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Lindhagen, Lars
Publications (10 of 30) Show all publications
Cars, T., Lindhagen, L. & Sundström, J. (2019). A framework for monitoring of new drugs in Sweden. Upsala Journal of Medical Sciences, 124(1), 46-50
Open this publication in new window or tab >>A framework for monitoring of new drugs in Sweden
2019 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 46-50Article in journal (Refereed) Published
Abstract [en]

In order to monitor the net public health benefit of new drugs, especially in the light of recent stepwise approval approaches, there is a need to optimize real-time post-marketing evaluation of new drugs using data collected in routine care. Sweden, with its unique possibilities for observational research, can provide these data. We herein propose a framework for continuous monitoring of the effectiveness, safety, and cost-effectiveness of new drugs, using prospectively determined protocols designed in collaboration between all relevant stakeholders. We believe that this framework can be a useful tool for healthcare authorities and reimbursement agencies in the introduction of new drugs.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
Keywords
Comparative effectiveness research, pharmacoepidemiology, propensity score, real-world evidence, sequential monitoring
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-381208 (URN)10.1080/03009734.2018.1550454 (DOI)000461811100011 ()30689485 (PubMedID)
Available from: 2019-04-09 Created: 2019-04-09 Last updated: 2019-04-09Bibliographically approved
MacDowall, A., Canto Moreira, N., Marques, C., Skeppholm, M., Lindhagen, L., Robinson, Y., . . . Olerud, C. (2019). Artificial disc replacement versus fusion in patients with cervical degenerative disc disease and radiculopathy: a randomized controlled trial with 5-year outcomes. Journal of Neurosurgery: Spine, 30(3), 323-331
Open this publication in new window or tab >>Artificial disc replacement versus fusion in patients with cervical degenerative disc disease and radiculopathy: a randomized controlled trial with 5-year outcomes
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2019 (English)In: Journal of Neurosurgery: Spine, ISSN 1547-5654, E-ISSN 1547-5646, Vol. 30, no 3, p. 323-331Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE

The method of artificial disc replacement (ADR) has been developed as an alternative treatment to fusion surgery after decompression for cervical degenerative disc disease (DDD) with radiculopathy. Preserving the motion of ADR devices aims to prevent immobilization side effects such as adjacent-segment pathology (ASP). However, long-term follow-up evaluations using MRI are needed to investigate if this intent is achieved.

METHODS

The authors performed a randomized controlled trial with 153 patients (mean age 47 years) undergoing surgery for cervical radiculopathy. Eighty-three patients received an ADR and 70 patients underwent fusion surgery. Outcomes after 5 years were assessed using patient-reported outcome measures using the Neck Disability Index (NDI) score as the primary outcome; motion preservation and heterotopic ossification by radiography; ASP by MRI; and secondary surgical procedures.

RESULTS

Scores on the NDI were approximately halved in both groups: the mean score after 5 years was 36 (95% confidence interval [CI] 31–41) in the ADR group and 32 (95% CI 27–38) in the fusion group (p = 0.48). There were no other significant differences between the groups in six other patient-related outcome measures. Fifty-four percent of the patients in the ADR group preserved motion at the operated cervical level and 25% of the ADRs were spontaneously fused. Seventeen ADR patients (21%) and 7 fusion patients (10%) underwent secondary surgery (p = 0.11), with 5 patients in each group due to clinical ASP.

CONCLUSIONS

In patients with cervical DDD and radiculopathy decompression as well as ADR, surgery did not result in better clinical or radiological outcomes after 5 years compared with decompression and fusion surgery.

Keywords
artificial disc replacement, treatment outcome, Neck Disability Index, cervical radiculopathy, adjacent-segment pathology
National Category
Orthopaedics Neurology
Research subject
Orthopaedics
Identifiers
urn:nbn:se:uu:diva-345965 (URN)10.3171/2018.9.SPINE18659 (DOI)000462447900004 ()30641852 (PubMedID)
Projects
Cervical radiculopathy, studies on pain analysis and treatment
Note

Title in thesis list of papers: Artificial Disc Replacement versus Fusion in Patients with Cervical Degenerative Disc Disease with radiculopathy ‒ 5-year Outcomes

Available from: 2018-03-13 Created: 2018-03-13 Last updated: 2019-04-16Bibliographically approved
MacDowall, A., Skeppholm, M., Lindhagen, L., Robinson, Y., Löfgren, H., Michaëlsson, K. & Olerud, C. (2019). Artificial Disc Replacement versus Fusion in Patients with Cervical Degenerative Disc Disease with radiculopathy: 5-year Outcomes from the National Swedish Spine Register. Journal of Neurosurgery: Spine, 30(2), 159-167
Open this publication in new window or tab >>Artificial Disc Replacement versus Fusion in Patients with Cervical Degenerative Disc Disease with radiculopathy: 5-year Outcomes from the National Swedish Spine Register
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2019 (English)In: Journal of Neurosurgery: Spine, ISSN 1547-5654, E-ISSN 1547-5646, Vol. 30, no 2, p. 159-167Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The long-term efficacy of artificial disc replacement (ADR) surgery compared with fusion after decompression for the treatment of cervical degenerative disc disease and radiculopathy has not previously been investigated in a population-based setting.

