Re: Hofmann et al. Overdiagnosis, one concept, three perspectives, and a model.

It is with great interest we have read the article "Overdiagnosis: one concept, three perspectives, and a model" by Hofmann and colleagues. We share the authors' ambition of understanding what overdiagnosis is and what it isn't. In our research, we define overdiagnosis on the basis of two interrelated phenomena: overdetection and overdefinition. Overdetection is the labelling of a person with a disease or abnormal condition, that would not have caused the person harm, e.g., symptoms or death, if left undiscovered. Overdefinition is the creation of new diagnoses by overmedicalising ordinary life experiences or expanding existing diagnoses by lowering thresholds or widening diagnostic criteria, without evidence of improved outcomes. These phenomena have different causes and thereby often different drivers. However, they have one important consequence in common: people are turned into patients unnecessarily, i.e., overdiagnosed. On a personal level, overdiagnosis cause various types of harms, including physical, psychological, social and financial harm. On a societal level, overdiagnosis may also cause harm to public health, cause resource waste, and cultural changes with overmedicalisation of normal life events. By definition, none of the aforementioned phenomena lead to any clinical benefit. Therefore, we disagree with Hofmann and colleagues' definition of overdiagnosis as diagnoses that "…on balance, do more harm than good.". We argue that introducing balance and benefits to the definition of overdiagnosis complicates the concept unnecessarily and cause problems operationalising overdiagnosis.

Interventions promoting recovery from depression for patients transitioning from outpatient mental health services to primary care: A scoping review.

INTRODUCTION: Major Depressive Disorder (MDD) is one of the most prevalent mental disorders worldwide with significant personal and public health consequences. After an episode of MDD, the likelihood of relapse is high. Therefore, there is a need for interventions that prevent relapse of depression when outpatient mental health care treatment has ended. This scoping review aimed to systematically map the evidence and identify knowledge gaps in interventions that aimed to promote recovery from MDD for patients transitioning from outpatient mental health services to primary care. MATERIALS AND METHODS: We followed the guidance by Joanna Briggs Institute in tandem with the PRISMA extension for Scoping Reviews checklist. Four electronic databases were systematically searched using controlled index-or thesaurus terms and free text terms, as well as backward and forward citation tracking of included studies. The search strategy was based on the identification of any type of intervention, whether simple, multicomponent, or complex. Three authors independently screened for eligibility and extracted data. RESULTS: 18 studies were included for review. The studies had high heterogeneity in design, methods, sample size, recovery rating scales, and type of interventions. All studies used several elements in their interventions; however, the majority used cognitive behavioural therapy conducted in outpatient mental health services. No studies addressed the transitioning phase from outpatient mental health services to primary care. Most studies included patients during their outpatient mental health care treatment of MDD. CONCLUSIONS: We identified several knowledge gaps. Recovery interventions for patients with MDD transitioning from outpatient mental health services to primary care are understudied. No studies addressed interventions in this transitioning phase or the patient's experience of the transitioning process. Research is needed to bridge this gap, both regarding interventions for patients transitioning from secondary to primary care, and patients' and health care professionals' experiences of the interventions and of what promotes recovery. REGISTRATION: A protocol was prepared in advance and registered in Open Science Framework (https://osf.io/ah3sv), published in the medRxiv server (https://doi.org/10.1101/2022.10.06.22280499) and in PLOS ONE (https://doi.org/10.1371/journal.pone.0291559).

Deaths and cardiopulmonary events following colorectal cancer screening-A systematic review with meta-analyses.

BACKGROUND: Colorectal cancer screening programmes (CRCSPs) are implemented worldwide despite recent evidence indicating more physical harm occurring during CRCSPs than previously thought. Therefore, we aimed to review the evidence on physical harms associated with endoscopic diagnostic procedures during CRCSPs and, when possible, to quantify the risk of the most serious types of physical harm during CRCSPs, i.e. deaths and cardiopulmonary events (CPEs). METHODS: Systematic review with descriptive statistics and random-effects meta-analyses of studies investigating physical harms following CRCSPs. We conducted a systematic search in the literature and assessed the risk of bias and the certainty of the evidence. RESULTS: We included 134 studies for review, reporting findings from 151 unique populations when accounting for multiple screening interventions per study. Physical harm can be categorized into 17 types of harm. The evidence was very heterogeneous with inadequate measurement and reporting of harms. The risk of bias was serious or critical in 95% of assessments of deaths and CPEs, and the certainty of the evidence was very low in all analyses. The risk of death was assessed for 57 populations with large variation across studies. Meta-analyses indicated that 3 to 23 deaths occur during CRCSPs per 100,000 people screened. Cardiopulmonary events were assessed for 55 populations. Despite our efforts to subcategorize CPEs into 17 distinct subtypes, 41% of CPE assessments were too poorly measured or reported to allow quantification. We found a tendency towards lower estimates of deaths and CPEs in studies with a critical risk of bias. DISCUSSION: Deaths and CPEs during CRCSPs are rare, yet they do occur during CRCSPs. We believe that our findings are conservative due to the heterogeneity and low quality of the evidence. A standardized system for the measurement and reporting of the harms of screening is warranted. TRIAL REGISTRATION: PROSPERO Registration number CRD42017058844.

