Elizabeth Buckley

Comparison of the clinical effectiveness of different off‐loading devices for the treatment of neuropathic foot ulcers in patients with diabetes: a systematic review and meta‐analysis

Effective off‐loading is considered to be an important part of the successful clinical management of diabetic foot ulcers. The aim of this systematic review is to investigate the safety and effectiveness of different off‐loading devices for the treatment of diabetic foot ulcers. The medical literature was extensively searched from January 1966 to May 2012. Systematic reviews and controlled studies that compared the use of different off‐loading devices formed the evidence base. Studies were critically appraised to determine their risk of methodological bias, and data were extracted. Results were pooled using random effects meta‐analysis and tested for heterogeneity. When compared with removable devices, non‐removable off‐loading devices were found, on average, to be more effective at promoting the healing of diabetic foot ulcers (RRp = 1.43; 95% CI 1.11, 1.84; I2 = 66.9%; p = 0.001; k = 10). Analysis, stratified by type of removable device, did not detect a statistically significant difference between non‐removable off‐loading devices and removable cast walkers; however, on average non‐removable off‐loading devices performed better than therapeutic shoes at promoting the healing of diabetic foot ulcers (RRp = 1.68; 95% CI 1.09, 2.58; I2 = 71.5%; p = 0.004; k = 6). The two types of non‐removable off‐loading devices i.e. total contact casts and instant total contact casts (removable cast walker rendered irremovable by securing with bandage or lace), were found to be equally effective (RRp = 1.06; 95% CI 0.88, 1.27; I2 = 3.3%; p = 0.31; k = 2). In conclusion, non‐removable off‐loading devices regardless of type, are more likely to result in ulcer healing than removable off‐loading devices, presumably because patient compliance with off‐loading is facilitated. Copyright

A systematic review of surgical biopsy for LCIS found at core needle biopsy - do we have the answer yet?

BACKGROUND The natural history of lobular carcinoma in-situ (LCIS) suggests that women are at increased risk of subsequent invasive breast cancer. Questions of effective management for women with this lesion have led to the need for evidence-based guidance and, in particular, guidance regarding management after LCIS is found at core needle biopsy (CNB). METHODS A systematic review was conducted to determine the most appropriate management for women with LCIS found at CNB. A comprehensive search of the scientific literature was conducted to identify the literature pertaining to this population. Critical appraisal of the literature, data extraction and a narrative synthesis of the results were conducted. The outcome of interest was upgrade of diagnosis to invasive breast cancer or ductal carcinoma in-situ (DCIS). RESULTS Sparse data, with limited generalisability and considerable uncertainty, are available for women with LCIS at CNB. Nine studies were identified that met pre-specified inclusion criteria. The reported estimates of upgrade of diagnosis from LCIS to invasive breast cancer or DCIS ranged from 2% to 25%. The body of evidence was limited by its retrospective nature, risk of selection bias and poor generalisability to all women with LCIS at CNB. Further, higher quality research is required to determine the best approach for women with LCIS at CNB with any certainty.

Risk profile of breast cancer following atypical hyperplasia detected through organized screening

BACKGROUND Few population-based data are available indicating the breast cancer risk following detection of atypia within a breast screening program. METHODS Prospectively collected data from the South Australian screening program were linked with the state cancer registry. Absolute and relative breast cancer risk estimates were calculated for ADH and ALH separately, and by age at diagnosis and time since diagnosis. Post-hoc analysis was undertaken of the effect of family history on breast cancer risk. RESULTS Women with ADH and ALH had an increase in relative risk for malignancy (ADH HR 2.81 [95% CI 1.72, 4.59] and (ALH HR 4.14 [95% CI 1.97, 8.69], respectively. Differences in risk profile according to time since diagnosis and age at diagnosis were not statistically significant. CONCLUSION Estimates of the relative risk of breast cancer are necessary to inform decisions regarding clinical management and/or treatment of women with ADH and ALH.

