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Biomedical subjects

S Ahmedzai

Publications and source records attributed to S Ahmedzai.

At least 19 recordsLinked to original sources

Supportive care for patients with gastrointestinal cancer.

BACKGROUND: Supportive care has traditionally been given to optimise the comfort of patients and their ability to function, as well as to minimise the side-effects of anti-cancer treatments. The scope of modern comprehensive supportive care however is broadening and covers not only specific palliative treatment but non-tumour specific treatment such as social, psychological and spiritual support. In oncology, best supportive care (BSC) has been used as a comparator arm of randomised controlled trials in chemotherapy. However the BSC arm is usually not well defined and its evaluation is therefore difficult because of the heterogeneity of the definitions. A systematic review was undertaken of the evidence from all RCTs of gastrointestinal cancers (includes gastrointestinal/gastric, colorectal/colon cancer but excludes pancreatic cancer trials) which include a BSC/SC arm. OBJECTIVES: 1. To examine the effectiveness/outcomes of best supportive care interventions versus cancer therapies for gastrointestinal cancer trials;2. To determine whether trials containing best supportive care include a definition of this. SEARCH STRATEGY: Electronic databases, grey literature sources, citation searching and reference checking, handsearches of journals and discussion with experts were used to identify potentially eligible trials from both published and unpublished sources. SELECTION CRITERIA: RCTs comparing BSC/SC versus anticancer therapies in patients with gastrointestinal cancers. DATA COLLECTION AND ANALYSIS: Four RCTs were found and reviewed. Because of the heterogeneity of studies, a meta-analysis was not attempted. Data was extracted from the included papers and the quality of each included study was assessed using the Jadad 1996 and Rinck 1997 methods of assessing the quality of RCTs. MAIN RESULTS: Data from four trials (483 patients) were included. Due to the heterogeneity of studies (in terms of populations studied, the interventions used, the variety of outcomes and assessments used) it was not possible to make direct comparisons between the studies. The primary outcome in all four trials was survival, in spite of patients with advanced/metastatic gastrointestinal cancer having a poor prognosis, and the interventions being primarily palliative. REVIEWERS' CONCLUSIONS: Overall the results show that for most of the trials included in this review, certain forms of chemotherapy plus supportive care improve both survival and quality of life in patients with gastrointestinal cancer (gastric and colorectal cancers) compared to receiving supportive care alone. Trials involving BSC/SC in patients with advanced gastrointestinal cancer require careful evaluation. Oncologists and researchers alike should strive for improvements in trial design and reporting. Future trials should focus on clearer definitions of supportive care. The EORTC definition of supportive care can be used as a guide. BSC/SC trials should use standardised validated outcome measures for symptom control, quality of life, toxicity and other useful palliative measures.

Gastrointestinal Neoplasms↗

Transdermal fentanyl versus sustained-release oral morphine in cancer pain: preference, efficacy, and quality of life. The TTS-Fentanyl Comparative Trial Group.

Cancer patients requiring strong opioid analgesia (n = 202; mean age, 61.5 years; range, 18-89 years; 55% men) were recruited from 38 United Kingdom palliative care centers into a randomized, open, two-period, crossover study comparing transdermal fentanyl with sustained-release oral morphine. Patients received one treatment for 15 days followed immediately by the other for 15 days. Daily diaries were completed. Both treatments appeared equally effective in terms of pain control, as assessed by the Memorial Pain Assessment Card and European Organization for Research and Treatment of Cancer (EORTC) pain scores. Fentanyl was associated with significantly less constipation (p < 0.001) and less daytime drowsiness (p = 0.015) but greater sleep disturbance (p = 0.004) and shorter sleep duration (p = 0.008) than morphine. The World Health Organization (WHO) performance status and EORTC global quality of life scores showed no significant difference between treatment groups. Of those patients who were able to express a preference (n = 136), significantly more preferred the fentanyl patches (p = 0.037). We conclude that, in this study, transdermal fentanyl provided pain relief that was acceptable to cancer patients and was associated with less constipation and sedation than morphine. These reduced side effects may contribute to patients preference for the patches.