METHODS: All patients with cervical degenerative disc disease and radiculopathy who were in the national Swedish Spine Registry (Swespine) beginning in January 1, 2006, were eligible for the study. Follow-up information was obtained up to November 15, 2017. The authors compared, using propensity score matching, patients treated with anterior decompression and insertion of an ADR with patients who underwent anterior decompression combined with fusion surgery. The primary outcome was the Neck Disability Index (NDI), a patient-reported function score ranging from 0% to 100%, with higher scores indicating greater disability and a minimum clinically important difference of > 15%.

RESULTS: A total of 3998 patients (2018: 1980 women/men) met the inclusion criteria, of whom 204 had undergone arthroplasty and 3794 had undergone fusion. After propensity score matching, 185 patients with a mean age of 49.7 years remained in each group. Scores on the NDI were approximately halved in both groups after 5 years, but without a significant mean difference in NDI (3.0%; 95% CI -8.4 to 2.4; p = 0.28) between the groups. There were no differences between the groups in EuroQol-5 Dimensions or in pain scores for the neck and arm.

CONCLUSIONS: In patients with cervical degenerative disc disease and radiculopathy, decompression plus ADR surgery did not result in a clinically important difference in outcomes after 5 years, compared with decompression and fusion surgery.

Keywords
Cervical radiculopathy, Artificial disc replacement, Surgical treatment outcome, Anterior decompression and fusion
National Category
Orthopaedics
Research subject
Orthopaedics
Identifiers
urn:nbn:se:uu:diva-345976 (URN)10.3171/2018.7.SPINE18657 (DOI)000461013000002 ()30485205 (PubMedID)
Projects
Cervical radiculopathy, studies on pain analysis and treatment
Available from: 2018-03-13 Created: 2018-03-13 Last updated: 2019-04-16Bibliographically approved
Batra, G., Ahlsson, A., Lindahl, B., Lindhagen, L., Wickbom, A. & Oldgren, J. (2019). Atrial fibrillation in patients undergoing coronary artery surgery is associated with adverse outcome. Upsala Journal of Medical Sciences, 124(1), 70-77
Open this publication in new window or tab >>Atrial fibrillation in patients undergoing coronary artery surgery is associated with adverse outcome
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2019 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 70-77Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The aim was to determine the association between atrial fibrillation (AF) and outcome in patients undergoing coronary artery bypass grafting (CABG).

METHODS: All patients undergoing CABG between January 2010 and June 2013 were identified in the Swedish Heart Surgery Registry. Outcomes studied were all-cause mortality, cardiovascular mortality, myocardial infarction, congestive heart failure, ischemic stroke, and recurrent AF. Patients with history of AF prior to surgery (preoperative AF) and patients without history of AF but with AF episodes post-surgery (postoperative AF) were compared to patients with no AF using adjusted Cox regression models.

RESULTS: Among 9,107 identified patients, 8.1% (n = 737) had preoperative AF, and 25.1% (n = 2,290) had postoperative AF. Median follow-up was 2.2 years. Compared to no AF, preoperative AF was associated with higher risk of all-cause mortality, adjusted hazard ratio with 95% confidence interval (HR) 1.76 (1.33-2.33); cardiovascular mortality, HR 2.43 (1.68-3.50); and congestive heart failure, HR 2.21 (1.72-2.84). Postoperative AF was associated with risk of all-cause mortality, HR 1.27 (1.01-1.60); cardiovascular mortality, HR 1.52 (1.10-2.11); congestive heart failure, HR 1.47 (1.18-1.83); and recurrent AF, HR 4.38 (2.46-7.78). No significant association was observed between pre- or postoperative AF and risk for myocardial infarction and ischemic stroke.

CONCLUSIONS: Approximately 1 in 3 patients undergoing CABG had pre- or postoperative AF. Patients with pre- or postoperative AF were at higher risk of all-cause mortality, cardiovascular mortality, and congestive heart failure, but not of myocardial infarction or ischemic stroke. Postoperative AF was associated with higher risk of recurrent AF.

