcomes. Results indicated that for high external health locus of control, the preparation was related to lower distress for people with high self-efficacy compared with those with low self-efficacy. When external health locus of control was low, the preparation was related to lower distress for those with lower self-efficacy. CONCLUSION: These findings caution against the use of preparations and education for surgical patients without accounting for control appraisals.

Chemotherapy for hormone-refractory prostate cancer.

BACKGROUND: Prostate cancer mainly affects elderly men, and its incidence has steadily increased over the last decade. The management of this disease is replete with controversy. In men with advanced, metastatic prostate cancer, hormone therapy is almost universally accepted as the initial treatment of choice and produces good responses in most patients. However, many patients will relapse and become resistant to further hormone manipulation; the outlook for these patients is poor. Many have disease extending to the skeleton, which is associated with severe pain. Therapies for these men include chemotherapy, bisphosphonates, palliative radiotherapy, and radioisotopes. Systemic chemotherapy has been evaluated in men with hormone-refractory prostate cancer (HRPC) for many years, with disappointing results. However, more recent studies with newer agents have shown encouraging results. There is therefore a need to explore the value of chemotherapy in this disease. OBJECTIVES: The present review aims to assess the role of chemotherapy in men with metastatic HRPC. The major outcome was overall survival. Secondary objectives include the effect of chemotherapy on pain relief, prostate-specific antigen (PSA) response, quality of life, and treatment-related toxicity. SEARCH STRATEGY: Trials were identified by searching electronic databases, such as MEDLINE, and handsearching of relevant journals and conference proceedings. There was no restriction of language or location. SELECTION CRITERIA: Only published randomised trials of chemotherapy in HRPC patients were eligible for inclusion in this review. Randomised comparisons of different chemotherapeutic regimens, chemotherapy versus best standard of care or placebo, were relevant to this review. Randomised, dose-escalation studies were not included in this review. DATA COLLECTION AND ANALYSIS: Data extraction tables were designed specifically for this review to aid data collection. Data from relevant studies were extracted and included information on trial design, participants, and outcomes. Trial quality was also assessed using a scoring system for randomisation, blinding, and description of patient withdrawal. MAIN RESULTS: Out of 107 randomised trials of chemotherapy in advanced prostate cancer identified by the search strategy, 47 were included in this review and represented 6929 patients with HRPC. Only two trials compared the same chemotherapeutic interventions and therefore a meta-analysis was considered inappropriate. The quality of some trials was poor because of poor reporting, low-patient recruitment, or poor trial design. For clarity, trials were categorised according to the major drug used, but this was not a definitive grouping, since many trials used several agents and would be eligible for inclusion in a number of categories. Drug categories included estramustine, 5-fluorouracil, cyclophosphamide, doxorubicin, mitoxantrone, and docetaxel. Only studies using docetaxel reported a significant improvement in overall survival compared to best standard of care, although the increase was small (< 2.5 months). The mean percentage of patients achieving at least a 50% reduction in PSA compared to baseline was as follows: estramustine 48%; 5-fluorouracil 20%; doxorubicin 50% (one study only); mitoxantrone 33%; and docetaxel 52%. Pain relief was reported in 35% to 76% of patients receiving either single agents or combination regimens. A three weekly regime of docetaxel significantly improved pain relief compared to mitoxantrone plus prednisone (the latter regimen approved as standard therapy for HRPC in the USA). All chemotherapeutics, either as single agents or in combination, were associated with toxicity; the major ones being myelosuppression, gastrointestinal toxicity, cardiac toxicity, neuropathy, and alopecia. Quality of life was significantly improved with docetaxel compared to mitoxantrone plus prednisone. AUTHORS' CONCLUSIONS: Patients with HRPC have not traditionally been offered chemotherapy as a routine treatment because of treatment-related toxicity and poor responses. Recent data from randomised studies, in particular those using docetaxel, have provided encouraging improvements in overall survival, palliation of symptoms, and improvements in quality of life. Chemotherapy should be considered as a treatment option for patients with HRPC. However, patients should make an informed decision based on the risks and benefits of chemotherapy.