Quantification of overdiagnosis in randomised trials of cancer screening: an overview and re-analysis of systematic reviews.

The degree of overdiagnosis in common cancer screening trials is uncertain due to inadequate design of trials, varying definition and methods used to estimate overdiagnosis. Therefore, we aimed to quantify the risk of overdiagnosis for the most widely implemented cancer screening programmes and assess the implications of design limitations and biases in cancer screening trials on the estimates of overdiagnosis by conducting an overview and re-analysis of systematic reviews of cancer screening. We searched PubMed and the Cochrane Library from their inception dates to November 29, 2021. Eligible studies included systematic reviews of randomised trials comparing cancer screening interventions to no screening, which reported cancer incidence for both trial arms. We extracted data on study characteristics, cancer incidence and assessed the risk of bias using the Cochrane Collaboration's risk of bias tool. We included 19 trials described in 30 articles for review, reporting results for the following types of screening: mammography for breast cancer, chest X-ray or low-dose CT for lung cancer, alpha-foetoprotein and ultrasound for liver cancer, digital rectal examination, prostate-specific antigen, and transrectal ultrasound for prostate cancer, and CA-125 test and/or ultrasound for ovarian cancer. No trials on screening for melanoma were eligible. Only one trial (5%) had low risk in all bias domains, leading to a post-hoc meta-analysis, excluding trials with high risk of bias in critical domains, finding the extent of overdiagnosis ranged from 17% to 38% across cancer screening programmes. We conclude that there is a significant risk of overdiagnosis in the included randomised trials on cancer screening. We found that trials were generally not designed to estimate overdiagnosis and many trials had high risk of biases that may draw the estimates of overdiagnosis towards the null. In effect, the true extent of overdiagnosis due to cancer screening is likely underestimated.

Methodological Quality of PROMs in Psychosocial Consequences of Colorectal Cancer Screening: A Systematic Review.

Objective: This systematic review aimed to assess the adequacy of measurement properties in Patient-Reported Outcome Measures (PROMs) used to quantify psychosocial consequences of colorectal cancer screening among adults at average risk. Methods: We searched four databases for eligible studies: MEDLINE, CINAHL, PsycINFO, and Embase. Our approach was inclusive and encompassed all empirical studies that quantified aspects of psychosocial consequences of colorectal cancer screening. We assessed the adequacy of PROM development and measurement properties for content validity using The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) risk of bias checklist. Results: We included 33 studies that all together used 30 different outcome measures. Two PROMs (6.7%) were developed in a colorectal cancer screening context. COSMIN rating for PROM development was inadequate for 29 out of 30 PROMs (97%). PROMs lacked proper cognitive interviews and pilot studies and therefore had no proven content validity. According to the COSMIN checklist, 27 out of 30 PROMs (90%) had inadequate measurement properties for content validity. Discussion: The majority of included PROMs had inadequate development and measurement properties. These findings shed light on the trustworthiness of the included studies' findings and call for reevaluation of existing evidence on the psychosocial consequences of colorectal cancer screening. To provide trustworthy evidence about the psychosocial consequences of colorectal cancer screening, editors could require that studies provide evidence of the methodological quality of the PROM. Alternatively, authors should transparently disclose their studies' methodological limitations in measuring psychosocial consequences of screening validly.

Interventions promoting recovery from depression for patients transitioning from outpatient mental health services to primary care: Protocol for a scoping review.

