Knowledge and practices regarding prostate cancer screening in Spanish men: The importance of personal and clinical characteristics (PROSHADE study).

INTRODUCTION: Patients' decisions on prostate cancer (PCa) opportunistic screening may vary. This study aimed to assess how demographic and health-related characteristics may influence knowledge and decisions regarding PCa screening. METHODS: A cross-sectional survey was conducted among men aged over 40, randomly sampled from the Spanish population, 2022. The survey underwent development and content validation using a modified Delphi method and was administered via telephone. Binomial logistic regression was used to explore the relationship between respondents' characteristics and participants' knowledge and practices concerning PCa and the PSA test. RESULTS: Out of 1,334 men, 1,067 (80%) respondents were interviewed with a mean age of 58.6 years (sd 11.9). Most had secondary or university studies (787, 73.8%) and 61 (5.7%) self-reported their health status as bad or very bad. Most of the respondents (1,018, 95.4%) had knowledge regarding PCa with nearly 70% expressed significant concern about its potential development (720, 70.8%), particularly among those under 64 years (p = 0.001). Out of 847 respondents, 573 (67.7%) reported that they have knowledge regarding the PSA test: 374 (65.4%) reported receiving information from a clinicians, 324 (86.6%) information about the benefits of the test and 189 (49,5%) about its risks, with differences based on educational background. In a multivariable analysis (adjusted for age, educational level and previous prostate problems), respondents with higher levels of education were more likely to have higher knowledge regarding the PSA test (OR 1.75, 95%CI 1.24-2.50, p<0.001). CONCLUSIONS: Although most of the patients reported to have knowledge regarding PCa, half of the interviewed men reported knowledge about PSA test. Differences in knowledge prostate cancer screening and undesirable consequences highlight the need to develop and provide tailored information for patients.

The impact of exposure to tobacco smoke and e-cigarettes on asthma-related outcomes: Systematic review informing the EAACI guidelines on environmental science for allergic diseases and asthma.

To inform the clinical practice guidelines' recommendations developed by the European Academy of Allergy and Clinical Immunology systematic reviews (SR) assessed using GRADE on the impact of environmental tobacco smoke (ETS) and active smoking on the risk of new-onset asthma/recurrent wheezing (RW)/low lung function (LF), and on asthma-related outcomes. Only longitudinal studies were included, almost all on combustion cigarettes, only one assessing e-cigarettes and LF. According to the first SR (67 studies), prenatal ETS increases the risk of RW (moderate certainty evidence) and may increase the risk of new-onset asthma and of low LF (low certainty evidence). Postnatal ETS increases the risk of new-onset asthma and of RW (moderate certainty evidence) and may impact LF (low certainty evidence). Combined in utero and postnatal ETS may increase the risk of new-onset asthma (low certainty evidence) and increases the risk of RW (moderate certainty evidence). According to the second SR (24 studies), ETS increases the risk of severe asthma exacerbations and impairs asthma control and LF (moderate certainty evidence). According to the third SR (25 studies), active smoking increases the risk of severe asthma exacerbations and of suboptimal asthma control (moderate certainty evidence) and may impact asthma-related quality-of-life and LF (low certainty evidence).

One-year Outcomes after Discharge from Noncardiac Surgery and Association between Predischarge Complications and Death after Discharge: Analysis of the VISION Prospective Cohort Study.

