Interventions for actinic keratoses.

BACKGROUND: Actinic keratoses are a skin disease caused by long-term sun exposure, and their lesions have the potential to develop into squamous cell carcinoma. Treatments for actinic keratoses are sought for cosmetic reasons, for the relief of associated symptoms, or for the prevention of skin cancer development. Detectable lesions are often associated with alteration of the surrounding skin (field) where subclinical lesions might be present. The interventions available for the treatment of actinic keratoses include individual lesion-based (e.g. cryotherapy) or field-directed (e.g. topical) treatments. These might vary in terms of efficacy, safety, and cosmetic outcomes. OBJECTIVES: To assess the effects of topical, oral, mechanical, and chemical interventions for actinic keratosis. SEARCH METHODS: We searched the following databases up to March 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2010), and LILACS (from 1982). We also searched trials registers, conference proceedings, and grey literature sources. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the treatment of actinic keratoses with either placebo, vehicle, or another active therapy. DATA COLLECTION AND ANALYSIS: At least two authors independently abstracted data, which included adverse events, and assessed the quality of evidence. We performed meta-analysis to calculate a weighted treatment effect across trials, and we expressed the results as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes (e.g. participant complete clearance rates), and mean difference (MD) and 95% CI for continuous outcomes (e.g. mean reduction in lesion counts). MAIN RESULTS: We included 83 RCTs in this review, with a total of 10,036 participants. The RCTs covered 18 topical treatments, 1 oral treatment, 2 mechanical interventions, and 3 chemical interventions, including photodynamic therapy (PDT). Most of the studies lacked descriptions of some methodological details, such as the generation of the randomisation sequence or allocation concealment, and half of the studies had a high risk of reporting bias. Study comparison was difficult because of the multiple parameters used to report efficacy and safety outcomes, as well as statistical limitations. We found no data on the possible reduction of squamous cell carcinoma.The primary outcome 'participant complete clearance' significantly favoured four field-directed treatments compared to vehicle or placebo: 3% diclofenac in 2.5% hyaluronic acid (RR 2.46, 95% CI 1.66 to 3.66; 3 studies with 420 participants), 0.5% 5-fluorouracil (RR 8.86, 95% CI: 3.67 to 21.44; 3 studies with 522 participants), 5% imiquimod (RR 7.70, 95% CI 4.63 to 12.79; 9 studies with1871 participants), and 0.025% to 0.05% ingenol mebutate (RR 4.50, 95% CI 2.61 to 7.74; 2 studies with 456 participants).It also significantly favoured the treatment of individual lesions with photodynamic therapy (PDT) compared to placebo-PDT with the following photosensitisers: aminolevulinic acid (ALA) (blue light: RR 6.22, 95% CI 2.88 to 13.43; 1 study with 243 participants, aminolevulinic acid (ALA) (red light: RR 5.94, 95% CI 3.35 to 10.54; 3 studies with 422 participants), and methyl aminolevulinate (MAL) (red light: RR 4.46, 95% CI 3.17 to 6.28; 5 studies with 482 participants). ALA-PDT was also significantly favoured compared to cryotherapy (RR 1.31, 95% CI 1.05 to 1.64).The corresponding comparative risks in terms of number of participants completely cleared per 1000 were as follows: 313 with 3% diclofenac compared to 127 with 2.5% hyaluronic acid; 136 with 0.5% 5-fluorouracil compared to 15 with placebo; 371 with 5% imiquimod compared to 48 with placebo; 331 with ingenol mebutate compared to 73 with vehicle; 527 to 656 with ALA/MAL-PDT treatment compared to 89 to 147 for placebo-PDT; and 580 with ALA-PDT compared to 443 with cryotherapy.5% 5-fluorouracil efficacy was not compared to placebo, but it was comparable to 5% imiquimod (RR 1.85, 95% Cl 0.41 to 8.33).A significant number of participants withdrew because of adverse events with 144 participants affected out of 1000 taking 3% diclofenac in 2.5% hyaluronic acid, compared to 40 participants affected out of 1000 taking 2.5% hyaluronic acid alone, and 56 participants affected out of 1000 taking 5% imiquimod compared to 21 participants affected out of 1000 taking placebo.Based on investigator and participant evaluation, imiquimod treatment and photodynamic therapy resulted in better cosmetic outcomes than cryotherapy and 5-fluorouracil. AUTHORS' CONCLUSIONS: For individual lesions, photodynamic therapy appears more effective and has a better cosmetic outcome than cryotherapy. For field-directed treatments, diclofenac, 5-fluorouracil, imiquimod, and ingenol mebutate had similar efficacy, but their associated adverse events and cosmetic outcomes are different. More direct comparisons between these treatments are needed to determine the best therapeutic approach.

