Full publication of preprint articles in prevention research: an analysis of publication proportions and results consistency.

There is concern that preprint articles will lead to an increase in the amount of scientifically invalid work available. The objectives of this study were to determine the proportion of prevention preprints published within 12 months, the consistency of the effect estimates and conclusions between preprint and published articles, and the reasons for the nonpublication of preprints. Of the 329 prevention preprints that met our eligibility criteria, almost half (48.9%) were published in a peer-reviewed journal within 12 months of being posted. While 16.8% published preprints showed some change in the magnitude of the primary outcome effect estimate, 4.4% were classified as having a major change. The style or wording of the conclusion changed in 42.2%, the content in 3.1%. Preprints on chemoprevention, with a cross-sectional design, and with public and noncommercial funding had the highest probabilities of publication. The main reasons for the nonpublication of preprints were journal rejection or lack of time. The reliability of preprint articles for evidence-based decision-making is questionable. Less than half of the preprint articles on prevention research are published in a peer-reviewed journal within 12 months, and significant changes in effect sizes and/or conclusions are still possible during the peer-review process.

[WHO Guideline for Screening and Treatment of Cervical Pre-Cancerous Lesions for Cervical Cancer Prevention (Second Edition)]. / WHO-Leitlinie zu Screening und Behandlung von präkanzerösen Zervixläsionen für die Prävention von Gebärmutterhalskrebs (2. Auflage).

BACKGROUND: Cervical cancer is a major health concern worldwide. Cancer screenings for secondary prevention aim at reducing morbidity and mortality among women. Objective The guideline provides both an updated and an extended overview for the prevention of cervical cancer by screening and therapy. METHOD: The World Health Organization (WHO) developed this guideline in accordance with WHO standards. The respective executive summary was translated by a team of Austria's WHO Collaborating Centre. RESULTS: The updated and extended guideline contains 23 recommendations and seven good practice statements which address screening methods, test regimens, age groups, screening intervals and other topics. Target populations are adult females without known risk factors (general population) and women living with HIV. It is recommended that women from the general population undergo screening every five to ten years, starting at the age of 30. Women living with HIV are advised to get screened every three to five years, starting at the age of 25. Preferred primary screening tests are HPV DNA tests which may be supplemented with further tests in order to triage for further interventions.

Screening for colorectal cancer : A recommendation statement of the Austrian National Committee for Cancer Screening.

BACKGROUND: Colorectal cancer is the fourth most common cancer in Austria. To date, colorectal cancer screening in Austria remains opportunistic and includes colonoscopy or stool-based blood tests. The Austrian National Committee for Cancer Screening developed evidence-based recommendations for a nationwide organized colorectal cancer screening program. METHODS: The methodological framework followed the approach of the United States Preventive Services Task Force. The evidence base underlying the newly developed recommendations comprised a review of the existing published evidence and a decision analytic model tailored to the Austrian context. Using a structured process, committee members considered 1) the magnitude of the net benefit of each screening strategy, 2) the certainty of evidence, and 3) the level of acceptance of the interventions among the target population. RECOMMENDATIONS: The Austrian National Committee for Cancer Screening recommends the implementation of a nationwide organized colorectal cancer screening program for all adults aged 45-75 years. For persons 65 years or older, screening decisions should occur on an individual basis in accordance with a person's overall health, prior screening history, and preferences. Specifically, the committee recommends either a 10-year screening colonoscopy or biennial fecal immunochemical tests with colonoscopy following a positive result, with both screening strategies considered equivalent. Each citizen should be able to make an informed decision about their preferred screening method. Switching between the two screening strategies should be possible. Following an unremarkable colonoscopy, screening by fecal immunochemical test (FIT) is only required after 10 years. Screening recommendations apply only to asymptomatic persons at average risk for colorectal cancer. The screening program must be pilot tested, and accompanied by a public information campaign, formative evaluation, quality assurance, and data collection.

Mammography in combination with breast ultrasonography versus mammography for breast cancer screening in women at average risk.

