| 1. |
- Palmqvist, Charlotta L, et al.
(författare)
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Monitoring and evaluating surgical care: defining perioperative mortality rate and standardising data collection.
- 2015
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Ingår i: The Lancet. - 1474-547X. ; 385 Suppl 2, s. 27-27
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Tidskriftsartikel (refereegranskat)abstract
- Case volume per 100 000 population and perioperative mortality rate (POMR) are key indicators to monitor and strengthen surgical services. However, comparisons of POMR have been restricted by absence of standardised approaches to when it is measured, the ideal denominator, need for risk adjustment, and whether data are available. We aimed to address these issues and recommend a minimum dataset by analysing four large mixed surgical datasets, two from well-resourced settings with sophisticated electronic patient information systems and two from resource-limited settings where clinicians maintain locally developed databases.
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| 2. |
- Ariyaratnam, Roshan, et al.
(författare)
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Toward a standard approach to measurement and reporting of perioperative mortality rate as a global indicator for surgery.
- 2015
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Ingår i: Surgery. - : Elsevier BV. - 1532-7361 .- 0039-6060. ; 158:1, s. 17-26
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Tidskriftsartikel (refereegranskat)abstract
- The proportion of patients who die during or after surgery, otherwise known as the perioperative mortality rate (POMR), is a credible indicator of the safety and quality of operative care. Its accuracy and usefulness as a metric, however, particularly one that enables valid comparisons over time or between jurisdictions, has been limited by lack of a standardized approach to measurement and calculation, poor understanding of when in relation to surgery it is best measured, and whether risk-adjustment is needed. Our aim was to evaluate the value of POMR as a global surgery metric by addressing these issues using 4, large, mixed, surgical datasets that represent high-, middle-, and low-income countries.
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| 3. |
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| 4. |
- Ng-Kamstra, J. S., et al.
(författare)
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Perioperative mortality rates in low-income and middle-income countries: a systematic review and meta-analysis
- 2018
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Ingår i: Bmj Global Health. - : BMJ. - 2059-7908. ; 3:3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The Lancet Commission on Global Surgery proposed the perioperative mortality rate (POMR) as one of the six key indicators of the strength of a country's surgical system. Despite its widespread use in high-income settings, few studies have described procedure-specific POMR across low-income and middle-income countries (LMICs). We aimed to estimate POMR across a wide range of surgical procedures in LMICs. We also describe how POMR is defined and reported in the LMIC literature to provide recommendations for future monitoring in resource-constrained settings. Methods We did a systematic review of studies from LMICs published from 2009 to 2014 reporting POMR for any surgical procedure. We extracted select variables in duplicate from each included study and pooled estimates of POMR by type of procedure using random-effects meta-analysis of proportions and the Freeman-Tukey double arcsine transformation to stabilise variances. Results We included 985 studies conducted across 83 LMICs, covering 191 types of surgical procedures performed on 1 020 869 patients. Pooled POMR ranged from less than 0.1% for appendectomy, cholecystectomy and caesarean delivery to 20%-27% for typhoid intestinal perforation, intracranial haemorrhage and operative head injury. We found no consistent associations between procedure-specific POMR and Human Development Index (HDI) or income-group apart from emergency peripartum hysterectomy POMR, which appeared higher in low-income countries. Inpatient mortality was the most commonly used definition, though only 46.2% of studies explicitly defined the time frame during which deaths accrued. Conclusions Efforts to improve access to surgical care in LMICs should be accompanied by investment in improving the quality and safety of care. To improve the usefulness of POMR as a safety benchmark, standard reporting items should be included with any POMR estimate. Choosing a basket of procedures for which POMR is tracked may offer institutions and countries the standardisation required to meaningfully compare surgical outcomes across contexts and improve population health outcomes.
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| 5. |
- Ng-Kamstra, Joshua S, et al.
(författare)
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Use and definitions of perioperative mortality rates in low-income and middle-income countries : a systematic review
- 2015
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Ingår i: The Lancet. - 1474-547X. ; 385:Suppl 2, s. 29-29
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Aggregate and risk-stratified perioperative mortality rates (POMR) are well-documented in high-income countries where surgical databases are common. In many low-income and middle-income country (LMIC) settings, such data are unavailable, compromising efforts to understand and improve surgical outcomes. We undertook a systematic review to determine how POMR is used and defined in LMICs and to inform baseline rates.METHODS: We searched PubMed for all articles published between Jan 1, 2009, and Sept 1, 2014, reporting surgical mortality in LMICs. Search criteria, inclusion and exclusion criteria, and study assessment methodology are reported in the appendix. Titles and abstracts were screened independently by two reviewers. Full-text review and data extraction were completed by four trained clinician coders with regular validation for consistency. We extracted the definition of POMR used, clinical risk scores reported, and strategies for risk adjustment in addition to reported mortality rates.FINDINGS: We screened 2657 abstracts and included 373 full-text articles. 493 409 patients in 68 countries and 12 surgical specialties were represented. The most common definition for the numerator of POMR was in-hospital deaths following surgery (55·3%) and for the denominator it was the number of operative patients (96·2%). Few studies reported preoperative comorbidities (41·8%), ASA status (11·3%), and HIV status (7·8%), with a smaller proportion stratifying on or adjusting mortality for these factors. Studies reporting on planned procedures recorded a median mortality of 1·2% (n=121 [IQR 0·0-4·7]). Median mortality was 10·1% (n=182 [IQR 2·5-16·2) for emergent procedures.INTERPRETATION: POMR is frequently reported in LMICs, but a standardised approach for reporting and risk stratification is absent from the literature. There was wide variation in POMR across procedures and specialties. A quality assessment checklist for surgical mortality studies could improve mortality reporting and facilitate benchmarking across sites and countries.FUNDING: None.
