Should low-risk DCIS lose the cancer label? An evidence review.

BACKGROUND: Population mammographic screening for breast cancer has led to large increases in the diagnosis and treatment of ductal carcinoma in situ (DCIS). Active surveillance has been proposed as a management strategy for low-risk DCIS to mitigate against potential overdiagnosis and overtreatment. However, clinicians and patients remain reluctant to choose active surveillance, even within a trial setting. Re-calibration of the diagnostic threshold for low-risk DCIS and/or use of a label that does not include the word 'cancer' might encourage the uptake of active surveillance and other conservative treatment options. We aimed to identify and collate relevant epidemiological evidence to inform further discussion on these ideas. METHODS: We searched PubMed and EMBASE databases for low-risk DCIS studies in four categories: (1) natural history; (2) subclinical cancer found at autopsy; (3) diagnostic reproducibility (two or more pathologist interpretations at a single time point); and (4) diagnostic drift (two or more pathologist interpretations at different time points). Where we identified a pre-existing systematic review, the search was restricted to studies published after the inclusion period of the review. Two authors screened records, extracted data, and performed risk of bias assessment. We undertook a narrative synthesis of the included evidence within each category. RESULTS: Natural History (n = 11): one systematic review and nine primary studies were included, but only five provided evidence on the prognosis of women with low-risk DCIS. These studies reported that women with low-risk DCIS had comparable outcomes whether or not they had surgery. The risk of invasive breast cancer in patients with low-risk DCIS ranged from 6.5% (7.5 years) to 10.8% (10 years). The risk of dying from breast cancer in patients with low-risk DCIS ranged from 1.2 to 2.2% (10 years). Subclinical cancer at autopsy (n = 1): one systematic review of 13 studies estimated the mean prevalence of subclinical in situ breast cancer to be 8.9%. Diagnostic reproducibility (n = 13): two systematic reviews and 11 primary studies found at most moderate agreement in differentiating low-grade DCIS from other diagnoses. Diagnostic drift: no studies found. CONCLUSION: Epidemiological evidence supports consideration of relabelling and/or recalibrating diagnostic thresholds for low-risk DCIS. Such diagnostic changes would need agreement on the definition of low-risk DCIS and improved diagnostic reproducibility.

Low-risk prostate lesions: An evidence review to inform discussion on losing the "cancer" label.

BACKGROUND: Active surveillance (AS) mitigates harms from overtreatment of low-risk prostate lesions. Recalibration of diagnostic thresholds to redefine which prostate lesions are considered "cancer" and/or adopting alternative diagnostic labels could increase AS uptake and continuation. METHODS: We searched PubMed and EMBASE to October 2021 for evidence on: (1) clinical outcomes of AS, (2) subclinical prostate cancer at autopsy, (3) reproducibility of histopathological diagnosis, and (4) diagnostic drift. Evidence is presented via narrative synthesis. RESULTS: AS: one systematic review (13 studies) of men undergoing AS found that prostate cancer-specific mortality was 0%-6% at 15 years. There was eventual termination of AS and conversion to treatment in 45%-66% of men. Four additional cohort studies reported very low rates of metastasis (0%-2.1%) and prostate cancer-specific mortality (0%-0.1%) over follow-up to 15 years. Overall, AS was terminated without medical indication in 1%-9% of men. Subclinical reservoir: 1 systematic review (29 studies) estimated that the subclinical cancer prevalence was 5% at <30 years, and increased nonlinearly to 59% by >79 years. Four additional autopsy studies (mean age: 54-72 years) reported prevalences of 12%-43%. Reproducibility: 1 recent well-conducted study found high reproducibility for low-risk prostate cancer diagnosis, but this was more variable in 7 other studies. Diagnostic drift: 4 studies provided consistent evidence of diagnostic drift, with the most recent (published 2020) reporting that 66% of cases were upgraded and 3% were downgraded when using contemporary diagnostic criteria compared to original diagnoses (1985-1995). CONCLUSIONS: Evidence collated may inform discussion of diagnostic changes for low-risk prostate lesions.

Armodafinil to reduce the sleepiness related side-effects of sleep restriction therapy being used to treat insomnia disorder: An open label clinical trial pilot study compared with historical controls.