Incidence, prevalence, mortality, disability-adjusted life years and risk factors of cancer in Australia and comparison with OECD countries, 1990–2015: findings from the Global Burden of Disease Study 2015

BACKGROUND Comparative evidence on the burden, trend, and risk factors of cancer is limited. Using data from the Global Burden of Disease (GBD) study, we aimed to assess cancer burden - incidence, prevalence, mortality, disability-adjusted life years (DALYs) - and attributable risk factors for Australia between 1990 and 2015, and to compare them with those of 34 members of the Organisation for Economic Co-operation and Development (OECD). METHODS The general GBD cancer estimation methods were used with data input from vital registration systems and cancer registries. A comparative risk assessment approach was used to estimate the population-attributable fractions due to risk factors. RESULTS In 2015 there were 198,880 (95% uncertainty interval [UI]: 183,908-217,365) estimated incident cancer cases and 47,562 (95% UI: 46,061-49,004) cancer deaths in Australia. Twenty-nine percent (95% UI: 28.2-29.8) of total deaths and 17.0% (95% UI: 15.0-19.1) of DALYs were caused by cancer in Australia in 2015. Cancers of the trachea, bronchus and lung, colon and rectum, and prostate were the most common causes of cancer deaths. Thirty-six percent (95% UI: 33.1-37.9) of all cancer deaths were attributable to behavioral risks. The age-standardized cancer incidence rate (ASIR) increased between 1990 and 2015, while the age-standardized cancer death rate (ASDR) decreased over the same period. In 2015, compared to 34 other OECD countries Australia ranked first (highest) and 24th based on ASIR and ASDR, respectively. CONCLUSION The incidence of cancer has increased over 25 years, and behavioral risks are responsible for a large proportion of cancer deaths. Scaling up of prevention (using strategies targeting cancer risk factors), early detection, and treatment of cancer is required to effectively address this growing health challenge.

Comorbidity and cervical cancer survival of Indigenous and non-Indigenous Australian women: A semi-national registry-based cohort study (2003-2012)

Background Little is known about the impact of comorbidity on cervical cancer survival in Australian women, including whether Indigenous women’s higher prevalence of comorbidity contributes to their lower survival compared to non-Indigenous women. Methods Data for cervical cancers diagnosed in 2003–2012 were extracted from six Australian state-based cancer registries and linked to hospital inpatient records to identify comorbidity diagnoses. Five-year cause-specific and all-cause survival probabilities were estimated using the Kaplan-Meier method. Flexible parametric models were used to estimate excess cause-specific mortality by Charlson comorbidity index score (0,1,2+), for Indigenous women compared to non-Indigenous women. Results Of 4,467 women, Indigenous women (4.4%) compared to non-Indigenous women had more comorbidity at diagnosis (score ≥1: 24.2% vs. 10.0%) and lower five-year cause-specific survival (60.2% vs. 76.6%). Comorbidity was associated with increased cervical cancer mortality for non-Indigenous women, but there was no evidence of such a relationship for Indigenous women. There was an 18% reduction in the Indigenous: non-Indigenous hazard ratio (excess mortality) when comorbidity was included in the model, yet this reduction was not statistically significant. The excess mortality for Indigenous women was only evident among those without comorbidity (Indigenous: non-Indigenous HR 2.5, 95%CI 1.9–3.4), indicating that factors other than those measured in this study are contributing to the differential. In a subgroup of New South Wales women, comorbidity was associated with advanced-stage cancer, which in turn was associated with elevated cervical cancer mortality. Conclusions Survival was lowest for women with comorbidity. However, there wasn’t a clear comorbidity-survival gradient for Indigenous women. Further investigation of potential drivers of the cervical cancer survival differentials is warranted. Impact The results highlight the need for cancer care guidelines and multidisciplinary care that can meet the needs of complex patients. Also, primary and acute care services may need to pay more attention to Indigenous Australian women who may not obviously need it (i.e. those without comorbidity).

Translation from clinical trials to routine practice: how to demonstrate community benefit.

