Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.

BACKGROUND: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. METHODS: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). RESULTS: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships. CONCLUSIONS: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

Health-related quality of life at hospital discharge as a predictor for 6-month unplanned readmission and all-cause mortality of acutely admitted older medical patients.

PURPOSE: To assess whether health-related quality of life (HRQOL) status, using the European Quality of life-5 dimensions (EQ5D), in acutely admitted older medical patients was associated with a combined end-point including first unplanned readmission or death without prior readmission within 6 months. Secondly, to assess if HRQOL was associated with death regardless of previous readmissions. METHODS: Patients from seven medical and two acute medical units were included and the EQ5D was obtained at discharge. Associations were assessed using Cox regression. Harrell's C-statistics indicated the predictive performance. RESULTS: 1328 patients were included, 50% (n = 664) were readmitted (n = 635) or had died without prior readmission (n = 29) within 6 months. In total, 15.2% (n = 202) died within 6 months. In the gender- and age-adjusted analysis, a lower EQ5D index score was associated with a higher hazard ratio (HR) of unplanned readmission or death without prior readmission for all categories of scores below 1 (< 1 to 0.741, < 0.741 to 0.438 and < 0.438 to - 0.40), HR 1.60, 1.93 and 2.02. Likewise, a lower EQ5D score was associated with a higher HR of death, HR 1.72, 2.54 and 3.79. Harrell's C values were 0.56 and 0.63. CONCLUSION: HRQOL measured at discharge may identify acutely admitted older medical patients at especially high risk of readmission or death up to 6 months after discharge. Incorporating assessment of HRQOL should be considered when risk stratifying a heterogeneous population of acutely admitted older medical patients.

As-indicated versus routine vision screening of preterm children: a 17-year retrospective regional study.

PURPOSE: To investigate outcomes of routine vision screening compared to as-indicated ophthalmological investigation of all children born preterm in a Danish region from 1997 to 2014. METHODS: All children born preterm (gestation age < 32 weeks or birthweight < 1500 g) screened for retinopathy of prematurity (ROP) were divided into two groups. From 1997 to 2009, only children treated for ROP or referred for visual problems received ophthalmological investigation (as-indicated group). From 2010 to 2014, all ROP-screened infants were offered ophthalmological investigation at 6 months and 3 years of age (screening group). RESULTS: A total of 560 children were included in the as-indicated period, 41 and 87 were referred for ophthalmological investigation at 6 months and 3 years, respectively. In the screening period, 295 children were included, 251 and 150 of whom underwent vision evaluation at 6 months and 3 years, respectively. Mean visual acuity was 4.1 cycles per degree with Teller acuity cards at 6 months and 0.78 decimal at 3 years. At 3 years, 2.7%(n = 11) in the as-indicated versus 3.5%(n = 10) screening group had visual acuity < 6/18 (p = 0.24). Cerebral palsy (n = 28) and epilepsy (n = 5) were significantly related to vision impairment (p = 0.001/0.006), while treated ROP was not (n = 13). Refractive error was common at 3 years (61%), especially astigmatism (50%). Gestational age, birthweight and ROP were not associated with vision impairment or refractive error. CONCLUSION: Screening preterm children at 6 months and 3 years did not reveal more visually impaired children compared to examination when indicated.

Decreasing incidence of registered hydatidiform moles in Denmark 1999-2014.

Incidences of hydatidiform mole (HM) registered in European countries varies from 0.98/1000 to 2.17/1000 deliveries, while higher incidences have been reported in other parts of the world. We calculated the incidence by selecting data on HMs classified as "first", "second" and "third" from 01.01.1999 to 31.12.2014 registered in the Danish Pathology Registry, which we previously showed to be the most complete data source on the number of HMs in Denmark. In the study period, 1976 first HMs were registered; 1080 (55%) were classified as PHMs (partial HMs) and 896 (45%) as NPHMs (HMs not registered as PHMs). The average incidence of HM was 1.98/1000 deliveries. The incidence of PHM was 1.08/1000 deliveries and the incidence of NPHM was 0.90/1000 deliveries. Forty HMs were registered as second HMs; 85% (34/40) were of the same histopathological type as the first HM. The registered incidence of HM decreased from 2.55/1000 deliveries in 1999 to 1.61/1000 deliveries in 2014 (p < 0.005). The decrease in the incidence of HM was identical with a decrease in the incidence of PHM. New medical practices such as medical abortion and only forwarding selected pregnancy products for histopathologic examination may cause a declining number of HMs registered.

Treatment of Benign Paroxysmal Positional Vertigo with the TRV Reposition Chair.

OBJECTIVES: The primary objective of this study was to evaluate how successful the reposition of retractable benign paroxysmal positional vertigo (BPPV) was when treating patients with the Thomas Richard Vitton (TRV) reposition chair. MATERIALS AND METHODS: This is a prospective clinical trial. A total of 81 BPPV patients who were referred to the tertiary Balance - Dizziness Centre at the Department of Otolaryngology, Head - Neck Surgery and Audiology, Aalborg University Hospital, Denmark were included and analyzed. All the patients were diagnosed and treated with the TRV reposition chair. RESULTS: The patients were successfully treated after an average of 2.23 (± 1.66 SD) treatments with the TRV reposition chair. There was a significant difference between the number of treatments needed in the single semicircular canal group and the multicanal group. Seventeen (22.6%) of the patients experienced either dislocation of otoconia, relapse, or new onset of BPPV during the trial period. The number of patients with BPPV located to the anterior, lateral, and multiple semicircular canals in this study was significantly higher than that in similar studies. Six patients (7.4%) were classified as treatment failures. CONCLUSION: We found the TRV reposition chair to be very successful in the diagnostics and treatment of patients with retractable and atypical BPPV. However, 7.4% experienced treatment failure.

