Introduction Data on omega-3 polyunsaturated fatty acids in relation to cardiovascular disease are limited in women. The aim of this study was to examine longitudinal relations of tuna and dark fish, ...α-linolenic acid, and marine omega-3 fatty acid intake with incident major cardiovascular disease in women. Methods This was a prospective cohort study of U.S. women participating in the Women’s Health Study from 1993 to 2014, during which the data were collected and analyzed. A total of 39,876 women who were aged ≥45 years and free of cardiovascular disease at baseline provided dietary data on food frequency questionnaires. Analyses used Cox proportional hazards models to evaluate the association between fish and energy-adjusted omega-3 polyunsaturated fatty acid intake and the risk of major cardiovascular disease, defined as a composite outcome of myocardial infarction, stroke, and cardiovascular death, in 38,392 women in the final analytic sample (96%). Results During 713,559 person years of follow-up, 1,941 cases of incident major cardiovascular disease were confirmed. Tuna and dark fish intake was not associated with the risk of incident major cardiovascular disease ( p -trend >0.05). Neither α-linolenic acid nor marine omega-3 fatty acid intake was associated with major cardiovascular disease or with individual cardiovascular outcomes (all p -trend >0.05). There was no effect modification by age, BMI, or baseline history of hypertension. Conclusions In this cohort of women without history of cardiovascular disease, intakes of tuna and dark fish, α-linolenic acid, and marine omega-3 fatty acids were not associated with risk of major cardiovascular disease.
Objective To evaluate the effects of intraoperative protective ventilation on major postoperative respiratory complications and to define safe intraoperative mechanical ventilator settings that do ...not translate into an increased risk of postoperative respiratory complications.Design Hospital based registry study.Setting Academic tertiary care hospital and two affiliated community hospitals in Massachusetts, United States.Participants 69 265 consecutively enrolled patients over the age of 18 who underwent a non-cardiac surgical procedure between January 2007 and August 2014 and required general anesthesia with endotracheal intubation.Interventions Protective ventilation, defined as a median positive end expiratory pressure (PEEP) of 5 cmH2O or more, a median tidal volume of less than 10 mL/kg of predicted body weight, and a median plateau pressure of less than 30 cmH2O.Main outcome measure Composite outcome of major respiratory complications, including pulmonary edema, respiratory failure, pneumonia, and re-intubation.Results Of the 69 265 enrolled patients 34 800 (50.2%) received protective ventilation and 34 465 (49.8%) received non-protective ventilation intraoperatively. Protective ventilation was associated with a decreased risk of postoperative respiratory complications in multivariable regression (adjusted odds ratio 0.90, 95% confidence interval 0.82 to 0.98, P=0.013). The results were similar in the propensity score matched cohort (odds ratio 0.89, 95% confidence interval 0.83 to 0.97, P=0.004). A PEEP of 5 cmH2O and median plateau pressures of 16 cmH2O or less were associated with the lowest risk of postoperative respiratory complications.Conclusions Intraoperative protective ventilation was associated with a decreased risk of postoperative respiratory complications. A PEEP of 5 cmH2O and a plateau pressure of 16 cmH2O or less were identified as protective mechanical ventilator settings. These findings suggest that protective thresholds differ for intraoperative ventilation in patients with normal lungs compared with those used for patients with acute lung injury.
Abstract
Background
Machine learning models promise to support diagnostic predictions, but may not perform well in new settings. Selecting the best model for a new setting without available data is ...challenging. We aimed to investigate the transportability by calibration and discrimination of prediction models for cognitive impairment in simulated external settings with different distributions of demographic and clinical characteristics.
Methods
We mapped and quantified relationships between variables associated with cognitive impairment using causal graphs, structural equation models, and data from the ADNI study. These estimates were then used to generate datasets and evaluate prediction models with different sets of predictors. We measured transportability to external settings under guided interventions on age, APOE ε4, and tau-protein, using performance differences between internal and external settings measured by calibration metrics and area under the receiver operating curve (AUC).
Results
Calibration differences indicated that models predicting with causes of the outcome were more transportable than those predicting with consequences. AUC differences indicated inconsistent trends of transportability between the different external settings. Models predicting with consequences tended to show higher AUC in the external settings compared to internal settings, while models predicting with parents or all variables showed similar AUC.
Conclusions
We demonstrated with a practical prediction task example that predicting with causes of the outcome results in better transportability compared to anti-causal predictions when considering calibration differences. We conclude that calibration performance is crucial when assessing model transportability to external settings.
