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Biomedical subjects

C Badger

Publications and source records attributed to C Badger.

At least 19 recordsLinked to original sources

Physical therapies for reducing and controlling lymphoedema of the limbs.

BACKGROUND: Lymphoedema is the accumulation of excess fluid in the body caused by obstruction of the lymphatic drainage mechanisms. Management involves decongesting the reduced lymphatic pathways in order to reduce the size of the limb. There is a great deal of debate as to which components of a physical treatment programme are the most crucial. OBJECTIVES: To assess the effect of physical treatment programmes on: volume, shape, condition and long-term control of oedema in lymphoedematous limbs; psycho-social benefits. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group trials register (September 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4,2003), MEDLINE, EMBASE, CINAHL, UnCover, PASCAL, SIGLE, reference lists produced by The British Lymphology Society, the National Research Register (NRR) and The International Society of Lymphology congress proceedings. SELECTION CRITERIA: Randomised controlled clinical trials that tested physical therapies with a follow-up period of at least six months. DATA COLLECTION AND ANALYSIS: Two blinded reviewers independently assessed trial quality and extracted data . Meta-analysis was not performed due to the poor quality of the trials. MAIN RESULTS: Only three studies involving 150 randomised patients were included. Since none studied the same intervention it was not possible to combine the data. One crossover study of manual lymph drainage (MLD) followed by self-administered massage versus no treatment, concluded that improvements seen in both groups were attributable to the use of compression sleeves and that MLD provided no extra benefit at any point during the trial. Another trial looked at hosiery versus no treatment and had a very high dropout rate, with only 3 out of 14 participants in the intervention group finishing the trial and only 1 out of 11 in the control group. The authors concluded that wearing a compression sleeve is beneficial. The bandage plus hosiery versus hosiery alone trial, concluded that in this mixed group of participants bandage plus hosiery resulted in a greater reduction in excess limb volume than hosiery alone and this difference in reduction was maintained long-term. REVIEWERS' CONCLUSIONS: All three trials have their limitations and have yet to be replicated, so their results must be viewed with caution. There is a clear need for well-designed, randomised trials of the whole range of physical therapies if the best approach to managing lymphoedema is to be determined.

Bandages↗

Benzo-pyrones for reducing and controlling lymphoedema of the limbs.

