Efficacy and safety of treatment with biologicals (benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab) for severe eosinophilic asthma. A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma.

Five biologicals have been approved for severe eosinophilic asthma, a well-recognized phenotype. Systematic reviews (SR) evaluated the efficacy and safety of benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab (alphabetical order) compared to standard of care for severe eosinophilic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated for each of the biologicals. The risk of bias and the certainty of the evidence were assessed using GRADE. 19 RCTs (three RCTs for benralizumab, three RCTs for dupilumab, three RCTs for mepolizumab, five RCTs for omalizumab and five RCTs for reslizumab), including subjects 12 to 75 years old (except for omalizumab including also subjects 6-11 years old), ranging from 12 to 56 weeks were evaluated. All biologicals reduce exacerbation rates with high certainty of evidence: benralizumab incidence rate ratio (IRR) 0.53 (95% CI 0.39 to 0.72), dupilumab (IRR) 0.43 (95% CI 0.32 to 0.59), mepolizumab IRR 0.49 (95% CI 0.38 to 0.66), omalizumab (IRR) 0.56 (95% CI 0.40 to 0.77) and reslizumab (IRR) 0.46 (95% CI 0.37 to 0.58). Benralizumab, dupilumab and mepolizumab reduce the daily dose of oral corticosteroids (OCS) with high certainty of evidence. All evaluated biologicals probably improve asthma control, QoL and FEV1 , without reaching the minimal important difference (moderate certainty). Benralizumab, mepolizumab and reslizumab slightly increase drug-related adverse events (AE) and drug-related serious AE (low to very low certainty of evidence). The incremental cost-effectiveness ratio per quality-adjusted life year value is above the willingness to pay threshold for all biologicals (moderate certainty). Potential savings are driven by decrease in hospitalizations, emergency and primary care visits. There is high certainty that all approved biologicals reduce the rate of severe asthma exacerbations and for benralizumab, dupilumab and mepolizumab for reducing OCS. There is moderate certainty for improving asthma control, QoL, FEV1 . More data on long-term safety are needed together with more efficacy data in the paediatric population.

"For and against" factors influencing participation in personalized breast cancer screening programs: a qualitative systematic review until March 2022.

BACKGROUND: Personalized breast cancer screening is a novel strategy that estimates individual risk based on age, breast density, family history of breast cancer, personal history of benign breast lesions, and polygenic risk. Its goal is to propose personalized early detection recommendations for women in the target population based on their individual risk. Our aim was to synthesize the factors that influence women's decision to participate in personalized breast cancer screening, from the perspective of women and health care professionals. METHODS: Systematic review of qualitative evidence on factors influencing participation in personalized Breast Cancer Screening. We searched in Medline, Web of science, Scopus, EMBASE, CINAHL and PsycINFO for qualitative and mixed methods studies published up to March 2022. Two reviewers conducted study selection and extracted main findings. We applied the best-fit framework synthesis and adopted the Multilevel influences on the cancer care continuum model for analysis. After organizing initial codes into the seven levels of the selected model, we followed thematic analysis and developed descriptive and analytical themes. We assessed the methodological quality with the Critical Appraisal Skills Program tool. RESULTS: We identified 18 studies published between 2017 and 2022, conducted in developed countries. Nine studies were focused on women (n = 478) and in four studies women had participated in a personalized screening program. Nine studies focused in health care professionals (n = 162) and were conducted in primary care and breast cancer screening program settings. Factors influencing women's decision to participate relate to the women themselves, the type of program (personalized breast cancer screening) and perspective of health care professionals. Factors that determined women participation included persistent beliefs and insufficient knowledge about breast cancer and personalized screening, variable psychological reactions, and negative attitudes towards breast cancer risk estimates. Other factors against participation were insufficient health care professionals knowledge on genetics related to breast cancer and personalized screening process. The factors that were favourable included the women's perceived benefits for themselves and the positive impact on health systems. CONCLUSION: We identified the main factors influencing women's decisions to participate in personalized breast cancer screening. Factors related to women, were the most relevant negative factors. A future implementation requires improving health literacy for women and health care professionals, as well as raising awareness of the strategy in society.

Effectiveness and Cost-Effectiveness of Case Management in Advanced Heart Failure Patients Attended in Primary Care: A Systematic Review and Meta-Analysis.

AIMS: Nurse-led case management (CM) may improve quality of life (QoL) for advanced heart failure (HF) patients. No systematic review (SR), however, has summarized its effectiveness/cost-effectiveness. We aimed to evaluate the effect of such programs in primary care settings in advanced HF patients. We examined and summarized evidence on QoL, mortality, hospitalization, self-care, and cost-effectiveness. METHODS AND RESULTS: The MEDLINE, CINAHL, Embase, Clinical Trials, WHO, Registry of International Clinical Trials, and Central Cochrane were searched up to March 2022. The Consensus Health Economic Criteria instrument to assess risk-of-bias in economic evaluations, Cochrane risk-of-bias 2 for clinical trials, and an adaptation of Robins-I for quasi-experimental and cohort studies were employed. Results from nurse-led CM programs did not reduce mortality (RR 0.78, 95% CI 0.53 to 1.15; participants = 1345; studies = 6; I2 = 47%). They decreased HF hospitalizations (HR 0.79, 95% CI 0.68 to 0.91; participants = 1989; studies = 8; I2 = 0%) and all-cause ones (HR 0.73, 95% CI 0.60 to 0.89; participants = 1012; studies = 5; I2 = 36%). QoL improved in medium-term follow-up (SMD 0.18, 95% CI 0.05 to 0.32; participants = 1228; studies = 8; I2 = 28%), and self-care was not statistically significant improved (SMD 0.66, 95% CI -0.84 to 2.17; participants = 450; studies = 3; I2 = 97%). A wide variety of costs ranging from USD 4975 to EUR 27,538 was observed. The intervention was cost-effective at ≤EUR 60,000/QALY. CONCLUSIONS: Nurse-led CM reduces all-cause hospital admissions and HF hospitalizations but not all-cause mortality. QoL improved at medium-term follow-up. Such programs could be cost-effective in high-income countries.