Administration, Cutaneous↗

New approaches to pain control in patients with cancer.

Pain affects most patients with malignant disease, and the prevalence of severe pain increases in the advanced stages of the condition. One in 5 patients with cancer has uncontrolled pain, even after 10 years of the use of the World Health Organization programme for cancer pain control and its 'three-step ladder' for the rational use of analgesics including morphine. Morphine has long been the 'gold standard' for the treatment of severe cancer pain. However, its side-effects, particularly sedation, cognitive impairment and myoclonus at high doses, have provoked the use of 'opioid rotation' to alternatives such as methadone and hydromorphone. The new 72-h transdermal patch for fentanyl also offers advantages of reduced side-effects and increased convenience over oral morphine. Intravenous strontium-89 and bisphosphonate therapy are effective for both short- and long-term control of metastatic bone pain. The spinal N-methyl-D-aspartate (NMDA) receptor is important in modulating the plasticity of the central nervous system and in aggravating chronic pain through the phenomenon of 'wind-up'. The NMDA antagonist ketamine, an anaesthetic, can be used at low doses for the management of refractory and neuropathic pains. Among adjuvant drugs, ketorolac has emerged as a potent non-steroidal anti-inflammatory drug. Palliative care is gaining acceptance as a new discipline in healthcare. Its strategic role is being reviewed as an adjunct to cancer therapy at all stages and its use is no longer confined to the terminal phase of disease after curative treatment has failed. Pain control and other aspects of symptom control are, therefore, viewed as an integral part of cancer management.

Humans↗

Current strategies for pain control.

Pain is the most feared symptom for patients diagnosed with cancer. Although our understanding of cancer pain and its management has greatly improved in the past decade, an unacceptably large proportion of patients still do not receive adequate pain relief. Before commencing any form of treatment, patients must receive a thorough assessment in order to define the pain, causes and severity. The recommendations for progressing a patient from step 2 to step 3 of the WHO analgesic ladder are discussed here as well as the choice of strong opioid substitution. An overview of the benefits of considering alternative routes of administering strong opioids, such as the transdermal delivery of fentanyl (TTS fentanyl), and the use of opioid substitution in patients intolerant to the adverse effects of morphine are also included. Finally, newer approaches to relieving refractory pain, such as neuropathic and bone pain, are considered.

Analgesics, Non-Narcotic↗

Xerostomia--a review.

Xerostomia, or dry mouth, is a very common symptom amongst the terminally ill and can have profound negative effects on patients' quality of life. Yet, it is often considered trivial and therefore tends to be neglected and ignored. This review examines the pathophysiology, aetiology and methods of assessing xerostomia and its effects and discusses its management, with particular emphasis upon palliation. If xerostomia is managed sensitively and effectively, it is possible to improve patients' comfort and sense of well-being and so improve overall care.

Humans↗

Recent clinical trials of pain control: impact on quality of life.