BACKGROUND: In previous analyses, myocardial injury after noncardiac surgery, major bleeding, and sepsis were independently associated with most deaths in the 30 days after noncardiac surgery, but most of these deaths occurred during the index hospitalization for surgery. The authors set out to describe outcomes after discharge from hospital up to 1 yr after inpatient noncardiac surgery and associations between predischarge complications and postdischarge death up to 1 yr after surgery. METHODS: This study was an analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007 to 2013 of patients aged 45 yr or older followed to 1 yr after surgery. The study estimated (1) the cumulative postdischarge incidence of death and other outcomes up to a year after surgery and (2) the adjusted time-varying associations between postdischarge death and predischarge complications including myocardial injury after noncardiac surgery, major bleeding, sepsis, infection without sepsis, stroke, congestive heart failure, clinically important atrial fibrillation or flutter, amputation, venous thromboembolism, and acute kidney injury managed with dialysis. RESULTS: Among 38,898 patients discharged after surgery, the cumulative 1-yr incidence was 5.8% (95% CI, 5.5 to 6.0%) for all-cause death and 24.7% (95% CI, 24.2 to 25.1%) for all-cause hospital readmission. Predischarge complications were associated with 33.7% (95% CI, 27.2 to 40.2%) of deaths up to 30 days after discharge and 15.0% (95% CI, 12.0 to 17.9%) up to 1 yr. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% [95% CI, 9.3 to 21.9%] of deaths within 30 days, 6.4% [95% CI, 4.1 to 8.7%] within 1 yr), major bleeding (15.0% [95% CI, 8.3 to 21.7%] within 30 days, 4.7% [95% CI, 2.2 to 7.2%] within 1 yr), and sepsis (5.4% [95% CI, 2.2 to 8.6%] within 30 days, 2.1% [95% CI, 1.0 to 3.1%] within 1 yr). CONCLUSIONS: One in 18 patients 45 yr old or older discharged after inpatient noncardiac surgery died within 1 yr, and one quarter were readmitted to the hospital. The risk of death associated with predischarge perioperative complications persists for weeks to months after discharge.

The Relevance of Implementing the Systematic Screening of Perioperative Myocardial Injury in Noncardiac Surgery Patients.

Perioperative myocardial injury (PMI) is a common cardiac complication. Recent guidelines recommend its systematic screening using high-sensitivity cardiac troponin (hs-cTn). However, there is limited evidence of local screening programs. We conducted a prospective, single-center study aimed at assessing the feasibility and outcomes of implementing systematic PMI screening. Hs-cTn concentrations were measured before and after surgery. PMI was defined as a postoperative hs-cTnT of ≥14 ng/L, exceeding the preoperative value by 50%. All patients were followed-up during the hospitalization, at one month and one year after surgery. The primary outcome was the incidence of death and major cardiovascular and cerebrovascular events (MACCE). The secondary outcomes focused on the individual components of MACCE. We included two-thirds of all eligible high-risk patients and achieved almost complete compliance with follow-ups. The prevalence of PMI was 15.7%, suggesting a higher presence of cardiovascular (CV) antecedents, increased perioperative CV complications, and higher preoperative hs-cTnT values. The all-cause death rate was 1.7% in the first month, increasing up to 11.2% at one year. The incidence of MACCE was 9.5% and 8.6% at the same time points. Given the observed elevated frequencies of PMI and MACCE, implementing systematic PMI screening is recommendable, particularly in patients with increased cardiovascular risk. However, it is important to acknowledge that achieving optimal screening implementation comes with various challenges and complexities.

Characteristics and impact of interventions to support healthcare providers' compliance with guideline recommendations for breast cancer: a systematic literature review.

BACKGROUND: Breast cancer clinical practice guidelines (CPGs) offer evidence-based recommendations to improve quality of healthcare for patients. Suboptimal compliance with breast cancer guideline recommendations remains frequent, and has been associated with a decreased survival. The aim of this systematic review was to characterize and determine the impact of available interventions to support healthcare providers' compliance with CPGs recommendations in breast cancer healthcare. METHODS: We searched for systematic reviews and primary studies in PubMed and Embase (from inception to May 2021). We included experimental and observational studies reporting on the use of interventions to support compliance with breast cancer CPGs. Eligibility assessment, data extraction and critical appraisal was conducted by one reviewer, and cross-checked by a second reviewer. Using the same approach, we synthesized the characteristics and the effects of the interventions by type of intervention (according to the EPOC taxonomy), and applied the GRADE framework to assess the certainty of evidence. RESULTS: We identified 35 primary studies reporting on 24 different interventions. Most frequently described interventions consisted in computerized decision support systems (12 studies); educational interventions (seven), audit and feedback (two), and multifaceted interventions (nine). There is low quality evidence that educational interventions targeted to healthcare professionals may improve compliance with recommendations concerning breast cancer screening, diagnosis and treatment. There is moderate quality evidence that reminder systems for healthcare professionals improve compliance with recommendations concerning breast cancer screening. There is low quality evidence that multifaceted interventions may improve compliance with recommendations concerning breast cancer screening. The effectiveness of the remaining types of interventions identified have not been evaluated with appropriate study designs for such purpose. There is very limited data on the costs of implementing these interventions. CONCLUSIONS: Different types of interventions to support compliance with breast cancer CPGs recommendations are available, and most of them show positive effects. More robust trials are needed to strengthen the available evidence base concerning their efficacy. Gathering data on the costs of implementing the proposed interventions is needed to inform decisions about their widespread implementation. TRIAL REGISTRATION: CRD42018092884 (PROSPERO).

