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1.
J Urol ; : 101097JU0000000000001700, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33617330

RESUMO

PURPOSE: To identify and validate known predictors of disease reclassification at 1 or 4 year(s) to support risk-based selection of patient suitable for AS. MATERIALS AND METHODS: An individual participant data meta-analysis using data from 25 established cohorts within the Movember Foundations GAP3 consortium. In total 5,530 men were included. Disease reclassification was defined as any increase in Gleason grade group (GGG) at biopsy at 1 and 4 years. Associations were estimated using random effect logistic regression models. The discriminative ability of combinations of predictors was assessed in an internal-external validation procedure using the area under the ROC (AUC). RESULTS: Among the 5,570 men evaluated at 1 year, we found 815 reclassifications to higher GGG at biopsy (pooled reclassification rate 13%, range 0%-31%). Important predictors were age, prostate-specific antigen (PSA), prostate volume, T-stage, and number of biopsy cores with PCa. Among the 1,515 men evaluated at 4 years, we found 205 reclassifications (pooled reclassification rates 14%, range 3%-40%), with similar predictors. The average AUCs at internal-external validation were 0.68 and 0.61 for 1 and 4-year reclassification respectively. CONCLUSIONS: Disease reclassification occurs typically in 13-14% of biopsies at 1 and 4 years after start of AS, with substantial between study heterogeneity. Current guidelines might be extended by considering prostate volume to improve individualized selection for AS. Additional predictors are needed to improve patient selection for AS.

2.
BMC Med Res Methodol ; 21(1): 4, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407167

RESUMO

BACKGROUND: There is a growing interest in assessment of the quality of hospital care, based on outcome measures. Many quality of care comparisons rely on binary outcomes, for example mortality rates. Due to low numbers, the observed differences in outcome are partly subject to chance. We aimed to quantify the gain in efficiency by ordinal instead of binary outcome analyses for hospital comparisons. We analyzed patients with traumatic brain injury (TBI) and stroke as examples. METHODS: We sampled patients from two trials. We simulated ordinal and dichotomous outcomes based on the modified Rankin Scale (stroke) and Glasgow Outcome Scale (TBI) in scenarios with and without true differences between hospitals in outcome. The potential efficiency gain of ordinal outcomes, analyzed with ordinal logistic regression, compared to dichotomous outcomes, analyzed with binary logistic regression was expressed as the possible reduction in sample size while keeping the same statistical power to detect outliers. RESULTS: In the IMPACT study (9578 patients in 265 hospitals, mean number of patients per hospital = 36), the analysis of the ordinal scale rather than the dichotomized scale ('unfavorable outcome'), allowed for up to 32% less patients in the analysis without a loss of power. In the PRACTISE trial (1657 patients in 12 hospitals, mean number of patients per hospital = 138), ordinal analysis allowed for 13% less patients. Compared to mortality, ordinal outcome analyses allowed for up to 37 to 63% less patients. CONCLUSIONS: Ordinal analyses provide the statistical power of substantially larger studies which have been analyzed with dichotomization of endpoints. We advise to exploit ordinal outcome measures for hospital comparisons, in order to increase efficiency in quality of care measurements. TRIAL REGISTRATION: We do not report the results of a health care intervention.

3.
J Neurotrauma ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33470157

RESUMO

In medical research, missing data is common. In acute diseases such as traumatic brain injury (TBI), even well conducted prospective studies may suffer from missing data in baseline characteristics and outcomes. Statistical models may simply drop patients with any missing values, potentially leaving a selected subset of the original cohort. Imputation is widely accepted by methodologists as an appropriate way to deal with missing data. We aim to provide practical guidance on handling missing data for prediction modelling. We hereto propose a five-step approach, centred around single and multiple imputation: 1) explore the missing data patterns; 2) choose a method of imputation; 3) perform imputation; 4) assess diagnostics of the imputation; and 5) analyse the imputed datasets. We illustrate these 5 steps with the estimation and validation of the IMPACT prognostic model in 1375 patients from the CENTER-TBI database, included in 53 centers across 17 countries, with moderate or severe TBI in the prospective European CENTER-TBI study. Future prediction modelling studies in acute diseases may benefit from following the suggested 5 steps for optimal statistical analysis and interpretation, after maximal effort have been made to minimize missing data.