BACKGROUND: Screening mammography can detect breast cancer at an early stage. Supporters of adding ultrasonography to the screening regimen consider it a safe and inexpensive approach to reduce false-negative rates during screening. However, those opposed to it argue that performing supplemental ultrasonography will also increase the rate of false-positive findings and can lead to unnecessary biopsies and treatments. OBJECTIVES: To assess the comparative effectiveness and safety of mammography in combination with breast ultrasonography versus mammography alone for breast cancer screening for women at average risk of breast cancer. SEARCH METHODS: We searched the Cochrane Breast Cancer Group's Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), and ClinicalTrials.gov up until 3 May 2021. SELECTION CRITERIA: For efficacy and harms, we considered randomised controlled trials (RCTs) and controlled non-randomised studies enrolling at least 500 women at average risk for breast cancer between the ages of 40 and 75. We also included studies where 80% of the population met our age and breast cancer risk inclusion criteria. DATA COLLECTION AND ANALYSIS: Two review authors screened abstracts and full texts, assessed risk of bias, and applied the GRADE approach. We calculated the risk ratio (RR) with 95% confidence intervals (CI) based on available event rates. We conducted a random-effects meta-analysis. MAIN RESULTS: We included eight studies: one RCT, two prospective cohort studies, and five retrospective cohort studies, enrolling 209,207 women with a follow-up duration from one to three years. The proportion of women with dense breasts ranged from 48% to 100%. Five studies used digital mammography; one study used breast tomosynthesis; and two studies used automated breast ultrasonography (ABUS) in addition to mammography screening. One study used digital mammography alone or in combination with breast tomosynthesis and ABUS or handheld ultrasonography. Six of the eight studies evaluated the rate of cancer cases detected after one screening round, whilst two studies screened women once, twice, or more. None of the studies assessed whether mammography screening in combination with ultrasonography led to lower mortality from breast cancer or all-cause mortality. High certainty evidence from one trial showed that screening with a combination of mammography and ultrasonography detects more breast cancer than mammography alone. The J-START (Japan Strategic Anti-cancer Randomised Trial), enrolling 72,717 asymptomatic women, had a low risk of bias and found that two additional breast cancers per 1000 women were detected over two years with one additional ultrasonography than with mammography alone (5 versus 3 per 1000; RR 1.54, 95% CI 1.22 to 1.94). Low certainty evidence showed that the percentage of invasive tumours was similar, with no statistically significant difference between the two groups (69.6% (128 of 184) versus 73.5% (86 of 117); RR 0.95, 95% CI 0.82 to 1.09). However, positive lymph node status was detected less frequently in women with invasive cancer who underwent mammography screening in combination with ultrasonography than in women who underwent mammography alone (18% (23 of 128) versus 34% (29 of 86); RR 0.53, 95% CI 0.33 to 0.86; moderate certainty evidence). Further, interval carcinomas occurred less frequently in the group screened by mammography and ultrasonography compared with mammography alone (5 versus 10 in 10,000 women; RR 0.50, 95% CI 0.29 to 0.89; 72,717 participants; high certainty evidence). False-negative results were less common when ultrasonography was used in addition to mammography than with mammography alone: 9% (18 of 202) versus 23% (35 of 152; RR 0.39, 95% CI 0.23 to 0.66; moderate certainty evidence). However, the number of false-positive results and necessary biopsies were higher in the group with additional ultrasonography screening. Amongst 1000 women who do not have cancer, 37 more received a false-positive result when they participated in screening with a combination of mammography and ultrasonography than with mammography alone (RR 1.43, 95% CI 1.37 to 1.50; high certainty evidence). Compared to mammography alone, for every 1000 women participating in screening with a combination of mammography and ultrasonography, 27 more women will have a biopsy (RR 2.49, 95% CI 2.28 to 2.72; high certainty evidence). Results from cohort studies with methodological limitations confirmed these findings. A secondary analysis of the J-START provided results from 19,213 women with dense and non-dense breasts. In women with dense breasts, the combination of mammography and ultrasonography detected three more cancer cases (0 fewer to 7 more) per 1000 women screened than mammography alone (RR 1.65, 95% CI 1.0 to 2.72; 11,390 participants; high certainty evidence). A meta-analysis of three cohort studies with data from 50,327 women with dense breasts supported this finding, showing that mammography and ultrasonography combined led to statistically significantly more diagnosed cancer cases compared to mammography alone (RR 1.78, 95% CI 1.23 to 2.56; 50,327 participants; moderate certainty evidence). For women with non-dense breasts, the secondary analysis of the J-START study demonstrated that more cancer cases were detected when adding ultrasound to mammography screening compared to mammography alone (RR 1.93, 95% CI 1.01 to 3.68; 7823 participants; moderate certainty evidence), whilst two cohort studies with data from 40,636 women found no statistically significant difference between the two screening methods (RR 1.13, 95% CI 0.85 to 1.49; low certainty evidence). AUTHORS' CONCLUSIONS: Based on one study in women at average risk of breast cancer, ultrasonography in addition to mammography leads to more screening-detected breast cancer cases. For women with dense breasts, cohort studies more in line with real-life clinical practice confirmed this finding, whilst cohort studies for women with non-dense breasts showed no statistically significant difference between the two screening interventions. However, the number of false-positive results and biopsy rates were higher in women receiving additional ultrasonography for breast cancer screening. None of the included studies analysed whether the higher number of screen-detected cancers in the intervention group resulted in a lower mortality rate compared to mammography alone. Randomised controlled trials or prospective cohort studies with a longer observation period are needed to assess the effects of the two screening interventions on morbidity and mortality.

Characteristics and recovery methods of studies falsely excluded during literature screening-a systematic review.

BACKGROUND: Due to the growing need to provide evidence syntheses under time constraints, researchers have begun focusing on the exploration of rapid review methods, which often employ single-reviewer literature screening. However, single-reviewer screening misses, on average, 13% of relevant studies, compared to 3% with dual-reviewer screening. Little guidance exists regarding methods to recover studies falsely excluded during literature screening. Likewise, it is unclear whether specific study characteristics can predict an increased risk of false exclusion. This systematic review aimed to identify supplementary search methods that can be used to recover studies falsely excluded during literature screening. Moreover, it strove to identify study-level predictors that indicate an elevated risk of false exclusions of studies during literature screening. METHODS: We performed literature searches for eligible studies in MEDLINE, Science Citation Index Expanded, Social Sciences Citation Index, Current Contents Connect, Embase, Epistemonikos.org, and Information Science & Technology Abstracts from 1999 to June 23, 2020. We searched for gray literature, checked reference lists, and conducted hand searches in two relevant journals and similar article searches current to January 28, 2021. Two investigators independently screened the literature; one investigator performed the data extraction, and a second investigator checked for correctness and completeness. Two reviewers assessed the risk of bias of eligible studies. We synthesized the results narratively. RESULTS: Three method studies, two with a case-study design and one with a case-series design, met the inclusion criteria. One study reported that all falsely excluded publications (8%) could be recovered through reference list checking compared to other supplementary search methods. No included methods study analyzed the impact of recovered studies on conclusions or meta-analyses. Two studies reported that up to 8% of studies were falsely excluded due to uninformative titles and abstracts, and one study showed that 11% of non-English studies were falsely excluded. CONCLUSIONS: Due to the limited evidence based on two case studies and one case series, we can draw no firm conclusion about the most reliable and most valid method to recover studies falsely excluded during literature screening or about the characteristics that might predict a higher risk of false exclusion. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/v2pjr/.