INTRODUCTION: Patients with severe Major Depressive Disorder (MDD) have an increasing risk of new psychiatric hospitalizations following each new episode of depression highlighting the recurrent nature of the disorder. Furthermore, patients are not fully recovered at the end of their treatment in outpatient mental health services, and residual symptoms of depression might explain why patients with MDD have a high risk of relapse. However, evidence of methods to promote recovery after discharge from outpatient mental health services is lacking. The proposed scoping review aims to systematically scope, map and identify the evidence and knowledge gaps on interventions that aims to promote recovery from MDD for patients transitioning from outpatient mental health services to primary care. MATERIALS AND METHODS: The proposed scoping review will follow the latest methodological guidance by the Joanna Briggs Institute (JBI) in tandem with the Preferred Reporting Items for Systematic reviews and Meta-Analysis-extension for Scoping Reviews (PRISMA-ScR) checklist. The review is ongoing. Four electronic databases (Medline via PubMed, PsycINFO, CINAHL, and Sociological Abstracts) were systematically searched from 20 January 2022 till 29 March 2022 using keywords and text words. The review team consists of three independent screeners. Two screeners have completed the initial title and abstract screening for all studies retrieved by the search strategy. Currently, we are in the full text screening phase. Reference lists of included studies will be screened, and data will be independently extracted by the review team. Results will be analyzed qualitatively and quantitatively. DISCUSSION: The chosen methodology is based on the use of publicly available information and does not require ethical approval. Results will be published in an international peer reviewed scientific journal, at national and international conferences and shared with relevant authorities. REGISTRATION: A pre-print has been registered at the medRxiv preprint server for health sciences (doi.org/10.1101/2022.10.06.22280499).

The SOFIA pilot study: assessing feasibility and fidelity of coordinated care to reduce excess mortality and increase quality of life in patients with severe mental illness in a general practice setting; a cluster-randomised pilot trial.

OBJECTIVE: To evaluate the feasibility and fidelity of implementing and assessing the SOFIA coordinated care program aimed at lowering mortality and increasing quality of life in patients with severe mental illness by improving somatic health care in general practice. DESIGN: A cluster-randomised, non-blinded controlled pilot trial. SETTING: General Practice in Denmark. INTERVENTION: The SOFIA coordinated care program comprised extended structured consultations carried out by the GP, group-based training of GPs and staff, and a handbook with information on signposting patients to relevant municipal, health, and social initiatives. PATIENTS: Persons aged 18 years or older with a diagnosis of psychotic, bipolar, or severe depressive disorder. MAIN OUTCOME MEASURES: We collected quantitative data on the delivery, recruitment and retention rates of practices and patients, and response rates of questionnaires MMQ and EQ-5D-5 L. RESULTS: From November 2020 to March 2021, nine practices were enrolled and assigned in a 2:1 ratio to the intervention group (n = 6) or control group (n = 3). Intervention group practices included 64 patients and Control practices included 23. The extended consultations were delivered with a high level of fidelity in the general practices; however, thresholds for collecting outcome measures, and recruitment of practices and patients were not reached. CONCLUSION: Our findings suggest that delivering the coordinated care program in a fully powered trial in primary care is likely feasible. However, the recruitment methodology requires improvement to ensure sufficient recruitment and minimize selective inclusion. TRIAL REGISTRATION: The date of pilot trial protocol registration was 05/11/2020, and the registration number is NCT04618250.

The risk of bleeding and perforation from sigmoidoscopy or colonoscopy in colorectal cancer screening: A systematic review and meta-analyses.

INTRODUCTION: Physical harm from Colorectal Cancer Screening tends to be inadequately measured and reported in clinical trials. Also, studies of ongoing Colorectal Cancer Screening programs have found more frequent and severe physical harm from screening procedures, e.g., bleeding and perforation, than reported in previous trials. Therefore, the objectives of the study were to systematically review the evidence on the risk of bleeding and perforation in Colorectal Cancer Screening. DESIGN: Systematic review with descriptive statistics and random-effects meta-analyses. METHODS: We systematically searched five databases for studies investigating physical harms related to Colorectal Cancer Screening. We assessed the internal and the external validity using the ROBINS-I tool and the GRADE approach. Harm estimates was calculated using mixed Poisson regression models in random-effect meta-analyses. RESULTS: We included 89 studies. Reporting and measurement of harms was inadequate in most studies. In effect, the risk of bias was critical in 97.3% and serious in 98.3% of studies. All GRADE ratings were very low. Based on severe findings with not-critical risk of bias and 30 days follow-up, the risk of bleedings per 100,000 people screened were 8 [2;24] for sigmoidoscopy, 229 [129;408] for colonoscopy following fecal immunochemical test, 68 [39;118] for once-only colonoscopy, and 698 [443;1045] for colonoscopy following any screening tests. The risk of perforations was 88 [56;138] for colonoscopy following fecal immunochemical test and 53 [25;112] for once-only colonoscopy. There were no findings within the subcategory severe perforation with long-term follow-up for colonoscopy following any screening tests and sigmoidoscopy. DISCUSSION: Harm estimates varied widely across studies, reporting and measurement of harms was mostly inadequate, and the risk of bias and GRADE ratings were very poor, collectively leading to underestimation of harm. In effect, we consider our estimates of perforation and bleeding as conservative, highlighting the need for better reporting and measurement in future studies. TRIAL REGISTRATION: PROSPERO registration number: CRD42017058844.