4.
BMJ Open ; 11(1): e038707, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33408198

RESUMO

OBJECTIVES: To determine prognostic factors for health status and recovery patterns during the first 2 years after injury in the clinical trauma population. DESIGN: A prospective longitudinal cohort study. SETTING: Ten participating hospitals in Brabant, the Netherlands. PARTICIPANTS: Injured adult patients admitted to a hospital between August 2015 and November 2016 were followed: 4883 (50%) patients participated. MAIN OUTCOME MEASURES: Primary outcome was health status, measured with the EuroQol-5-dimensions-3-levels (EQ-5D), including a cognition item and the EuroQol Visual Analogue Scale. Health status was collected at 1 week, 1, 3, 6, 12 and 24 months after injury. Potential prognostic factors were based on literature and clinical experience (eg, age, sex, pre-injury frailty (Groningen Frailty Index), pre-injury EQ-5D). RESULTS: Health status increased mainly during the first 6 months after injury with a mean EQ-5D utility score at 1 week of 0.49 and 0.79 at 24 months. The dimensions mobility, pain/discomfort and usual activities improved up to 2 years after injury. Lower pre-injury health status, frailty and longer length of stay at the hospital were important prognostic factors for poor recovery. Spine injury, lower and upper extremity injury showed to be prognostic factors for problems after injury. Traumatic brain injury was a prognostic factor for cognitive problems. CONCLUSION: This study contributes to the increase in knowledge of health recovery after injury. It could be a starting point to develop prediction models for specific injury classifications and implementation of personalised medicine. TRIAL REGISTRATION NUMBER: NCT02508675.

6.
J Surg Res ; 257: 32-41, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32818782

RESUMO

BACKGROUND: Older patients often have iron deficiency anemia before surgery, which can be effectively treated with intravenous iron supplementation (IVIS). Anemia and blood transfusions are associated with an increased risk of delirium. The aim of this research was to assess the effectiveness and safety of using IVIS in a prehabilitation program. MATERIAL AND METHODS: Patients ≥70 y who underwent abdominal surgery between November 2015 and June 2018 were included in this single-center prospective cohort study. All patients were prehabilitated; however, only anemic patients received a single dose of 1000 mg intravenous iron (ferric carboxymaltose) to increase preoperative hemoglobin levels (IVIS group). Nonanemic patients received standard care (SC). The hemoglobin levels (primary outcome) were assessed at the outpatient clinic visit, at admission, and at discharge. Secondary outcomes were postoperative delirium, postoperative anemia, blood transfusion, complications other than delirium, and length of hospital stay. All outcomes were compared between the IVIS group and SC group. RESULTS: Of all patients (n = 248), 97 anemic patients received IVIS (39%). Of the anemic patients, 50 patients (52%) had iron deficiency. Initial differences in hemoglobin concentrations between the IVIS group and SC group at T1 and T2 (7.2 versus 8.8; P < 0.001 and 7.4 versus 8.6; P = 0.023, respectively) were no longer present at discharge (6.6 versus 7.2; P = 0.35). No statistically significant differences were observed for all secondary outcomes between the IVIS group and the SC group. No infusion-related adverse events occurred. CONCLUSIONS: Adding IVIS to prehabilitation programs is safe and diminishes differences in these concentrations between preoperatively anemic and nonanemic patients. IVIS may be worthwhile as an additional component of prehabilitation programs. Results merit further investigation.