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: It is uncertain whether hormone therapy should be used for the primary prevention of chronic conditions such as heart disease, osteoporosis, or some types of cancers. Objective: To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions. Data Sources: PubMed/MEDLINE, Cochrane Library, EMBASE, and trial registries from January 1, 2016, through October 12, 2021; surveillance through July 2022. Study Selection: English-language randomized clinical trials and prospective cohort studies of fair or good quality. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available. Main Outcomes and Measures: Morbidity and mortality related to chronic conditions; health-related quality of life. Results: Twenty trials (N = 39 145) and 3 cohort studies (N = 1 155 410) were included. Participants using estrogen only compared with placebo had significantly lower risks for diabetes over 7.1 years (1050 vs 903 cases; 134 fewer [95% CI, 18-237]) and fractures over 7.2 years (1024 vs 1413 cases; 388 fewer [95% CI, 277-489]) per 10 000 persons. Risks per 10 000 persons were statistically significantly increased for gallbladder disease over 7.1 years (1113 vs 737 cases; 377 more [95% CI, 234-540]), stroke over 7.2 years (318 vs 239 cases; 79 more [95% CI, 15-159]), venous thromboembolism over 7.2 years (258 vs 181 cases; 77 more [95% CI, 19-153]), and urinary incontinence over 1 year (2331 vs 1446 cases; 885 more [95% CI, 659-1135]). Participants using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 persons, for colorectal cancer over 5.6 years (59 vs 93 cases; 34 fewer [95% CI, 9-51]), diabetes over 5.6 years (403 vs 482 cases; 78 fewer [95% CI, 15-133]), and fractures over 5 years (864 vs 1094 cases; 230 fewer [95% CI, 66-372]). Risks, per 10 000 persons, were significantly increased for invasive breast cancer (242 vs 191 cases; 51 more [95% CI, 6-106]), gallbladder disease (723 vs 463 cases; 260 more [95% CI, 169-364]), stroke (187 vs 135 cases; 52 more [95% CI, 12-104]), and venous thromboembolism (246 vs 126 cases; 120 more [95% CI, 68-185]) over 5.6 years; probable dementia (179 vs 91 cases; 88 more [95% CI, 15-212]) over 4.0 years; and urinary incontinence (1707 vs 1145 cases; 562 more [95% CI, 412-726]) over 1 year. Conclusions and Relevance: Use of hormone therapy in postmenopausal persons for the primary prevention of chronic conditions was associated with some benefits but also with an increased risk of harms.

Filamentous Fungal Infections in a Tertiary Care Setting: Epidemiology and Clinical Outcome.

Information on the distribution of filamentous fungal pathogens, which cause potential life-threatening invasive infections mostly in immunocompromised persons, is of great importance. The aim of this study was to evaluate the epidemiology and clinical outcome in patients with infections due to filamentous fungi at the University Hospital of Vienna, Austria. We conducted a retrospective observational study and consecutively included patients of any age with filamentous fungal infections between 2009 and 2017. The classification for probable and proven invasive filamentous fungal infections was based on the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group (EORTC) criteria or the expert opinion of an experienced clinical mycologist. We included 129 patients (median age: 52 years; 47.3% female) with episodes of 101 proven and probable invasive and 35 localized filamentous fungal infections (16 sinus, 14 eye, one ear, and four deep cutaneous). Aspergillus fumigatus alone accounted for 50.3% of the fungi, which was followed by the Mucorales group (13.7%) and Fusarium spp. (8.5%). Diagnosis was mainly based on culture findings. The lung was the most frequent site of infection. The 30-day and 90-day overall mortality of invasive fungal infections was 30.2% and 42.7%, respectively. We observed a high all-cause mortality among patients with invasive filamentous fungal infections. Prospective data collection in a nationwide registry would be necessary to provide important information on surveillance to clinicians and other decision-makers.

Surgical and Non-Surgical Interventions in Complete Rotator Cuff Tears.

