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Biomedical subjects

K E Broadley

Publications and source records attributed to K E Broadley.

10 recordsLinked to original sources
PubMed2004

Systematic review of bisphosphonates for hypercalcaemia of malignancy.

BACKGROUND: Bisphosphonates are the treatment of choice for hypercalcaemia of malignancy (HCM) but there is no consensus regarding which drug or dose should be given. We designed a systematic review to investigate the efficacy of bisphosphonates in the treatment of HCM. METHODS: We identified randomized controlled trials (RCTs) by searching electronic databases, scanning of reference lists, and consultation with experts and pharmaceutical companies. Foreign papers were translated. Inclusion criteria were RCTs, confirmed malignant disease and measurement of serum calcium (ionized or corrected for albumin) postrehydration. The primary outcome was number of patients achieving normocalcaemia. Secondary outcomes were time to normocalcaemia, time to relapse and toxicity. RESULTS: Twenty-seven papers and two abstracts, using intravenous bisphosphonates, fulfilled the inclusion criteria. Data from 26 studies were used in analyses. Due to the heterogeneity of studies, meta-analysis could not be performed. Pamidronate was more effective than placebo, mithramycin, etidronate (7.5 mg/kg) and low-dose clodronate (600 mg), but equal to higher dose clodronate (1500 mg). Clodronate and etidronate were superior to placebo; incadronate was superior to elcatonin; gallium nitrate was superior to etidronate. No difference was seen between alendronate and clodronate. Three dose finding studies showed no difference between 30-90 mg of pamidronate, but one well designed study showed increasing efficacy with increasing dose. Studies using increasing doses of ibandronate (0.6-4 mg), alendronate (2.5-15 mg), and incadronate (2.5-10mg), showed a dose response. Duration of administration of pamidronate did not affect efficacy (six studies). CONCLUSION: Bisphosphonates normalize calcium in >70% patients with minimal side effects. Aminobisphosphonates are most effective at maintaining normocalcaemia and should be given in high dose irrespective of baseline serum calcium.

Diphosphonates↗
PubMed2003

Systematic review of role of bisphosphonates on skeletal morbidity in metastatic cancer.

OBJECTIVE: To review the evidence for the use of bisphosphonates to reduce skeletal morbidity in cancer patients with bone metastases. DATA SOURCES: Electronic databases, scanning reference lists, and consultation with experts and pharmaceutical companies. Foreign language papers were included. STUDY SELECTION: Included trials were randomised controlled trials of patients with malignant disease and bone metastases who were treated with oral or intravenous bisphosphonate compared with another bisphosphonate, placebo, or standard care. All trials measured at least one outcome of skeletal morbidity. RESULTS: 95 articles were identified; 30 studies fulfilled inclusion criteria. In studies that lasted > or = 6 months, compared with placebo bisphosphonates significantly reduced the odds ratio for fractures (vertebral 0.69, 95% confidence interval 0.57 to 0.84, P < 0.0001; non-vertebral 0.65, 0.54 to 0.79, P < 0.0001; combined 0.65, 0.55 to 0.78, P < 0.0001), radiotherapy (0.67, 0.57 to 0.79, P < 0.0001), and hypercalcaemia (0.54, 0.36 to 0.81, P = 0.003) but not for orthopaedic surgery (0.70, 0.46 to 1.05, P = 0.086) or spinal cord compression (0.71, 0.47 to 1.08, P = 0.113). The reduction in orthopaedic surgery was significant in studies that lasted over a year (0.59, 0.39 to 0.88, P = 0.009). Use of bisphosphonates significantly increased time to first skeletal related event but did not increase survival. Subanalyses showed that most evidence supports use of intravenous aminobisphosphonates. CONCLUSIONS: In people with metastatic bone disease bisphosphonates significantly decrease skeletal morbidity, except for spinal cord compression and increased time to first skeletal related event. Treatment should start when bone metastases are diagnosed and continue until it is no longer clinically relevant.

Bone Neoplasms↗
PubMed2002

A systematic review of the use of opioids in the management of dyspnoea.

BACKGROUND: Opioids are commonly used to treat dyspnoea in palliative medicine but there has been no formal evaluation of the evidence for their effectiveness in the treatment of dyspnoea. A systematic review was therefore carried out to examine this. METHODS: The criteria for inclusion required that studies were double blind, randomised, placebo controlled trials of opioids for the treatment of dyspnoea secondary to any cause. The methods used to identify suitable studies included electronic searching of the literature, hand searching of the literature, and personal contact with relevant individuals and organisations. Random effects meta-analyses were performed on all included studies and on various subgroups (studies involving nebulised opioids or patients with chronic obstructive pulmonary disease (COPD)). Subgroups were compared using meta-regression. Some studies included in the systematic review could not be included in the meta-analysis because insufficient data were presented. RESULTS: Eighteen studies fulfilled the criteria for the review. The meta-analysis showed a statistically significant positive effect of opioids on the sensation of breathlessness (p=0.0008). Meta-regression indicated a greater effect for studies using oral or parenteral opioids than for studies using nebulised opioids (p=0.02). The subgroup analysis failed to show a positive effect of nebulised opioids on the sensation of breathlessness. The results of the subgroup analysis of the COPD studies were essentially similar to the results of the main analysis. CONCLUSION: This review supports the continued use of oral and parenteral opioids to treat dyspnoea in patients with advanced disease. There are insufficient data from the meta-analysis to conclude whether nebulised opioids are effective, but the results from included studies that did not contribute to the meta-analysis suggest that they are no better than nebulised normal saline.