Cost-effectiveness of a high-sensitivity cardiac troponin T systematic screening strategy compared with usual care to identify patients with peri-operative myocardial injury after major noncardiac surgery.

BACKGROUND: About 300 million surgeries are performed worldwide annually and this figure is increasing constantly. Peri-operative myocardial injury (PMI), detected by cardiac troponin (cTn) elevation, is a common cardiac complication of noncardiac surgery, strongly associated with short- and long-term mortality. Without systematic peri-operative cTn screening, most cases of PMI may go undetected. However, little is known about cost effectiveness of a systematic PMI screening strategy with high-sensitivity cardiac troponin T (hs-cTnT) after noncardiac surgery. OBJECTIVE: To assess, in patients with high cardiovascular risk, the cost-effectiveness of a systematic screening strategy using a hs-cTnT assay, to identify patients with PMI after major noncardiac surgery, compared with usual care. DESIGN: Cost-effectiveness analysis; single centre prospective cohort study. SETTING: Spanish University Hospital. PATIENTS: From July 2016 to March 2019, we included 1477 consecutive surgical patients aged ≥65 or if <65, with documented history of cardiovascular disease or impaired renal function, who underwent major noncardiac surgery and required at least an overnight hospital stay. We excluded patients aged <65 years without cardiovascular disease, undergoing minor surgery, or with an expected <24 h hospital stays. INTERVENTIONS: We conducted a decision-tree analysis, comparing a systematic screening strategy measuring hs-cTnT before surgery, and at the 2nd and 3rd days after surgery vs. a usual care strategy. We considered a third-party payer perspective and the outcomes of both strategies in the short-term (30 days follow-up). Information about costs was expressed in Euros-2021. We calculated the incremental cost-effectiveness ratio (ICER) of the systematic hs-cTnT strategy, defined as the expected cost per any additional PMI detected, and explored the robustness of the model using deterministic and probabilistic sensitivity analysis. MAIN OUTCOME MEASURES: ICER of the systematic hs-cTnT screening strategy. RESULTS: The ICER was €425 per any additionally detected PMI. The deterministic sensitivity analysis showed that a 15% variation in costs, and a 1% variation in the predictive values, had a minor impact over the ICER, except in case of the negative predictive value of the systematic hs-cTnT screening strategy. Monte Carlo simulations (probabilistic sensitivity analysis) showed that systematic hs-cTnT screening would be cost-effective in 100% of cases with a 'willingness to pay' of €780. CONCLUSIONS: Our results suggest that systematic peri-operative PMI screening with hs-cTnT may be cost-effective in the short-term in patients undergoing major noncardiac surgery. Economic evaluations, with a long-term horizon, are still needed. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03438448.

Methodological transparency of preoperative clinical practice guidelines for elective surgery. Systematic review.

BACKGROUND: Clinical practice guidelines (CPG) are statements that provide recommendations regarding the approach to different diseases and aim to increase quality while decreasing the risk of complications in health care. Numerous guidelines in the field of perioperative care have been published in the previous decade but their methodological quality and transparency are relatively unknown. OBJECTIVE: To critically evaluate the transparency and methodological quality of published CPG in the preoperative assessment and management of adult patients undergoing elective surgery. DESIGN: Systematic review and methodological appraisal study. DATA SOURCES: We searched for eligible CPG published in English or Spanish between January 1, 2010, and June 30, 2022, in Pubmed MEDLINE, TRIP Database, Embase, the Cochrane Library, as well as in representatives' medical societies of Anaesthesiology and developers of CPG. ELIGIBILITY CRITERIA: CPG dedicated on preoperative fasting, cardiac assessment for non-cardiac surgery, and the use of routine preoperative tests were included. Methodological quality and transparency of CPG were assessed by 3 evaluators using the 6 domains of the AGREE-II tool. RESULTS: We included 20 CPG of which 14 were classified as recommended guidelines. The domain of "applicability" scored the lowest (44%), while the domains "scope and objective" and "editorial interdependence" received the highest median scores of 93% and 97% respectively. The remaining domains received scores ranging from 44% to 84%. The top mean scored CPG in preoperative fasting was ASA 2017 (93%); among cardiac evaluation, CPG for non-cardiac surgery were CCS 2017 (91%), ESC-ESA 2014 (90%), and AHA-ACC 2014 (89%); in preoperative testing ICSI 2020 (97%). CONCLUSIONS: In the last ten years, most published CPG in the preoperative assessment or management of adult patients undergoing elective surgery focused on preoperative fasting, cardiac assessment for non-cardiac surgery, and use of routine preoperative tests, present moderate to high methodological quality and can be recommended for their use or adaptation. Applicability and stakeholder involvement domains must be improved in the development of future guidelines.