BACKGROUND: This systematic review compares the efficacy and safety of surgical and non-surgical interventions for full- thickness rotator cuff tears. METHODS: A systematic literature search was conducted in five databases. Randomized (RCTs) and non-randomized controlled trials of interventions (non-RCTs) for the surgical or non-surgical treatment of patients with traumatic or atraumatic full-thickness rotator cuff tears were included. The review protocol was published in the PROSPERO registry (CRD42018100343). RESULTS: Ten studies (three RCTs with 332 participants; seven non-RCTs with 650 participants) met the inclusion criteria. One year after treatment, shoulder function, measured with the 100-point Constant score, had improved by 6.7 points (95% confidence interval [2.3; 11.0]) and pain, measured with the 10-cm visual analog scale, by 1.1 cm (0.5; 1.7] in the full-thickness rotator cuff tears treated surgically compared with non-surgical treatment. In one study the difference in favor of surgery persisted after 10 years' follow-up. For other outcomes, such as range of motion, muscle strength, quality of life, and adverse events, the data were sparse and the group differences were similar. The findings of the non-RCTs were comparable with those of the RCTs. CONCLUSION: With regard to functional improvement and pain reduction, surgical treatment of full-thickness rotator cuff tears was superior to non-surgical treatment in the short and the long term. Whether the differences between the groups are relevant for individual cases is uncertain, as the measured results were distributed below and above the threshold of clinical relevance. The conclusions may not be applicable to rotator cuff tears over 3 cm in size or to young persons.

Screening for Hypertension in Children and Adolescents: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Childhood hypertension can result in adverse outcomes during adulthood; identifying and treating primary and secondary childhood hypertension may reduce such risks. Objective: To update the evidence on screening and treatment of hypertension in childhood and adolescence for the US Preventive Services Task Force. Data Sources: PubMed, Cochrane Library, International Pharmaceutical Abstracts, EMBASE, and trial registries through September 3, 2019; bibliographies from retrieved articles, experts, and surveillance of the literature through October 6, 2020. Study Selection: Fair- or good-quality English-language studies evaluating diagnostic accuracy of blood pressure screening; cohort studies assessing the association of hypertension in childhood and adolescence with blood pressure or other intermediate outcomes in adulthood; randomized clinical trials (RCTs) or meta-analyses of pharmacological and lifestyle interventions. Data Extraction and Synthesis: Two reviewers independently assessed titles/abstracts and full-text articles, extracted data, and assessed study quality; the evidence was synthesized qualitatively. Main Outcomes and Measures: Sensitivity, specificity, and measures of association between childhood and adulthood blood pressure; reduction of childhood blood pressure; adverse effects of treatments. Results: Forty-two studies from 43 publications were included (N>12 400). No studies evaluated the benefits or harms of screening and the effect of treating childhood hypertension on outcomes in adulthood. One study reported a sensitivity of 0.82 and a specificity of 0.70 for 2 office-based blood pressure measurements. Twenty observational studies suggested a significant association between childhood hypertension and abnormal blood pressure in adulthood (odds ratios, 1.1-4.5; risk ratios, 1.45-3.60; hazard ratios, 2.8-3.2). Thirteen placebo-controlled RCTs and 1 meta-analysis assessed reductions in systolic (SBP) and diastolic blood pressure from pharmacological treatments. Pooled reductions of SBP were -4.38 mm Hg (95% CI, -7.27 to -2.16) for angiotensin-converting enzyme inhibitors and -3.07 mm Hg (95% CI, -4.99 to -1.44) for angiotensin receptor blockers. Candesartan reduced SBP by -6.56 mm Hg (P < .001; n = 240). ß-Blockers, calcium channel blockers, and mineralocorticoid receptor antagonists did not achieve significant reductions over 2 to 4 weeks. SBP was significantly reduced by exercise over 8 months (-4.9 mm Hg, P ≤ .05; n = 69), by dietary approaches to stop hypertension over 3 months (-2.2 mm Hg, P < .01; n = 57), and by a combination of drug treatment and lifestyle interventions over 6 months (-7.6 mm Hg; P < .001; n = 95). Low-salt diet did not achieve reductions of blood pressure. Conclusions and Relevance: Observational studies indicate an association between hypertension in childhood and hypertension in adulthood. However, the evidence is inconclusive whether the diagnostic accuracy of blood pressure measurements is adequate for screening asymptomatic children and adolescents in primary care.

Efficacy and safety of immune checkpoint inhibitors in patients with advanced non-small cell lung cancer (NSCLC): a systematic literature review.

Background: Therapeutic strategies with immune checkpoint inhibitors (ICIs) counteract the immunosuppressive effects of programmed cell death protein-1 (PD-1) and ligand-1 (PD-L1). ICI treatment has emerged in first- and second-line therapy of non-small cell lung cancer (NSCLC). As immunotherapeutic treatment with ICIs is a dynamic field where new drugs and combinations are constantly evaluated, we conducted an up-to-date systematic review on comparative efficacy and safety in patients with advanced NSCLC. Methods: We searched PubMed up to February 2020 and Embase, CENTRAL, and clinical trial registries up to August 2018. Additionally, we checked reference lists. We dually screened titles, abstracts and, subsequently, full-texts for eligibility. Two reviewers assessed the risk of bias and graded the certainty of evidence following GRADE (Grading of Recommendations Assessment, Development and Evaluation). For second-line therapy, we performed random-effects meta-analyses. Due to considerable clinical heterogeneity, we reported first-line results narratively. Results: Of 1497 references, we identified 22 relevant publications of 16 studies. For first-line therapy, a combination of an ICI with chemotherapy improved progression-free survival and overall survival compared to chemotherapy but increased the risk of serious adverse events. Single-agent pembrolizumab increased overall and progression-free survival in patients with PD-L1 expression of ≥50% and resulted in less TRAE than chemotherapy. Compared to placebo, maintenance therapy with durvalumab increased overall and progression-free survival at the downside of higher risk of TRAE. For second-line therapy, a random-effects meta-analysis yielded a statistically significantly improved overall survival (OS) and progression-free survival (PFS) for ICIs compared to docetaxel (HR 0.69; 95% CI: 0.63-0.75 for OS; HR 0.85; 95% CI: 0.77 - 0.93 for PFS; 6 studies, 3478 patients; median OS benefit in months: 2.4 to 4.2). In meta-analysis, risk of any treatment-related adverse events of any grade was lower for ICI than docetaxel as second-line therapy (RR 0.76, 95% CI: 0.73-0.79; 6 studies, 3763 patients). Conclusion: In first-line therapy of patients with advanced NSCLC, ICI is effective when combined with chemotherapy not depending on PD-L1 expression, or as monotherapy in high PD-L1 expressing tumors. For second-line therapy, single-agent ICI improves efficacy and safety compared to docetaxel.