Rural surgeons' attitudes towards and usage of evidence-based medicine in rural surgical practice.

INTRODUCTION: Rural and remote surgical practice presents unique barriers to the uptake of the evidence-based medicine (EBM) paradigm. As medical and education institutions around Australia develop practices and support for EBM, there are growing questions about how EBM is situated in the rural and remote context. The Monash University Department of Surgery at Monash Medical Centre implemented a study to explore the current understandings, attitudes and practices of rural surgeons towards the EBM paradigm. METHODS: Descriptive survey of rural surgeons based in a tertiary care environment. RESULTS: The overall results of the survey demonstrate that: (1) rural surgeons have a good understanding of EBM; (2) EBM evidence is somewhat useful but not very important to clinical decision making; and (3) while rural surgeons are relatively confident in most sources listed, they are most confident in their own judgment and clinical practice guidelines, and least confident in telephone contact with colleagues. Rural surgeons' understanding, usage and confidence in EBM purports that rural surgeons have contradictory, ambivalent and complex views of the EBM paradigm and its place in rural surgical practice. DISCUSSION: Professional isolation and context specificity are important to consider when extending the EBM paradigm to rural surgical practice and understanding the EBM uptake in the rural surgery context.

Lung diffusing capacity in adult bronchiectasis: a longitudinal study.

BACKGROUND: Recent studies described a progressive decline in lung volumes in adult bronchiectasis. Interstitial lung disease is also a feature of bronchiectasis, but whether this is associated with a decline in lung diffusing capacity (measured as the diffusing capacity of the lung for carbon monoxide [D(LCO)]) is not well known. OBJECTIVE: To assess longitudinal decline in diffusing capacity of the lung for carbon monoxide (D(LCO)) in adult bronchiectasis. METHODS: Sixty-one subjects had a detailed baseline clinical and laboratory assessment, then were followed regularly with clinical and lung-function assessment for a median 7 years. RESULTS: Baseline spirometry demonstrated mild obstructive lung disease, with a mean FEV(1) of 72% of predicted, mean forced vital capacity 87% of predicted, and normal D(LCO) (mean D(LCO) 88% of predicted, and mean D(LCO) adjusted for alveolar volume [D(LCO)/V(A)] 100% of predicted). There was an accelerated decline in D(LCO) and D(LCO)/V(A) over the 7-year period. The median D(LCO) decline was 2.9% of predicted per year (95% CI 2.3-4.1% of predicted per year). The median D(LCO)/V(A) decline was 2.4% of predicted per year (95% CI 2.1-4.0% of predicted per year). There was a significant relationship between D(LCO) decline and age and decline in FEV(1). CONCLUSIONS: In our cohort of patients with bronchiectasis there was a progressive D(LCO) decline.

Botulinum toxin A as an adjunct to treatment in the management of the upper limb in children with spastic cerebral palsy (UPDATE).