Validity of Current Assessment Tools Aiming to Measure the Affective Component of Pain: A Systematic Review.

The objective of this study was to identify patient-reported outcome measures (PROMs), which aim to measure the affective component of pain and to assess their content validity, unidimensionality, measurement invariance, and Internal consistency in patients with chronic pain. The study was reported according to the PRISMA guidelines. A protocol of the review was submitted to PROSPERO before data extraction. Eligible studies were any type of study that investigated at least one of the domains: PROM development, content validity, dimensionality, internal consistency, or measurement invariance of any type of scale that claimed to measure the affective component of pain among patients with chronic pain. The databases Medline, Embase, PsycINFO, and the Cochrane Library were searched for eligible studies. The database search was supplemented by looking for relevant articles in the reference list of included studies, ie backtracking. All included studies were assessed independently by two authors according to the "COSMIN methodology on Systematic Reviews of Patient-Reported Outcome Measures". Descriptive data synthesis of the identified PROMs was conducted. The search yielded 11,242 titles of which 283 were assessed at the full-text level. Full-text screening led to the inclusion of 11 studies and an additional 28 studies were identified via backtracking, leading to the inclusion of 39 studies in total in the review. Included studies described the development and validity of 10 unique PROMs, all of which we assessed to have potentially inadequate content validity and doubtful psychometric properties. No studies reported whether the PROMs possessed invariant measurement properties. The existing PROMs measuring affective components of chronic pain potentially lack content validity and have inadequate psychometric measurement properties. There is a need for new PROMs measuring the affective component of chronic pain that possess high content validity and adequate psychometric measurement properties.

Overdiagnosis of lung cancer with low-dose computed tomography screening: meta-analysis of the randomised clinical trials.

In low-dose computed tomography (LDCT) screening for lung cancer, all three main conditions for overdiagnosis in cancer screening are present: 1) a reservoir of slowly or nongrowing lung cancer exists; 2) LDCT is a high-resolution imaging technology with the potential to identify this reservoir; and 3) eligible screening participants have a high risk of dying from causes other than lung cancer. The degree of overdiagnosis in cancer screening is most validly estimated in high-quality randomised controlled trials (RCTs), with enough follow-up time after the end of screening to avoid lead-time bias and without contamination of the control group. Nine RCTs investigating LDCT screening were identified. Two RCTs were excluded because lung cancer incidence after the end of screening was not published. Two other RCTs using active comparators were also excluded. Therefore, five RCTs were included: two trials were at low risk of bias, two of some concern and one at high risk of bias. In a meta-analysis of the two low risk of bias RCTs including 8156 healthy current or former smokers, 49% of the screen-detected cancers were overdiagnosed. There is uncertainty about this substantial degree of overdiagnosis due to unexplained heterogeneity and low precision of the summed estimate across the two trials. KEY POINTS: Nine randomised controlled trials (RCTs) on low-dose computed tomography screening were identified; five were included for meta-analysis but only two of those were at low risk of bias.In a meta-analysis of recent low risk of bias RCTs including 8156 healthy current or former smokers from developed countries, we found that 49% of the screen-detected cancers may be overdiagnosed.There is uncertainty about the degree of overdiagnosis in lung cancer screening due to unexplained heterogeneity and low precision of the point estimate.If only high-quality RCTs are included in the meta-analysis, the degree of overdiagnosis is substantial. EDUCATIONAL AIMS: To appreciate that low-dose computed tomography screening for lung cancer meets all three main conditions for overdiagnosis in cancer screening: a reservoir of indolent cancers exists in the population; the screening test is able to "tap" this reservoir by detecting biologically indolent cancers as well as biologically important cancers; and the population being screened is characterised by a relatively high competing risk of death from other causesTo learn about biases that might affect the estimates of overdiagnosis in randomised controlled trials in cancer screening.