Combining abbreviated literature searches with single-reviewer screening: three case studies of rapid reviews.

BACKGROUND: Decision-makers increasingly request rapid answers to clinical or public health questions. To save time, personnel, and financial resources, rapid reviews streamline the methodological steps of the systematic review process. We aimed to explore the validity of a rapid review approach that combines a substantially abbreviated literature search with a single-reviewer screening of abstracts and full texts using three case studies. METHODS: We used a convenience sample of three ongoing Cochrane reviews as reference standards. Two reviews addressed oncological topics and one addressed a public health topic. For each of the three topics, three reviewers screened the literature independently. Our primary outcome was the change in conclusions between the rapid reviews and the respective Cochrane reviews. In case the rapid approach missed studies, we recalculated the meta-analyses for the main outcomes and asked Cochrane review authors if the new body of evidence would change their original conclusion compared with the reference standards. Additionally, we assessed the sensitivity of the rapid review approach compared with the results of the original Cochrane reviews. RESULTS: For the two oncological topics (case studies 1 and 2), the three rapid reviews each yielded the same conclusions as the Cochrane reviews. However, the authors would have had less certainty about their conclusion in case study 2. For case study 3, the public health topic, only one of the three rapid reviews led to the same conclusion as the Cochrane review. The other two rapid reviews provided insufficient information for the authors to draw conclusions. Using the rapid review approach, the sensitivity was 100% (3 of 3) for case study 1. For case study 2, the three rapid reviews identified 40% (4 of 10), 50% (5 of 10), and 60% (6 of 10) of the included studies, respectively; for case study 3, the respective numbers were 38% (8 of 21), 43% (9 of 21), and 48% (10 of 21). CONCLUSIONS: Within the limitations of these case studies, a rapid review approach that combines abbreviated literature searches with single-reviewer screening may be feasible for focused clinical questions. For complex public health topics, sensitivity seems to be insufficient.

Quarantine alone or in combination with other public health measures to control COVID-19: a rapid review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a rapidly emerging disease classified as a pandemic by the World Health Organization (WHO). To support the WHO with their recommendations on quarantine, we conducted a rapid review on the effectiveness of quarantine during severe coronavirus outbreaks. OBJECTIVES: To assess the effects of quarantine (alone or in combination with other measures) of individuals who had contact with confirmed or suspected cases of COVID-19, who travelled from countries with a declared outbreak, or who live in regions with high disease transmission. SEARCH METHODS: An information specialist searched the Cochrane COVID-19 Study Register, and updated the search in PubMed, Ovid MEDLINE, WHO Global Index Medicus, Embase, and CINAHL on 23 June 2020. SELECTION CRITERIA: Cohort studies, case-control studies, time series, interrupted time series, case series, and mathematical modelling studies that assessed the effect of any type of quarantine to control COVID-19. We also included studies on SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) as indirect evidence for the current coronavirus outbreak. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and titles in duplicate. Two review authors then independently screened all potentially relevant full-text publications. One review author extracted data, assessed the risk of bias and assessed the certainty of evidence with GRADE and a second review author checked the assessment. We used three different tools to assess risk of bias, depending on the study design: ROBINS-I for non-randomised studies of interventions, a tool provided by Cochrane Childhood Cancer for non-randomised, non-controlled studies, and recommendations from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) for modelling studies. We rated the certainty of evidence for the four primary outcomes: incidence, onward transmission, mortality, and costs. MAIN RESULTS: We included 51 studies; 4 observational studies and 28 modelling studies on COVID-19, one observational and one modelling study on MERS, three observational and 11 modelling studies on SARS, and three modelling studies on SARS and other infectious diseases. Because of the diverse methods of measurement and analysis across the outcomes of interest, we could not conduct a meta-analysis and undertook a narrative synthesis. We judged risk of bias to be moderate for 2/3 non-randomized studies of interventions (NRSIs) and serious for 1/3 NRSI. We rated risk of bias moderate for 4/5 non-controlled cohort studies, and serious for 1/5. We rated modelling studies as having no concerns for 13 studies, moderate concerns for 17 studies and major concerns for 13 studies. Quarantine for individuals who were in contact with a confirmed/suspected COVID-19 case in comparison to no quarantine Modelling studies consistently reported a benefit of the simulated quarantine measures, for example, quarantine of people exposed to confirmed or suspected cases may have averted 44% to 96% of incident cases and 31% to 76% of deaths compared to no measures based on different scenarios (incident cases: 6 modelling studies on COVID-19, 1 on SARS; mortality: 2 modelling studies on COVID-19, 1 on SARS, low-certainty evidence). Studies also indicated that there may be a reduction in the basic reproduction number ranging from 37% to 88% due to the implementation of quarantine (5 modelling studies on COVID-19, low-certainty evidence). Very low-certainty evidence suggests that the earlier quarantine measures are implemented, the greater the cost savings may be (2 modelling studies on SARS). Quarantine in combination with other measures to contain COVID-19 in comparison to other measures without quarantine or no measures When the models combined quarantine with other prevention and control measures, such as school closures, travel restrictions and social distancing, the models demonstrated that there may be a larger effect on the reduction of new cases, transmissions and deaths than measures without quarantine or no interventions (incident cases: 9 modelling studies on COVID-19; onward transmission: 5 modelling studies on COVID-19; mortality: 5 modelling studies on COVID-19, low-certainty evidence). Studies on SARS and MERS were consistent with findings from the studies on COVID-19. Quarantine for individuals travelling from a country with a declared COVID-19 outbreak compared to no quarantine Very low-certainty evidence indicated that the effect of quarantine of travellers from a country with a declared outbreak on reducing incidence and deaths may be small for SARS, but might be larger for COVID-19 (2 observational studies on COVID-19 and 2 observational studies on SARS). AUTHORS' CONCLUSIONS: The current evidence is limited because most studies on COVID-19 are mathematical modelling studies that make different assumptions on important model parameters. Findings consistently indicate that quarantine is important in reducing incidence and mortality during the COVID-19 pandemic, although there is uncertainty over the magnitude of the effect. Early implementation of quarantine and combining quarantine with other public health measures is important to ensure effectiveness. In order to maintain the best possible balance of measures, decision makers must constantly monitor the outbreak and the impact of the measures implemented. This review was originally commissioned by the WHO and supported by Danube-University-Krems. The update was self-initiated by the review authors.