BACKGROUND: Cerebral palsy (CP) is "a group of permanent disorders of the development of movement and posture causing activity limitation(s) that are attributed to non-progressive disturbance that occurred in the developing fetal or infant brain" (Rosenbaum 2007, p.9). The spastic motor type is the most common form of CP. Therapeutic management may include splinting/casting, passive stretching, facilitation of posture/movement, spasticity-reducing medication and surgery. Botulinum toxin-A (BoNT-A) is now used as an adjunct to these techniques in an attempt to reduce spasticity, improve range of movement and function. OBJECTIVES: To assess the effectiveness of injections of BoNT-A or BoNT-A and occupational therapy in the treatment of the upper limb in children with CP. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register/CENTRAL (The Cochrane Library, Issue 3, 2008), MEDLINE (1966 to August Week 1 2008), EMBASE (1980 to 2008 Week 28) and CINAHL (1982 to August Week 1 2008). SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing BoNT-A injection or BoNT-A injection and occupational therapy in the upper limb(s) with other types of treatment (including no treatment or placebo) in children with CP. DATA COLLECTION AND ANALYSIS: Two authors using standardised forms extracted the data independently. Each trial was assessed for internal validity and rated for quality using the PEDro scale. Data were extracted and entered into RevMan 5.0.15. MAIN RESULTS: Ten trials met the inclusion criteria. PEDro quality ratings ranged from 6/10 to 10/10. Concentration of BoNT-A ranged from 50U/1.0ml to 200U/1.0ml saline with doses of 0.5U to 16U/kg body weight and total doses of 220 to 410 Units (Botox(R)).A combination of BoNT-A and occupational therapy is more effective than occupational therapy alone in reducing impairment, improving activity level outcomes and goal achievement, but not for improving quality of life or perceived self-competence. When compared with placebo or no treatment, there is moderate evidence that BoNT-A alone is not effective. AUTHORS' CONCLUSIONS: This systematic review found high level evidence supporting the use of BoNT-A as an adjunct to managing the upper limb in children with spastic CP. BoNT-A should not be used in isolation but should be accompanied by planned occupational therapy.Further research is essential to identify children most likely to respond to BoNT-A injections, monitor longitudinal outcomes, determine timing and effect of repeated injections and the most effective dosage, dilution and volume schedules. The most effective adjunct therapies including frequency and intensity of delivery also requires investigation.

Phenotypes of adult bronchiectasis: onset of productive cough in childhood and adulthood.

Bronchiectasis is a heterogeneous disorder with a large number of etiologic factors. The main symptom is a chronic productive cough. The aim of this study was to describe the phenotypes of patients with bronchiectasis who had developed a chronic productive cough in childhood (before 16 years of age) compared with those who had developed a productive cough as adults. One hundred and eighty-two subjects with bronchiectasis diagnosed by computed tomography scanning were studied. Subjects all had a detailed clinical review and assessment of potential etiologic factors performed by the investigators. There were 107 (59%) subjects who developed a chronic productive cough in childhood and 75 (41%) subjects who developed a chronic productive cough in adulthood. There were significant differences in a number of parameters between the two groups including duration of cough, frequency of exacerbations, presence of rhinosinusitis, crackles on examination and lung function. The adult group could be further divided into those who had developed a cough whilst smoking and those who had no obvious relationship with smoking. In conclusion there were a number of significant differences between the child onset and adult onset group that may reflect different phenotypes of bronchiectasis.

The 2003 Australian Breast Health Survey: survey design and preliminary results.

BACKGROUND: The Breast Health Surveys, conducted by the National Breast Cancer Centre (NBCC) in 1996 and 2003, are designed to gain insight into the knowledge, attitudes and behaviours of a nationally representative sample of Australian women on issues relevant to breast cancer. In this article, we focus on major aspects of the design and present results on respondents' knowledge about mammographic screening. METHODS: The 2003 BHS surveyed English-speaking Australian women aged 30-69 without a history of breast cancer using computer-assisted telephone interviewing. Questions covered the following themes: knowledge and perceptions about incidence, mortality and risk; knowledge and behaviour regarding early detection, symptoms and diagnosis; mammographic screening; treatment; and accessibility and availability of information and services. Respondents were selected using a complex sample design involving stratification. Sample weights against Australian population benchmarks were used in all statistical analyses. Means and proportions for the entire population and by age group and area of residence were calculated. Statistical tests were conducted using a level of significance of 0.01. RESULTS: Of the 3,144 respondents who consented to being interviewed, 138 (4.4%) had a previous diagnosis of breast cancer and were excluded leaving 3,006 completed interviews eligible for analysis. A majority of respondents (61.1%) reported ever having had a mammogram and 29.1% identified mammography as being the best way of finding breast cancer. A majority of women (85.9%) had heard of the BreastScreen Australia (BSA) program, the national mammographic screening program providing free biennial screening mammograms, with 94.5% believing that BSA attendance was available regardless of the presence or absence of symptoms. There have been substantial gains in women's knowledge about mammographic screening over the seven years between the two surveys. CONCLUSION: The NBCC Breast Health Surveys provide a valuable picture of the knowledge of Australian women about a range of issues. The present analysis shows significant gains in knowledge and behaviours relating to mammographic screening, while identifying additional areas for targeted improvement, as in the need to better communicate with women about screening and diagnostic services. Further analysis of additional core topic areas (eg., incidence, mortality, risk and treatment) will provide equally noteworthy insight.