BACKGROUND: Lymphoedema is the accumulation of excess fluid in the body caused by obstruction of the lymphatic drainage mechanisms. It can be caused by a number of factors, including congenital predisposition, parasitic infection or surgery. Lymphoedema is chronic and progressive and affects a significant proportion of the population. The standard treatment regimes include compression hosiery, skin care and exercise. The use of drugs in treatment, particularly benzo-pyrones, has gained favour over the last ten years. Benzo-pyrones, originally developed for use in vascular medicine, are prescribed to reduce vascular permeability and thus the amount of fluid forming in the subcutaneous tissues. Advocates for this treatment method believe that, as a result of reducing filtration, the drugs have some beneficial effect on pain and discomfort in the swollen areas. Proponents also claim that these drugs increase macrophage activity, encouraging the lysis of protein, which in turn reduces the formation of fibrotic tissue in the lymphoedematous limb. OBJECTIVES: To assess the effectiveness of benzo-pyrones compared to placebo or to different benzo-pyrones in reducing limb volume, pain and discomfort in lymphoedematous limbs. To assess the effect of benzo-pyrones on the quality of affected tissues and on the patient's quality of life and, finally, to establish the incidence of adverse effects SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group register (September 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4,2003), MEDLINE, EMBASE, CINAHL, UnCover, PASCAL, SIGLE, reference lists produced by The British Lymphology Society, the National Research Register (NRR) and The International Society of Lymphology congress proceedings. SELECTION CRITERIA: Types of studies considered for review were randomised controlled trials testing Paroven, coumarin, Venastat, Cyclo 3 Fort or Daflon versus placebo (with both groups having or not having standard physical treatment DATA COLLECTION AND ANALYSIS: Eligibility for inclusion was confirmed by two blinded reviewers who screened the papers independently using a checklist of criteria relating to the randomisation and blinding of the trial. Both reviewers extracted data from the eligible studies using a data extraction form. MAIN RESULTS: Overall, 15 trials were included that evaluated the role of benzo-pyrones. Three trials of oxerutin were found. Each tested the drug over 6 months using the same dose of drug against placebo. Two were crossover trials and one a parallel group trial with a total number of 127 participants and data available for only 81 of them. There were insufficient data provided in any of the trials to calculate the per cent reduction or increase in baseline excess limb volume. Standard deviations or confidence intervals and the numbers in the groups at the different stages of the trial were missing for all the data in two of the reports and for much of the data in the third, making any attempt at meta-analysis impossible. One trial testing Cyclo 3 Fort (approved name) over 3 months was found and involved 57 patients but provided insufficient data to allow a proper analysis of its findings. A single trial of Daflon (approved name) was found, lasting 6 months and involving 104 participants; once again there was insufficient information provided in the report to reach a conclusion about the effectiveness of the drug. Three trials of coumarin combined with troxerutin were found and tested two different doses of the drug against each other with no placebo, however, numbers of participants in the trial groups and baseline data were not provided. Eight trials of coumarin were identified. Two of the reports were confirmed as reporting the same trial and a further trial potentially also referred to the same trial but this was unconfirmed. A further two papers appeared to refer to the same trial but this was not confirmed. Three trials involved the same researcher. Five studies were conducted in India or China and they added anti-filarial dia or China and they added anti-filarial drugs to the interventions tested. The numbers of participants withdrawn and the numbers included in the analyses in all these trials were not extractable; the reporting of outcome measures in most of the trials was not clear. Loprinzi's 1999 trial in the USA reported the conduct of the trial and its findings with more detail, however, its conclusions were very much at odds with the findings of the other trials, finding that no difference was observed between those on the active preparation (coumarin) and placebo in any of the outcomes under investigation. This trial also reported a case of hepato-toxicity in a patient receiving the active preparation. REVIEWERS' CONCLUSIONS: Meta-analysis was not performed due to the poor quality of the trials. It is not possible to draw conclusions about the effectiveness of Benzopyrones in reducing limb volume, pain, or discomfort in lymphoedematous limbs from these trials.

Anticoagulants↗

Antibiotics / anti-inflammatories for reducing acute inflammatory episodes in lymphoedema of the limbs.

BACKGROUND: Lymphoedema is a chronic and progressive condition and current debate revolves around the best course of management for infective/inflammatory episodes. OBJECTIVES: To determine whether antibiotic/anti-inflammatory drugs given prophylactically reduce the number and severity of infective/inflammatory episodes in patients with lymphoedema. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group register in September 2003, the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), CINAHL, MEDLINE, PASCAL, SIGLE, UnCover, reference lists produced by The British Lymphology Society, the National Research Register (NRR) and the International Society of Lymphology congress proceedings. SELECTION CRITERIA: Types of studies considered for review were randomised controlled trials testing an antibiotic or anti-inflammatory drug against placebo (with or without physical therapies). DATA COLLECTION AND ANALYSIS: Eligibility for inclusion was confirmed by two blinded reviewers who screened the papers independently using a checklist of criteria relating to the randomisation and blinding of a trial. Both reviewers extracted data from the eligible studies using a data extraction form. MAIN RESULTS: Overall, four studies (364 randomised patients) were included. Two of these studied the effects of intensive physical treatment plus selenium or placebo in preventing AIE, and two studied the effects of Ivermectin, Diethylcarbamazine (DEC) (anti-filarial agents) and penicillin as prophylactic treatment for adeno lymphangitis(ADL) versus placebo. Both selenium trials reported no inflammatory episodes during the trial period in the treated group but one case of infection in the two placebo groups respectively during the first three weeks of each trial. Seven additional cases of infection in trial one and 14 cases in trial two required treatment in the three month follow up period. One anti filarial trial reported a total of 127 ADL episodes for all groups during the treatment year (compared with 684 episodes reported for the same participants during the pre-treatment year). Another 228 ADL episodes were reported during the trial follow-up year but no significant differences were found between the three groups. No apparent link was found between the grade of oedema and the frequency of ADL episodes. However, there was a significant link between increased episodes and the rainy season. In the penicillin group the mean number of inflammatory episodes was reduced from 4.6 to 0.5 after treatment and increased to 1.9 at the end of the follow-up year. REVIEWERS' CONCLUSIONS: The effectiveness of selenium in preventing AIE in lymphoedema remains inconclusive in the absence of properly conducted randomised controlled trials. Anti-filarials (DEC and Ivermectin) do not appear to reduce ADL episodes in filarial lymphoedema. Foot care may be important in reducing ADL episodes, and penicillin appears to contribute to a significant reduction in ADL, when combined with foot-care. It seems reasonable to emphasise the importance of foot-care to patients and practitioners in preventing infection and this may also apply to care of the arm in women who develop lymphoedema following breast cancer treatment. However, properly conducted trials are needed to demonstrate any efficacy of these interventions.