The understanding and treatment of pain is one of the oldest challenges for physicians, scientists and philosophers. Much of our present rationale of pain control is based on the Cartesian idea that pain mostly originates from external or internal noxious stimuli, which are transmitted to and interpreted in the brain. Consequently, removal (blocking) of the stimuli and modification of cerebral awareness have been the prime targets of analgesic interventions. Only recently has the relationship between pain and other physical, psychological and social aspects of illness been considered in the overall management plan. Most of the literature on pain control reveals the physical bias of measurement. Apart from simple but reliable tools such as visual analogue scales and Likert-type verbal scales, more sophisticated measures such as multidimensional pain inventories have also been used when it is necessary to characterise pain more specifically. In clinical studies, it is usual to ask the patient to report on his own pain, although proxy measures such as mobility, performance status and analgesic consumption are also often used. The hospice concept of "total pain", in which the psychological, social, spiritual and other aspects are emphasised, has been influential in our new approach to pain measurement. Particularly when it is chronic and related to advancing disease as in metastatic cancer, pain can interact significantly with many facets of daily living. A holistic model of quality of life in such patients should, therefore, include a multidimensional or modular assessment of these areas. Medical interventions themselves can affect quality of life in both positive and negative ways. Some side-effects may be so common as to be accepted as "normal", e.g. constipation or sedation with opioids: it is only by their careful evaluation, when comparing opioids with essentially similar analgesic potentials, that differential toxicities may be revealed. Simple recording of physical side-effects of drugs is really not sufficient, because analgesics as well as other therapies may be associated with mood changes and broader consequences for quality of life. Only in the past few years has quality of life been seriously addressed in palliation research. For example, standardised quality of life scales are now included almost routinely in oncological studies involving radiotherapy or chemotherapy by the Medical Research Council (MRC) of Great Britain. Trials of the new biphosphonates, which can reduce bone pain in metastatic cancer, have been enhanced by incorporating quality of life measures. Based on the experience from earlier efficacy/safety studies with the new transdermal route of drug delivery for the opioid fentanyl, important areas of life such as sleep and cognitive function have been addressed. Randomised controlled trials of analgesics which include quality of life endpoints are still rare, but should be encouraged as these represent the most rigorous way of evaluating new therapies. The current preoccupation with quality assurance in healthcare is directed, ultimately, to the delivery of a better quality of care, which should also be more cost-effective, for large populations. An important intermediate step towards that ideal is the collection of data on pain and other symptoms, but also validated quality of life parameters on well-defined groups. Only by widening the scope of analgesic studies to include these dimensions can we hope to define appropriate strategies for more rational healthcare.

Clinical Trials as Topic↗

A regional survey of opioid use by patients receiving specialist palliative care.

A study was conducted to determine the patterns of opioid use in patients under the care of specialist palliative care (SPC) teams in Trent Region, both in the community and in inpatient settings. The design was a survey of point prevalence by case note and drug chart review. The case notes and prescription records of 1007 patients were reviewed, and data collected on age, sex, diagnosis, date of referral, care settings, opioid form and dose on referral, and most recent opioid form and dose. Nine hundred and seventy patients had cancer; their ages ranged from 18 to 98 years (mean 66.5; median 69). Care was delivered by community specialist nurse for 39%, hospice daycare (DC) for 31%, hospice based homecare for 11%, hospice inpatient unit (IPU) for 15%, hospice outpatient (OP) for 5%, and other for 0.5%. There was no record of medication in 2% of the notes. No opioids had been prescribed for 43% of patients (range 24% IPU to 49% DC), 10% of patients were using weak opioids only (range 0.9% IPU to 16% OP), and 45% of patients were using strong opioids (range 39% DC to 75% IPU), the majority being on morphine (87% of total strong opioids). Daily oral morphine equivalence (OME) dosages ranged form 0.4 mg to 3600 mg (mean 166; median 60; mode 60). Dose changes under SPC ranged from -780 mg to +3900 mg OME, 42% patients having had no change in their dosage and 15% having reduced their opioid dose whilst under SPC. This survey challenges the popular impression that patients receiving SPC require large doses of morphine. The highest prevalence of potent opioid prescribing was in hospice IPUs, largely owing to the use of parenteral diamorphine. Conversely, IPUs had the lowest prevalence of weak opioids. Staff caring for patients with cancer must consider the need for downward as well as upward titration of opioid dosages.

Adolescent↗

Intracranial metastases from malignant pleural mesothelioma.

Although intracranial metastases from malignant pleural mesothelioma are rare, their presence should be suspected in cases of high-grade mesothelioma and should possibly be included in routine preoperative evaluation. An unusual case of cerebral metastases from pleural mesothelioma is presented and the literature is reviewed.

Brain Neoplasms↗

The EORTC QLQ-LC13: a modular supplement to the EORTC Core Quality of Life Questionnaire (QLQ-C30) for use in lung cancer clinical trials. EORTC Study Group on Quality of Life.

