Showing papers by "Katy J.L. Bell published in 2020"

Estimating the extent of asymptomatic COVID-19 and its potential for community transmission: Systematic review and meta-analysis

Abstract: Background: Knowing the prevalence of true asymptomatic coronavirus disease 2019 (COVID-19) cases is critical for designing mitigation measures against the pandemic. We aimed to synthesize all avai...

Estimating the extent of asymptomatic COVID-19 and its potential for community transmission: systematic review and meta-analysis

Abstract: Background The prevalence of true asymptomatic COVID-19 cases is critical to policy makers considering the effectiveness of mitigation measures against the SARS-CoV-2 pandemic. We aimed to synthesize all available research on the asymptomatic rates and transmission rates where possible. Methods We searched PubMed, Embase, Cochrane COVID-19 trials, and Europe PMC (which covers pre-print platforms such as MedRxiv). We included primary studies reporting on asymptomatic prevalence where: (a) the sample frame includes at-risk population, and (b) there was sufficiently long follow up to identify pre-symptomatic cases. Meta-analysis used fixed effect and random effects models. We assessed risk of bias by combination of questions adapted from risk of bias tools for prevalence and diagnostic accuracy studies. Results We screened 998 articles and included nine low risk-of-bias studies from six countries that tested 21,035 at-risk people, of which 559 were positive and 83 were asymptomatic. Diagnosis in all studies was confirmed using a RT-qPCR test. The proportion of asymptomatic cases ranged from 4% to 41%. Meta-analysis (fixed effect) found that the proportion of asymptomatic cases was 15% (95% CI: 12% - 18%) overall; higher in non-aged care 16% (13% - 19%), and lower in long-term aged care 8% (3% - 18%). Four studies provided direct evidence of forward transmission of the infection by asymptomatic cases but suggested considerably lower rates than symptomatic cases. Discussion Our estimates of the prevalence of asymptomatic COVID-19 cases and asymptomatic transmission rates are lower than many highly publicized studies, but still sufficient to warrant policy attention. Further robust epidemiological evidence is urgently needed, including in sub-populations such as children, to better understand the importance of asymptomatic cases for driving spread of the pandemic. Funding OB is supported by NHMRC Grant APP1106452. PG is supported by NHMRC Australian Fellowship grant 1080042. KB was supported by NHMRC Fellowship grant 1174523. All authors had full access to all data and agreed to final manuscript to be submitted for publication. There was no funding source for this study.

Estimating the magnitude of cancer overdiagnosis in Australia

Abstract: Objectives To estimate the proportion of cancer diagnoses in Australia that might reasonably be attributed to overdiagnosis by comparing current and past lifetime risks of cancer. Design, setting, and participants Routinely collected Australian Institute of Health and Welfare national data were analysed to estimate recent (2012) and historical (1982) lifetime risks (adjusted for competing risk of death and changes in risk factors) of diagnoses with five cancers: prostate, breast, renal, thyroid cancers, and melanoma. Main outcome measure Difference in lifetime risks of cancer diagnosis between 1982 and 2012, interpreted as probable overdiagnosis. Results For women, absolute lifetime risk increased by 3.4 percentage points for breast cancer (invasive cancers, 1.7 percentage points), 0.6 percentage point for renal cancer, 1.0 percentage point for thyroid cancer, and 5.1 percentage points for melanoma (invasive melanoma, 0.7 percentage point). An estimated 22% of breast cancers (invasive cancers, 13%), 58% of renal cancers, 73% of thyroid cancers, and 54% of melanomas (invasive melanoma, 15%) were overdiagnosed, or 18% of all cancer diagnoses (8% of invasive cancer diagnoses). For men, absolute lifetime risk increased by 8.2 percentage points for prostate cancer, 0.8 percentage point for renal cancer, 0.4 percentage point for thyroid cancer, and 8.0 percentage points for melanoma (invasive melanoma, 1.5 percentage points). An estimated 42% of prostate cancers, 42% of renal cancers, 73% of thyroid cancers, and 58% of melanomas (invasive melanomas, 22%) were overdiagnosed, or 24% of all cancer diagnoses (16% of invasive cancer diagnoses). Alternative assumptions slightly modified the estimates for overdiagnosis of breast cancer and melanoma. Conclusions About 11 000 cancers in women and 18 000 in men may be overdiagnosed each year. Rates of overdiagnosis need to be reduced and health services should monitor emerging areas of overdiagnosis.