Anti-Bacterial Agents↗

Lymphoedema: an underestimated health problem.

BACKGROUND: Lymphoedema/chronic oedema is an important cause of morbidity in the population, but little is known of its epidemiology and impact on patients or health services. AIM: To determine the magnitude of the problem of chronic oedema in the community, and the likely impact of oedema on use of health resources, employment and patient's quality of life. DESIGN: Questionnaire-based survey. METHODS: Health professionals from dedicated lymphoedema services, specific out-patient clinics, hospital wards and community services (GP clinics and district nurses) were contacted to provide information on patients from within South West London Community Trust. A subset of the identified patients was interviewed. RESULTS: Within the catchment area, 823 patients had chronic oedema (crude prevalence 1.33/1000). Prevalence increased with age (5.4/1000 in those aged > 65 years), and was higher in women (2.15 vs. 0.47/1000). Only 529 (64%) were receiving treatment, despite two specialist lymphoedema clinics within the catchment area. Of 228 patients interviewed, 78% had oedema lasting > 1 year. Over the previous year, 64/218 (29%) had had an acute infection in the affected area, 17/64 (27%) being admitted for intravenous antibiotics. Mean length of stay for this condition was 12 days, estimated mean cost pound 2300. Oedema caused time off work in > 80%, and affected employment status in 9%. Quality of life was below normal, with 50% experiencing pain or discomfort from their oedema. DISCUSSION: Chronic oedema is a common problem in the community with at least 100 000 patients suffering in the UK alone, a problem poorly recognized by health professionals. Lymphoedema arising for reasons other than cancer treatment is much more prevalent than generally perceived, yet resources for treatment are mainly cancer-based, leading to inequalities of care.

Adolescent↗

Non-invasive assessment of the lymphedematous limb.

Accurate assessment of the swollen limb is crucial to effective management, and usually consists of measurement of volume and assessment of skin condition. Here, we review the different methods available to measure volume, and their accuracy, together with other non-invasive methods available to assess the characteristics of the swelling. These include the measurement of fluid mobility by recording deformation of tissue by a mass (tonometry) and the step compression method; the measurement of truncal swelling by skinfold calipers; imaging techniques (magnetic resonance imaging, computed tomography, ultrasound) which provide information on size and other characteristics of the different tissue compartments; and measurement of impedance (amount of extracellular water and total water content). The varying quality of swelling, as well as its extent and distribution, indicates the need for objective methods of assessment other than simple limb volume measurement. Such detailed information should improve the understanding of peripheral lymphedema.

Anthropometry↗

A review of outcome indicators in the treatment of chronic limb oedema.

OBJECTIVES: To provide an overview of physical and psychological outcome indicators which have been used to evaluate conservative treatments for chronic oedema. METHODS OF FINDING PAPERS: Papers were located via the MedLine, CINAHL and GEARS databases, and the British Lymphology Interest Group Key References lists. ISSUES REVIEWED: The literature reveals that only a small amount of work has addressed conceptual issues in outcome evaluation. Above all, outcome indicators have been adopted in clinical practice in a haphazard manner, with little discussion regarding the purpose of outcome assessment/measurement and little agreement on the most appropriate assessment/measurement techniques. RESULTS: Eleven outcome indicators appear in the literature, each of which is discussed in terms of instrumentation and application in clinical practice. Practitioners have focused on objective measures, with change in limb volume the outcome measure most commonly used. CONCLUSION: It is concluded that more rigour is needed in many aspects of outcome evaluation. Practitioners and researchers in this field should become more questioning of existing evaluation practices, and should explore the many potential outcome indicators, such as limb movement and limb function, which have to date been neglected.