Administration, Oral↗
PubMed2000

Corticosteroids for the resolution of malignant bowel obstruction in advanced gynaecological and gastrointestinal cancer.

BACKGROUND: Gastrointestinal and ovarian cancers are common cancers. The incidence of associated malignant bowel obstruction in patients with advanced cancers of these types is not known, and the best management of these patients is controversial. Inappropriate management may result in uncontrolled (faeculant) vomiting, pain and distress. Management of the symptoms can include palliative surgery, nasogastric tube suction together with intravenous fluids, or pharmacological means, such as corticosteroids. There is uncertainty regarding both the efficacy and possible harmful effects of corticosteroids, and also the most effective type, dose/dosing regime, route and period of administration. OBJECTIVES: To locate, appraise and summarise evidence from scientific studies on intestinal obstruction due to advanced gynaecological and gastrointestinal cancer, in order to assess the efficacy of corticosteroids. SEARCH STRATEGY: A comprehensive list of all studies was provided by an extensive search of the electronic databases, relevant journals, reference lists, the grey literature, contact with investigators and other search strategies outlined in the methods. SELECTION CRITERIA: As the review concentrates on the 'best evidence' available of the role of corticosteroids in malignant bowel obstruction due to advanced gynaecological and gastrointestinal cancer the inclusion criteria were kept fairly broad so as to include all studies relevant to the question DATA COLLECTION AND ANALYSIS: Data extraction forms were used to collect data from the studies included in the review. The data was checked by a secondary searcher to reduce error. A qualitative analysis was performed of the dichotomous data of resolution of obstruction and death at one month, obtained from the randomised controlled trials of corticosteroids versus placebo. Both fixed and random effect models were used. Number needed to treat (NNT) was derived from the odds ratio. Kaplan-Meier survival curves from individual patient data were also analysed. Studies of lower methodological quality were assessed in a qualitative manner. MAIN RESULTS: Three unpublished, randomised, placebo, double blind controlled trials and seven published (prospective and retrospective) trials were considered eligible. Using only the randomised trials, there is a trend, which is not statistically significant, for the resolution of bowel obstruction using corticosteroids. There is no statistically significant difference in mortality at one month, nor in the Kaplan-Meier curves, which describe the survival of patients on corticosteroids or placebo. Number needed to treat is 6 (3, infinity) ie six patients need to be treated with corticosteroids to resolve one episode of bowel obstruction. The results are robust to fixed and random effects models and to 'best' and 'worst case' scenarios on the missing data from patients. The morbidity associated with corticosteroids appears to be very low, though the quality of the data limits this conclusion. No other outcomes were available from the published data or from the authors. REVIEWER'S CONCLUSIONS: There is a trend for evidence that corticosteroids of dose range 6-16 mg dexamethasone given intravenously may bring about the resolution of bowel obstruction. Equally, the incidence of side effects in all the included studies is extremely low. Corticosteroids do not seem to affect the length of survival of these patients.

Female↗
PubMed2000

Surgery for the resolution of symptoms in malignant bowel obstruction in advanced gynaecological and gastrointestinal cancer.

BACKGROUND: Intestinal obstruction commonly occurs in progressive advanced gynaecological and gastrointestinal cancers. Management of these patients is difficult due to the patients deteriorating mobility and function (performance status), the lack of further chemotherapeutic options and the high mortality and morbidity associated with palliative surgery. There are marked variations in clinical practice concerning surgery in these patients between different countries, gynaecological oncology units, and general hospitals as well as referral patterns from oncologists under whom these patients are often admitted under. There is therefore a need for all the present information to be collated, analysed (with appropriate palliative care outcomes) to establish if surgery is of benefit and what further research is needed. OBJECTIVES: The objective was to locate, appraise and summarise evidence from scientific studies on intestinal obstruction due to advanced gynaecological and gastrointestinal cancer, in order to assess the efficacy of surgery. SEARCH STRATEGY: A comprehensive list of studies was provided by an extensive search of electronic databases, relevant journals, bibliographic databases, conference proceedings, reference lists, the grey literature, personal contact and the world wide web. SELECTION CRITERIA: As the review concentrates on the 'best evidence' available of the role of surgery in malignant bowel obstruction in advanced gynaecological and gastrointestinal cancer the inclusion criteria were kept broad (included both prospective and retrospective studies) so as to include all studies relevant to the question. DATA COLLECTION AND ANALYSIS: Data extraction forms were used to collect data from the studies included in the review. Two researchers extracted the data independently to reduce error. Due to the methodological quality of the studies, only a qualitative assessment was possible. MAIN RESULTS: The role of surgery in malignant bowel obstruction remains controversial, and no firm conclusions from the many retrospective case series can be made. Control of symptoms varies from 42% to over 80%, though it is often unclear how symptoms were measured and whether the tools used to collect symptom scores are validated. There is a large range in the rates of re-obstruction, from 10-50%, though time to re-obstruction was often not included. There is a wide range of postoperative morbidity and mortality, although again the definition of both these surgical outcomes varied between many of the papers. REVIEWER'S CONCLUSIONS: The role of surgery in malignant bowel obstruction needs careful evaluation, using validated outcome measures of symptom control and quality of life scores. Further information would include re-obstruction rates together with the morbidity associated with the various surgical procedures. Currently, bowel obstruction is managed empirically, and there are marked variations in clinical practice by different units. There needs to be a greater standardisation of management so that comparisons between different series can be made.