An evaluation of methods used in health technology assessments produced for the Medical Services Advisory Committee.

OBJECTIVE: To examine the methods used in health technology assessments (HTAs) produced for the Medical Services Advisory Committee (MSAC) reviewing the effectiveness of a technology or procedure. DESIGN AND SETTING: Data were extracted from the effectiveness section of HTA application assessment reports published between 1 January 1998 and 17 July 2006 and available on the MSAC website. Only HTAs of effectiveness interventions were examined, as the methods used to undertake such reviews are well established. MAIN OUTCOME MEASURES: Variables reflecting methods used in the HTAs to evaluate the effectiveness of health technologies or procedures. RESULTS: Of 56 MSAC HTA reports available, 31 met the inclusion criteria. Considerable variability was shown to exist between the various indicators of quality and the methodology used within the HTAs. Reports did not describe potential conflicts of interest of participants. The majority of reports (19/31) did not formally state the research question that the assessment was attempting to answer. Just over half of the reports (18/31) provided details of validity assessment of the included studies. CONCLUSIONS: Minimum and consistent standards of methodology and reporting are required in Australian HTAs, using international recommendations of best practice to increase the transparency and applicability of these reports.

Bariatric surgery in Australia: who, why and how?

A review of published reports was conducted to identify gaps in the research regarding bariatric surgery. Much of the research that has been conducted is clinical outcome based; however, little research has been conducted in many key areas. Data on the demographics of the bariatric surgery group are patchy at best. The role of best practice and evidence-based medicine in bariatric surgery seems to be poorly understood, and equity issues and the role of clinical pathways in bariatric surgery need to be clarified. Significant gaps were identified in the published reports regarding pathways to bariatric surgery and multidisciplinary team use. Additionally, much of the published report and research data were from US studies, as few Australian studies have been conducted. Further research and policy and practice developments in bariatric surgery are needed, especially with regard to the Australian context.

Microbiologic follow-up study in adult bronchiectasis.

There is minimal published longitudinal data about pathogenic microorganisms in adults with bronchiectasis. Therefore a study was undertaken to assess the microbiologic profile over time in bronchiectasis. A prospective study of clinical and microbiologic outcomes was performed. Subjects were assessed by a respiratory physician and sputum sample were collected for analysis. Subjects were followed up and had repeat assessment performed. Eighty-nine subjects were followed up for a period of 5.7+/-3.6 years. On initial assessment the two most common pathogens isolated were Haemophilus influenzae (47%) and Pseudomonas aeruginosa (12%) whilst 21% had no pathogens isolated. On follow-up review results were similar (40% H. influenzae, 18% P. aeruginosa and 26% no pathogens). The prevalence of antibiotic resistance of isolates increased from 13% to 30%. Analysis of a series of H. influenzae isolates showed they were nearly all nontypeable and all were different subtypes. Subjects with no pathogens isolated from their sputum had the mildest disease, while subjects with P. aeruginosa had the most severe bronchiectasis. Many subjects with bronchiectasis are colonized with the same bacterium over an average follow-up of 5 years. Different pathogens are associated with different patterns of clinical disease.

Surgeons' attitudes towards and usage of evidence-based medicine in surgical practice: a pilot study.

BACKGROUND: Within surgery the debate about the place of evidence-based medicine (EBM) has focused on the nature and compatibility of EBM with surgical practice with an inevitable polarization of opinion. However, EBM techniques are being embedded into undergraduate medical curricula and surgical training programs across Australia. The Monash University Department of Surgery at Monash Medical Centre implemented a pilot study to explore current knowledge, attitudes and behaviours of practising surgeons towards EBM techniques. METHODS: Descriptive survey of surgeons based in a tertiary care environment. RESULTS: The results from the surgeons surveyed suggest that (i) they believe that EBM marginalizes patient involvement in decision-making; (ii) they believe that EBM-generated knowledge is useful and is commonly used in daily clinical decision-making--however, not using EBM does not adversely affect their daily clinical decision-making; (iii) they have high confidence in their own judgement compared with low confidence in clinical practice guidelines and other sources of evidence; and (iv) journal summaries of the latest research related to a subject are the most useful resources in clinical practice above clinical practice guidelines. CONCLUSION: The importance of incorporating concepts of the 'culture' of surgery as an important factor in understanding and developing new ways to mobilize Australian surgeons to adopt EBM into their practice is discussed.