Assuntos
Ferro/administração & dosagem , Cuidados Pré-Operatórios/métodos , Abdome/cirurgia , Idoso , Idoso de 80 Anos ou mais , Anemia/epidemiologia , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/epidemiologia , Transfusão de Sangue/estatística & dados numéricos , Estudos de Coortes , Delírio/epidemiologia , Procedimentos Cirúrgicos Eletivos , Feminino , Hemoglobinas/análise , Humanos , Infusões Intravenosas , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos
8.
NPJ Breast Cancer ; 6(1): 60, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33298933

RESUMO

We aimed to assess contralateral breast cancer (CBC) risk in patients with ductal carcinoma in situ (DCIS) compared with invasive breast cancer (BC). Women diagnosed with DCIS (N = 28,003) or stage I-III BC (N = 275,836) between 1989 and 2017 were identified from the nationwide Netherlands Cancer Registry. Cumulative incidences were estimated, accounting for competing risks, and hazard ratios (HRs) for metachronous invasive CBC. To evaluate effects of adjuvant systemic therapy and screening, separate analyses were performed for stage I BC without adjuvant systemic therapy and by mode of first BC detection. Multivariable models including clinico-pathological and treatment data were created to assess CBC risk prediction performance in DCIS patients. The 10-year cumulative incidence of invasive CBC was 4.8% for DCIS patients (CBC = 1334). Invasive CBC risk was higher in DCIS patients compared with invasive BC overall (HR = 1.10, 95% confidence interval (CI) = 1.04-1.17), and lower compared with stage I BC without adjuvant systemic therapy (HR = 0.87; 95% CI = 0.82-0.92). In patients diagnosed ≥2011, the HR for invasive CBC was 1.38 (95% CI = 1.35-1.68) after screen-detected DCIS compared with screen-detected invasive BC, and was 2.14 (95% CI = 1.46-3.13) when not screen-detected. The C-index was 0.52 (95% CI = 0.50-0.54) for invasive CBC prediction in DCIS patients. In conclusion, CBC risks are low overall. DCIS patients had a slightly higher risk of invasive CBC compared with invasive BC, likely explained by the risk-reducing effect of (neo)adjuvant systemic therapy among BC patients. For support of clinical decision making more information is needed to differentiate CBC risks among DCIS patients.

9.
PLoS One ; 15(12): e0241427, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33347441

RESUMO

In the last decades, statistical methodology has developed rapidly, in particular in the field of regression modeling. Multivariable regression models are applied in almost all medical research projects. Therefore, the potential impact of statistical misconceptions within this field can be enormous Indeed, the current theoretical statistical knowledge is not always adequately transferred to the current practice in medical statistics. Some medical journals have identified this problem and published isolated statistical articles and even whole series thereof. In this systematic review, we aim to assess the current level of education on regression modeling that is provided to medical researchers via series of statistical articles published in medical journals. The present manuscript is a protocol for a systematic review that aims to assess which aspects of regression modeling are covered by statistical series published in medical journals that intend to train and guide applied medical researchers with limited statistical knowledge. Statistical paper series cannot easily be summarized and identified by common keywords in an electronic search engine like Scopus. We therefore identified series by a systematic request to statistical experts who are part or related to the STRATOS Initiative (STRengthening Analytical Thinking for Observational Studies). Within each identified article, two raters will independently check the content of the articles with respect to a predefined list of key aspects related to regression modeling. The content analysis of the topic-relevant articles will be performed using a predefined report form to assess the content as objectively as possible. Any disputes will be resolved by a third reviewer. Summary analyses will identify potential methodological gaps and misconceptions that may have an important impact on the quality of analyses in medical research. This review will thus provide a basis for future guidance papers and tutorials in the field of regression modeling which will enable medical researchers 1) to interpret publications in a correct way, 2) to perform basic statistical analyses in a correct way and 3) to identify situations when the help of a statistical expert is required.