To compare sarcopenia and frailty for outcome prediction in surgical intensive care unit (SICU) patients.
Frailty has been associated with adverse outcomes and describes a status of muscle weakness ...and decreased physiological reserve leading to increased vulnerability to stressors. However, frailty assessment depends on patient cooperation. Sarcopenia can be quantified by ultrasound and the predictive value of sarcopenia at SICU admission for adverse outcome has not been defined.
We conducted a prospective, observational study of SICU patients. Sarcopenia was diagnosed by ultrasound measurement of rectus femoris cross-sectional area. Frailty was diagnosed by the Frailty Index Questionnaire based on 50 variables. Relationship between variables and outcomes was assessed by multivariable regression analysis NCT02270502.
Sarcopenia and frailty were quantified in 102 patients and observed in 43.1% and 38.2%, respectively. Sarcopenia predicted adverse discharge disposition (discharge to nursing facility or in-hospital mortality, odds ratio 7.49; 95% confidence interval 1.47-38.24; P = 0.015) independent of important clinical covariates, as did frailty (odds ratio 8.01; 95% confidence interval 1.82-35.27; P = 0.006); predictive ability did not differ between sarcopenia and frailty prediction model, reflected by χ values of 21.74 versus 23.44, respectively, and a net reclassification improvement (NRI) of -0.02 (P = 0.87). Sarcopenia and frailty predicted hospital length of stay and the frailty model had a moderately better predictive accuracy for this outcome.
Bedside diagnosis of sarcopenia by ultrasound predicts adverse discharge disposition in SICU patients equally well as frailty. Sarcopenia assessed by ultrasound may be utilized as rapid beside modality for risk stratification of critically ill patients.
Summary Background Immobilisation predicts adverse outcomes in patients in the surgical intensive care unit (SICU). Attempts to mobilise critically ill patients early after surgery are frequently ...restricted, but we tested whether early mobilisation leads to improved mobility, decreased SICU length of stay, and increased functional independence of patients at hospital discharge. Methods We did a multicentre, international, parallel-group, assessor-blinded, randomised controlled trial in SICUs of five university hospitals in Austria (n=1), Germany (n=1), and the USA (n=3). Eligible patients (aged 18 years or older, who had been mechanically ventilated for <48 h, and were expected to require mechanical ventilation for ≥24 h) were randomly assigned (1:1) by use of a stratified block randomisation via restricted web platform to standard of care (control) or early, goal-directed mobilisation using an inter-professional approach of closed-loop communication and the SICU optimal mobilisation score (SOMS) algorithm (intervention), which describes patients’ mobilisation capacity on a numerical rating scale ranging from 0 (no mobilisation) to 4 (ambulation). We had three main outcomes hierarchically tested in a prespecified order: the mean SOMS level patients achieved during their SICU stay (primary outcome), and patient's length of stay on SICU and the mini-modified functional independence measure score (mmFIM) at hospital discharge (both secondary outcomes). This trial is registered with ClinicalTrials.gov ( NCT01363102 ). Findings Between July 1, 2011, and Nov 4, 2015, we randomly assigned 200 patients to receive standard treatment (control; n=96) or intervention (n=104). Intention-to-treat analysis showed that the intervention improved the mobilisation level (mean achieved SOMS 2·2 SD 1·0 in intervention group vs 1·5 0·8 in control group, p<0·0001), decreased SICU length of stay (mean 7 days SD 5–12 in intervention group vs 10 days 6–15 in control group, p=0·0054), and improved functional mobility at hospital discharge (mmFIM score 8 4–8 in intervention group vs 5 2–8 in control group, p=0·0002). More adverse events were reported in the intervention group (25 cases 2·8%) than in the control group (ten cases 0·8%); no serious adverse events were observed. Before hospital discharge 25 patients died (17 16% in the intervention group, eight 8% in the control group). 3 months after hospital discharge 36 patients died (21 22% in the intervention group, 15 17% in the control group). Interpretation Early, goal-directed mobilisation improved patient mobilisation throughout SICU admission, shortened patient length of stay in the SICU, and improved patients’ functional mobility at hospital discharge. Funding Jeffrey and Judy Buzen.
Summary Migraine and stroke are two common and heterogeneous neurovascular disorders with complex relations. Data show no firm association between stroke and migraine without aura—by far the most ...common type of migraine—but a doubling of the risk of ischaemic stroke in people who have migraine with aura. Migraine with aura is characterised by a low brain threshold for cortical spreading depression, the biological substrate of the aura, which can be triggered by many factors, including specific diseases that can by themselves increase the risk of ischaemic stroke. Whether the increased risk of ischaemic stroke applies to migraine with aura as a primary headache disorder or is partly due to migraine with aura secondary to other disorders remains to be elucidated.