National Breast Cancer Audit: ductal carcinoma in situ management in Australia and New Zealand.

BACKGROUND: Ductal carcinoma in situ (DCIS) is a significant issue in Australia and New Zealand with rising incidence because of the implementation of mammographic screening. Current information on its natural history is unable to accurately predict progression to invasive cancer. In 2003, the National Breast Cancer Centre in Australia published recommendations for DCIS. In Australia and New Zealand, the National Breast Cancer Audit collects information on DCIS cases. This article will examine these recommendations and provide information from the audit on current DCIS management. METHODS: Three thousand six hundred and twenty-nine cases of DCIS were entered by 274 breast surgeons between January 1998 and December 2004. Data items in the National Breast Cancer Audit database that were covered in the National Breast Cancer Centre recommendations were reviewed. Information was available on the following: diagnostic biopsy rates for all cases and mammographically positive cases and rates of breast conserving surgery (BCS), clear margins following BCS, postoperative radiotherapy following BCS for groups at high risk of recurrence as well as axillary procedures and tamoxifen prescription. RESULTS: Close adherence was found in diagnostic biopsy, BCS and clear margin rates. Some high-risk groups received radiotherapy, although women with 'close' margins did not in 33% of cases. Axillary procedures were conducted in 23% of cases and most (81%) patients were not prescribed tamoxifen. CONCLUSION: There was predominantly close adherence to recommendations with three possible areas of improvement: fewer axillary procedures, an appraisal of radiotherapy practice following BCS and more investigation into tamoxifen prescription practices for DCIS.

National breast cancer audit: overview of invasive breast cancer management.

BACKGROUND: The National Breast Cancer Audit is an initiative of the Breast Section of the Royal Australasian College of Surgeons collecting surgical information in early breast cancer. It is managed in conjunction with the Australian Safety and Efficacy Register of New Interventional Procedures - Surgical. An overview of results for invasive breast cancer from January 1999 until December 2004 is presented to provide preliminary data for participating surgeons. METHODS: Invasive breast cancer cases were retrieved from the National Breast Cancer Audit database for the 274 participating breast surgeons in Australia and New Zealand. Data for a variety of clinical parameters were analysed to provide an overview of the diagnostic, histological, surgical and adjuvant therapy management issues. RESULTS: There were 25,026 cases of invasive breast cancer. Annual percentages of mammographically detected cancers from 1999 to 2004 did not differ significantly. Breast-conserving surgery rates also remained stable at 60%. Margins were involved in 5% of patients; an additional 9% had final margins of less than 1 mm. Radiotherapy followed breast-conserving surgery in most cases (86%). Patients undergoing mastectomy with large tumours (>5 cm) underwent radiotherapy in 71% of cases. When at least four lymph nodes were positive, radiotherapy followed mastectomy in the majority (75%) of cases. The most frequently carried out axillary procedure was a level 2 dissection. Chemotherapy was received by 78% of oestrogen receptor negative, axillary node positive, postmenopausal patients. Tamoxifen was used in the majority (83%) of oestrogen receptor positive cases. CONCLUSION: Surgeons contributing their invasive breast cancer data show a high quality of treatment. Some further improvement may be possibly related to excision margins and tamoxifen prescription for oestrogen receptor negative cancers. Chemotherapy prescription might also warrant further investigation.

Characterisation of the onset and presenting clinical features of adult bronchiectasis.

BACKGROUND: There is little information available on the features of initial presentation of bronchiectasis and documentation of the onset and progress of symptoms leading up to this. Therefore a study was performed on a large cohort of adult patients presenting to Monash Medical Centre (MMC) to survey the course of their disease up to the time of diagnosis. OBJECTIVES: To characterise the onset and presenting clinical features of bronchiectasis in adults. METHODS: A cross-sectional study of 103 adults presenting to a tertiary referral hospital with newly diagnosed bronchiectasis. Clinical features of bronchiectasis and results of spirometry, sputum microbiology and radiology were assessed and correlated. RESULTS: Most patients had idiopathic bronchiectasis (74%) and did not have other significant disease. The dominant symptom was chronic productive cough present in 98% of patients with other important symptoms being chronic rhinosinusitis (70%), dyspnoea (62%), and fatigue (74%). Most patients had had a chronic productive cough for over 30 years prior to diagnosis and over 80% of patients had chronic respiratory symptoms from childhood. The dominant finding on physical examination was the presence of crackles which were generally bi-basal. Spirometry showed mild airway obstruction with an average forced expiratory volume in 1s of the cohort of 76% predicted. Radiologic imaging generally showed multilobar disease (80%). CONCLUSIONS: The typical profile of bronchiectasis in this group of patients was of longstanding productive cough, rhinosinusitis and fatigue in non-smokers with crackles on chest auscultation.