The paper by Lok et al. in the APJCO December issue demonstrates the use of a clinical database for assessing research translation. It shows uptake of treatments proven to be effective in earlier clinical trials and improved survival for metastatic colorectal cancer at four major Melbourne hospitals. It is important as population benefits from trials depend on research translation. Even with vigorous research translation into clinical practice, outcomes may not reflect trial results due to differences in clinical environments and patient profiles. For pragmatic reasons, trials may involve clinical centers where specialist interest is high, and larger centers where stronger infrastructure support exists, but the relevance of results to the broader community may be questionable. Trials often exclude patients with significant comorbidity or age-related frailty to gain a clearer view of treatment efficacy under optimal conditions, but this can raise questions about the generalizability of results to excluded groups. Moreover, while it may be feasible to optimize clinical rigor within a trial environment, this rigor may be difficult to maintain in all routine practice settings. Clinical databases and registries are important means for testing translation of treatment and survival outcomes. Greater interpretational judgment is needed, however, when data come from routine practice environments. Questions generally arising include whether findings may be biased either due to: (i) unidentified confounders; (ii) identified confounders for which measures are insufficiently accurate for complete statistical adjustment; or (iii) lead time or related artificial effects on survival. Questions about bias are often directed more at survival outcomes than patterns of care. Data interpretations for routine practice settings may be compromised by suboptimum data quality and completeness for potential confounders (as in this study where performance status data were incomplete). Lok et al. show a favorable survival trend, both in patients not receiving as well as those receiving active treatment, indicating potential effects on results of unmeasured or poorly measured confounding factors. Despite such uncertainties, data from clinical databases and registries are of great value when assessing research translation. For example, they provide reassurance when they show favorable practice changes and the improvements in outcomes expected from trial data. In addition, they can reveal quality improvement opportunities when heterogeneity in research translation is evident across patient subgroups. They can also add value by providing new evidence on outcomes for patient subgroups who were excluded from trial participation, such as older patients with multiple complex comorbidities who are becoming a larger proportion of patient populations in Australia and many other Asian-Pacific countries. Questions can also arise about representativeness, such as the mix of public and private patients and of large and small centers. Clinical databases and registries are often located in large centers where there is a special interest in research and larger number of patients. Questions arise as to how practices and outcomes can best be monitored in smaller settings, including those in rural and remote areas where there may be greater variation in quality of care due to low patient volumes and more limited access to multidisciplinary teams and other clinical support. This is an important issue as case complexity may be higher in these settings, as for example, in Australia among rural and remote Aboriginal and Torres Strait Islander populations where high levels of diabetes, chronic renal disease and other comorbidity can complicate treatment decisions. An ideal option may be to extend clinical cancer databases and registries across the whole population. This may be difficult for governments to achieve, however, due to budgetary constraints and/or legislative and administrative complexities (as can apply in Australia’s multijurisdictional government structure). Other options therefore need be considered. Increasingly clinical cancer registries are being developed separately from governments and led by clinical leaders. Examples in Australia include the Movember Australian Prostate Cancer Clinical Registry that is currently under development. Furthermore, the long-standing and successful ANZ Breast Cancer Quality database has been extending its coverage incrementally and is now covering the great majority of early breast cancers. An “opt-out” approach, as recently supported in the National Statement on Ethical Conduct in Human Research in Australia, is now a legitimate option for including patient data in clinical registries, greatly increasing the potential for registries to achieve sufficient population coverage to obtain representative data without requiring special legislation. This approach has been included in reports on clinical quality registries prepared by the Ausbs_bs_banner

High quality data are the key to understanding inequalities in cancer outcomes for Aboriginal and Torres Strait Islander Australians

j 2 1 N o ve m b e r 2 0 16 T cancer data forAboriginal andTorres Strait Islander people resulting from poor recording of Indigenous Australian status in source databases. To improve the evidence base, the Australian Institute of Health and Welfare has limited analyses of cancer incidence amongAboriginal and Torres Strait Islander Australians to four Australian states and territories — the Northern Territory, Queensland, New South Wales and Western Australia — as their data are regarded as being of better quality.

Lutein Intake and Blood Lutein Concentration Are Positively Associated with Physical Activity in Adults: A Systematic Review

Lutein is a carotenoid that reduces the risk of some chronic diseases, possibly by altering physical activity behavior. The objective of this study was to conduct a systematic review of studies examining the relationship between lutein status (dietary intake/blood concentration) and physical activity. Peer-reviewed studies published in Medline, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and Embase were included if they reported a measure of association between lutein status and physical activity. Seventeen studies met the inclusion criteria. Eleven reported positive associations, three reported mixed results, and three reported no association. Two studies used objective measures of lutein status (blood concentration) and physical activity (accelerometry) and reported positive associations, with correlations of ≥0.36 and differences of ≥57% in physical activity between upper and lower tertiles. Studies using self-report measures reported weaker correlations (r = 0.06 to 0.25), but still more physical activity (18% to ≥600% higher) in those with the highest compared with the lowest lutein status. Higher lutein status may be associated with higher levels of physical activity, which may contribute to a reduced risk of chronic disease.