Myocardial injury after major non-cardiac surgery evaluated with advanced cardiac imaging: a pilot study.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) is a frequent complication caused by cardiac and non-cardiac pathophysiological mechanisms, but often it is subclinical. MINS is associated with increased morbidity and mortality, justifying the need to its diagnose and the investigation of their causes for its potential prevention. METHODS: Prospective, observational, pilot study, aiming to detect MINS, its relationship with silent coronary artery disease and its effect on future adverse outcomes in patients undergoing major non-cardiac surgery and without postoperative signs or symptoms of myocardial ischemia. MINS was defined by a high-sensitive cardiac troponin T (hs-cTnT) concentration > 14 ng/L at 48-72 h after surgery and exceeding by 50% the preoperative value; controls were the operated patients without MINS. Within 1-month after discharge, cardiac computed tomography angiography (CCTA) and magnetic resonance imaging (MRI) studies were performed in MINS and control subjects. Significant coronary artery disease (CAD) was defined by a CAD-RADS category ≥ 3. The primary outcomes were prevalence of CAD among MINS and controls and incidence of major cardiovascular events (MACE) at 1-year after surgery. Secondary outcomes were the incidence of individual MACE components and mortality. RESULTS: We included 52 MINS and 12 controls. The small number of included patients could be attributed to the study design complexity and the dates of later follow-ups (amid COVID-19 waves). Significant CAD by CCTA was equally found in 20 MINS and controls (30% vs 33%, respectively). Ischemic patterns (n = 5) and ischemic segments (n = 2) depicted by cardiac MRI were only observed in patients with MINS. One-year MACE were also only observed in MINS patients (15.4%). CONCLUSION: This study with advanced imaging methods found a similar CAD frequency in MINS and control patients, but that cardiac ischemic findings by MRI and worse prognosis were only observed in MINS patients. Our results, obtained in a pilot study, suggest the need of further, extended studies that screened systematically MINS and evaluated its relationship with cardiac ischemia and poor outcomes. Trial registration Clinicaltrials.gov identifier: NCT03438448 (19/02/2018).

[Preventive activities in women. PAPPS update 2022]. / Actividades preventivas en la mujer. Actualización PAPPS 2022.

In the 2022 PAPPS update we present those specific preventive activities for women's health, except those related to cancer prevention (which are included in another document) and those aspects related to differential gender morbidity, a cross-cutting aspect for all working groups. Contraception is an essential preventive activity, considering basic the right to decide both the number of children and the time to have them. We must inform about the possible contraceptive methods, guaranteeing the monitoring of their safety, efficacy and effectiveness (tables are included on changing from one method to another to preserve contraceptive protection). We must inform about emergency contraception and propose it in the event of unprotected intercourse. All this will be done through opportunistic screening without requiring screening for thrombophilia or dyslipidemia, but for arterial hypertension. Pregnancy is an important life experience and the family doctor should not remain oblivious. We must be competent both in the preconception consultation (recommending the intake of folic acid, avoiding exposure to occupational and environmental risks, screening for certain pathologies and assessing the intake of drugs not indicated during pregnancy) and in the monitoring of pregnancy. Whether or not we monitor the pregnancy, we must not disregard its control, taking advantage of this period to promote healthy lifestyles and participating in the intercurrent processes that may occur. Menopause in general and osteoporosis in particular exemplify the strategy of medicalization of vital processes that has been followed from different instances and organizations. In our update we address the prevention and treatment of symptoms secondary to estrogen deprivation. We also propose the prevention of osteoporosis, including carrying out densitometry based on the risk of fracture in the next 10 years, and therefore densitometric screening is not recommended in women under 60 years of age. In risk assessment we recommend the use of the frax tool or better, the calibration of the risk of hip fracture with prevalence data from our setting. We linked the indication for treatment with the Z-Score (bone mineral density compared with women of the same age), as it is a condition associated with aging.

