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Background Latin American and Hispanic women are less likely to develop breast cancer (BC) than women of European descent. Observational studies have found an inverse relationship between the individual proportion of Native American ancestry and BC risk. Here, we use ancestry-informative markers to rule out potential confounding of this relationship, estimating the confounder-free effect of Native American ancestry on BC risk. Methods and study population We used the informativeness for assignment measure to select robust instrumental variables for the individual proportion of Native American ancestry. We then conducted separate Mendelian randomization (MR) analyses based on 1401 Colombian women, most of them from the central Andean regions of Cundinamarca and Huila, and 1366 Mexican women from Mexico City, Monterrey and Veracruz, supplemented by sensitivity and stratified analyses. Results The proportion of Colombian Native American ancestry showed a putatively causal protective effect on BC risk (inverse variance-weighted odds ratio [OR] = 0.974 per 1% increase in ancestry proportion, 95% confidence interval [CI] 0.970–0.978, p  = 3.1 × 10 –40 ). The corresponding OR for Mexican Native American ancestry was 0.988 (95% CI 0.987–0.990, p  = 1.4 × 10 –44 ). Stratified analyses revealed a stronger association between Native American ancestry and familial BC (Colombian women: OR = 0.958, 95% CI 0.952–0.964; Mexican women: OR = 0.973, 95% CI 0.969–0.978), and stronger protective effects on oestrogen receptor (ER)-positive BC than on ER-negative and triple-negative BC. Conclusions The present results point to an unconfounded protective effect of Native American ancestry on BC risk in both Colombian and Mexican women which appears to be stronger for familial and ER-positive BC. These findings provide a rationale for personalised prevention programmes that take genetic ancestry into account, as well as for future admixture mapping studies.

A strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association. Genetic markers of Mapuche ancestry were selected based on the informativeness for assignment measure, and then used as instrumental variables in two-sample Mendelian randomization analyses and complementary sensitivity analyses. Results suggested a putatively causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% per 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.7 × 10−5) and also on gallstone disease (3.6% IVW risk increase, 95% CI 3.1% to 4.0%), pointing to a mediating effect of gallstones on the association between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative effect on BMI (IVW estimate −0.006 kg/m2, 95% CI −0.009 to −0.003). The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between the individual proportion of Mapuche ancestry and GBC risk previously noted in observational studies appears to be free of confounding, primary and secondary prevention strategies that consider genetic ancestry could be particularly efficient.

Processed electroencephalography (pEEG) may help clinicians optimize depth of general anesthesia. Avoiding excessive depth of anesthesia may reduce intraoperative hypotension and the need for vasopressors. We tested the hypothesis that pEEG-guided – compared to non-pEEG-guided – general anesthesia reduces the amount of norepinephrine needed to keep intraoperative mean arterial pressure above 65 mmHg in patients having vascular surgery. Randomized controlled clinical trial. University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 110 patients having vascular surgery. pEEG-guided general anesthesia. Our primary endpoint was the average norepinephrine infusion rate from the beginning of induction of anesthesia until the end of surgery. 96 patients were analyzed. The mean ± standard deviation average norepinephrine infusion rate was 0.08 ± 0.04 μg kg−1 min−1 in patients assigned to pEEG-guided and 0.12 ± 0.09 μg kg−1 min−1 in patients assigned to non-pEEG-guided general anesthesia (mean difference 0.04 μg kg−1 min−1, 95% confidence interval 0.01 to 0.07 μg kg−1 min−1, p = 0.004). Patients assigned to pEEG-guided versus non-pEEG-guided general anesthesia, had a median time-weighted minimum alveolar concentration of 0.7 (0.6, 0.8) versus 0.8 (0.7, 0.8) (p = 0.006) and a median percentage of time Patient State Index was <25 of 12 (1, 41) % versus 23 (3, 49) % (p = 0.279). pEEG-guided – compared to non-pEEG-guided – general anesthesia reduced the amount of norepinephrine needed to keep mean arterial pressure above 65 mmHg by about a third in patients having vascular surgery. Whether reduced intraoperative norepinephrine requirements resulting from pEEG-guided general anesthesia translate into improved patient-centered outcomes remains to be determined in larger trials. •To prevent and treat intraoperative hypotension, vasopressors are commonly used.•Avoiding excessive depth of anesthesia may reduce the need for vasopressors.•Processed electroencephalography helps avoid excessive anesthetic depth.•Processed electroencephalography reduces norepinephrine requirements

The QoR-PACU was developed in German language based on the 40-item QoR-40 questionnaire. Between March and November 2020, adult patients scheduled for elective urologic surgery completed the QoR-PACU preoperatively and during the PACU stay. We evaluated feasibility, validity, reliability, and responsiveness. We included 375 patients. After two piloting phases including 72 and 48 patients, respectively, we administered the final version of the QoR-PACU to 255 patients, with a completion rate of 96.5%. Patients completed the QoR-PACU at a median of 125.0 (83.0; 156.8) min after arrival in the PACU. Construct validity was good with postoperative QoR-PACU sum scores correlating with age (r = 0.23, 95% CI: 0.11 to 0.35, p < 0.001), length of PACU stay (r = -0.15, 95%CI: -0.27 to -0.03, p = 0.02), pain in the PACU (r = -0.48, 95% CI: -0.57 to -0.37, p < 0.001) and piritramide dose administered (r = -0.29, 95% CI: -0.40 to -0.17, p < 0.001). Cronbach's alpha was 0.67 (95% CI: 0.61-0.73) with moderate test-retest reliability (ICC of 0.67, 95% CI: 0.38 to 0.83). Cohen's effect size was 3.08 and the standardized response mean was 1.65 indicating adequate responsiveness. The assessment of QoR in the early postoperative period is feasible. We found high acceptability, good validity, adequate responsiveness, and moderate reliability. Future studies should evaluate the psychometric properties of the QoR-PACU in more heterogeneous patient populations including female and gender-diverse patients with varying degress of perioperative risk.