Developing a comorbidity index for comparing cancer outcomes in Aboriginal and non-Aboriginal Australians

BackgroundComorbidity is known to increase risk of death in cancer patients, both Aboriginal and non-Aboriginal. The means of measuring comorbidity to assess risk of death has not been studied in any depth in Aboriginal patients in Australia. In this study, conventional and customized comorbidity indices were used to investigate effects of comorbidity on cancer survival by Aboriginal status and to determine whether comorbidity explains survival disparities.MethodsA retrospective cohort study was undertaken using linked population-based South Australian Cancer Registry and hospital inpatient data for 777 Aboriginal people diagnosed with primary cancer between 1990 and 2010 and 777 randomly selected non-Aboriginal controls matched by sex, birth year, diagnosis year and tumour type. A customised comorbidity index was developed by examining associations of comorbid conditions with 1-year all-cause mortality within the Aboriginal and non-Aboriginal patient groups separately using Cox proportional hazard model, adjusting for age, stage, sex and primary site. The adjusted hazard ratios for comorbid conditions were used as weights for these conditions in index development. The comorbidity index score for combined analyses was the sum of the weights across the comorbid conditions for each case from the two groups.ResultsThe two most prevalent comorbidities in the Aboriginal cohort were “uncomplicated” hypertension (13.5%) and diabetes without complications (10.8%), yet in non-Aboriginal people, the comorbidities were “uncomplicated” hypertension (7.1%) and chronic obstructive pulmonary disease (4.4%). Higher comorbidity scores were associated with higher all-cause and cancer-specific mortality. The new index showed minor improvements in predictive ability and model fit when compared with three common generic comparison indices. After accounting for the competing risk of other deaths, stage at diagnosis, socioeconomic status, area remoteness and comorbidity, the increased risk of cancer death in Aboriginal people remained.ConclusionsOur new customised index performed at least as well, although not markedly better than the generic indices. We conclude that in broad terms, the generic indices are reasonably effective for adjusting for comorbidity when comparing survival outcomes by Aboriginal status. Irrespective of the index used, comorbidity has a negative impact on cancer-specific survival, but this does not fully explain the lower survival in Aboriginal patients.

Using hospital registries in Australia to extend data availability on vulval cancer treatment and survival

BackgroundThe value of hospital registries for describing treatment and survival outcomes for vulval cancer was investigated. Hospital registry data from four major public hospitals in 1984–2016 were used because population-based data lacked required treatment and outcomes data. Unlike population registries, the hospital registries had recorded FIGO stage, grade and treatment.MethodsUnadjusted and adjusted disease-specific survival and multiple logistic regression were used. Disease-specific survivals were explored using Kaplan-Meier product-limit estimates. Hazards ratios (HRs) were obtained from proportional hazards regression for 1984–1999 and 2000–2016. Repeat analyses were undertaken using competing risk regression.ResultsFive-year disease-specific survival was 70%, broadly equivalent to the five-year relative survivals reported for Australia overall (70%), the United Kingdom (70%), USA (72%), Holland (70%), and Germany (Munich) (68%). Unadjusted five-year survival tended to be lower for cancers diagnosed in 2000–2016 than 1984–1999, consistent with survival trends reported for the USA and Canada, but higher for 2000–2016 than 1984–1999 after adjusting for stage and other covariates, although differences were small and did not approach statistical significance (p ≥ 0.40). Surgery was provided as part of the primary course of treatment for 94% of patients and radiotherapy for 26%, whereas chemotherapy was provided for only 6%. Less extensive surgical procedures applied in 2000–2016 than 1984–1999 and the use of chemotherapy increased over these periods. Surgery was more common for early FIGO stages, and radiotherapy for later stages with a peak for stage III. Differences in treatment by surgery and radiotherapy were not found by geographic measures of remoteness and socioeconomic status in adjusted analyses, suggesting equity in service delivery.ConclusionsThe data illustrate the complementary value of hospital-registry data to population-registry data for informing local providers and health administrations of trends in management and outcomes, in this instance for a comparatively rare cancer that is under-represented in trials and under-reported in national statistics. Hospital registries can fill an evidence gap when clinical data are lacking in population-based registries.