Estimating the Extent of True Asymptomatic COVID-19 and Its Potential for Community Transmission: Systematic Review and Meta-Analysis

Abstract: Background: The prevalence of true asymptomatic COVID-19 cases is critical to policy makers considering the effectiveness of mitigation measures against the SARS-CoV-2 pandemic. We aimed to synthesise all available research on the asymptomatic rates. Methods: We searched PubMed, Embase, Cochrane COVID 19 trials, and European PMC for pre-print platforms such as MedRxiv, Research Square, and F1000 Research. We included primary studies reporting on asymptomatic prevalence where: (a) the sample frame was not contingent on the presence or absence of symptoms, and (b) there was sufficiently long follow up to identify pre-symptomatic cases. Meta-analysis used fixed effect and random effects models. Results: We screened 571 articles and included five studies from three countries (China (2), USA (2), Italy (1)) that include 599 COVID-19 cases and 9,297 contacts. Diagnosis in all studies was confirmed using a RT-PCR test. The proportion of asymptomatic cases ranged from 6% to 41%. Meta-analysis (fixed effect) found that the proportion of asymptomatic cases was 16% (95% CI: 12% - 20%) overall; higher in non-aged care 19% (15% - 24%), and lower in long-term aged care 8% (4% - 14%). Two studies provided direct evidence of forward transmission of the infection by asymptomatic cases, but suggested lower rates than symptomatic cases. Conclusion: Our meta-analytic estimates of the prevalence of asymptomatic COVID-19 cases are lower than many highly publicized studies, but still substantial. Further robust epidemiological evidence is urgently needed, including in sub-populations such as children, to better understand the importance of asymptomatic cases for driving spread of the pandemic. Funding Statement: OB is supported by NHMRC Grant APP1106452. PG is supported by NHMRC Australian Fellowship grant 1080042. KB was supported by NHMRC Fellowship grant 1174523 and Program grant 1113532. There was no funding source for this study. Declaration of Interests: Prof Mary-Louise McLaws is a member of World Health Organization Health Emergencies Program Experts Advisory Panel for Infection Prevention and Control Preparedness, Readiness and Response to COVID-19. All other authors declare no competing interests.

The carbon footprint of pathology testing.

Abstract: OBJECTIVES To estimate the carbon footprint of five common hospital pathology tests: full blood examination; urea and electrolyte levels; coagulation profile; C-reactive protein concentration; and arterial blood gases. DESIGN, SETTING Prospective life cycle assessment of five pathology tests in two university-affiliated health services in Melbourne. We included all consumables and associated waste for venepuncture and laboratory analyses, and electricity and water use for laboratory analyses. MAIN OUTCOME MEASURE Greenhouse gas footprint, measured in carbon dioxide equivalent (CO2 e) emissions. RESULTS CO2 e emissions for haematology tests were 82 g/test (95% CI, 73-91 g/test) for coagulation profile and 116 g/test (95% CI, 101-135 g/test) for full blood examination. CO2 e emissions for biochemical tests were 0.5 g/test CO2 e (95% CI, 0.4-0.6 g/test) for C-reactive protein (low because typically ordered with urea and electrolyte assessment), 49 g/test (95% CI, 45-53 g/test) for arterial blood gas assessment, and 99 g/test (95% CI, 84-113 g/test) for urea and electrolyte assessment. Most CO2 e emissions were associated with sample collection (range, 60% for full blood examination to 95% for coagulation profile); emissions attributable to laboratory reagents and power use were much smaller. CONCLUSION The carbon footprint of common pathology tests was dominated by those of sample collection and phlebotomy. Although the carbon footprints were small, millions of tests are performed each year in Australia, and reducing unnecessary testing will be the most effective approach to reducing the carbon footprint of pathology. Together with the detrimental health and economic effects of unnecessary testing, our environmental findings should further motivate clinicians to test wisely.

Legacy effect of fibrate add-on therapy in diabetic patients with dyslipidemia: a secondary analysis of the ACCORDION study.