Assuntos
Pesquisa Biomédica/estatística & dados numéricos , Modelos Estatísticos , Análise de Regressão , Viés , Pesquisa Biomédica/educação , Bioestatística/métodos , Coleta de Dados , Gerenciamento de Dados , Ciência de Dados/educação , Ciência de Dados/estatística & dados numéricos , Humanos , Estudos Observacionais como Assunto , Publicações Periódicas como Assunto
10.
J Neurotrauma ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33161840

RESUMO

The International Mission on Prognosis and Analysis of Clinical trials in Traumatic brain injury (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models predict functional outcome after moderate and severe traumatic brain injury (TBI). We aimed to assess their performance in a contemporary cohort of patients across Europe. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study is a prospective observational cohort study in patients presenting with TBI and an indication for brain computed tomography. The CENTER-TBI core cohort consists of 4509 TBI patients available for analyses from 59 centers in 18 countries across Europe and Israel. The IMPACT validation cohort included 1173 patients with GCS≤12, age≥14 and 6-month Glasgow Outcome Scale Extended (GOSE) available. The CRASH validation cohort contained 1742 patients with GCS≤14, age16 and 14-day mortality or 6-month GOSE available. Performance of the three IMPACT and two CRASH model variants was assessed with discrimination (area under the receiver operating characteristic curve; AUC) and calibration (comparison of observed versus predicted outcome rates). For IMPACT, model discrimination was good, with AUCs ranging between 0.77-0.85 in 1173 patients and between 0.80-0.88 in the broader CRASH selection (n=1742). For CRASH, AUCs ranged between 0.82-0.88 in 1742 patients and between 0.66-0.80 in the stricter IMPACT selection (n=1173). Calibration of the IMPACT and CRASH models was generally moderate, with calibration-in-the-large and calibration slopes ranging between -2.02-0.61 and between 0.48-1.39, respectively. The IMPACT and CRASH models adequately identify patients at high risk for mortality or unfavorable outcome, which supports their use in research settings and for benchmarking in the context of quality of care assessment.

12.
BMC Med Inform Decis Mak ; 20(1): 288, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33148227

RESUMO

BACKGROUND: The use of statins for primary prevention of cardiovascular diseases is associated with different benefit and harm outcomes. The aime of this study is how important these outcomes are for people and what people's preferences are. METHODS: We conducted a preference-eliciting survey incorporating a best-worst scaling (BWS) instrument in Iran from June to November 2019. The relative importance of 13 statins-related outcomes was assessed on a sample of 1085 participants, including 913 general population (486 women) and 172 healthcare providers from the population covered by urban and rural primary health care centers. The participants made trade-off decisions and selected the most and least worrisome outcomes concurrently from 13 choice sets; each contains four outcomes generated using the balanced incomplete block design. RESULTS: According to the mean (SD) BWS scores, which can be (+ 4) in maximum and (- 4) in minimum, in the general population, the most worrisome outcomes were severe stroke (3.37 (0.8)), severe myocardial infarction (2.71(0.7)), and cancer (2.69 (1.33)). While myopathy (- 3. 03 (1.03)), nausea/headache (- 2.69 (0.94)), and treatment discontinuation due to side effects (- 2.24 (1.14)) were the least worrisome outcomes. Preferences were similar between rural and urban areas and among health care providers and the general population with overlapping uncertainty intervals. CONCLUSION: The rank of health outcomes may be similar in various socio-cultural contexts. The preferences for benefits and harms of statin therapy are essential to assess benefit-harm balance when recommending statins for primary prevention of cardiovascular diseases.