Keywords
Atrial fibrillation, cardiovascular disease, coronary artery bypass grafting
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-374222 (URN)10.1080/03009734.2018.1504148 (DOI)000461811100015 ()30265179 (PubMedID)
Funder
Swedish Foundation for Strategic Research , KF10-0024
Available from: 2019-01-18 Created: 2019-01-18 Last updated: 2019-04-10Bibliographically approved
Ventimiglia, E., Van Hemelrijck, M., Lindhagen, L., Stattin, P. & Garmo, H. (2019). How to measure temporal changes in care pathways for chronic diseases using health care registry data. BMC Medical Informatics and Decision Making, 19, Article ID 103.
Open this publication in new window or tab >>How to measure temporal changes in care pathways for chronic diseases using health care registry data
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2019 (English)In: BMC Medical Informatics and Decision Making, ISSN 1472-6947, E-ISSN 1472-6947, Vol. 19, article id 103Article in journal (Refereed) Published
Abstract [en]

Background: Disease trajectories for chronic diseases can span over several decades, with several time-dependent factors affecting treatment decisions. Thus, there is a need for long-term predictions of disease trajectories to inform patients and healthcare professionals on the long-term outcomes and provide information on the need of future health care. Here, we propose a state transition model to describe and predict disease trajectories up to 25 years after diagnosis in men with prostate cancer (PCa), as a proof of principle. Methods: States, state transitions, and transition probabilities were identified and estimated in Prostate Cancer data Base of Sweden (PCBaSeTraject), using nationwide population-based data from 118,743 men diagnosed with PCa. A state transition model in discrete time steps (i.e., 4 weeks) was developed and applied to capture all possible transitions (PCBaSeSim). Transition probabilities were estimated for changes in both treatment and comorbidity. These models combined yielded parameter estimates to run an individual-level simulation based on the state-transition model to obtain prediction estimates. Predicted estimates were then compared to real world data in PCBaSeTraject. Results: PCBaSeSim estimates for the cumulative incidence of first and second transitions, death from PCa and death from other causes were compared to observed transitions in PCBaSeTraject. A good agreement was found between simulated and observed estimates. Conclusions: We developed a reliable and accurate simulation tool, PCBaSeSim that provides information on disease trajectories for subjects with a chronic disease on an individual and population-based level.

Place, publisher, year, edition, pages
BMC, 2019
Keywords
Ageing, Chronic disease, Prostate cancer, State transition
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-386444 (URN)10.1186/s12911-019-0823-y (DOI)000469777500001 ()31146754 (PubMedID)
Funder
Swedish Research Council, 825-2008-5910Forte, Swedish Research Council for Health, Working Life and WelfareVästerbotten County CouncilThe Cancer Society in Stockholm
Available from: 2019-06-26 Created: 2019-06-26 Last updated: 2019-06-26Bibliographically approved
Hjort, M., Eggers, K. M., Lindhagen, L., Agewall, S., Brolin, E. B., Collste, O., . . . Lindahl, B. (2019). Increased Inflammatory Activity in Patients 3 Months after Myocardial Infarction with Nonobstructive Coronary Arteries. Clinical Chemistry, 65(8), 1023-1030
Open this publication in new window or tab >>Increased Inflammatory Activity in Patients 3 Months after Myocardial Infarction with Nonobstructive Coronary Arteries
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2019 (English)In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 65, no 8, p. 1023-1030Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Around 5%-10% of patients with myocardial infarction (MI) present with nonobstructive coronary arteries (MINOCA). We aimed to assess pathophysiological mechanisms in MINOCA by extensively evaluating cardiovascular biomarkers in the stable phase after an event, comparing MINOCA patients with cardiovascular healthy controls and MI patients with obstructive coronary artery disease (MI-CAD).

METHODS: Ninety-one biomarkers were measured with a proximity extension assay 3 months after MI in 97 MINOCA patients, 97 age-and sex-matched MI-CAD patients, and 98 controls. Lasso analyses (penalized logistic regression models) and adjusted multiple linear regression models were used for statistical analyses.

RESULTS: In the Lasso analysis (MINOCA vs MI-CAD), 8 biomarkers provided discriminatory value: P-selectin glycoprotein ligand 1, C-X-C motif chemokine 1, TNF-related activation-induced cytokine, and pappalysin-1 (PAPPA) with increasing probabilities of MINOCA, and tissue-type plasminogen activator, B-type natriuretic peptide, myeloperoxidase, and interleukin-1 receptor antagonist protein with increasing probabilities of MI-CAD. Comparing MINOCA vs controls, 7 biomarkers provided discriminatory value: N-terminal pro-B-type natriuretic peptide, renin, NF-kappa-B essential modulator, PAPPA, interleukin-6, and soluble urokinase plasminogen activator surface receptor with increasing probabilities of MINOCA, and agouti-related protein with increasing probabilities of controls. Adjusted multiple linear regression analyses showed that group affiliation was associated with the concentrations of 7 of the 8 biomarkers in the comparison MINOCA vs MI-CAD and 5 of the 7 biomarkers in MINOCA vs controls.