Background
Migraine, particularly with aura, increases the risk for ischemic stroke, at least in a subset of patients. The underlying mechanisms are poorly understood and probably multifactorial.
...Methods
We carried out an extended literature review of experimental and clinical evidence supporting the association between migraine and ischemic stroke to identify potential mechanisms that can explain the association.
Results
Observational, imaging and genetic evidence support a link between migraine and ischemic stroke. Based on clinical and experimental data, we propose mechanistic hypotheses to explain the link, such as microembolic triggers of migraine and enhanced sensitivity to ischemic injury in migraineurs.
Discussion
We discuss the possible practical implications of clinical and experimental data, such as aggressive risk factor screening and management, stroke prophylaxis and specific acute stroke management in migraineurs. However, evidence from prospective clinical trials is required before modifying the practice in this patient population.
Objective To evaluate the association between migraine and incident cardiovascular disease and cardiovascular mortality in women.Design Prospective cohort study among Nurses’ Health Study II ...participants, with follow-up from 1989 and through June 2011.Setting Cohort of female nurses in United States.Participants 115 541 women aged 25-42 years at baseline and free of angina and cardiovascular disease. Cumulative follow-up rates were more than 90%.Main outcome measures The primary outcome of the study was major cardiovascular disease, a combined endpoint of myocardial infarction, stroke, or fatal cardiovascular disease. Secondary outcome measures included individual endpoints of myocardial infarction, stroke, angina/coronary revascularization procedures, and cardiovascular mortality.Results 17 531 (15.2%) women reported a physician’s diagnosis of migraine. Over 20 years of follow-up, 1329 major cardiovascular disease events occurred and 223 women died from cardiovascular disease. After adjustment for potential confounding factors, migraine was associated with an increased risk for major cardiovascular disease (hazard ratio 1.50, 95% confidence interval 1.33 to 1.69), myocardial infarction (1.39, 1.18 to 1.64), stroke (1.62, 1.37 to 1.92), and angina/coronary revascularization procedures (1.73, 1.29 to 2.32), compared with women without migraine. Furthermore, migraine was associated with a significantly increased risk for cardiovascular disease mortality (hazard ratio 1.37, 1.02 to 1.83). Associations were similar across subgroups of women, including by age (<50/≥50), smoking status (current/past/never), hypertension (yes/no), postmenopausal hormone therapy (current/not current), and oral contraceptive use (current/not current).Conclusions Results of this large, prospective cohort study in women with more than 20 years of follow-up indicate a consistent link between migraine and cardiovascular disease events, including cardiovascular mortality. Women with migraine should be evaluated for their vascular risk. Future targeted research is warranted to identify preventive strategies to reduce the risk of future cardiovascular disease among patients with migraine.
To examine the association between lipid levels and hemorrhagic stroke risk among women.
We performed a prospective cohort study among 27,937 women enrolled in the Women's Health Study with measured ...total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), as well as triglycerides. Strokes were confirmed by medical record review. We used Cox proportional hazards models to analyze associations between lipid categories and hemorrhagic stroke risk.
During a mean of 19.3 years of follow-up, 137 hemorrhagic strokes occurred. Compared to those with LDL-C levels 100-129.9 mg/dL, after multivariable adjustment, those with LDL-C levels <70 mg/dL had 2.17 times the risk (95% confidence interval CI 1.05, 4.48) of experiencing a hemorrhagic stroke. No significant increase in risk was seen for those with LDL-C levels 130-159.9 mg/dL (relative risk RR 1.14; 95% CI 0.72, 1.80) or 70-99.9 mg/dL (RR 1.25; 95% CI 0.76, 2.04). There was a suggestion, although not significant, of increased risk for those with LDL-C levels ≥160 mg/dL (RR 1.53; 95% CI 0.92, 2.52). Women in the lowest quartile of triglycerides had a significantly increased risk of hemorrhagic stroke compared to women in the top quartile after multivariable adjustment (RR 2.00; 95% CI 1.18, 3.39). We observed no significant associations between total cholesterol or HDL-C levels and hemorrhagic stroke risk.
LDL-C levels <70 mg/dL and low triglyceride levels were associated with increased risk of hemorrhagic stroke among women.
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