Universal screening for SARS-CoV-2 infection: a rapid review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by the novel betacoronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Most people infected with SARS-CoV-2 have mild disease with unspecific symptoms, but about 5% become critically ill with respiratory failure, septic shock and multiple organ failure. An unknown proportion of infected individuals never experience COVID-19 symptoms although they are infectious, that is, they remain asymptomatic. Those who develop the disease, go through a presymptomatic period during which they are infectious. Universal screening for SARS-CoV-2 infections to detect individuals who are infected before they present clinically, could therefore be an important measure to contain the spread of the disease. OBJECTIVES: We conducted a rapid review to assess (1) the effectiveness of universal screening for SARS-CoV-2 infection compared with no screening and (2) the accuracy of universal screening in people who have not presented to clinical care for symptoms of COVID-19. SEARCH METHODS: An information specialist searched Ovid MEDLINE and the Centers for Disease Control (CDC) COVID-19 Research Articles Downloadable Database up to 26 May 2020. We searched Embase.com, the CENTRAL, and the Cochrane Covid-19 Study Register on 14 April 2020. We searched LitCovid to 4 April 2020. The World Health Organization (WHO) provided records from daily searches in Chinese databases and in PubMed up to 15 April 2020. We also searched three model repositories (Covid-Analytics, Models of Infectious Disease Agent Study [MIDAS], and Society for Medical Decision Making) on 8 April 2020. SELECTION CRITERIA: Trials, observational studies, or mathematical modelling studies assessing screening effectiveness or screening accuracy among general populations in which the prevalence of SARS-CoV2 is unknown. DATA COLLECTION AND ANALYSIS: After pilot testing review forms, one review author screened titles and abstracts. Two review authors independently screened the full text of studies and resolved any disagreements by discussion with a third review author. Abstracts excluded by a first review author were dually reviewed by a second review author prior to exclusion. One review author independently extracted data, which was checked by a second review author for completeness and accuracy. Two review authors independently rated the quality of included studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool for diagnostic accuracy studies and a modified form designed originally for economic evaluations for modelling studies. We resolved differences by consensus. We synthesized the evidence in narrative and tabular formats. We rated the certainty of evidence for days to outbreak, transmission, cases missed and detected, diagnostic accuracy (i.e. true positives, false positives, true negatives, false negatives) using the GRADE approach. MAIN RESULTS: We included 22 publications. Two modelling studies reported on effectiveness of universal screening. Twenty studies (17 cohort studies and 3 modelling studies) reported on screening test accuracy. Effectiveness of screening We included two modelling studies. One study suggests that symptom screening at travel hubs, such as airports, may slightly slow but not stop the importation of infected cases (assuming 10 or 100 infected travellers per week reduced the delay in a local outbreak to 8 days or 1 day, respectively). We assessed risk of bias as minor or no concerns, and certainty of evidence was low, downgraded for very serious indirectness. The second modelling study provides very low-certainty evidence that screening of healthcare workers in emergency departments using laboratory tests may reduce transmission to patients and other healthcare workers (assuming a transmission constant of 1.2 new infections per 10,000 people, weekly screening reduced infections by 5.1% within 30 days). The certainty of evidence was very low, downgraded for high risk of bias (major concerns) and indirectness. No modelling studies reported on harms of screening. Screening test accuracy All 17 cohort studies compared an index screening strategy to a reference reverse transcriptase polymerase chain reaction (RT-PCR) test. All but one study reported on the accuracy of single point-in-time screening and varied widely in prevalence of SARS-CoV-2, settings, and methods of measurement. We assessed the overall risk of bias as unclear in 16 out of 17 studies, mainly due to limited information on the index test and reference standard. We rated one study as being at high risk of bias due to the inclusion of two separate populations with likely different prevalences. For several screening strategies, the estimates of sensitivity came from small samples. For single point-in-time strategies, for symptom assessment, the sensitivity from 12 cohorts (524 people) ranged from 0.00 to 0.60 (very low-certainty evidence) and the specificity from 12 cohorts (16,165 people) ranged from 0.66 to 1.00 (low-certainty evidence). For screening using direct temperature measurement (3 cohorts, 822 people), international travel history (2 cohorts, 13,080 people), or exposure to known infected people (3 cohorts, 13,205 people) or suspected infected people (2 cohorts, 954 people), sensitivity ranged from 0.00 to 0.23 (very low- to low-certainty evidence) and specificity ranged from 0.90 to 1.00 (low- to moderate-certainty evidence). For symptom assessment plus direct temperature measurement (2 cohorts, 779 people), sensitivity ranged from 0.12 to 0.69 (very low-certainty evidence) and specificity from 0.90 to 1.00 (low-certainty evidence). For rapid PCR test (1 cohort, 21 people), sensitivity was 0.80 (95% confidence interval (CI) 0.44 to 0.96; very low-certainty evidence) and specificity was 0.73 (95% CI 0.39 to 0.94; very low-certainty evidence). One cohort (76 people) reported on repeated screening with symptom assessment and demonstrates a sensitivity of 0.44 (95% CI 0.29 to 0.59; very low-certainty evidence) and specificity of 0.62 (95% CI 0.42 to 0.79; low-certainty evidence). Three modelling studies evaluated the accuracy of screening at airports. The main outcomes measured were cases missed or detected by entry or exit screening, or both, at airports. One study suggests very low sensitivity at 0.30 (95% CI 0.1 to 0.53), missing 70% of infected travellers. Another study described an unrealistic scenario to achieve a 90% detection rate, requiring 0% asymptomatic infections. The final study provides very uncertain evidence due to low methodological quality. AUTHORS' CONCLUSIONS: The evidence base for the effectiveness of screening comes from two mathematical modelling studies and is limited by their assumptions. Low-certainty evidence suggests that screening at travel hubs may slightly slow the importation of infected cases. This review highlights the uncertainty and variation in accuracy of screening strategies. A high proportion of infected individuals may be missed and go on to infect others, and some healthy individuals may be falsely identified as positive, requiring confirmatory testing and potentially leading to the unnecessary isolation of these individuals. Further studies need to evaluate the utility of rapid laboratory tests, combined screening, and repeated screening. More research is also needed on reference standards with greater accuracy than RT-PCR. Given the poor sensitivity of existing approaches, our findings point to the need for greater emphasis on other ways that may prevent transmission such as face coverings, physical distancing, quarantine, and adequate personal protective equipment for frontline workers.