CONCLUSIONS: Three months after the MI, the biomarker concentrations indicated greater inflammatory activity in MINOCA patients than in both MI-CAD patients and healthy controls, and a varying degree of myocardial dysfunction among the 3 cohorts. 

Place, publisher, year, edition, pages
AMER ASSOC CLINICAL CHEMISTRY, 2019
National Category
Cardiac and Cardiovascular Systems Clinical Laboratory Medicine
Identifiers
urn:nbn:se:uu:diva-392574 (URN)10.1373/clinchem.2018.301085 (DOI)000477776700013 ()31072836 (PubMedID)
Available from: 2019-09-10 Created: 2019-09-10 Last updated: 2019-09-10Bibliographically approved
Cars, T., Lindhagen, L., Malmström, R. E., Neovius, M., Schwieler, J., Wettermark, B. & Sundström, J. (2018). Effectiveness of Drugs in Routine Care: A Model for Sequential Monitoring of New Medicines Using Dronedarone as Example. Clinical Pharmacology and Therapeutics, 103(3), 493-501
Open this publication in new window or tab >>Effectiveness of Drugs in Routine Care: A Model for Sequential Monitoring of New Medicines Using Dronedarone as Example
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2018 (English)In: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6535, Vol. 103, no 3, p. 493-501Article in journal (Refereed) Published
Abstract [en]

Although there is no doubt about the scientific value of randomized controlled clinical trials, they are usually conducted in selected populations different fromthose treated in clinical practice. Therefore, it is important to optimize real-time post-marketing evaluation of the effectiveness, safety, and cost of new drugs. Using electronic health records and administrative health databases froma well-defined region with universal access to healthcare, we have built a framework for real-time sequential monitoring of the effectiveness of newly marketed drugs in routine care. We chose the antiarrhythmic agent dronedarone as the study drug and flecainide as the comparator drug for illustration of the model. We demonstrate that this model produces consistent results with increasing precision over time as data accumulates in the clinical systems. We believe that use of this model at the introduction of new drugs can provide complementary evidence, especially in settings of adaptive licensing of new drugs.

Place, publisher, year, edition, pages
WILEY, 2018
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-348840 (URN)10.1002/cpt.751 (DOI)000424520000030 ()28560722 (PubMedID)
Available from: 2018-04-23 Created: 2018-04-23 Last updated: 2018-04-23Bibliographically approved
MacDowall, A., Skeppholm, M., Lindhagen, L., Robinson, Y. & Olerud, C. (2018). Effects of preoperative mental distress versus surgical modality, arthroplasty, or fusion on long-term outcome in patients with cervical radiculopathy. Journal of Neurosurgery: Spine, 29(4), 371-379
Open this publication in new window or tab >>Effects of preoperative mental distress versus surgical modality, arthroplasty, or fusion on long-term outcome in patients with cervical radiculopathy
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2018 (English)In: Journal of Neurosurgery: Spine, ISSN 1547-5654, E-ISSN 1547-5646, Vol. 29, no 4, p. 371-379Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE Several efforts have been made to investigate the long-term efficacy of artificial disc replacement surgery compared with that of fusion after decompression for the treatment of cervical degenerative disc disease and radiculopathy. However, research on the impact of mental distress on surgical treatment outcome has been sparse. The aim of the authors was to investigate the potential predictive value of preoperative risk factors in determining long-term outcome. METHODS A total of 153 patients (mean age 47 years) with single-or double-level cervical degenerative disc disease and radiculopathy were randomly assigned to undergo either anterior cervical discectomy and fusion (n = 70) or artificial disc replacement (n = 83). The primary outcome was the Neck Disability Index (NDI) score, a patient-reported function score that ranges from 0% to 100%; higher scores indicate greater disability. Preoperative variables such as sex, age, smoking status, employment status, having a strenuous job, neck pain duration, arm pain duration, amount of regular exercise, Hospital Anxiety and Depression Scale (HADS) score, NDI score, whether surgery was performed on 1 or 2 levels, and allocated treatment were analyzed in multiple linear regression models with the 5-year NDI score as the outcome. RESULTS A total of 47 (31%) patients had either a HADS anxiety or HADS depression score of 10 points or higher. High values on the preoperative HADS were a negative predictor of outcome (p = 0.009). Treatment allocation had no effect on 5-year NDI scores (p = 0.32). CONCLUSIONS Preoperative mental distress measured with the HADS affects long-term outcome in surgically treated patients with cervical radiculopathy.