13.
J Neurotrauma ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33108942

RESUMO

Loss to follow-up and missing outcomes data are important issues for longitudinal observational studies and clinical trials in traumatic brain injury. One popular solution to missing 6-month outcomes has been to use the last observation carried forward (LOCF). The purpose of the current study was to compare the performance of model-based single-imputation methods with that of the LOCF approach. We hypothesized that model-based methods would perform better as they potentially make better use of available outcome data. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study (n = 4509) included longitudinal outcome collection at 2 weeks, 3 months, 6 months, and 12 months post-injury; a total of 8185 Glasgow Outcome Scale extended (GOSe) observations were included in the database. We compared single imputation of 6-month outcomes using LOCF, a multiple imputation (MI) panel imputation, a mixed-effect model, a Gaussian process regression, and a multi-state model. Model performance was assessed via cross-validation on the subset of individuals with a valid GOSe value within 180 ± 14 days post-injury (n = 1083). All models were fit on the entire available data after removing the 180 ± 14 days post-injury observations from the respective test fold. The LOCF method showed lower accuracy (i.e., poorer agreement between imputed and observed values) than model-based methods of imputation, and showed a strong negative bias (i.e., it imputed lower than observed outcomes). Accuracy and bias for the model-based approaches were similar to one another, with the multi-state model having the best overall performance. All methods of imputation showed variation across different outcome categories, with better performance for more frequent outcomes. We conclude that model-based methods of single imputation have substantial performance advantages over LOCF, in addition to providing more complete outcome data.

14.
BMC Med Res Methodol ; 20(1): 264, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33096986

RESUMO

BACKGROUND: Recent evidence suggests that there is often substantial variation in the benefits and harms across a trial population. We aimed to identify regression modeling approaches that assess heterogeneity of treatment effect within a randomized clinical trial. METHODS: We performed a literature review using a broad search strategy, complemented by suggestions of a technical expert panel. RESULTS: The approaches are classified into 3 categories: 1) Risk-based methods (11 papers) use only prognostic factors to define patient subgroups, relying on the mathematical dependency of the absolute risk difference on baseline risk; 2) Treatment effect modeling methods (9 papers) use both prognostic factors and treatment effect modifiers to explore characteristics that interact with the effects of therapy on a relative scale. These methods couple data-driven subgroup identification with approaches to prevent overfitting, such as penalization or use of separate data sets for subgroup identification and effect estimation. 3) Optimal treatment regime methods (12 papers) focus primarily on treatment effect modifiers to classify the trial population into those who benefit from treatment and those who do not. Finally, we also identified papers which describe model evaluation methods (4 papers). CONCLUSIONS: Three classes of approaches were identified to assess heterogeneity of treatment effect. Methodological research, including both simulations and empirical evaluations, is required to compare the available methods in different settings and to derive well-informed guidance for their application in RCT analysis.