The comparative efficacy and risk of harms of the intravenous and subcutaneous formulations of trastuzumab in patients with HER2-positive breast cancer: a rapid review.

BACKGROUND: Trastuzumab is a monoclonal antibody for patients with HER2 (human epidermal growth factor receptor 2)-positive breast cancer, which is added to regular treatment and reduces mortality. Originally, trastuzumab had to be administered intravenously (IV) over 30 min every 3 weeks for 1 year. Since 2012, a formulation for the subcutaneous (SC) administration of trastuzumab has been available, which has not yet been approved in the USA. Advocates claim that the SC formulation saves time and money, despite higher costs. The purpose of this study is to review existing literature concerning the comparative efficacy and risk of harms of trastuzumab IV and SC concerning patient-relevant health outcomes. METHODS: We conducted searches in the Cochrane Library and MEDLINE for articles published through May 2018 in English or German. In addition, we searched ClinicalTrials.gov to identify unpublished studies. We dually reviewed the abstracts and full-text articles based on a priori defined inclusion criteria, rated the risk of bias of included studies, and assessed the strength of the evidence for each outcome of interest. Because data was insufficient for quantitative synthesis, we summarized results narratively. RESULTS: We identified three RCTs (randomized controlled trials) meeting our eligibility criteria, which included data on 1003 patients. We found moderate evidence for similar event rates (20.05% vs. 18%, HR (hazard ratio) 0.88, CI 95% = 0.62-1.27), and mortality rates (10% vs. 8%, HR 0.76, CI 95% = 0.44-1.32) after 1.7 years for patients receiving trastuzumab IV and for patients receiving SC. Results remained similar after 3.3 years, though evidence lacked strength due to a high dropout rate. All trials reported more adverse events among the SC group than in the IV group. Evidence for these findings was of moderate strength. Nevertheless, more than 85% of the patients preferred trastuzumab SC over IV. Results concerning serious adverse events appeared to be heterogeneous. CONCLUSION: Results of studies indicate similar efficacy between the two routes of administration. The higher rates of adverse events for SC administration were mainly attributable to injection site-related events. The clinical decision of whether to administer trastuzumab SC or IV requires the consideration of several factors and should be determined individually.

Comparative Effectiveness of Combining MTX with Biologic Drug Therapy Versus Either MTX or Biologics Alone for Early Rheumatoid Arthritis in Adults: a Systematic Review and Network Meta-analysis.