PROSHADE Protocol: Designing and Evaluating a Decision Aid for Promoting Shared Decision Making in Opportunistic Screening for Prostate Cancer: A Mix-Method Study.

Background: Opportunistic prostate-specific antigen (PSA) screening may reduce prostate cancer mortality risk but is associated with false positive results, biopsy complications and overdiagnosis. Although different organisations have emphasised the importance of shared decision making (SDM) to assist men in deciding whether to undergo prostate cancer screening, recent evaluations show that the available decision aids fail to facilitate SDM, mainly because they do not consider the patients' perspective in their design. We aim to systematically develop and test a patient decision aid to promote SDM in prostate cancer screening, following the Knowledge to Action framework. Methods: (1) Feasibility study: a quantitative survey evaluating the population and clinician (urologists and general practitioners) knowledge of the benefits and risks derived from PSA determination and the awareness of the available recommendations. Focus groups to explore the challenges patients and clinicians face when discussing prostate cancer screening, the relevance of a decision aid and how best to integrate it into practice. (2) Patient decision aid development: Based on this data, an evidence-based multicomponent SDM patient decision aid will be developed. (3) User-testing: an assessment of the prototype of the initial patient decision aid through a user-testing design based on mix-methods (questionnaire and semi-structured review). The decision aid will be refined through several iterative cycles of feedback and redesign. (4) Validation: an evaluation of the patient decision aid through a cluster-randomised controlled trial. Discussion: The designed patient decision aid will provide balanced information on screening benefits and risks and should help patients to consider their personal preferences and to take a more active role in decision making. Conclusions: The well-designed patient decision aid (PDA) will provide balanced information on screening benefits and risks and help patients consider their personal preferences.

Values and preferences influencing willingness to change red and processed meat consumption in response to evidence-based information: a mixed methods study.

OBJECTIVES: (1) to assess the extent to which omnivores are willing to stop or reduce their consumption of red and processed meat in response to evidence-based information regarding the possible reduction of cancer mortality and incidence achieved by dietary modification; (2) to identify sociodemographic categories associated with higher willingness to change meat consumption; (3) to understand the motives facilitating and hindering such a change. DESIGN: During an initial computer-assisted web interview, respondents were presented with scenarios containing the estimates of the absolute risk reduction in overall cancer incidence and mortality tailored to their declared level of red and processed meat consumption. Respondents were asked whether they would stop or reduce their average meat consumption based on the information provided. Their dietary choices were assessed at 6-month follow-up. Additionally, we conducted semi-structured interviews to better understand the rationale for dietary practices and the perception of health information. PARTICIPANTS: The study was conducted among students and staff of 3 universities in Krakow, Poland. RESULTS: Most of the 513 respondents were unwilling to change their consumption habits. We found gender to be a significant predictor of the willingness. Finally, we identified 4 themes reflecting key motives that determined meat consumption preferences: the importance of taste and texture, health consciousness, the habitual nature of cooking, and persistence of omnivorous habits. CONCLUSIONS: When faced with health information about the uncertain reduction in the risk of cancer mortality and incidence, the vast majority of study participants were unwilling to introduce changes in their consumption habits.

Benefits and harms of annual, biennial, or triennial breast cancer mammography screening for women at average risk of breast cancer: a systematic review for the European Commission Initiative on Breast Cancer (ECIBC).

BACKGROUND: Although mammography screening is recommended in most European countries, the balance between the benefits and harms of different screening intervals is still a matter of debate. This review informed the European Commission Initiative on Breast Cancer (BC) recommendations. METHODS: We searched PubMed, EMBASE, and the Cochrane Library to identify RCTs, observational or modelling studies, comparing desirable (BC deaths averted, QALYs, BC stage, interval cancer) and undesirable (overdiagnosis, false positive related, radiation related) effects from annual, biennial, or triennial mammography screening in women of average risk for BC. We assessed the certainty of the evidence using the GRADE approach. RESULTS: We included one RCT, 13 observational, and 11 modelling studies. In women 50-69, annual compared to biennial screening may have small additional benefits but an important increase in false positive results; triennial compared to biennial screening may have smaller benefits while avoiding some harms. In younger women (aged 45-49), annual compared to biennial screening had a smaller gain in benefits and larger harms, showing a less favourable balance in this age group than in women 50-69. In women 70-74, there were fewer additional harms and similar benefits with shorter screening intervals. The overall certainty of the evidence for each of these comparisons was very low. CONCLUSIONS: In women of average BC risk, screening intervals have different trade-offs for each age group. The balance probably favours biennial screening in women 50-69. In younger women, annual screening may have a less favourable balance, while in women aged 70-74 years longer screening intervals may be more favourable.