The ugly beast has reared its head again. Some of Delta's pilots are refusing to work overtime and are thereby creating some serious scheduling problems (\"Delta cancels 300 flights,\" Metro, Dec. 4). I am slowly resigning myself to the idea that George W. Bush will probably be the next president, even though I fully believe that Al Gore most likely won the election. Gore clearly won the popular vote nationwide and I think it probable that he also won Florida. It is a shame that the \"Catch-22\" nature of the Florida election contest procedures have prevented us from finding out what the voters' intent there really was. Gore must concede if his last breath of ballot life has run its course. His noble quest for a ballot recount has taken a toll on the country. A cottage industry of pundits and talking heads have literally taken to the streets inflaming a divided electorate. Gore must also act as a statesman and realize when all is said and done, he must step aside.

Background. Methicillin-resistant Staphylococcus aureus (MRSA) remains sensitive to vancomycin; when vancomycin-resistant S. aureus (VRSA) emerges, treatment becomes more complex. VRSA emergence is attributed to conjugative transfer of the vancomycin-resistance gene cluster from vancomycin-resistant enterococci (VRE) to MRSA. Because cocolonization with MRSA and VRE precedes VRSA development, this study investigates the epidemiology of cocolonization in skilled nursing facility (SNF) residents at high risk for MRSA or VRE colonization. Methods. A prospective observational study conducted at 15 SNFs in southeast Michigan. Overall, 178 residents (90 with indwelling urinary catheters and/or feeding tubes and 88 device-free) were cultured monthly for MRSA and VRE, and clinical data were recorded. Results. The incidence of MRSA/VRE cocolonization among residents with indwelling devices was 6.5 per 100 resident-months; 5.2 (95% confidence interval [CI]: 1.49-18.1) times that among those without devices. MRSA/ VRE cocolonization in the device group occurred most frequently in wounds (4.1 per 100 resident-months). In a logistic regression analysis limited to residents with devices, functional disability (rate ratio [RR], 1.3; 95% CI: 1.1-1.4) and wound presence (RR, 3.4; 95% CI: 1.4-8.6) were independent risk factors of cocolonization. Conclusions. In a population of SNF residents, individuals with indwelling devices who also had functional disability or wounds were at greatest risk of MRSA/VRE cocolonization. These individuals should be routinely monitored for the presence of VRSA colonization.

Background: This study aimed to determine whether prehospital qSOFA (quick sequential organ failure assessment) assessment was associated with a shortened ‘time to antibiotics’ and ‘time to intravenous fluid resuscitation’ compared with standard assessment. Methods: This retrospective study included patients who were referred to our Emergency Department between 2014 and 2018 by emergency medical services, in whom sepsis was diagnosed during hospitalization. Two multivariable regression models were fitted, with and without qSOFA parameters, for ‘time to antibiotics’ (primary endpoint) and ‘time to intravenous fluid resuscitation’. Results: In total, 702 patients were included. Multiple linear regression analysis showed that antibiotics and intravenous fluids were initiated earlier if infections were suspected and emergency medical services involved emergency physicians. A heart rate above 90/min was associated with a shortened time to antibiotics. If qSOFA parameters were added to the models, a respiratory rate ≥ 22/min and altered mentation were independent predictors for earlier antibiotics. A systolic blood pressure ≤ 100 mmHg and altered mentation were independent predictors for earlier fluids. When qSOFA parameters were added, the explained variability of the model increased by 24% and 38%, respectively (adjusted R² 0.106 versus 0.131 for antibiotics and 0.117 versus 0.162 for fluids). Conclusion: Prehospital assessment of qSOFA parameters was associated with a shortened time to a targeted sepsis therapy.

Background: An inter-incisor gap <3 cm is considered critical for videolaryngoscopy. It is unknown if new generation GlideScope Spectrum™ videolaryngoscopes with low-profile hyperangulated blades might facilitate safe tracheal intubation in these patients. This prospective pilot study aims to evaluate feasibility and safety of GlideScopeTM videolaryngoscopes in severely restricted mouth opening. Methods: Feasibility study in 30 adults with inter-incisor gaps between 1.0 and 3.0 cm scheduled for ENT or maxillofacial surgery. Individuals at risk for aspiration or rapid desaturation were excluded. Results: The mean mouth opening was 2.2 ± 0.5 cm (range 1.1–3.0 cm). First attempt success rate was 90% and overall success was 100%. A glottis view grade 1 or 2a was achieved in all patients. Nasotracheal intubation was particularly difficult if Magill forceps were required (n = 4). Intubation time differed between orotracheal (n = 9; 33 (25; 39) s) and nasotracheal (n = 21; 55 (38; 94) s); p = 0.049 intubations. The airway operator’s subjective ratings on visual analogue scales (0–100) revealed that tube placement was more difficult in individuals with an inter-incisor gap <2.0 cm (n = 10; 35 (29; 54)) versus ≥2.0 cm (n = 20; 20 (10; 30)), p = 0.007, while quality of glottis exposure did not differ. Conclusions: GlidescopeTM videolaryngoscopy is feasible and safe in patients with severely restricted mouth opening if given limitations are respected.