Health care services use among long-term breast cancer survivors: a systematic review.

PURPOSE: Long-term breast cancer survivors are women surviving at least 5 years after diagnosis. This systematic review aimed to summarize the main characteristics and patterns of healthcare service use (frequency of visits, health providers visited, and preventive care performed) among long-term breast cancer survivors. METHODS: We used standard Cochrane Collaboration methods and searched the MEDLINE and EMBASE databases up to January 2018. We included English language observational studies reporting health service use among long-term cancer survivors. The quality of the studies was appraised through the ROBINS-I assessment tool. Two independent reviewers performed both the study quality assessment and the data extraction. RESULTS: A total of 23 observational studies were included that reported data on health services use by long-term breast cancer survivors. Despite heterogeneity among studies, about half of them reported that breast cancer survivors visited a medical provider at least once a year, as recommended by breast cancer survival guidelines. Although survivors visited medical providers with the recommended frequency, a substantial number used specialist care instead of primary care during follow-up. The results showed underuse of the recommended annual mammogram. CONCLUSIONS: Long-term breast cancer survivors differ in their health services use with regard to the frequency of visits as well as the health providers seen. Our results indicate the need for active surveillance through primary care providers in coordination with specialized care. IMPLICATIONS FOR CANCER SURVIVORS: This review could help to standardize the management of breast cancer survivors and decision-makers to adapt their guidelines and clinical protocols.

Validation Of Cancer Diagnoses In Electronic Health Records: Results From The Information System For Research In Primary Care (SIDIAP) In Northeast Spain.

BACKGROUND: Electronic health records are becoming an increasingly valuable resource for epidemiology but their data quality needs to be quantified. We aimed to validate twenty-five types of incident cancer cases in the Information System for Research in Primary Care (SIDIAP) in Catalonia with the population-based cancer registries of Girona and Tarragona as the gold-standard. METHODS: We calculated the sensitivity, positive predictive values (PPV), and the time-difference between the date of diagnosis entered into the SIDIAP and into the registries. We added hospital discharge cancer diagnoses to the SIDIAP to assess sensitivity changes. RESULTS: We identified 27,046 incident cancer diagnoses in the SIDIAP from 2009-2015 among the 949,841 residents of Girona and Tarragona. The cancer types with the highest sensitivity were breast (89%, 95% CI: 88-90%), colorectal (81%, 95% CI: 80-82%), and prostate (81%, 95% CI: 80-83%). Trachea, bronchus and lung cancers had the highest PPV (76%, 95% CI: 74%-78%) followed by stomach (72%, 95% CI: 68-75%) and pancreas (71%, 95% CI: 67-75%). Most cancer diagnoses were reported with less than three months of difference between the SIDIAP and the registries. More cases were registered first in the registries than in the SIDIAP. By adding cancer diagnoses based on hospital discharge data, sensitivity increased for all cancers, especially for gallbladder and biliary tract for which the sensitivity increased by 21%. CONCLUSION: The SIDIAP includes 76% of the cancer diagnoses in the cancer registries but includes a considerable number of cases that are not in the registries. The SIDIAP reports most of the cancer diagnoses within a three-month period difference from the date of diagnosis in the cancer registries. Our results support the use of the SIDIAP cancer diagnoses for epidemiological research when cancer is the outcome of interest. We recommend adding hospital discharge data to the SIDIAP to increase data quality, particularly for less frequent cancer types.

Emergency presentation of colorectal patients in Spain.

BACKGROUND: Colorectal cancer (CRC) is the leading cause of cancer deaths in Europe. Survival is poorer in patients admitted to hospitals through the emergency department than in electively admitted patients. Knowledge of factors associated with a cancer diagnosis through presentation at an emergency department may reduce the likelihood of an emergency diagnosis. This study evaluated factors influencing the diagnosis of CRC in the emergency department. METHODS AND FINDINGS: This is a cross-sectional study in 5 Spanish regions; subjects were incident cases of CRC diagnosed in 9 public hospitals, between 2006 and 2008. Data were obtained from patient interviews and primary care and hospital clinical records. We found that approximately 40% of CRC patients first contacted a hospital for CRC through an emergency service. Women were more likely than men to be emergency presenters. The type of symptom associated with emergency presentation differed between patients with colon cancer and those with rectal cancer, in that the frequency of "alarm symptoms" was significantly lower in colon than in rectal cancer patients who initially presented to emergency services. Soon after symptom onset, some patients went to a hospital emergency service, whereas others contacted their GP. Lack of contact with a GP for CRC-related symptoms was consistently related to emergency presentation. Among patients who contacted a GP, a higher number of consultations for CRC symptoms and any referral to outpatient consultations reduced the likelihood of emergency presentation. All diagnostic time intervals were shorter in emergency presenters than in elective patients. CONCLUSIONS: Emergency presenters are not a uniform category and can be divided into categories according to their symptoms, help seeking behavior trajectory and interaction with their GPs. Time constraints for testing and delays in obtaining outpatient appointments led patients to visit a hospital service either on their own or after referral by their GP.