Health Related Values and Preferences Regarding Meat Intake: A Cross-Sectional Mixed-Methods Study.

BACKGROUND: In addition to social and environmental determinants, people's values and preferences determine daily food choices. This study evaluated adults' values and preferences regarding unprocessed red meat (URM) and processed meat (PM) and their willingness to change their consumption in the face of possible undesirable health consequences. METHODS: A cross-sectional mixed-methods study including a quantitative assessment through an online survey, a qualitative inquiry through semi-structured interviews, and a follow-up assessment through a telephone survey. We performed descriptive statistics, logistic regressions, and thematic analysis. RESULTS: Of 304 participants, over 75% were unwilling to stop their consumption of either URM or PM, and of those unwilling to stop, over 80% were also unwilling to reduce. Men were less likely to stop meat intake than women (odds ratios < 0.4). From the semi-structured interviews, we identified three main themes: the social and/or family context of meat consumption, health- and non-health-related concerns about meat, and uncertainty of the evidence. At three months, 63% of participants reported no changes in meat intake. CONCLUSIONS: When informed about the cancer incidence and mortality risks of meat consumption, most respondents would not reduce their intake. Public health and clinical nutrition guidelines should ensure that their recommendations are consistent with population values and preferences.

Values and Preferences Related to Cancer Risk among Red and Processed Meat Eaters: A Pilot Cross-Sectional Study with Semi-Structured Interviews.

Introduction: Over the last decade, the possible impact of meat intake on overall cancer incidence and mortality has received considerable attention, and authorities have recommended decreasing consumption; however, the benefits of reducing meat consumption are small and uncertain. As such, individual decisions to reduce consumption are value- and preference-sensitive. Consequently, we undertook a pilot cross-sectional study to explore people's values and preferences towards meat consumption in the face of cancer risk. Methods and analysis: The mixed-method pilot study included a quantitative questionnaire followed by qualitative evaluation to explore the dietary habits of 32 meat eaters, their reasons for eating meat, and willingness to change their meat consumption when faced with a potential risk reduction of cancer over a lifetime based on a systematic review and dose-response meta-analysis. We recruited a convenience sample of participants from two Canadian provinces: Nova Scotia and Prince Edward Island. This project was approved by the Research Ethics Board for Health Sciences research at Dalhousie University, Canada. Results: The average weekly consumption of red meat was 3.4 servings and the average weekly consumption of processed meat was 3 servings. The determinants that influenced meat intake were similar for both red and processed meat. Taste, cost, and family preferences were the three most commonly cited factors impacting red meat intake. Taste, cost, and (lack of) cooking time were the three most commonly cited factors impacting processed meat intake. None of the participants were willing to eliminate red or processed meat from their diet. About half of participants were willing to potentially reduce their meat consumption, with one third definitely willing to reduce their consumption. Strengths and limitations: This study is the first that we are aware of to share data with participants on the association of red meat and processed meat consumption and the risk of cancer mortality and cancer incidence, including the certainty of evidence for the risk reduction. The limitations of this study include its small sample size and its limited geographic sampling. Conclusions: When presented explicit information about the small uncertain cancer risk associated with red and processed meat consumption, study participants were unwilling to eliminate meat, while about one-third were willing to reduce their meat intake.

Preoperative breast magnetic resonance imaging in patients with ductal carcinoma in situ: a systematic review for the European Commission Initiative on Breast Cancer (ECIBC).