Risk factors for intensive care in children with acute asthma.

OBJECTIVE: A retrospective case-control study at Monash Medical Centre (MMC), a tertiary referral hospital in Melbourne, Australia, was conducted to identify risk factors associated with very severe asthma in paediatric patients. METHODOLOGY: Asthmatics admitted to an intensive care unit (ICU; n=52) were identified and considered to represent cases of very severe/near fatal asthma (NFA group). This group was compared to asthmatics who had been admitted on one occasion only to the emergency department at MMC (non-NFA controls, n=53). Patient files were examined and factors that may be linked to NFA were recorded. Information not on file was obtained from patients/parents during a structured telephone interview. Data for the two groups were compared, univariate and multivariate logistic regression analyses were performed, and odds ratios (OR) were calculated. RESULTS: Univariate analysis indicated that asthmatics with NFA were more likely to be older (P=0.01) and have a longer duration of asthma (P=0.02). They were also more likely to have hay fever (P=0.002; OR, 7.6), use inhaled corticosteroids (P=0.001), long acting beta(2) agonists (P=0.02), have an asthma management plan (P=0.006), and see a respiratory specialist (P=0.001). Parental smoking habits were not different between the groups. Multivariate logistic regression analysis identified male gender (P=0.05; OR, 5.7) and use of inhaled corticosteroids (P=0.07; OR, 7.2) as factors that may be predictive of NFA. CONCLUSIONS: This study identifies a number of factors associated with NFA; many are similar to those reported in adult patients. Asthma severity explains some findings, but the data also suggest that additional independent risk factors such as gender and duration of asthma may operate in children.

Outcome in adult bronchiectasis.

The outcome in adult bronchiectasis has not been well described; in particular there has been a lack of long-term prospective studies. Therefore a follow-up study was performed to assess outcome in bronchiectasis in a cohort of adult patients. One hundred-and-one sequential adults, 33 male and 68 female; age 54 +/- 14 years (mean +/- SD) with bronchiectasis had a clinical assessment and spirometry performed. All were non-smokers and 84 were classified as having idiopathic disease. Patients were commenced on a standardized treatment regime and followed up for a minimum period of 2 years. On their last review when patients were clinically stable, a repeat clinical assessment and spirometry was performed and compared with the initial review. The primary endpoints measured were symptoms and FEV1. Subjects were followed up for 8.0 +/- 4.9 years. Clinical review showed that the patients had persistent symptoms that, in the case of dyspnea and sputum volume, were worse on follow-up. Spirometry showed a significant decline in FEV1 over the follow-up period with an average loss of 49 ml per year. This study showed in this group of predominantly female adult patients with bronchiectasis followed up for 8 years, patients had persistent symptoms and an excess loss in FEV1.

Evaluating heterogeneity in cumulative meta-analyses.

BACKGROUND: Recently developed measures such as I2 and H allow the evaluation of the impact of heterogeneity in conventional meta-analyses. There has been no examination of the development of heterogeneity in the context of a cumulative meta-analysis. METHODS: Cumulative meta-analyses of five smoking cessation interventions (clonidine, nicotine replacement therapy using gum and patch, physician advice and acupuncture) were used to calculate I2 and H. These values were plotted by year of publication, control event rate and sample size to trace the development of heterogeneity over these covariates. RESULTS: The cumulative evaluation of heterogeneity varied according to the measure of heterogeneity used and the basis of cumulation. Plots produced from the calculations revealed areas of heterogeneity useful in the consideration of potential sources for further study. CONCLUSION: The examination of heterogeneity in conjunction with summary effect estimates in a cumulative meta-analysis offered valuable insight into the evolution of variation. Such information is not available in the context of conventional meta-analysis and has the potential to lead to the development of a richer picture of the effectiveness of interventions.