| 21. |
- Ruggeri, Kai, et al.
(författare)
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The general fault in our fault lines
- 2021
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Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 5:10, s. 1369-1380
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Tidskriftsartikel (refereegranskat)abstract
- Pervading global narratives suggest that political polarization is increasing, yet the accuracy of such group meta-perceptions has been drawn into question. A recent US study suggests that these beliefs are inaccurate and drive polarized beliefs about out-groups. However, it also found that informing people of inaccuracies reduces those negative beliefs. In this work, we explore whether these results generalize to other countries. To achieve this, we replicate two of the original experiments with 10,207 participants across 26 countries. We focus on local group divisions, which we refer to as fault lines. We find broad generalizability for both inaccurate meta-perceptions and reduced negative motive attribution through a simple disclosure intervention. We conclude that inaccurate and negative group meta-perceptions are exhibited in myriad contexts and that informing individuals of their misperceptions can yield positive benefits for intergroup relations. Such generalizability highlights a robust phenomenon with implications for political discourse worldwide.
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| 22. |
- Trabert, Britton, et al.
(författare)
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The Risk of Ovarian Cancer Increases with an Increase in the Lifetime Number of Ovulatory Cycles : An Analysis from the Ovarian Cancer Cohort Consortium (OC3)
- 2020
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Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 80:5, s. 1210-1218
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Tidskriftsartikel (refereegranskat)abstract
- Repeated exposure to the acute proinflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2,045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted HRs between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than women in the 10th percentile (<294) [HR (95% confidence interval): 1.92 (1.60-2.30)]. Risk increased 14% per 5-year increase in LOC (60 cycles) [(1.10-1.17)]; this association remained after adjustment for LOC components: number of pregnancies and oral contraceptive use [1.08 (1.04-1.12)]. The association varied by histotype, with increased risk of serous [1.13 (1.09-1.17)], endometrioid [1.20 (1.10-1.32)], and clear cell [1.37 (1.18-1.58)], but not mucinous [0.99 (0.88-1.10), P-heterogeneity = 0.01] tumors. Heterogeneity across histotypes was reduced [P-heterogeneity = 0.15] with adjustment for LOC components [1.08 serous, 1.11 endometrioid, 1.26 clear cell, 0.94 mucinous]. Although the 10-year absolute risk of ovarian cancer is small, it roughly doubles as the number of LOC rises from approximately 300 to 500. The consistency and linearity of effects strongly support the hypothesis that each ovulation leads to small increases in the risk of most ovarian cancers, a risk that cumulates through life, suggesting this as an important area for identifying intervention strategies.
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| 23. |
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| 24. |
- Wentzensen, Nicolas, et al.
(författare)
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Ovarian Cancer Risk Factors by Histologic Subtype : An Analysis From the Ovarian Cancer Cohort Consortium
- 2016
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Ingår i: Journal of Clinical Oncology. - : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 34:24, s. 2888-2898
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3).Patients and Methods: Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test.Results: Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas.Conclusion: The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype.
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| 25. |
- Atabaki-Pasdar, Naeimeh, et al.
(författare)
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Inferring causal pathways between metabolic processes and liver fat accumulation: an IMI DIRECT study
- 2021
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) often co-occur. Defining causal pathways underlying this relationship may help optimize the prevention and treatment of both diseases. Thus, we assessed the strength and magnitude of the putative causal pathways linking dysglycemia and fatty liver, using a combination of causal inference methods.Measures of glycemia, insulin dynamics, magnetic resonance imaging (MRI)-derived abdominal and liver fat content, serological biomarkers, lifestyle, and anthropometry were obtained in participants from the IMI DIRECT cohorts (n=795 with new onset T2D and 2234 individuals free from diabetes). UK Biobank (n=3641) was used for modelling and replication purposes. Bayesian networks were employed to infer causal pathways, with causal validation using two-sample Mendelian randomization.Bayesian networks fitted to IMI DIRECT data identified higher basal insulin secretion rate (BasalISR) and MRI-derived excess visceral fat (VAT) accumulation as the features of dysmetabolism most likely to cause liver fat accumulation; the