BACKGROUND: Comparative effectiveness of early rheumatoid arthritis (RA) treatments remains uncertain. PURPOSE: Compare benefits and harms of biologic drug therapies for adults with early RA within 1 year of diagnosis. DATA SOURCES: English language articles from the 2012 review to October 2017 identified through MEDLINE, Cochrane Library and International Pharmaceutical Abstracts, gray literature, expert recommendations, reference lists of published literature, and supplemental evidence data requests. STUDY SELECTION: Two persons independently selected studies based on predefined inclusion criteria. DATA EXTRACTION: One reviewer extracted data; a second reviewer checked accuracy. Two independent reviewers assigned risk of bias ratings. DATA SYNTHESIS: We identified 22 eligible studies with 9934 participants. Combination therapy with tumor necrosis factor (TNF) or non-TNF biologics plus methotrexate (MTX) improved disease control, remission, and functional capacity compared with monotherapy of either MTX or a biologic. Network meta-analyses found higher ACR50 response (50% improvement) for combination therapy of biologic plus MTX than for MTX monotherapy (relative risk range 1.20 [95% confidence interval (CI), 1.04 to 1.38] to 1.57 [95% CI, 1.30 to 1.88]). No significant differences emerged between treatment discontinuation rates because of adverse events or serious adverse events. Subgroup data (disease activity, prior therapy, demographics, serious conditions) were limited. LIMITATIONS: Trials enrolled almost exclusively selected populations with high disease activity. Network meta-analyses were derived from indirect comparisons relative to MTX due to the dearth of head-to-head studies comparing interventions. No eligible data on biosimilars were found. CONCLUSIONS: Qualitative and network meta-analyses suggest that the combination of MTX with TNF or non-TNF biologics reduces disease activity and improves remission when compared with MTX monotherapy. Overall adverse event and discontinuation rates were similar between treatment groups. REGISTRATION: PROSPERO (available at http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017079260 ).

[Evidence-based recommendations for the revision of the Austrian periodic health examination]. / Evidenzbasierte Empfehlungen zur Überarbeitung der österreichischen Vorsorgeuntersuchung.

The Austrian periodic health examination (PHE) was introduced in 1974 as a health insurance benefit and was redesigned for the last time in 2005. Therefore, the aim of this work was to revise the scientific basis of the PHE using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. We updated the scientific evidence of examinations and consultations that are currently part of the PHE and searched and integrated new examinations. We assessed the expectations of the population towards the PHE in three focus groups. A panel of experts developed evidence-based recommendations for the revised PHE. They formulated 26 recommendations on 20 target diseases or risk factors. In comparison to the previous PHE, the panel added screening for abdominal aortic aneurysm, osteoporotic fracture risk, and chronic kidney disease to the recommendations, while screening for asymptomatic bacteriuria, screening for iron deficiency/pernicious anaemia, and risk identification of glaucoma should no longer be included.

Second-generation antidepressants for preventing seasonal affective disorder in adults.

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review - one of four reviews on efficacy and safety of interventions to prevent SAD - focuses on second-generation antidepressants (SGAs). OBJECTIVES: To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. SEARCH METHODS: We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library, the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. SELECTION CRITERIA: For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non-randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and full-text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random-effects (Mantel-Haenszel) meta-analyses. We assessed statistical heterogeneity by calculating the Chi2 statistic and the Cochran Q. We used the I2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. MAIN RESULTS: We identified 3745 citations after de-duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full-text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates.Overall, moderate-quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate-quality evidence), insomnia and nausea (both low-quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively.We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. AUTHORS' CONCLUSIONS: Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high-risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences.Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non-pharmacological interventions.

Screening for periodontal diseases by non-dental health professionals: a protocol for a systematic review and overview of reviews.

BACKGROUND: Periodontal diseases are responsible for a vast burden of disease globally and are associated with other severe illnesses such as cardiovascular diseases or diabetes. Tests for early diagnosis of periodontal diseases and effective treatments are available. The effectiveness of screening for periodontal diseases to detect periodontal diseases at an early stage during periodic health examinations at primary care facilities, however, is unclear. The objective of this systematic review is to assess the benefits and risks of screening for periodontal diseases in adults during the periodic health examinations. METHODS: We will use two methodological approaches: (1) a systematic review to assess the effectiveness and risk of harms of screening for periodontal diseases during periodic health examinations and (2) an overview of systematic reviews to determine the effectiveness of treatment approaches for early periodontal disease. We will search electronic databases (Ovid MEDLINE, Embase.com , the Cochrane Library, Epistemonikos, Centre for Reviews and Dissemination databases, PubMed (non-MEDLINE content)) for published studies as well as sources for grey literature to detect unpublished studies. Two authors will independently screen abstracts and full texts using pre-defined eligibility criteria, select studies, extract data, and assess the risk of bias of included studies or reviews. In general, we will conduct a systematic narrative synthesis. Criteria for conducting meta-analyses were defined a priori. Our primary outcomes of interest are tooth loss, loosening of teeth, and depletion of bone tissue. Secondary outcomes are gingivitis/gum inflammation, pocket depths, dental hygiene, lifestyle modifications (e.g., smoking, alcohol, nutrition), and toothache. We consulted a panel of experts and patient representatives to prioritize these outcomes. Two investigators will assess independently the certainty of the evidence for each outcome using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. DISCUSSION: We anticipate that our review will highlight the gaps in the available evidence about the effectiveness of screening for periodontal diseases during periodic health examinations. Implications for screening programs may be based on linked evidence about the validity of available screening tools and the effectiveness of early treatment. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017081150.