The EORTC Study Group on Quality of Life has developed a modular system for assessing the quality of life of cancer patients in clinical trials composed of two basic elements: (1) a core quality of life questionnaire, the EORTC QLQ-C30, covering general aspects of health-related quality of life, and (2) additional disease- or treatment-specific questionnaire modules. Two international field studies were carried out to evaluate the practicality, reliability and validity of the core questionnaire, supplemented by a 13-item lung cancer-specific questionnaire module, the EORTC QLQ-LC13. In this paper, the results of an evaluation of the QLQ-LC13 are reported. The lung cancer questionnaire module comprises both multi-item and single-item measures of lung cancer-associated symptoms (i.e. coughing, haemoptysis, dyspnoea and pain) and side-effects from conventional chemo- and radiotherapy (i.e. hair loss, neuropathy, sore mouth and dysphagia). It was administered to patients with non-resectable lung cancer recruited from 17 countries. In total, 883 and 735 patients, respectively, completed the questionnaire prior to and once during treatment. The symptom measures discriminated clearly between patients differing in performance status. All item scores changed significantly in the expected direction (i.e. lung cancer symptoms decreased and treatment toxicities increased) during treatment. With one exception (problems with a sore mouth), the change of toxicity measures over time was related specifically to either chemo- or radiotherapy. However, the single item on neuropathy did not measure adequately the full range of symptoms. The hypothesised scale structure of the questionnaire was partially supported by the data. The multi-item dyspnoea scale met the minimal standards for reliability (Cronbach alpha coefficient > 0.70), while the pain items did not form a scale with reliability estimates acceptable for group comparisons. In conclusion, the results form international field testing lend support to the EORTC QLQ-LC13 as a clinically valid and useful tool for assessing disease- and treatment-specific symptoms in lung cancer patients participating in clinical trials, when combined with the EORTC core quality of life questionnaire. In a few areas, however, the questionnaire module could benefit from further refinements. In addition, its performance over a longer period of time still needs to be investigated.

Adult↗

Experience with dipipanone elixir in the management of cancer related pain--case study.

The synthetic opioid dipipanone is infrequently used in the UK in the management of malignant pain, principally because of the inflexibility of the Diconal combination preparation (dipipanone 10 mg with cyclizine 30 mg). We present three patients in which dipipanone elixir proved to be their own drug of choice in the management of opioid responsive cancer pain, and our experience with 15 other patients. Dipipanone elixir was formulated 10 mg/5 ml, in single strength chloroform water.

Aged↗

The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology.

BACKGROUND: In 1986, the European Organization for Research and Treatment of Cancer (EORTC) initiated a research program to develop an integrated, modular approach for evaluating the quality of life of patients participating in international clinical trials. PURPOSE: We report here the results of an international field study of the practicality, reliability, and validity of the EORTC QLQ-C30, the current core questionnaire. The QLQ-C30 incorporates nine multi-item scales: five functional scales (physical, role, cognitive, emotional, and social); three symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality-of-life scale. Several single-item symptom measures are also included. METHODS: The questionnaire was administered before treatment and once during treatment to 305 patients with nonresectable lung cancer from centers in 13 countries. Clinical variables assessed included disease stage, weight loss, performance status, and treatment toxicity. RESULTS: The average time required to complete the questionnaire was approximately 11 minutes, and most patients required no assistance. The data supported the hypothesized scale structure of the questionnaire with the exception of role functioning (work and household activities), which was also the only multi-item scale that failed to meet the minimal standards for reliability (Cronbach's alpha coefficient > or = .70) either before or during treatment. Validity was shown by three findings. First, while all interscale correlations were statistically significant, the correlation was moderate, indicating that the scales were assessing distinct components of the quality-of-life construct. Second, most of the functional and symptom measures discriminated clearly between patients differing in clinical status as defined by the Eastern Cooperative Oncology Group performance status scale, weight loss, and treatment toxicity. Third, there were statistically significant changes, in the expected direction, in physical and role functioning, global quality of life, fatigue, and nausea and vomiting, for patients whose performance status had improved or worsened during treatment. The reliability and validity of the questionnaire were highly consistent across the three language-cultural groups studied: patients from English-speaking countries, Northern Europe, and Southern Europe. CONCLUSIONS: These results support the EORTC QLQ-C30 as a reliable and valid measure of the quality of life of cancer patients in multicultural clinical research settings. Work is ongoing to examine the performance of the questionnaire among more heterogenous patient samples and in phase II and phase III clinical trials.

Activities of Daily Living↗