16.
Lancet ; 396(10260): 1399-1412, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33038944

RESUMO

BACKGROUND: Randomised controlled trials are considered the gold standard for testing the efficacy of novel therapeutic interventions, and typically report the average treatment effect as a summary result. As the result of treatment can vary between patients, basing treatment decisions for individual patients on the overall average treatment effect could be suboptimal. We aimed to develop an individualised decision making tool to select an optimal revascularisation strategy in patients with complex coronary artery disease. METHODS: The SYNTAX Extended Survival (SYNTAXES) study is an investigator-driven extension follow-up of a multicentre, randomised controlled trial done in 85 hospitals across 18 North American and European countries between March, 2005, and April, 2007. Patients with de-novo three-vessel and left main coronary artery disease were randomly assigned (1:1) to either the percutaneous coronary intervention (PCI) group or coronary artery bypass grafting (CABG) group. The SYNTAXES study ascertained 10-year all-cause deaths. We used Cox regression to develop a clinical prognostic index for predicting death over a 10-year period, which was combined, in a second stage, with assigned treatment (PCI or CABG) and two prespecified effect-modifiers, which were selected on the basis of previous evidence: disease type (three-vessel disease or left main coronary artery disease) and anatomical SYNTAX score. We used similar techniques to develop a model to predict the 5-year risk of major adverse cardiovascular events (defined as a composite of all-cause death, non-fatal stroke, or non-fatal myocardial infarction) in patients receiving PCI or CABG. We then assessed the ability of these models to predict the risk of death or a major adverse cardiovascular event, and their differences (ie, the estimated benefit of CABG versus PCI by calculating the absolute risk difference between the two strategies) by cross-validation with the SYNTAX trial (n=1800 participants) and external validation in the pooled population (n=3380 participants) of the FREEDOM, BEST, and PRECOMBAT trials. The concordance (C)-index was used to measure discriminative ability, and calibration plots were used to assess the degree of agreement between predictions and observations. FINDINGS: At cross-validation, the newly developed SYNTAX score II, termed SYNTAX score II 2020, showed a helpful discriminative ability in both treatment groups for predicting 10-year all-cause deaths (C-index=0·73 [95% CI 0·69-0·76] for PCI and 0·73 [0·69-0·76] for CABG) and 5-year major adverse cardiovascular events (C-index=0·65 [0·61-0·69] for PCI and C-index=0·71 [0·67-0·75] for CABG). At external validation, the SYNTAX score II 2020 showed helpful discrimination (C-index=0·67 [0·63-0·70] for PCI and C-index=0·62 [0·58-0·66] for CABG) and good calibration for predicting 5-year major adverse cardiovascular events. The estimated treatment benefit of CABG over PCI varied substantially among patients in the trial population, and the benefit predictions were well calibrated. INTERPRETATION: The SYNTAX score II 2020 for predicting 10-year deaths and 5-year major adverse cardiovascular events can help to identify individuals who will benefit from either CABG or PCI, thereby supporting heart teams, patients, and their families to select optimal revascularisation strategies. FUNDING: The German Heart Research Foundation and the Patient-Centered Outcomes Research Institute.

17.
Can J Surg ; 63(5): E422-E430, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33009903

RESUMO

BACKGROUND: Failure to rapidly identify bleeding in trauma patients leads to substantial morbidity and mortality. We aimed to develop and validate a simple bedside score for identifying bleeding patients requiring escalation of care beyond initial resuscitation. METHODS: We included patients with major blunt or penetrating trauma, defined as those with an Injury Severity Score greater than 12 or requiring trauma team activation, at The Ottawa Hospital from September 2014 to September 2017. We used logistic regression for derivation. The primary outcome was a composite of the need for massive transfusion, embolization or surgery for hemostasis. We prespecified clinical, laboratory and imaging predictors using findings from our prior systematic review and survey of Canadian traumatologists. We used an AIC-based stepdown procedure based on the Akaike information criterion and regression coefficients to create a 5-variable score for bedside application. We used bootstrap internal validation to assess optimism-corrected performance. RESULTS: We included 890 patients, of whom 133 required a major intervention. The main model comprised systolic blood pressure, clinical examination findings suggestive of hemorrhage, lactate level, focused assessment with sonography in trauma (FAST) and computed tomographic imaging. The C statistic was 0.95, optimism-corrected to 0.94. A simplified Canadian Bleeding (CAN-BLEED) score was devised. A score cut-off of 2 points yielded sensitivity of 97.7% (95% confidence interval [CI] 93.6 to 99.5) and specificity 73.2% (95% CI 69.9 to 76.3). An alternative version that included mechanism of injury rather than CT had lower discriminative ability (C statistic = 0.89). CONCLUSION: A simple yet promising bleeding score is proposed to identify highrisk patients in need of major intervention for traumatic bleeding and determine the appropriateness of early transfer to specialized trauma centres. Further research is needed to evaluate the performance of the score in other settings, define interrater reliability and evaluate the potential for reduction of time to intervention.