Hydatidiform mole: validity of the registration in the Danish National Patient Registry, the Danish Cancer Registry, and the Danish Pathology Registry 1999-2009.

PURPOSE: To examine the validity of registration of hydatidiform mole (HM) in the Danish National Patient Registry (NPR), the Danish Cancer Registry (DCR), and the Danish Pathology Registry (DPR). PATIENTS AND METHODS: We selected women registered with a first-time HM code in NPR, DCR, and DPR from 1999 to 2009. We found most women registered in DPR. For a random sample of women registered in DPR, the coding was validated by comparing with the pathology report. Completeness and positive predictive value (PPV) of registration with an HM code in NPR and DCR were calculated using DPR as the reference. Details of women registered in NPR or DCR, but not in DPR, were scrutinized. RESULTS: In NPR and DPR, 1,520 women were identified in total; 1,057 (70%) were found in both registries, 65 (4%) only in NPR, and 398 (26%) only in DPR. In DCR and DPR, 1,498 women were identified in total; 1,174 (78%) in both registries, 47 (3%) only in DCR, and 277 (19%) only in DPR. For 149/150 randomly selected women registered with an HM code in DPR (99%), the pathology report was consistent with the diagnosis of HM. Completeness of NPR was 73% (95% CI: 70%-75%) and PPV was 94% (95% CI: 93%-95%). Completeness of DCR was 72% (95% CI: 69%-75%) in 1999-2003 and 90% (95% CI: 87%-92%) in 2004-2009. PPV of DCR was 96% (95% CI: 95%-97%) throughout the period. CONCLUSION: Validation of registry data is important before using these. For research on the number of HMs in Denmark, DPR is the most valid data source. NPR and DCR appear to be equally valid before 2004. However, for research after 2004, DCR should be preferred rather than NPR.

Associations and predictions of readmission or death in acutely admitted older medical patients using self-reported frailty and functional measures. A Danish cohort study.

OBJECTIVE: To assess whether frailty in acutely admitted older medical patients, assessed by a self-report questionnaire and evaluation of functional level at discharge, was associated with readmission or death within 6 months after discharge. A second objective was to assess the predictive performance of models including frailty, functional level, and known risk factors. METHODS: A cohort study including acutely admitted older patients 65+ from seven medical and two acute medical units. The Tilburg Frailty Indicator (TFI), Timed-Up-and-Go (TUG), and grip strength (GS) exposure variables were measured. Associations were assessed using Cox regression with first unplanned readmission or death (all-causes) as the outcome. Prediction models including the three exposure variables and known risk factors were modelled using logistic regression and C-statistics. RESULTS: Of 1328 included patients, 50% were readmitted or died within 6 months. When adjusted for gender and age, there was an 88% higher risk of readmission or death if the TFI scores were 8-13 points compared to 0-1 points (HR 1.88, CI 1.38;2.58). Likewise, higher TUG and lower GS scores were associated with higher risk of readmission or death. The area under the curve for the prediction models ranged from 0.64 (0.60;0.68) to 0.72 (0.68;0.76). CONCLUSION: In acutely admitted older medical patients, higher frailty assessed by TFI, TUG, and GS was associated with a higher risk of readmission or death within 6 months after discharge. The performance of the prediction models was mediocre, and the models cannot stand alone as risk stratification tools in clinical practice.

Venous thromboembolism in chronic lymphocytic leukemia: a Danish nationwide cohort study.

Venous thromboembolism (VTE) is associated with inferior survival in cancer patients. The risk of VTE and its effect on survival in chronic lymphocytic leukemia (CLL) patients remains unclear. The present study investigated the impact of patient-related factors, CLL prognostic markers, and CLL treatment on the risk of VTE and assessed overall survival relative to VTE. All patients in the Danish National CLL Registry (2008-2015) were followed from the date of CLL diagnosis to death, VTE, emigration, or administrative censoring. Hazard ratios (HRs) were estimated using Cox models, and second primary cancers and anticoagulation treatment were included as time-varying exposures. During a median follow-up of 2.6 years, 92 VTEs occurred among 3609 CLL patients, corresponding to a total incidence rate of 8.2 VTEs per 1000 person-years (95% confidence interval [CI], 6.7-10.1). A history of VTE or second primary cancer was associated with HRs of VTE of 5.09 (95% CI, 2.82-9.17) and 3.72 (95% CI, 2.15-6.34), respectively, while ß2-microglobulin >4 mg/L, unmutated immunoglobulin HV and unfavorable cytogenetics had lower HRs. CLL patients with VTE had marginally higher mortality, which was most pronounced among patients <60 years of age (HR, 7.74; 95% CI, 2.12-28.29). Our findings suggest that markers of unfavorable CLL prognosis contribute to an increased risk of VTE; however, previous VTE or a second primary cancer is more strongly associated with the risk of VTE than any CLL-specific marker. Focusing attention on this preventable complication may improve survival in young CLL patients.