Radioisotopes for the palliation of metastatic bone cancer: a systematic review.

Strontium-89 and samarium-153 are radioisotopes that are approved in the USA and Europe for the palliation of pain from metastatic bone cancer, whereas rhenium-186 and rhenium-188 are investigational. Radioisotopes are effective in providing pain relief with response rates of between 40% and 95%. Pain relief starts 1-4 weeks after the initiation of treatment, continues for up to 18 months, and is associated with a reduction in analgesic use in many patients. Thrombocytopenia and neutropenia are the most common toxic effects, but they are generally mild and reversible. Repeat doses are effective in providing pain relief in many patients. The effectiveness of radioisotopes can be greater when they are combined with chemotherapeutic agents such as cisplatin. Some studies with 89Sr and 153Sm indicate a reduction of hot spots on bone scans in up to 70% of patients, and suggest a possible tumoricidal action. Further studies are needed to address the questions of which isotope to use, what dose and schedule to use, and which patients will respond.

Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy - a systematic review of the randomised trials.

BACKGROUND: Recent randomised studies reported that single fraction radiotherapy was as effective as multifraction radiotherapy in relieving pain due to bone metastasis. However, there are concerns about the higher re-treatment rates and the efficacy of preventing future complications such as pathological fracture and spinal cord compression by single fraction radiotherapy. OBJECTIVES: To undertake a systematic review and meta-analysis of single fraction radiotherapy versus multifraction radiotherapy for metastatic bone pain relief and prevention of bone complications. SEARCH STRATEGY: Trials were identified through MEDLINE, EMBASE, Cancerlit, reference lists of relevant articles and conference proceedings. Relevant data was extracted. SELECTION CRITERIA: Randomised studies comparing single fraction radiotherapy with multifraction radiotherapy on metastatic bone pain DATA COLLECTION AND ANALYSIS: The analyses were performed using intention-to-treat principle. The results were pooled using meta-analysis to estimate the effect of treatment on pain response, re-treatment rate, pathological fracture rate and spinal cord compression rate. MAIN RESULTS: Eleven trials that involved 3435 patients were identified. Of 3435 patients, 52 patients were randomised more than once for different painful bone metastasis sites. Altogether, 3487 painful sites were randomised. The trials included patients with painful bone metastases of any primary sites, but were mainly prostate, breast and lung. The overall pain response rates for single fraction radiotherapy and multifraction radiotherapy were 60% (1059/1779) and 59% (1038/1769) respectively, giving an odds ratio of 1.03 (95% confidence interval [CI], 0.89 - 1.19) indicating no difference between the two radiotherapy schedules. There was also no difference in complete pain response rates for single fraction radiotherapy (34% [497/1441]) and multifraction radiotherapy (32% [463/1435]) with an odds ratio of 1.11 (95%CI 0.94-1.30). Patients treated by single fraction radiotherapy had a higher re-treatment rate with 21.5% (267/1240) requiring re-treatment compared to 7.4% (91/1236) of patients in the multifraction radiotherapy arm (odds ratio 3.44 [95%CI 2.67-4.43]). The pathological fracture rate was also higher in single fraction radiotherapy arm patients. Three percent (37/1240) of patients treated by single fraction radiotherapy developed pathological fracture compared to 1.6% (20/1236) for those treated by multifraction radiotherapy (odds ratio 1.82 [95%CI 1.06-3.11]). The spinal cord compression rates were similar for both arms (odds ratio 1.41 [95%CI 0.72-2.75]). Repeated analyses excluding dropout patients gave similar results. REVIEWERS' CONCLUSIONS: Single fraction radiotherapy was as effective as multifraction radiotherapy in relieving metastatic bone pain. However, the re-treatment rate and pathological fracture rates were higher after single fraction radiotherapy. Studies with quality of life and health economic end points are warranted to find out the optimal treatment option.