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Combe Martin, United Kingdom

Jaaback K.,Hunter New England Center for Gynaecological Cancer | Johnson N.,Royal United Hospital NHS Trust | Lawrie T.A.,Royal United Hospital
Cochrane Database of Systematic Reviews

Background: Ovarian cancer tends to be chemosensitive and confine itself to the surface of the peritoneal cavity for much of its natural history. These features have made it an obvious target for intraperitoneal (IP) chemotherapy. Chemotherapy for ovarian cancer is usually given as an intravenous (IV) infusion repeatedly over five to eight cycles. Intraperitoneal chemotherapy is given by infusion of the chemotherapeutic agent directly into the peritoneal cavity. There are biological reasons why this might increase the anticancer effect and reduce some systemic adverse effects in comparison to IV therapy. Objectives: To determine if adding a component of the chemotherapy regime into the peritoneal cavity affects overall survival, progression-free survival, quality of life (QOL) and toxicity in the primary treatment of epithelial ovarian cancer. Search methods: We searched the Gynaecological Cancer Review Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2011, MEDLINE (1951 to May 2011) and EMBASE (1974 to May 2011). We updated these searches in February 2007, August 2010, May 2011 and September 2015. In addition, we handsearched and cascade searched the major gynaecological oncology journals up to May 2011. Selection criteria: The analysis was restricted to randomised controlled trials (RCTs) assessing women with a new diagnosis of primary epithelial ovarian cancer, of any FIGO stage, following primary cytoreductive surgery. Standard IV chemotherapy was compared with chemotherapy that included a component of IP administration. Data collection and analysis: We extracted data on overall survival, disease-free survival, adverse events and QOL and performed meta-analyses of hazard ratios (HR) for time-to-event variables and relative risks (RR) for dichotomous outcomes using RevMan software. Main results: Nine randomised trials studied 2119 women receiving primary treatment for ovarian cancer. We considered six trials to be of high quality. Women were less likely to die if they received an IP component to chemotherapy (eight studies, 2026 women; HR = 0.81; 95% confidence interval (CI): 0.72 to 0.90). Intraperitoneal component chemotherapy prolonged the disease-free interval (five studies, 1311 women; HR = 0.78; 95% CI: 0.70 to 0.86). There was greater serious toxicity with regard to gastrointestinal effects, pain, fever and infection but less ototoxicity with the IP than the IV route. Authors' conclusions: Intraperitoneal chemotherapy increases overall survival and progression-free survival from advanced ovarian cancer. The results of this meta-analysis provide the most reliable estimates of the relative survival benefits of IP over IV therapy and should be used as part of the decision making process. However, the potential for catheter related complications and toxicity needs to be considered when deciding on the most appropriate treatment for each individual woman. The optimal dose, timing and mechanism of administration cannot be addressed from this meta-analysis. This needs to be addressed in the next phase of clinical trials. © 2016 The Cochrane Collaboration. Source

Miles T.,Royal United Hospital NHS Trust
Cochrane database of systematic reviews (Online)