Place, publisher, year, edition, pages
AMER ASSOC NEUROLOGICAL SURGEONS, 2018
Keywords
artificial disc replacement, Hospital Anxiety and Depression Scale, treatment outcome, Neck Disability Index, cervical radiculopathy
National Category
Orthopaedics
Identifiers
urn:nbn:se:uu:diva-367408 (URN)10.3171/2018.2.SPINE171378 (DOI)000446246000004 ()30004317 (PubMedID)
Funder
Stockholm County Council
Available from: 2018-12-03 Created: 2018-12-03 Last updated: 2018-12-03Bibliographically approved
Eggers, K. M., Jernberg, T., Lindhagen, L. & Lindahl, B. (2018). High-Sensitivity Cardiac Troponin T Levels Identify Patients With Non-ST-Segment Elevation Acute Coronary Syndrome Who Benefit From Invasive Assessment [Letter to the editor]. JACC: Cardiovascular Interventions, 11(16), 1665-1667
Open this publication in new window or tab >>High-Sensitivity Cardiac Troponin T Levels Identify Patients With Non-ST-Segment Elevation Acute Coronary Syndrome Who Benefit From Invasive Assessment
2018 (English)In: JACC: Cardiovascular Interventions, ISSN 1936-8798, E-ISSN 1876-7605, Vol. 11, no 16, p. 1665-1667Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-363868 (URN)10.1016/j.jcin.2018.03.027 (DOI)000442425900029 ()30139480 (PubMedID)
Funder
Swedish Foundation for Strategic Research
Available from: 2018-11-14 Created: 2018-11-14 Last updated: 2019-01-24Bibliographically approved
Grip, O., Wanhainen, A., Michaëlsson, K., Lindhagen, L. & Björck, M. (2018). Open versus endovascular revascularization in the treatment of acute lower limb ischaemia. British Journal of Surgery, 105(12), 1598-1606
Open this publication in new window or tab >>Open versus endovascular revascularization in the treatment of acute lower limb ischaemia
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2018 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 105, no 12, p. 1598-1606Article in journal (Refereed) Published
Abstract [en]

Background: Consensus is lacking regarding intervention for patients with acute lower limb ischaemia (ALI). The aim was to study amputation-free survival in patients treated for ALI by either primary open or endovascular revascularization.

Methods: The Swedish Vascular Registry (Swedvasc) was combined with the Population Registry and National Patient Registry to determine follow-up on mortality and amputation rates. Revascularization techniques were compared by propensity score matching 1:1.

Results: Of 9736 patients who underwent open surgery and 6493 who had endovascular treatment between 1994 and 2014, 3365 remained in each group after propensity score matching. Results are from the matched cohort only. Mean age of the patients was 74⋅7 years; 47⋅5 per cent were women and mean follow-up was 4⋅3 years. At 30-day follow-up, the endovascular group had better patency (83⋅0 versus 78⋅6 per cent; P < 0⋅001). Amputation rates were similar at 30 days (7⋅0 per cent in the endovascular group versus 8⋅2 per cent in the open group; P = 0⋅113) and at 1 year (13⋅8 versus 14⋅8 per cent; P = 0⋅320). The mortality rate was lower after endovascular treatment, at 30 days (6⋅7 versus 11⋅1 per cent; P < 0⋅001) and after 1 year (20⋅2 versus 28⋅6 per cent; P < 0⋅001). Accordingly, endovascular treatment had better amputation-free survival at 30 days (87⋅5 versus 82⋅1 per cent; P < 0⋅001) and 1 year (69⋅9 versus 61⋅1 per cent; P < 0⋅001). The number needed to treat to prevent one death within the rst year was 12 with an endovascular compared with an open approach. Five years after surgery, endovascular treatment still had improved survival (HR 0⋅78, 99 per cent c.i. 0⋅70 to 0⋅86) but the difference between the treatment groups occurred mainly in the rst year.

Conclusion: Primary endovascular treatment for ALI appeared to reduce mortality compared with open surgery, without any difference in the risk of amputation.

National Category
Medical and Health Sciences Surgery
Research subject
Medical Science; Surgery
Identifiers
urn:nbn:se:uu:diva-363353 (URN)10.1002/bjs.10954 (DOI)000447124200007 ()
Available from: 2018-10-17 Created: 2018-10-17 Last updated: 2018-12-12Bibliographically approved
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