unconditional probability of fatty liver (>5%) increased significantly when conditioning on high levels of BasalISR and VAT (by 23%, 32% respectively; 40% for both). Analyses in UK Biobank yielded comparable results. MR confirmed most causal pathways predicted by the Bayesian networks.Here, BasalISR had the highest causal effect on fatty liver predisposition, providing mechanistic evidence underpinning the established association of NAFLD and T2D. BasalISR may represent a pragmatic biomarker for NAFLD prediction in clinical practice.Competing Interest StatementHR is an employee and shareholder of Sanofi. MIM: The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. MIM has served on advisory panels for Pfizer, NovoNordisk and Zoe Global, has received honoraria from Merck, Pfizer, Novo Nordisk and Eli Lilly, and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier, and Takeda. As of June 2019, MIM is an employee of Genentech, and a holder of Roche stock. AM is a consultant for Lilly and has received research grants from several diabetes drug companies. PWF has received research grants from numerous diabetes drug companies and fess as consultant from Novo Nordisk, Lilly, and Zoe Global Ltd. He is currently the Scientific Director in Patient Care at the Novo Nordisk Foundation. Other authors declare non competing interests.Funding StatementThe work leading to this publication has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement 115317 (DIRECT) resources of which are composed of financial contribution from the European Union Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. NAP is supported in part by Henning och Johan Throne-Holsts Foundation, Hans Werthen Foundation, an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. HPM is supported by an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. AGJ is supported by an NIHR Clinician Scientist award (17/0005624). RK is funded by the Novo Nordisk Foundation (NNF18OC0031650) as part of a postdoctoral fellowship, an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. AK, PM, HF, JF and GNG are supported by an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. TJM is funded by an NIHR clinical senior lecturer fellowship. S.Bru acknowledges support from the Novo Nordisk Foundation (grants NNF17OC0027594 and NNF14CC0001). ATH is a Wellcome Trust Senior Investigator and is also supported by the NIHR Exeter Clinical Research Facility. JMS acknowledges support from Science for Life Laboratory (Plasma Profiling Facility), Knut and Alice Wallenberg Foundation (Human Protein Atlas) and Erling-Persson Foundation (KTH Centre for Precision Medicine). MIM is supported by the following grants; Wellcome (090532, 098381, 106130, 203141, 212259); NIH (U01-DK105535). PWF is supported by an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Approval for the study protocol was obtained from each of the regional research ethics review boards separately (Lund, Sweden: 20130312105459927, Copenhagen, Denmark: H-1-2012-166 and H-1-2012-100, Amsterdam, Netherlands: NL40099.029.12, Newcastle, Dundee and Exeter, UK: 12/NE/0132), and all participants provided written informed consent at enrolment. The research conformed to the ethical principles for medical research involving human participants outlined in the Declaration of Helsinki.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAuthors agree to make data and materials supporting the results or analyses presented in their paper available upon reasonable request
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| 26. |
- Bizzotto, Roberto, et al.
(författare)
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Processes Underlying Glycemic Deterioration in Type 2 Diabetes : An IMI DIRECT Study
- 2021
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 44:2, s. 511-518
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: A total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), β-cell glucose sensitivity (GS), and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA1c deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression. RESULTS: Faster HbA1c progression was independently associated with faster deterioration of OGIS and GS and increasing CLIm; visceral or liver fat, HDL-cholesterol, and triglycerides had further independent, though weaker, roles (R2 = 0.38). A subgroup of patients with a markedly higher progression rate (fast progressors) was clearly distinguishable considering these variables only (discrimination capacity from area under the receiver operating characteristic = 0.94). The proportion of fast progressors was reduced from 56% to 8-10% in subgroups in which only one trait among OGIS, GS, and CLIm was relatively stable (odds ratios 0.07-0.09). T2D polygenic risk score and baseline pancreatic fat, glucagon-like peptide 1, glucagon, diet, and physical activity did not show an independent role. CONCLUSIONS: Deteriorating insulin sensitivity and β-cell function, increasing insulin clearance, high visceral or liver fat, and worsening of the lipid profile are the crucial factors mediating glycemic deterioration of patients with T2D in the initial phase of the disease. Stabilization of a single trait among insulin sensitivity, β-cell function, and insulin clearance may be relevant to prevent progression.
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| 27. |
- Eriksen, Rebeca, et al.