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| 6. |
- Ossenkoppele, Rik, et al.
(författare)
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Accuracy of Tau Positron Emission Tomography as a Prognostic Marker in Preclinical and Prodromal Alzheimer Disease : A Head-to-Head Comparison against Amyloid Positron Emission Tomography and Magnetic Resonance Imaging
- 2021
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 78:8, s. 961-971
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Tau positron emission tomography (PET) tracers have proven useful for the differential diagnosis of dementia, but their utility for predicting cognitive change is unclear. Objective: To examine the prognostic accuracy of baseline fluorine 18 (18F)-flortaucipir and [18F]RO948 (tau) PET in individuals across the Alzheimer disease (AD) clinical spectrum and to perform a head-to-head comparison against established magnetic resonance imaging (MRI) and amyloid PET markers. Design, Setting, and Participants: This prognostic study collected data from 8 cohorts in South Korea, Sweden, and the US from June 1, 2014, to February 28, 2021, with a mean (SD) follow-up of 1.9 (0.8) years. A total of 1431 participants were recruited from memory clinics, clinical trials, or cohort studies; 673 were cognitively unimpaired (CU group; 253 [37.6%] positive for amyloid-β [Aβ]), 443 had mild cognitive impairment (MCI group; 271 [61.2%] positive for Aβ), and 315 had a clinical diagnosis of AD dementia (315 [100%] positive for Aβ). Exposures: [18F]Flortaucipir PET in the discovery cohort (n = 1135) or [18F]RO948 PET in the replication cohort (n = 296), T1-weighted MRI (n = 1431), and amyloid PET (n = 1329) at baseline and repeated Mini-Mental State Examination (MMSE) evaluation. Main Outcomes and Measures: Baseline [18F]flortaucipir/[18F]RO948 PET retention within a temporal region of interest, MRI-based AD-signature cortical thickness, and amyloid PET Centiloids were used to predict changes in MMSE using linear mixed-effects models adjusted for age, sex, education, and cohort. Mediation/interaction analyses tested whether associations between baseline tau PET and cognitive change were mediated by baseline MRI measures and whether age, sex, and APOE genotype modified these associations. Results: Among 1431 participants, the mean (SD) age was 71.2 (8.8) years; 751 (52.5%) were male. Findings for [18F]flortaucipir PET predicted longitudinal changes in MMSE, and effect sizes were stronger than for AD-signature cortical thickness and amyloid PET across all participants (R2, 0.35 [tau PET] vs 0.24 [MRI] vs 0.17 [amyloid PET]; P <.001, bootstrapped for difference) in the Aβ-positive MCI group (R2, 0.25 [tau PET] vs 0.15 [MRI] vs 0.07 [amyloid PET]; P <.001, bootstrapped for difference) and in the Aβ-positive CU group (R2, 0.16 [tau PET] vs 0.08 [MRI] vs 0.08 [amyloid PET]; P <.001, bootstrapped for difference). These findings were replicated in the [18F]RO948 PET cohort. MRI mediated the association between [18F]flortaucipir PET and MMSE in the groups with AD dementia (33.4% [95% CI, 15.5%-60.0%] of the total effect) and Aβ-positive MCI (13.6% [95% CI, 0.0%-28.0%] of the total effect), but not the Aβ-positive CU group (3.7% [95% CI, -17.5% to 39.0%]; P =.71). Age (t = -2.28; P =.02), but not sex (t = 0.92; P =.36) or APOE genotype (t = 1.06; P =.29) modified the association between baseline [18F]flortaucipir PET and cognitive change, such that older individuals showed faster cognitive decline at similar tau PET levels. Conclusions and Relevance: The findings of this prognostic study suggest that tau PET is a promising tool for predicting cognitive change that is superior to amyloid PET and MRI and may support the prognostic process in preclinical and prodromal stages of AD.