Chronic Disease↗

Pause for thought: nurses use research--don't they?

The issues surrounding nurses and their use of research are many and complex. Experience in a newly developing area of nursing--the management of lymphodema--has revealed three key reasons why nurses do not, on the whole, use the research process to answer clinical problems or use the results of research to change clinical practice. First, nurses tend not to see research as their own responsibility; secondly, they tend not to read on a regular basis; and finally, nurses are neither taught nor encouraged to think critically about what they do. The situation can be improved if senior nurses make a positive effort to foster an atmosphere of enquiry, report research findings in a language all can understand, and encourage fellow nurses in the pursuit of knowledge.

Clinical Nursing Research↗

Autologous bone marrow transplantation for acute lymphoblastic leukemia.

Between December 1979 and February 1991, 89 patients with ALL received autologous BMT. Median patient age was 18.4 years. Ten patients were in first remission, 52 were in second or greater remission and 27 were in relapse at the time of transplant. Conditioning regimens utilized chemotherapy alone (5 patients) or in combination with 10-15.75 Gy total body irradiation (84 patients). Disease-free survival at 1 year is 50% for patients transplanted in first remission, 27% for those in > or = second remission and 8% for patients in relapse. Pre- and post-transplant variables were evaluated in univariate and multivariate analyses for their effect on survival and relapse. Factors significantly associated with improved survival were being transplanted in first remission and achieving a self-sustained platelet count > or = 20 x 10(9)/l in a shorter period of time. A decreased relapse rate after transplant was associated with a lower white blood count at diagnosis, being transplanted in first remission and not being transplanted in relapse.

Adolescent↗

The use of colour Doppler to define venous abnormalities in the swollen arm following therapy for breast carcinoma.

Colour Doppler vascular mapping is a suitable alternative in patients for whom venography is a relative contraindication. The post mastectomy/radiotherapy swollen arm is one such situation where invasive tests could further compromise a disabling iatrogenic condition. Four patients are described in whom significant venous abnormalities were demonstrated using colour Doppler ultrasound. In three cases the information helped in patient management. The technique is safe with no risk of further compromising vascular drainage.

Adult↗

Effects of propylthiouracil on the biodistribution of an iodine-131-labeled anti-myeloid antibody in normal dogs: dosimetry and clinical implications.

Despite the use of near maximal doses of chemoradiotherapy, tumor recurrence remains the most frequent cause of treatment failure following marrow transplantation for leukemia. We have previously demonstrated that it is possible to selectively deliver radiation to the marrow space. In that study an initial short half-life of the radionuclide was observed. In this study we attempted to prolong the retention of the radioiodine in marrow through the use of propylthiouracil (PTU). When administered to normal dogs, PTU pretreatment resulted in improved marrow localization of 131I-labeled DM-5. There was no appreciable loss of activity from the marrow during the 2-4 hr postinjection time interval; a finding in contrast to the control animals where marrow activity declined a mean 45 +/- 0.5% over the same time period. Additionally, in contrast to controls, a rise in plasma trichloroacetic acid (TCA) nonprecipitable activity was not demonstrated in the PTU treated group during this 2-4 hr period. These results suggest that PTU's inhibition of deiodinases resulted in longer residence time of the radionuclide in its target tissue without adversely affecting distribution to non-target organs.

Animals↗

Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia.