OBJECTIVE: To evaluate the impact of preoperative MRI in the management of Ductal carcinoma in situ (DCIS). METHODS: We searched the PubMed, EMBASE and Cochrane Library databases to identify randomised clinical trials (RCTs) or cohort studies assessing the impact of preoperative breast MRI in surgical outcomes, treatment change or loco-regional recurrence. We provided pooled estimates for odds ratios (OR), relative risks (RR) and proportions and assessed the certainty of the evidence using the GRADE approach. RESULTS: We included 3 RCTs and 23 observational cohorts, corresponding to 20,415 patients. For initial breast-conserving surgery (BCS), the RCTs showed that MRI may result in little to no difference (RR 0.95, 95% CI 0.90 to 1.00) (low certainty); observational studies showed that MRI may have no difference in the odds of re-operation after BCS (OR 0.96; 95% CI 0.36 to 2.61) (low certainty); and uncertain evidence from RCTs suggests little to no difference with respect to total mastectomy rate (RR 0.91; 95% CI 0.65 to 1.27) (very low certainty). We also found that MRI may change the initial treatment plans in 17% (95% CI 12 to 24%) of cases, but with little to no effect on locoregional recurrence (aHR = 1.18; 95% CI 0.79 to 1.76) (very low certainty). CONCLUSION: We found evidence of low to very low certainty which may suggest there is no improvement of surgical outcomes with pre-operative MRI assessment of women with DCIS lesions. There is a need for large rigorously conducted RCTs to evaluate the role of preoperative MRI in this population. KEY POINTS: • Evidence of low to very low certainty may suggest there is no improvement in surgical outcomes with pre-operative MRI. • There is a need for large rigorously conducted RCTs evaluating the role of preoperative MRI to improve treatment planning for DCIS.

Efficacy and safety of treatment with biologicals for severe chronic rhinosinusitis with nasal polyps: A systematic review for the EAACI guidelines.

This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared with the standard of care. PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CRSwNP-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. RCTs evaluated (dupilumab-2, omalizumab-4, mepolizumab-2, and reslizumab-1) included 1236 adults, with follow-up of 20-64 weeks. Dupilumab reduces the need for surgery (NFS) or oral corticosteroid (OCS) use (RR 0.28; 95% CI 0.20-0.39, moderate certainty) and improves with high certainty smell evaluated with UPSIT score (mean difference (MD) +10.54; 95% CI +9.24 to +11.84) and quality of life (QoL) evaluated with SNOT-22 (MD -19.14; 95% CI -22.80 to -15.47), with fewer treatment-related adverse events (TAEs) (RR 0.95; 95% CI 0.89-1.02, moderate certainty). Omalizumab reduces NFS (RR 0.85; 95% CI 0.78-0.92, high certainty), decreases OCS use (RR 0.38; 95% CI 0.10-1.38, moderate certainty), and improves high certainty smell (MD +3.84; 95% CI +3.64 to +4.04) and QoL (MD -15.65; 95% CI -16.16 to -15.13), with increased TAE (RR 1.73; 95% CI 0.60-5.03, moderate certainty). There is low certainty for mepolizumab reducing NFS (RR 0.78; 95% CI 0.64-0.94) and improving QoL (MD -13.3; 95% CI -23.93 to -2.67) and smell (MD +0.7; 95% CI -0.48 to +1.88), with increased TAEs (RR 1.64; 95% CI 0.41-6.50). The evidence for reslizumab is very uncertain.

Digital breast tomosynthesis compared to diagnostic mammographic projections (including magnification) among women recalled at screening mammography: a systematic review for the European Commission Initiative on Breast Cancer (ECIBC).

BACKGROUND: Diagnostic mammography projections (DxMM) have been traditionally used in the assessment of women recalled after a suspicious screening mammogram. Digital breast tomosynthesis (DBT) reduces the tissue overlap effect, thus improving image assessment. Some studies have suggested DBT might replace DxMM with at least equivalent performance. OBJECTIVE: To evaluate the replacement of DxMM with DBT in women recalled at screening. METHODS: We searched PubMed, EMBASE, and the Cochrane Library databases to identify diagnostic paired cohort studies or RCTs comparing DBT vs DxMM, published in English that: reported accuracy outcomes, recruited women recalled for assessment at mammography screening, and included a reference standard. Subgroup analysis was performed over lesion characteristics. We provided pooled accuracy estimates and differences between tests using a quadrivariate model. We assessed the certainty of the evidence using the GRADE approach. RESULTS: We included ten studies that reported specificity and sensitivity. One study included 7060 women while the remaining included between 52 and 738 women. DBT compared with DxMM showed a pooled difference for the sensitivity of 2% (95% CI 1%-3%) and a pooled difference for the specificity of 6% (95%CI 2%-11%). Restricting the analysis to the six studies that included women with microcalcification lesions gave similar results. In the context of a prevalence of 21% of breast cancer (BC) in recalled women, DBT probably detects 4 (95% CI 2-6) more BC cases and has 47 (95%CI 16-87) fewer false-positive results per 1000 assessments. The certainty of the evidence was moderate due to risk of bias. CONCLUSION: The evidence in the assessment of screen-recalled findings with DBT is sparse and of moderate certainty. DBT probably has higher sensitivity and specificity than DxMM. Women, health care providers and policymakers might value as relevant the reduction of false-positive results and related fewer invasive diagnostic procedures with DBT, without missing BC cases.