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| 7. |
- Ossenkoppele, Rik, et al.
(författare)
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Assessment of Demographic, Genetic, and Imaging Variables Associated with Brain Resilience and Cognitive Resilience to Pathological Tau in Patients with Alzheimer Disease
- 2020
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 77:5, s. 632-642
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Better understanding is needed of the degree to which individuals tolerate Alzheimer disease (AD)-like pathological tau with respect to brain structure (brain resilience) and cognition (cognitive resilience). Objective: To examine the demographic (age, sex, and educational level), genetic (APOE-ϵ4 status), and neuroimaging (white matter hyperintensities and cortical thickness) factors associated with interindividual differences in brain and cognitive resilience to tau positron emission tomography (PET) load and to changes in global cognition over time. Design, Setting, an Participants: In this cross-sectional, longitudinal study, tau PET was performed from June 1, 2014, to November 30, 2017, and global cognition monitored for a mean [SD] interval of 2.0 [1.8] years at 3 dementia centers in South Korea, Sweden, and the United States. The study included amyloid-β-positive participants with mild cognitive impairment or AD dementia. Data analysis was performed from October 26, 2018, to December 11, 2019. Exposures: Standard dementia screening, cognitive testing, brain magnetic resonance imaging, amyloid-β PET and cerebrospinal fluid analysis, and flortaucipir (tau) labeled with fluor-18 (18F) PET. Main Outcomes and Measures: Separate linear regression models were performed between whole cortex [18F]flortaucipir uptake and cortical thickness, and standardized residuals were used to obtain a measure of brain resilience. The same procedure was performed for whole cortex [18F]flortaucipir uptake vs Mini-Mental State Examination (MMSE) as a measure of cognitive resilience. Bivariate and multivariable linear regression models were conducted with age, sex, educational level, APOE-ϵ4 status, white matter hyperintensity volumes, and cortical thickness as independent variables and brain and cognitive resilience measures as dependent variables. Linear mixed models were performed to examine whether changes in MMSE scores over time differed as a function of a combined brain and cognitive resilience variable. Results: A total of 260 participants (145 [55.8%] female; mean [SD] age, 69.2 [9.5] years; mean [SD] MMSE score, 21.9 [5.5]) were included in the study. In multivariable models, women (standardized β =-0.15, P =.02) and young patients (standardized β =-0.20, P =.006) had greater brain resilience to pathological tau. Higher educational level (standardized β = 0.23, P <.001) and global cortical thickness (standardized β = 0.23, P <.001) were associated with greater cognitive resilience to pathological tau. Linear mixed models indicated a significant interaction of brain resilience × cognitive resilience × time on MMSE (β [SE] =-0.235 [0.111], P =.03), with steepest slopes for individuals with both low brain and cognitive resilience. Conclusions and Relevance: Results of this study suggest that women and young patients with AD have relative preservation of brain structure when exposed to neocortical pathological tau. Interindividual differences in resilience to pathological tau may be important to disease progression because participants with both low brain and cognitive resilience had the most rapid cognitive decline over time.
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| 8. |
- Ossenkoppele, Rik, et al.
(författare)
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Discriminative Accuracy of F-18 flortaucipir Positron Emission Tomography for Alzheimer Disease vs Other Neurodegenerative Disorders
- 2018
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Ingår i: Jama-Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484. ; 320:11, s. 1151-1162
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The positron emission tomography (PET) tracer [F-18]flortaucipir allows in vivo quantification of paired helical filament tau, a core neuropathological feature of Alzheimer disease (AD), but its diagnostic utility is unclear. OBJECTIVE To examine the discriminative accuracy of [F-18]flortaucipir for AD vs non-AD neurodegenerative disorders. DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional study, 719 participants were recruited from 3 dementia centers in South Korea, Sweden, and the United States between June 2014 and November 2017 (160 cognitively normal controls, 126 patients with mild cognitive impairment [MCI], of whom 65.9% were amyloid-beta [A beta]positive [ie, MCI due to AD], 179 patients with AD dementia, and 254 patients with various non-AD neurodegenerative disorders). EXPOSURES The index testwas the [F-18]flortaucipir PET standardized uptake value ratio (SUVR) in 5 predefined regions of interest (ROIs). Cut points for tau positivity were determined using the mean +2 SDs observed in controls and Youden Index for the contrast AD dementia vs controls. MAIN OUTCOMES AND MEASURES The reference standard was the clinical diagnosis determined at the specialized memory centers. In the primary analysis, the discriminative accuracy (ie, sensitivity and specificity) of [F-18]flortaucipir was examined for AD dementia vs all non-AD neurodegenerative disorders. In secondary analyses, the