Abstract: The Action to Control Cardiovascular Risk in Diabetes (ACCORD)-Lipid study found no evidence of a beneficial effect of statin-fibrate combined treatment, compared to statins alone, on cardiovascular outcomes and mortality in type 2 diabetes mellitus after 5 years of active treatment. However, a beneficial reduction in major CVD events was shown in a pre-specified sub-group of participants with dyslipidemia. The extended follow-up of this trial provides the opportunity to further investigate possible beneficial effects of fibrates in this group of patients. We aimed to evaluate possible “legacy effects” of fibrate add-on therapy on mortality and major cardiovascular outcomes in patients with dyslipidemia. The ACCORD-lipid study was a randomized controlled trial of 5518 participants assigned to receive simvastatin plus fenofibrate vs simvastatin plus placebo. After randomized treatment allocation had finished at the end of the trial, all surviving participants were invited to attend an extended follow-up study (ACCORDION) to continue prospective collection of clinical outcomes. We undertook a secondary analysis of trial and post-trial data in patients who had dyslipidemia. The primary outcome was all-cause and cardiovascular mortality, and secondary outcomes were nonfatal myocardial infarction, stroke, congestive heart failure and major coronary heart disease. We used an intention-to-treat approach to analysis to make comparisons between the original randomized treatment groups. 853 participants with dyslipidemia had survived at the end of the trial. Most participants continued to use statins, but few used fibrates in either group during the post-trial period. The incidence rates in the fenofibrate group were lower with respect to all-cause mortality, CVD mortality, nonfatal myocardial infarction, congestive heart failure and major coronary heart disease than those in the placebo group over a post-trial follow-up. Allocation to the combined fibrate-statin treatment arm during the trial period had a beneficial legacy effect on all-cause mortality (adjusted HR = 0.65, 95% CI 0.45–0.94; P = 0.02). Fibrate treatment during the initial trial period was associated with a legacy benefit of improved survival over a post-trial follow-up. These findings support re-evaluation of fibrates as an add-on strategy to statins in order to reduce cardiovascular risk in diabetic patients with dyslipidemia. Trial registration clinicaltrials.gov, Identifier: NCT00000620

Why clinicians overtest: development of a thematic framework

Abstract: Medical tests provide important information to guide clinical management. Overtesting, however, may cause harm to patients and the healthcare system, including through misdiagnosis, false positives, false negatives and overdiagnosis. Clinicians are ultimately responsible for test requests, and are therefore ideally positioned to prevent overtesting and its unintended consequences. Through this narrative literature review and workshop discussion with experts at the Preventing Overdiagnosis Conference (Sydney, 2019), we aimed to identify and establish a thematic framework of factors that influence clinicians to request non-recommended and unnecessary tests. Articles exploring factors affecting clinician test ordering behaviour were identified through a systematic search of MedLine in April 2019, forward and backward citation searches and content experts. Two authors screened abstract titles and abstracts, and two authors screened full text for inclusion. Identified factors were categorised into a preliminary framework which was subsequently presented at the PODC for iterative development. The MedLine search yielded 542 articles; 55 were included. Another 10 articles identified by forward-backward citation and content experts were included, resulting in 65 articles in total. Following small group discussion with workshop participants, a revised thematic framework of factors was developed: This thematic framework may raise awareness of overtesting and prompt clinicians to change their test request behaviour. The development of a scale to assess clinician knowledge, attitudes and practices is planned to allow evaluation of clinician-targeted interventions to reduce overtesting.

Estimating the seroprevalence of SARS-CoV-2 infections: systematic review

Abstract: Background Accurate seroprevalence estimates of SARS-CoV-2 in different populations could clarify the extent to which current testing strategies are identifying all active infection, and hence the true magnitude and spread of the infection. Our primary objective was to identify valid seroprevalence studies of SARS-CoV-2 infection and compare their estimates with the reported and imputed COVID-19 case rates within the same population at the same time point. Methods We searched PubMed, Embase, the Cochrane COVID-19 trials, and Europe-PMC for published studies and pre-prints that reported anti-SARS-CoV-2 IgG, IgM and/or IgA antibodies for serosurveys of the general community from 1 Jan to 12 Aug 2020. Results Of the 2199 studies identified, 170 were assessed for full text and 17 studies representing 15 regions and 118,297 subjects were includable. The seroprevalence proportions in 8 studies ranged between 1%-10%, with 5 studies under 1%, and 4 over 10% - from the notably hard-hit regions of Gangelt, Germany; Northwest Iran; Buenos Aires, Argentina; and Stockholm, Sweden. For seropositive cases who were not previously identified as COVID-19 cases, the majority had prior COVID-like symptoms. The estimated seroprevalences ranged from 0.56-717 times greater than the number of reported cumulative cases – half of the studies reported greater than 10 times more SARS-CoV-2 infections than the cumulative number of cases. Conclusions The findings show SARS-CoV-2 seroprevalence is well below herd immunity in all countries studied. The estimated number of infections, however, were much greater than the number of reported cases and deaths in almost all locations. The majority of seropositive people reported prior COVID-like symptoms, suggesting that undertesting of symptomatic people may be causing a substantial under-ascertainment of SARS-CoV-2 infections. Key messages Systematic assessment of 17-country data show SARS-CoV-2 seroprevalence is mostly less than 10% - levels well below “herd immunity”. High symptom rates in seropositive cases suggest undertesting of symptomatic people and could explain gaps between seroprevalence rates and reported cases. The estimated number of infections for majority of the studies ranged from 2-717 times greater than the number of reported cases in that region and up to 13 times greater than the cases imputed from number of reported deaths.