To assess the influence of graft-versus-host disease (GVHD) on recurrent leukemia and survival after allogeneic marrow transplantation, we studied 1,202 patients with acute nonlymphocytic leukemia (ANL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML) given unmodified marrow grafts from HLA-identical siblings. Proportional hazards regression models using acute GVHD and chronic GVHD as time-dependent covariates demonstrated a significant association of GVHD with a decreased relative risk (RR, 0.33 to 0.42) of relapse in patients with ANL, ALL, and CML transplanted in advanced disease. Among patients developing either acute or chronic GVHD, treatment failure (that is, mortality or relapse) was decreased in patients with ALL transplanted in relapse (RR = 0.70, P less than .033) and CML in blast crisis (RR = 0.37, P less than .009). This effect was independent of age, sex, preparative regimen, GVHD prophylaxis, or length of follow-up. Five-year actuarial estimates were derived for the subset of 657 patients who survived in remission 150 days after transplant and were at risk for development of chronic GVHD. Among patients with ANL in first remission or CML in chronic phase, GVHD had an adverse effect on survival and no apparent influence on relapse. Among patients with ANL and ALL transplanted in relapse, the probability of relapse after day 150 was 74% without [corrected] GVHD, 45% with acute and chronic GVHD, 35% with [corrected] only acute GVHD, and 34% with only chronic GVHD (P less than .001). Actuarial survival in these four GVHD groups was 25%, 34%, 59%, and 62%, respectively (P less than .009). Among patients with CML in acceleration or blast crisis, the probability of relapse after day 150 was 65% without GVHD and 36% with acute and/or chronic GVHD (P less than .017). We conclude that acute and chronic GVHD were associated with a durable antileukemic effect and improved survival in patients transplanted in advanced stages of ALL and CML.

Bone Marrow Transplantation↗

Antibody-radionuclide conjugates as part of a myeloablative preparative regimen for marrow transplantation.

The behaviors of an anti-Ia antibody (7.2) and an antibody directed at a lymphocyte adhesion molecule (S.5) radiolabeled with 131I were studied in normal dogs. Antibody 7.2 localized to spleen and, to a lesser extent, to marrow and lymph nodes. Antibody S.5 rapidly localized to marrow and spleen, achieving tissue/blood ratios greater than 6:1 within three hours of injection that were maintained for at least 48 hours. Prior treatment with cyclophosphamide (CY) markedly altered the distribution of S.5 but had much less effect on the distribution of 7.2 and almost no effect on the distribution of a control antibody. When animals were treated with increasing doses of 131I labeled to S.5, lethal myelosuppression occurred when a dose of 6 mCi/kg was reached. At this dose, the otherwise lethal effects of 131I could be reversed with autologous marrow transplant support.

Animals↗

Specific marrow localization of an 131I-labeled anti-myeloid antibody in normal dogs: effects of a "cold" antibody pretreatment dose on marrow localization.

Tumor recurrence and regimen-related toxicity remain major obstacles in the successful use of marrow transplantation as therapy for hematologic malignancies. By attaching radionuclides to monoclonal antibodies (MoAbs) targeted at myeloid-associated antigenic determinants, a more effective and directed delivery of therapy may be possible without increasing toxicity. We investigated the biodistribution over time of an anti-myeloid antibody (DM-5) labeled with trace amounts of 131I in normal dogs. This study demonstrates the ability to target marrow with a high degree of selectivity, achieving marrow/blood ratios of 25-30:1 with the greatest concentration in any other organ being a tissue/blood ratio of 1.4:1 for stomach at 48 h. A pretreatment dose of unlabeled antibody effectively reduced early hepatic uptake by 80%, resulting in improved marrow localization with an estimated 58.6% of the injected dose localized in marrow within 2 h following infusion, compared to 32.8% without pretreatment. The marrow concentration clearance curve for the radioimmunoconjugate revealed an initial short half-life (4.75 h), suggesting rapid internalization, digestion, and release of free iodine (dehalogenation). This view was supported by a corresponding rise in trichloroacetic acid-non-precipitable activity during this period. Methods aimed at decreasing dehalogenation may result in longer residence time of the radionuclide within the marrow space, resulting in more effective tumor cell kill. This approach may provide a way to improve upon the current results obtained with marrow transplantation as treatment for patients with leukemia and other hematologic malignancies.

Animals↗

Allogeneic marrow transplantation for acute leukemia in relapse.

The results of allogeneic marrow transplantation in 75 patients with acute lymphoblastic leukemia and 63 patients with acute non-lymphoblastic leukemia in relapse are reviewed. The effects of various chemotherapeutic regimens added to the basic regimen of cyclophosphamide (Cy) 60 mg/kg given on each of two successive days followed by 1000 rad of total body irradiation (TBI) were evaluated. The regimens tested were dimethylbusulphan (DMB), 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU) and daunorubicin. Seventeen of 138 patients are alive between three and nine and a half years from transplantation. The addition of other chemotherapeutic agents to th basic Cy and TBI regimen did not decrease relapse frequency or prolong survival.

Adolescent↗