BACKGROUND: Many vaginal dilator therapy guidelines advocate routine vaginal dilation during and after pelvic radiotherapy to prevent stenosis (abnormal narrowing of the vagina). The UK Gynaecological Oncology Nurse Forum recommend dilation "three times weekly for an indefinite time period". The UK patient charity Cancer Backup advises using vaginal dilators from two to eight weeks after the end of radiotherapy treatment. Australian guidelines recommend dilation after brachytherapy "as soon as is comfortably possible" and "certainly within four weeks and to continue for three years or indefinitely if possible". However, dilation is intrusive, uses health resources and can be psychologically distressing. It has also caused rare but very serious damage to the rectum. OBJECTIVES: To review the benefits and harms of vaginal dilation therapy associated with pelvic radiotherapy for cancer. SEARCH STRATEGY: Searches included the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 4), MEDLINE (1950 to 2008), EMBASE (1980 to 2008) and CINAHL (1982 to 2008). SELECTION CRITERIA: Any comparative randomised controlled trials (RCT) or data of any type which compared dilation or penetration of the vagina after pelvic radiotherapy treatment for cancer. DATA COLLECTION AND ANALYSIS: The review authors independently abstracted data and assessed risk of bias. We analysed the mean difference in sexual function scores and the risk ratio for non-compliance at six weeks and three months in single trial analyses. No trials met the inclusion criteria. MAIN RESULTS: Dilation during or immediately after radiotherapy can, in rare cases, cause damage and there is no persuasive evidence from any study to demonstrate that it prevents stenosis. Data from one RCT showed no improvement in sexual scores in women who were encouraged to practice dilation. Two case series and one comparative study using historical controls suggest that dilation might be associated with a longer vaginal length but these data cannot reasonably be interpreted to show that dilation caused the change in the vagina. AUTHORS' CONCLUSIONS: Routine dilation during or soon after cancer treatment may be harmful. There is no reliable evidence to show that routine regular vaginal dilation during or after radiotherapy prevents the late effects of radiotherapy or improves quality of life. Gentle vaginal exploration might separate the vaginal walls before they can stick together and some women may benefit from dilation therapy once inflammation has settled but there are no good comparative supporting data. Source

Evidence for the impact of prehospital, physician-delivered advanced cardiac life support (ACLS) on survival from out-of-hospital cardiac arrest is conflicting. The prospective observational study by Yasunaga and co-workers demonstrates an improved survival at 1 month associated with prehospital physician-delivered ACLS over emergency life-saving technician-delivered ACLS. These effects are additive to the survival benefit seen with bystander-initiated cardiopulmonary resuscitation (BCPR) compared with no BCPR. The present commentary places these findings in the context of the existing literature and discusses some of the unresolved controversies. © 2011 BioMed Central Ltd Source

Johnson N.,Royal United Hospital NHS Trust
Cochrane database of systematic reviews (Online)

Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly favouring the addition of postoperative platinum based chemotherapy. The HR for progression-free survival is 0.75 (0.64 to 0.89). This means that chemotherapy reduces the risk of being dead at any censorship by a quarter. Chemotherapy reduces the risk of developing the first recurrence outside the pelvis (RR = 0.79 (0.68 to 0.92), 5% absolute risk reduction; NNT = 20). The analysis of pelvic recurrence rates is underpowered but the trend suggests that chemotherapy may be less effective than radiotherapy in a direct comparison (RR = 1.28 (0.97 to 1.68)) but it may have added value when used with radiotherapy (RR = 0.48 (0.20 to 1.18)). Postoperative platinum based chemotherapy is associated with a small benefit in progression-free survival and overall survival irrespective of radiotherapy treatment. It reduces the risk of developing a metastasis, could be an alternative to radiotherapy and has added value when used with radiotherapy. Source

Peden C.J.,Royal United Hospital NHS Trust | Peden C.J.,Health Services Research Center | Grocott M.P.W.,Health Services Research Center | Grocott M.P.W.,University of Southampton | Grocott M.P.W.,Southampton NIHR Respiratory Biomedical Research Unit

Outcomes are essential measures of healthcare effectiveness and efficiency. Traditional measures of outcome, such as mortality and length of stay, are important and easy to measure but have significant limitations when evaluating the peri-operative care of elderly patients.alternative measures, including clinician-described (e.g. complication rates, functional status, frailty) and patient-reported outcome and experience measures, are important to provide a comprehensive description of peri-operative outcome in the older patient. However, few measurement tools have been developed or validated specifically for the elderly surgical patient. This paper describes the outcome measures currently in use, explores how they might be used to improve the quality of care provision, and indicates priority areas for perioperative outcomes research in the elderly surgical patients.©2013 The Association of Anaesthetists of Great Britain and Ireland. Source

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