(författare)
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Dietary metabolite profiling brings new insight into the relationship between nutrition and metabolic risk : An IMI DIRECT study
- 2020
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dietary advice remains the cornerstone of prevention and management of type 2 diabetes (T2D). However, understanding the efficacy of dietary interventions is confounded by the challenges inherent in assessing free living diet. Here we profiled dietary metabolites to investigate glycaemic deterioration and cardiometabolic risk in people at risk of or living with T2D. Methods: We analysed data from plasma collected at baseline and 18-month follow-up in individuals from the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohort 1 n = 403 individuals with normal or impaired glucose regulation (prediabetic) and cohort 2 n = 458 individuals with new onset of T2D. A dietary metabolite profile model (Tpred) was constructed using multivariable regression of 113 plasma metabolites obtained from targeted metabolomics assays. The continuous Tpred score was used to explore the relationships between diet, glycaemic deterioration and cardio-metabolic risk via multiple linear regression models. Findings: A higher Tpred score was associated with healthier diets high in wholegrain (β=3.36 g, 95% CI 0.31, 6.40 and β=2.82 g, 95% CI 0.06, 5.57) and lower energy intake (β=-75.53 kcal, 95% CI -144.71, -2.35 and β=-122.51 kcal, 95% CI -186.56, -38.46), and saturated fat (β=-0.92 g, 95% CI -1.56, -0.28 and β=–0.98 g, 95% CI -1.53, -0.42 g), respectively for cohort 1 and 2. In both cohorts a higher Tpred score was also associated with lower total body adiposity and favourable lipid profiles HDL-cholesterol (β=0.07 mmol/L, 95% CI 0.03, 0.1), (β=0.08 mmol/L, 95% CI 0.04, 0.1), and triglycerides (β=-0.1 mmol/L, 95% CI -0.2, -0.03), (β=-0.2 mmol/L, 95% CI -0.3, -0.09), respectively for cohort 1 and 2. In cohort 2, the Tpred score was negatively associated with liver fat (β=-0.74%, 95% CI -0.67, -0.81), and lower fasting concentrations of HbA1c (β=-0.9 mmol/mol, 95% CI -1.5, -0.1), glucose (β=-0.2 mmol/L, 95% CI -0.4, -0.05) and insulin (β=-11.0 pmol/mol, 95% CI -19.5, -2.6). Longitudinal analysis showed at 18-month follow up a higher Tpred score was also associated lower total body adiposity in both cohorts and lower fasting glucose (β=-0.2 mmol/L, 95% CI -0.3, -0.01) and insulin (β=-9.2 pmol/mol, 95% CI -17.9, -0.4) concentrations in cohort 2. Interpretation: Plasma dietary metabolite profiling provides objective measures of diet intake, showing a relationship to glycaemic deterioration and cardiometabolic health. Funding: This work was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115,317 (DIRECT), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007–2013) and EFPIA companies.
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| 28. |
- Geerts, Jaason M., et al.
(författare)
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Guidance for Health Care Leaders During the Recovery Stage of the COVID-19 Pandemic A Consensus Statement
- 2021
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Ingår i: JAMA Network Open. - : American Medical Association. - 2574-3805. ; 4:7
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The COVID-19 pandemic is the greatest global test of health leadership of our generation. There is an urgent need to provide guidance for leaders at all levels during the unprecedented preresolution recovery stage.OBJECTIVE: To create an evidence- and expertise-informed framework of leadership imperatives to serve as a resource to guide health and public health leaders during the postemergency stage of the pandemic.EVIDENCE REVIEW: A literature search in PubMed, MEDLINE, and Embase revealed 10 910 articles published between 2000 and 2021 that included the terms leadership and variations of emergency, crisis, disaster, pandemic, COVID-19, or public health. Using the Standards for Quality Improvement Reporting Excellence reporting guideline for consensus statement development, this assessment adopted a 6-round modified Delphi approach involving 32 expert coauthors from 17 countries who participated in creating and validating a framework outlining essential leadership imperatives.FINDINGS: The 10 imperatives in the framework are; (1) acknowledge staff and celebrate successes; (2) provide support for staff well-being; (3) develop a clear understanding of the current local and global context, along with informed projections; (4) prepare for future emergencies (personnel, resources, protocols, contingency plans, coalitions, and training); (5) reassess priorities explicitly and regularly and provide purpose, meaning, and direction; (6) maximize team, organizational, and system performance and discuss enhancements; (7) manage the backlog of paused services and consider improvements while avoiding burnout and moral distress; (8) sustain learning, innovations, and collaborations, and imagine future possibilities; (9) provide regular communication and engender trust; and (10) in consultation with public health and fellow leaders, provide safety information and recommendations to government, other organizations, staff, and the community to improve equitable and integrated care and emergency preparedness systemwide.CONCLUSIONS AND RELEVANCE: Leaders who most effectively implement these imperatives are ideally positioned to address urgent needs and inequalities in health systems and to cocreate with their organizations a future that best serves stakeholders and communities.