Female↗
PubMed1999

Systematic review of surgery in malignant bowel obstruction in advanced gynecological and gastrointestinal cancer. The Systematic Review Steering Committee.

OBJECTIVE: The objective was to locate, appraise, and summarize evidence from scientific studies on intestinal obstruction due to advanced gynecological and gastrointestinal cancer in order to assess the efficacy of surgery. MATERIALS AND METHODS DATA SOURCES: A comprehensive list of studies was provided by an extensive search of electronic databases, relevant journals, bibliographic databases, conference proceedings, reference lists, the gray literature, personal contact, and the worldwide web. DATA SYNTHESIS: Two researchers extracted the data independently. Due to the methodological quality of the studies, only a qualitative assessment was possible. RESULTS: The role of surgery in malignant bowel obstruction remains controversial, and no firm conclusions from the many retrospective case series can be made. Control of symptoms varies from 42% to over 80%, although it is often unclear how symptoms were measured and whether the symptom scores used are validated. There is a large range in the rates of reobstruction, from 10 to 50%, although time to reobstruction was often not included. There is a wide range of postoperative morbidity and mortality, although again the definition of both of these surgical outcomes varied among many of the papers. CONCLUSION: The role of surgery in malignant bowel obstruction needs careful evaluation, using validated outcome measures on symptom control and quality of life scores. Further information would include reobstruction rates together with the morbidity associated with the various surgical procedures. Currently, bowel obstruction is managed empirically, and there are marked variations in clinical practice by different units. There needs to be a greater standardization of management so that comparisons between different series can be made.

Female↗
PubMed1999

Systematic review and meta-analysis of corticosteroids for the resolution of malignant bowel obstruction in advanced gynaecological and gastrointestinal cancers. Systematic Review Steering Committee.

BACKGROUND: The objective was to locate, appraise and summarise evidence from scientific studies on intestinal obstruction due to advanced gynaecological and gastrointestinal cancers, in order to assess the efficacy of corticosteroids. MATERIALS AND METHODS. DATA SOURCES: A comprehensive list of studies was provided by an extensive search of electronic databases, relevant journals, bibliographic databases, conference proceedings, reference lists, the grey literature, personal contact and the world wide web. DATA SYNTHESIS: Two researchers extracted the data independently. A qualitative analysis was performed of the dichotomous data of resolution of obstruction and death at one month. Both fixed and random effect models were used. Number needed to treat (with corticosteroids to resolve one episode of bowel obstruction) was derived from the odds ratio. Kaplan-Meier survival curves from individual patient data were also analysed. Studies of lower methodological quality were assessed in a qualitative manner. RESULTS: There is a trend towards resolution of bowel obstruction using corticosteroids but this result does not achieve statistical significance. There is no statistically significant difference in mortality at one month, nor in the Kaplan Meier survival curves. Number needed to treat is 6, though with wide confidence intervals (3-infinity). The results are robust to fixed and random effects models and to 'best' and 'worst case' scenarios on the data from missing patients. The morbidity associated with corticosteroids appears to be very low. CONCLUSIONS: The role of corticosteroids needs further elucidation. More patients need to be recruited in order to obtain more precise results. Further trials should include quality of life measures as primary outcomes as well as most effective type of corticosteroid, dose or dosing regime, route of administration and morbidity.

Adrenal Cortex Hormones↗
PubMed1996

Ketamine injection used orally.

Ketamine has been used parenterally for pain unresponsive to opioids, including neuropathic pain, and has also been used as an alternative analgesic agent after surgery. Although oral administration of ketamine has been used for some time as a single dose, it has not been given by this route on a regular basis. The use of ketamine administered orally is described for two patients with severe neuropathic pain who were intolerant of, or whose pain was unrelieved by, more commonly used agents. Pain relief was achieved without significant side effects.

Administration, Oral↗
PubMed1995

The role of embolization in palliative care.

Transcatheter arterial embolization (TCAE) is a well recognized radiological technique that has been used for over 25 years. It is a method of diminishing blood flow through selected vessels by inserting haemostatic material under angiographic control. The procedure is performed under local anaesthetic through a femoral or, occasionally, an axillary approach. We present our experience of the use of TCAE in the management of pain and haemorrhage in three hospice inpatients in whom other options had been exhausted. The use of TCAE as a technique for the palliation of these symptoms in the hospice setting is discussed.

Adenocarcinoma, Follicular↗