Recommendations from the European Commission Initiative on Breast Cancer for multigene testing to guide the use of adjuvant chemotherapy in patients with early breast cancer, hormone receptor positive, HER-2 negative.

BACKGROUND: Predicting the risk of recurrence and response to chemotherapy in women with early breast cancer is crucial to optimise adjuvant treatment. Despite the common practice of using multigene tests to predict recurrence, existing recommendations are inconsistent. Our aim was to formulate healthcare recommendations for the question "Should multigene tests be used in women who have early invasive breast cancer, hormone receptor-positive, HER2-negative, to guide the use of adjuvant chemotherapy?" METHODS: The European Commission Initiative on Breast Cancer (ECIBC) Guidelines Development Group (GDG), a multidisciplinary guideline panel including experts and three patients, developed recommendations informed by systematic reviews of the evidence. Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision frameworks were used. Four multigene tests were evaluated: the 21-gene recurrence score (21-RS), the 70-gene signature (70-GS), the PAM50 risk of recurrence score (PAM50-RORS), and the 12-gene molecular score (12-MS). RESULTS: Five studies (2 marker-based design RCTs, two treatment interaction design RCTs and 1 pooled individual data analysis from observational studies) were included; no eligible studies on PAM50-RORS or 12-MS were identified and the GDG did not formulate recommendations for these tests. CONCLUSIONS: The ECIBC GDG suggests the use of the 21-RS for lymph node-negative women (conditional recommendation, very low certainty of evidence), recognising that benefits are probably larger in women at high risk of recurrence based on clinical characteristics. The ECIBC GDG suggests the use of the 70-GS for women at high clinical risk (conditional recommendation, low certainty of evidence), and recommends not using 70-GS in women at low clinical risk (strong recommendation, low certainty of evidence).

Benefits and harms of breast cancer mammography screening for women at average risk of breast cancer: A systematic review for the European Commission Initiative on Breast Cancer.

OBJECTIVES: Mammography screening is generally accepted in women aged 50-69, but the balance between benefits and harms remains controversial in other age groups. This study systematically reviews these effects to inform the European Breast Cancer Guidelines. METHODS: We searched PubMed, EMBASE and Cochrane Library for randomised clinical trials (RCTs) or systematic reviews of observational studies in the absence of RCTs comparing invitation to mammography screening to no invitation in women at average breast cancer (BC) risk. We extracted data for mortality, BC stage, mastectomy rate, chemotherapy provision, overdiagnosis and false-positive-related adverse effects. We performed a pooled analysis of relative risks, applying an inverse-variance random-effects model for three age groups (<50, 50-69 and 70-74). GRADE (Grading of Recommendations Assessment, Development and Evaluation) was used to assess the certainty of evidence. RESULTS: We identified 10 RCTs including 616,641 women aged 38-75. Mammography reduced BC mortality in women aged 50-69 (relative risk (RR) 0.77, 95%CI (confidence interval) 0.66-0.90, high certainty) and 70-74 (RR 0.77, 95%CI 0.54-1.09, high certainty), with smaller reductions in under 50s (RR 0.88, 95%CI 0.76-1.02, moderate certainty). Mammography reduced stage IIA+ in women 50-69 (RR 0.80, 95%CI 0.64-1.00, very low certainty) but resulted in an overdiagnosis probability of 23% (95%CI 18-27%) and 17% (95%CI 15-20%) in under 50s and 50-69, respectively (moderate certainty). Mammography was associated with 2.9% increased risk of invasive procedures with benign outcomes (low certainty). CONCLUSIONS: For women 50-69, high certainty evidence that mammography screening reduces BC mortality risk would support policymakers formulating strong recommendations. In other age groups, where the net balance of effects is less clear, conditional recommendations will be more likely, together with shared decision-making.