Assuntos
Hemorragia/diagnóstico , Modelos Biológicos , Triagem/métodos , Ferimentos não Penetrantes/complicações , Ferimentos Penetrantes/complicações , Adulto , Transfusão de Sangue/estatística & dados numéricos , Canadá/epidemiologia , Tomada de Decisão Clínica , Embolização Terapêutica/estatística & dados numéricos , Feminino , Hemorragia/epidemiologia , Hemorragia/etiologia , Hemorragia/terapia , Hemostasia Cirúrgica/estatística & dados numéricos , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Transferência de Pacientes/estatística & dados numéricos , Estudos Prospectivos , Reprodutibilidade dos Testes , Medição de Risco/métodos , Centros de Traumatologia/estatística & dados numéricos , Ferimentos não Penetrantes/terapia , Ferimentos Penetrantes/terapia
18.
Am J Hum Genet ; 107(5): 837-848, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-33022221

RESUMO

Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.

19.
Respir Med ; 173: 106158, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33011445

RESUMO

OBJECTIVE: To develop and validate a prediction model for airflow obstruction (AO) in older Chinese. DESIGN: Multivariable logistic regression analysis in large population cohort of Chinese aged ≥50 years. PARTICIPANTS: Model development: 8762 Chinese aged ≥50 years were selected from the early phase recruits to the Guangzhou Biobank Cohort Study (GBCS) (recruited from September 2003 to May 2006). Internal validation: 100 bootstrap samples drawn with replacement from the development sample. External validation: 8395 Chinese aged ≥50 years from later phase GBCS (recruited from September 2006 to January 2008). OUTCOMES: AO was defined by a forced expiratory volume in 1 s/forced vital capacity ratio < lower limits of normal. RESULTS: 839 (9.6%) and 764 (9.1%) individuals had AO in the development and temporal validation samples respectively. The predictors in the prediction model included sex, age, body mass index groups, smoking status, presence of respiratory symptoms, and history of asthma. Model development and validation was stratified by sex. Model performance including calibration (calibration-in-the-large -0.017 vs. -0.157; and calibration slope 0.88 vs. 1.02), discrimination (C-statistic 0.72 vs. 0.63 with 95% confidence interval 0.69-0.75 vs. 0.62-0.73) and clinical usefulness (decision curve analysis) in the external temporal validation sample were more satisfactory in men than that in women. Prediction models with risk thresholds (13% in men and 7% in women) and easy-to-use nomograms were developed to assess the probability of AO. CONCLUSION: The diagnostic models based on readily available epidemiologic and clinical information with satisfactory performance can assist physicians to identify older individuals at high risk of AO and may improve the efficiency of spirometry for active case finding. Further validation beyond the Chinese population is warranted.

20.
BMJ Paediatr Open ; 4(1): e000687, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32984551

RESUMO

Background: The aim was to study the characteristics and management of children visiting the emergency department (ED) during out-of-office hours. Methods: We analysed electronic health record data from 119 204 children visiting one of five EDs in four European countries. Patient characteristics and management (diagnostic tests, treatment, hospital admission and paediatric intensive care unit admission) were compared between children visiting during office hours and evening shifts, night shifts and weekend day shifts. Analyses were corrected for age, gender, Manchester Triage System urgency, abnormal vital signs, presenting problems and hospital. Results: Patients presenting at night were younger (median (IQR) age: 3.7 (1.4-8.2) years vs 4.8 (1.8-9.9)), more often classified as high urgent (16.3% vs 9.9%) and more often had ≥2 abnormal vital signs (22.8% vs 18.1%) compared with office hours. After correcting for disease severity, laboratory and radiological tests were less likely to be requested (adjusted OR (aOR): 0.82, 95% CI 0.78-0.86 and aOR: 0.64, 95% CI 0.60-0.67, respectively); treatment was more likely to be undertaken (aOR: 1.56, 95% CI 1.49-1.63) and patients were more likely to be admitted to the hospital (aOR: 1.32, 95% CI 1.24-1.41) at night. Patterns in management during out-of-office hours were comparable between the different hospitals, with variability remaining. Conclusions: Children visiting during the night are relatively more seriously ill, highlighting the need to keep improving emergency care on a 24-hour-a-day basis. Further research is needed to explain the differences in management during the night and how these differences affect patient outcomes.

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