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| 29. |
- Hollis, Chris, et al.
(författare)
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Online remote behavioural intervention for tics in 9- to 17-year-olds : the ORBIT RCT with embedded process and economic evaluation
- 2023
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Ingår i: Health Technology Assessment. - 1366-5278. ; 27:18, s. 1-120
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Behavioural therapy for tics is difficult to access, and little is known about its effectiveness when delivered online.OBJECTIVE: To investigate the clinical and cost-effectiveness of an online-delivered, therapist- and parent-supported therapy for young people with tic disorders.DESIGN: Single-blind, parallel-group, randomised controlled trial, with 3-month (primary end point) and 6-month post-randomisation follow-up. Participants were individually randomised (1 : 1), using on online system, with block randomisations, stratified by site. Naturalistic follow-up was conducted at 12 and 18 months post-randomisation when participants were free to access non-trial interventions. A subset of participants participated in a process evaluation.SETTING: Two hospitals (London and Nottingham) in England also accepting referrals from patient identification centres and online self-referrals.PARTICIPANTS: Children aged 9-17 years (1) with Tourette syndrome or chronic tic disorder, (2) with a Yale Global Tic Severity Scale-total tic severity score of 15 or more (or > 10 with only motor or vocal tics) and (3) having not received behavioural therapy for tics in the past 12 months or started/stopped medication for tics within the past 2 months.INTERVENTIONS: Either 10 weeks of online, remotely delivered, therapist-supported exposure and response prevention therapy (intervention group) or online psychoeducation (control).OUTCOME: Primary outcome: Yale Global Tic Severity Scale-total tic severity score 3 months post-randomisation; analysis done in all randomised patients for whom data were available. Secondary outcomes included low mood, anxiety, treatment satisfaction and health resource use. Quality-adjusted life-years are derived from parent-completed quality-of-life measures. All trial staff, statisticians and the chief investigator were masked to group allocation.RESULTS: Two hundred and twenty-four participants were randomised to the intervention (n = 112) or control (n = 112) group. Participants were mostly male (n = 177; 79%), with a mean age of 12 years. At 3 months the estimated mean difference in Yale Global Tic Severity Scale-total tic severity score between the groups adjusted for baseline and site was -2.29 points (95% confidence interval -3.86 to -0.71) in favour of therapy (effect size -0.31, 95% confidence interval -0.52 to -0.10). This effect was sustained throughout to the final follow-up at 18 months (-2.01 points, 95% confidence interval -3.86 to -0.15; effect size -0.27, 95% confidence interval -0.52 to -0.02). At 18 months the mean incremental cost per participant of the intervention compared to the control was £662 (95% confidence interval -£59 to £1384), with a mean incremental quality-adjusted life-year of 0.040 (95% confidence interval -0.004 to 0.083) per participant. The mean incremental cost per quality-adjusted life-year gained was £16,708. The intervention was acceptable and delivered with high fidelity. Parental engagement predicted child engagement and more positive clinical outcomes.HARMS: Two serious, unrelated adverse events occurred in the control group.LIMITATIONS: We cannot separate the effects of digital online delivery and the therapy itself. The sample was predominately white and British, limiting generalisability. The design did not compare to face-to-face services.CONCLUSION: Online, therapist-supported behavioural therapy for young people with tic disorders is clinically and cost-effective in reducing tics, with durable benefits extending up to 18 months.FUTURE WORK: Future work should compare online to face-to-face therapy and explore how to embed the intervention in clinical practice.TRIAL REGISTRATION: This trial is registered as ISRCTN70758207; ClinicalTrials.gov (NCT03483493). The trial is now complete.FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Technology Assessment programme (project number 16/19/02) and will be published in full in Health and Technology Assessment; Vol. 27, No. 18. See the NIHR Journals Library website for further project information.
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| 30. |
- Jones, Robert P., et al.
(författare)
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Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma : A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
- 2019
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Ingår i: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 154:11, s. 1038-1048
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Tidskriftsartikel (refereegranskat)abstract
- Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P=.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P=.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P=.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P=.85 and P=.35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P=.03).Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.Trial Registration: ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434. This secondary analysis of a randomized clinical trial investigates patterns of recurrence after adjuvant chemotherapy in pancreatic cancer and the association with survival.
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