area under the curve (AUC) of [F-18]flortaucipir SUVR was compared with 3 established magnetic resonance imaging measures (hippocampal volumes and AD signature and whole-brain cortical thickness), and sensitivity and specificity of [F-18]flortaucipir in MCI due to AD vs non-AD neurodegenerative disorders were determined. RESULTS Among 719 participants, the overall mean (SD) age was 68.8 (9.2) years and 48.4% were male. The proportions of patients who were amyloid-beta positive were 26.3%, 65.9%, 100%, and 23.8% among cognitively normal controls, patients with MCI, patients with AD dementia, and patients with non-AD neurodegenerative disorders, respectively. [F-18]flortaucipir uptake in the medial-basal and lateral temporal cortex showed 89.9% (95% CI, 84.6%-93.9%) sensitivity and 90.6%(95% CI, 86.3%-93.9%) specificity using the threshold based on controls (SUVR, 1.34), and 96.8%(95% CI, 92.0%-99.1%) sensitivity and 87.9%(95% CI, 81.9%-92.4%) specificity using the Youden Index-derived cutoff (SUVR, 1.27) for distinguishing AD dementia from all non-AD neurodegenerative disorders. The AUCs for all 5 [F-18]flortaucipir ROIs were higher (AUC range, 0.92-0.95) compared with the 3 volumetric MRI measures (AUC range, 0.63-0.75; all ROIs P<.001). Diagnostic performance of the 5 [F-18]flortaucipir ROIs were lower in MCI due to AD (AUC range, 0.75-0.84). CONCLUSIONS AND RELEVANCE Among patients with established diagnoses at a memory disorder clinic, [F-18]flortaucipir PET was able to discriminate AD from other neurodegenerative diseases. The accuracy and potential utility of this test in patient care require further research in clinically more representative populations.
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| 9. |
- Ossenkoppele, Rik, et al.
(författare)
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Distinct tau PET patterns in atrophy-defined subtypes of Alzheimer's disease
- 2020
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:2, s. 335-344
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Differential patterns of brain atrophy on structural magnetic resonance imaging (MRI) revealed four reproducible subtypes of Alzheimer's disease (AD): (1) “typical”, (2) “limbic-predominant”, (3) “hippocampal-sparing”, and (4) “mild atrophy”. We examined the neurobiological characteristics and clinical progression of these atrophy-defined subtypes. Methods: The four subtypes were replicated using a clustering method on MRI data in 260 amyloid-β–positive patients with mild cognitive impairment or AD dementia, and we subsequently tested whether the subtypes differed on [18F]flortaucipir (tau) positron emission tomography, white matter hyperintensity burden, and rate of global cognitive decline. Results: Voxel-wise and region-of-interest analyses revealed the greatest neocortical tau load in hippocampal-sparing (frontoparietal-predominant) and typical (temporal-predominant) patients, while limbic-predominant patients showed particularly high entorhinal tau. Typical patients with AD had the most pronounced white matter hyperintensity load, and hippocampal-sparing patients showed the most rapid global cognitive decline. Discussion: Our data suggest that structural MRI can be used to identify biologically and clinically meaningful subtypes of AD.
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| 10. |
- Ossenkoppele, Rik, et al.
(författare)
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The impact of demographic, clinical, genetic, and imaging variables on tau PET status
- 2021
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 48:7, s. 2245-2258
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: A substantial proportion of amyloid-β (Aβ)+ patients with clinically diagnosed Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI) are tau PET–negative, while some clinically diagnosed non-AD neurodegenerative disorder (non-AD) patients or cognitively unimpaired (CU) subjects are tau PET–positive. We investigated which demographic, clinical, genetic, and imaging variables contributed to tau PET status. Methods: We included 2338 participants (430 Aβ+ AD dementia, 381 Aβ+ MCI, 370 non-AD, and 1157 CU) who underwent [18F]flortaucipir (n = 1944) or [18F]RO948 (n = 719) PET. Tau PET positivity was determined in the entorhinal cortex, temporal meta-ROI, and Braak V-VI regions using previously established cutoffs. We performed bivariate binary logistic regression models with tau PET status (positive/negative) as dependent variable and age, sex, APOEε4, Aβ status (only in CU and non-AD analyses), MMSE, global white matter hyperintensities (WMH), and AD-signature cortical thickness as predictors. Additionally, we performed multivariable binary logistic regression models to account for all other predictors in the same model. Results: Tau PET positivity in the temporal meta-ROI was 88.6% for AD dementia, 46.5% for MCI, 9.5% for non-AD, and 6.1% for CU. Among Aβ+ participants with AD dementia and MCI, lower age, MMSE score, and AD-signature cortical thickness showed the strongest associations with tau PET positivity. In non-AD and CU participants, presence of Aβ was the strongest predictor of a positive tau PET scan. Conclusion: We identified several demographic, clinical, and neurobiological factors that are important to explain the variance in tau PET retention observed across the AD pathological continuum, non-AD neurodegenerative disorders, and cognitively unimpaired persons.
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