Sleep restriction therapy (SRT) is an effective stand-alone behavioural intervention for insomnia disorder. However, its daytime side effects, particularly sleepiness, may be troubling for patients and/or may be a necessary part of the patient's treatment journey. This pilot trial aims to explore the potential benefit of armodafinil, a wakefulness promoter. Patients were treated with SRT with open label adjunctive armodafinil (150 mg/day). Thirty-three patients from previous studies that have undergone exactly the same SRT intervention acted as controls. The primary outcome measure was the insomnia severity index (ISI), and secondary outcomes were the Epworth sleepiness scale, sleep restriction adherence scale (SRAS), and safety from baseline through to 12 weeks. We recruited 25 patients into the trial. Data for the primary end point (ISI at 12 weeks) was available for 20 of the participants. The baseline insomnia severity index was 20.2 (SD 3.3) and decreased to 9.1 (SE 1.1), with no change, to 10.2 and 11.2 at weeks 6 and 12 respectively (all p > 0.05 compared with baseline). The insomnia severity index values for armodafinil patients were statistically inferior to historical controls at the primary time point of 12 weeks (11.2 vs. 6.7, p < 0.01). Sleep restriction therapy plus armodafinil treatment was associated with frequent minor side effects but was generally safe and acceptable to patients. Sleep restriction therapy was associated with a robust clinical response in the insomnia severity index values for insomnia patients. Based upon historical control data, armodafinil does not appear to have beneficial adjunctive effects in addition to sleep restriction therapy alone.

The need for sleep and circadian education in Australian high schools: incidental results from a survey of university students.

ISSUE ADDRESSED: To describe the need for high school sleep education from the perspective of undergraduate university students. METHODS: Undergraduate students who completed an online course on sleep and circadian health were surveyed 6 months after course completion. Students were asked whether a similar course would have benefited them as high school students, and about the need for sleep education in high schools. Thematic analysis of this qualitative data was carried out. RESULTS: Eighty-nine students who had attended 71 unique high schools provided responses. Eight-one per cent thought they would have benefitted from a similar course during high school and identified domains of sleep knowledge particularly relevant to high school students. They cited environmental barriers to healthy sleep present during high school and believed that sleep education could improve students' lifestyle, sleep and performance. Nineteen per cent of students said they would not have benefited, because they perceived sleeping patterns during high school to be nonmodifiable or believed that previous sleep education was sufficient. Of the respondents who did not think students would benefit, 53% would still tell their high school principal that there was a need for sleep education. CONCLUSIONS: The findings support the need for engaging sleep education for high school students. Future studies should examine the perspectives of students in high school directly, rather than undergraduate students who have already shown an interest in sleep health. SO WHAT?: Sleep health is missing from the Australian school curriculum. Online courses may be an engaging method of promoting sleep and circadian health to high school students.

Impact of an Online Sleep and Circadian Education Program on University Students' Sleep Knowledge, Attitudes, and Behaviours.

University students consistently report poor sleep. We conducted a before-and-after study to evaluate the impact of an online 10-week course on undergraduate students' sleep knowledge, attitudes, and behaviours at 6-month follow-up. Data were collected via baseline course surveys (August-September 2020) and follow-up surveys distributed via email (February-March 2021). n = 212 students completed baseline surveys and n = 75 (35%) completed follow-up. Students retained to follow-up possessed higher baseline sleep knowledge and received higher course grades. At the 6-month follow-up, sleep knowledge had increased (mean score out of 5: 3.0 vs. 4.2, p < 0.001). At baseline, 85% of students aimed to increase their sleep knowledge and 83% aimed to improve their sleep. At follow-up, 91% reported being more knowledgeable and 37% reported improved sleep. A novel Stages of Change item revealed that 53% of students' attitudes towards their sleep behaviours had changed from baseline. There was a reduction in sleep latency at follow-up (mean 33.3 vs. 25.6 min, p = 0.015), but no change in the total Pittsburgh Sleep Quality Index score. In summary, completion of an online course led to increased sleep and circadian knowledge and changed sleep attitudes, with no meaningful change in sleep behaviours. Future interventions should consider components of behavioural change that go beyond the knowledge-attitudes-behaviour continuum.

Rethinking Low-Risk Papillary Thyroid Cancers < 1cm (Papillary Microcarcinomas): An Evidence Review for Recalibrating Diagnostic Thresholds and/or Alternative Labels.