Trends in knee magnetic resonance imaging, arthroscopies and joint replacements in older Australians: still too much low‐value care?

Abstract: Background The objective of the study is to describe temporal trends and regional variations in the use of knee magnetic resonance imaging (MRI), knee arthroscopy and total knee replacement surgery in Australians older than 55 years.Methods Design: A retrospective descriptive study using routinely collected administrative data. Main outcome measures: Age-standardized rates of knee MRI, knee arthroscopy and knee replacement surgery from 2003 to 2017.Results Knee MRI rates increased from 216/100 000 in 2003, to 1509/100 000 in 2017 (sevenfold relative increase). Knee arthroscopy rates initially increased from 372/100 000 in 2003 to a maximum of 475/100 000 in 2011, before declining to 283/100 000 in 2017. Knee joint replacement surgery increased from 535/100 000 in 2003 to 840/100 000 in 2017 (57% relative increase). The use of MRI increased in all regions of Australia but to differing extents. Knee arthroscopy rates declined in all regions from 2011, but to differing extents. Knee joint replacement surgery increased at roughly the same rate across Australia.Conclusion Knee arthroscopy rates increased before declining modestly in more recent years, most likely in response to evidence against its effectiveness. Knee MRI rates have continued to increase despite consistent recommendations against their routine use in the evaluation of knee pain. Future research could investigate potential drivers of the increased use of MRI, and of the continued use of arthroscopy. Further exploration of the extent to which either procedure explains the increase in numbers of knee joint replacements is also warranted.

Potential Consequences of Changing Disease Classifications

Abstract: This Viewpoint discusses the potential harms that can emerge from changing disease classifications, generally to broaden criteria for diagnosing greater numbers of patients, and calls for a balanced and systematic evaluation of the benefits and risks of shifting illness thresholds before formalizing changes.

Is the risk of cancer in Australia overstated? The importance of competing mortality for estimating lifetime risk

Abstract: Objectives To calculate lifetime risks of cancer diagnosis and cancer-specific death, adjusted for competing mortality, and to compare these estimates with the corresponding risks published by the Australian Institute of Health and Welfare (AIHW). Design, setting Analysis of publicly available annual AIHW data on age-specific cancer incidence and mortality - for breast cancer, colorectal cancer, prostate cancer, melanoma of the skin, and lung cancer - and all-cause mortality in Australia, 1982-2013. Outcome measures Lifetime risks of cancer diagnosis and mortality (to age 85), adjusted for competing mortality. Results During 1982-2013, AIHW estimates were consistently higher than our competing mortality-adjusted estimates of lifetime risks of diagnosis and death for all five cancers. Differences between AIHW and adjusted estimates declined with time for breast cancer, prostate cancer, colorectal cancer, and lung cancer (for men only), but remained steady for lung cancer (women only) and melanoma of the skin. In 2013, the respective estimated lifetime risks of diagnosis (AIHW and adjusted) were 12.7% and 12.1% for breast cancer, 18.7% and 16.2% for prostate cancer, 9.0% and 7.0% (men) and 6.4% and 5.5% (women) for colorectal cancer, 7.5% and 6.0% (men) and 4.4% and 4.0% (women) for melanoma of the skin, and 7.6% and 5.8% (men) and 4.5% and 3.9% (women) for lung cancer. Conclusion The method employed in Australia to calculate the lifetime risks of cancer diagnosis and mortality overestimates these risks, especially for men.

Test accuracy and potential sources of bias in diagnostic test evaluation.

Abstract: Understanding how to interpret diagnostic test accuracy studies is a key skill that health practitioners need to develop in order to undertake evidencebased practice.1 In this article we guide the reader through how to interpret a diagnostic test accuracy study, including the potential for bias. In subsequent articles we will discuss how diagnostic tests may be applied in clinical practice and consider key concepts in population screening and overdiagnosis.

Why We Might Not Need to Stress About Ruling Out Inducible Myocardial Ischemia.

Abstract: Walter and colleagues investigated whether high-sensitivity cardiac troponin tests could be used to rule out inducible ischemia in patients with stable angina and conclude that they cannot. The edi...