Background: Recalibrating diagnostic thresholds or using alternative labels may mitigate overdiagnosis and overtreatment of papillary microcarcinoma (mPTC). We aimed at identifying and collating relevant epidemiological evidence on mPTC, to assess the case for recalibration and/or new labels. Methods: We searched EMBASE and PubMed databases from inception to December 2020 for natural history, autopsy, diagnostic drift, and diagnostic reproducibility studies. Where a relevant systematic review was pre-identified, only new articles were additionally included. Non-English articles were excluded. One author screened titles and abstracts. Two authors screened full text articles, performed quality assessments, and extracted data. We undertook narrative synthesis of included evidence (pooled estimates from systematic reviews and single estimates from primary studies). Results: One systematic review of patients undergoing active surveillance found that after 5 years of follow-up, 5.3% (95% confidence interval [CI 4.4-6.4%]) of the mPTC lesions had increased in size by ≥3 mm, and 1.6% [CI 1.1-2.4%] of patients had lymph node metastases. Among 7 new primary studies (including 3 updates on 2 studies included in the systematic review), 1-5% of patients undergoing active surveillance had lymph node metastases after a median follow-up of 1-10 years. One systematic review found that subclinical thyroid cancer incidentally discovered at autopsy is relatively common, with a pooled prevalence of 11.2% [CI 6.7-16.1%] among studies that examined the whole thyroid. Four diagnostic drift studies evaluated the new classification of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Three studies of cases previously diagnosed as papillary thyroid cancer found 1.3-2.3% were reclassified as NIFTP (reclassifications were from follicular variation of papillary thyroid cancer [FVPTC]). One study of 48 cases previously diagnosed as mPTC found that 23.5% were reclassified as NIFTP. Thirteen reproducibility studies of papillary thyroid lesions found substantial variation in the histopathological diagnosis of thyroid lesions, including FVPTC and NIFTP classifications (no study evaluated mPTC). Conclusions: This review supports consideration of recalibrating diagnostic thresholds and/or alternative labels for low-risk mPTC.

Clinical Profile and Health Disparities in a Multiethnic Cohort of Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: Clinical studies of hypertrophic cardiomyopathy are over-represented by individuals of European ethnicity, with less known about other ethnic groups. We investigated differences between patients in a multiethnic Australian hypertrophic cardiomyopathy population. METHODS: We performed a retrospective cohort study of 836 unrelated hypertrophic cardiomyopathy probands attending a specialized clinic between 2002 and 2020. Major ethnic groups were European (n=611), East Asian (n=75), South Asian (n=58), and Middle Eastern and North African (n=68). The minor ethnicity groups were Oceanian (n=9), People of the Americas (n=7), and African (n=8). One-way ANOVA with Dunnett post hoc test and Bonferroni adjustment were performed. RESULTS: Mean age of the major ethnic groups was 54.9±16.9 years, and 527 (65%) were male. Using the European group as the control, East Asian patients had a lower body mass index (29 versus 25 kg/m2, P<0.0001). South Asians had a lower prevalence of atrial fibrillation (10% versus 31%, P=0.024). East Asians were more likely to have apical hypertrophy (23% versus 6%, P<0.0001) and Middle Eastern and North African patients more likely to present with left ventricular outflow tract obstruction (46% versus 34%, P=0.0003). East Asians were less likely to undergo genetic testing (55% versus 85%, P<0.0001) or have an implantable cardioverter-defibrillator implanted (19% versus 36%, P=0.037). East Asians were more likely to have a causative variant in a gene other than MYBPC3 or MYH7, whereas Middle Eastern and North African and South Asians had the highest rates of variants of uncertain significance (27% and 21%, P<0.0001). CONCLUSIONS: There are few clinical differences based on ethnicity, but importantly, we identify health disparities relating to access to genetic testing and implantable cardioverter-defibrillator use. Unless addressed, these gaps will likely widen as we move towards precision-medicine-based care of individuals with hypertrophic cardiomyopathy.

Journey to glaucoma care - trusting but uncertain and uninformed: a qualitative study.

BACKGROUND: This study aims to explore patient perspectives regarding their journey to glaucoma care and sought to understand the determinants that guide their access to tertiary glaucoma care. METHODS: Twenty-nine patients who are glaucoma suspects or had definitive diagnosis of glaucoma were recruited from a large public glaucoma clinic and a private ophthalmology clinic in Sydney. Face-to-face, in-depth semi-structured interviews were conducted between April and December 2017. Interviews were recorded and transcribed verbatim. A framework method was used for thematic analysis of the data. RESULTS: Thematic analysis resulted in the emergence of eight main themes. There was limited patient participation in decision making in their journey to glaucoma care. Consequently, there was great trust placed in the referring clinician. Patients valued their vision and therefore expressed a desire for high-quality care. They placed considerable trust in their specialist but were often unsure how to evaluate the quality of care received. Patients lacked an understanding of the cost of glaucoma care and for some, cost remained a barrier to the access of private care. There were variable experiences with waiting times and the journey to clinic, with many patients making concessions and requiring support to access care. CONCLUSION: This study is the first qualitative study exploring the perspectives of glaucoma patients in Australia and the determinants of access to care. These findings support and can inform development of patient-centred models of care furthering patient trust and empowerment.