; for the Postoperative Vascular Complications in Unrecognized Obstructive Sleep Apnea (POSA) Study Investigators IMPORTANCE Unrecognized obstructive sleep apnea increases cardiovascular risks in the general population, but whether obstructive sleep apnea poses a similar risk in the perioperative period remains uncertain. OBJECTIVES To determine the association between obstructive sleep apnea and 30-day risk of cardiovascular complications after major noncardiac surgery. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study involving adult at-risk patients without prior diagnosis of sleep apnea and undergoing major noncardiac surgery from 8 hospitals in 5 countries between January 2012 and July 2017, with follow-up until August 2017. Postoperative monitoring included nocturnal pulse oximetry and measurement of cardiac troponin concentrations. EXPOSURES Obstructive sleep apnea was classified as mild (respiratory event index [REI] 5-14.9 events/h), moderate (REI 15-30), and severe (REI >30), based on preoperative portable sleep monitoring. MAIN OUTCOMES AND MEASURES The primary outcome was a composite of myocardial injury, cardiac death, heart failure, thromboembolism, atrial fibrillation, and stroke within 30 days of surgery. Proportional-hazards analysis was used to determine the association between obstructive sleep apnea and postoperative cardiovascular complications. RESULTS Among a total of 1364 patients recruited for the study, 1218 patients (mean age, 67 [SD, 9] years; 40.2% women) were included in the analyses. At 30 days after surgery, rates of the primary outcome were 30.1% (41/136) for patients with severe OSA, 22.1% (52/235) for patients with moderate OSA, 19.0% (86/452) for patients with mild OSA, and 14.2% (56/395) for patients with no OSA. OSA was associated with higher risk for the primary outcome

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BACKGROUND: Obstructive sleep apnea (OSA) has been found to be associated with difficult airway, although there is a paucity of prospective studies investigating thresholds of OSA severity with difficult airway outcomes. The aim of this study was to examine the association between OSA and difficult intubation or difficult mask ventilation. We also explored the utility of the Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, and Gender (STOP-Bang) score for difficult airway prediction. METHODS: The Postoperative Vascular Complications in Unrecognized Obstructive Sleep Apnea (POSA) trial was an international prospective cohort study of surgical patients 45 years or older with one or more cardiac risk factor presenting for noncardiac surgery, with planned secondary analyses of difficult airway outcomes. Multivariable logistic regression analyses tested associations between OSA severity and predictors of difficult airway with difficult intubation or difficult mask ventilation. Overall, 869 patients without prior diagnosis of OSA were screened for OSA risk with the STOP-Bang tool, underwent preoperative sleep study, and had routine perioperative care, including general anesthesia with tracheal intubation. The primary outcome analyzed was difficult intubation, and the secondary outcome was difficult mask ventilation. RESULTS: Based on the sleep studies, 287 (33%), 324 (37%), 169 (20%), and 89 (10%) of the 869 patients had no, mild, moderate, and severe OSA, respectively. One hundred and seventy-two (20%) had a STOP-Bang score of 0–2 (low risk), 483 (55%) had a STOP-Bang score of 3–4 (intermediate risk), and 214 (25%) had a STOP-Bang score 5–8 (high risk). The incidence of difficult intubation was 6.7% (58 of 869), and difficult mask ventilation was 3.7% (32 of 869). Multivariable logistic regression demonstrated that moderate OSA (odds ratio [OR] = 3.26 [95% confidence interval {CI}, 1.37-8.38], adjusted P = .010) and severe OSA (OR = 4.05 [95% CI, 1.51-11.36], adjusted P = .006) but not mild OSA were independently associated with difficult intubation compared to patients without OSA. Relative to scores of 0–2, STOP-Bang scores of 3–4 and 5–8 were associated with increased odds of difficult intubation (OR = 3.01 [95% CI, 1.13-10.40, adjusted P = .046] and 4.38 [95% CI, 1.46-16.36, adjusted P = .014]), respectively. OSA was not associated with difficult mask ventilation, and only increasing neck circumference was found to be associated (adjusted P = .002). CONCLUSIONS: Moderate and severe OSA were associated with difficult intubation, and increasing neck circumference was associated with difficult mask ventilation. A higher STOP-Bang score of 3 or more may be associated with difficult intubation versus STOP-Bang score of 0–2. Anesthesiologists should be vigilant for difficult intubation when managing patients suspected or diagnosed with OSA.

Migraine secondary to meningeal input is referred to extracranial regions innervated by somatic afferents that project to homologous regions in the trigeminal nucleus caudalis (TNC). Reported efficacy of extracranial botulinum toxin (BoNT) in treating migraine is surprising since a local extracranial effect of BoNT cannot account for its effect upon meningeal input. We hypothesize that intradermal BoNT acts through central transport in somatic afferents. Anesthetized C57Bl/6 mice (male) received unilateral supraorbital (SO) injections of BoNT-B (1.5 U/40 μl) or saline. 3 days later, mice received ipsilateral (ipsi) -SO capsaicin (2.5 μg/30 μl) or meningeal capsaicin (4 μl of 1mg/ml). Pre-treatment with ipsi-SO BONT-B i) decreased nocicsponsive ipsilateral wiping behavior following ipsi-SO capsaicin; ii) produced cleavage of VAMP in the V1 region of ipsi-TG and in TG neurons showing WGA after SO injection; iii) reduced expression of c-fos in ipsi-TNC following ipsi-SO capsaicin; iv) reduced c-fos activation and NK-1 internalization in ipsi-TNC secondary to ipsi-meningeal capsaicin; vi) SO WGA did not label dural afferents. We conclude that BoNT-B is taken up by peripheral afferents and transported to central terminals where it inhibits transmitter release resulting in decreased activation of second order neurons. Further, this study supports the hypothesis that SO BoNT exerts a trans-synaptic action on either the second order neuron (which receives convergent input from the meningeal afferent) or the terminal/TG of the converging meningeal afferent.

Background/Aims: The Remission in Schizophrenia Working Group has defined remission as ‘a low-mild symptom intensity level, maintained for a minimum of 6 months, where such symptoms do not affect an individual's behaviour' [Andreasen et al.: Am J Psychiatry 2005;162:441-449]. Since brain morphology relates to symptomatology, treatment and illness progression, MRI may assist in predicting remission. Methods: Thirty-nine patients newly diagnosed with DSM-IV schizophrenia underwent MRI brain scan prior to antipsychotic exposure. The Global Assessment of Functioning (GAF) score was entered into a voxel-based analysis to evaluate its relationship with cerebral grey matter volume from the baseline MRI. We entered age, total intracranial volume and intake GAF score as co-variates. Males and females were analysed separately because gender is a potent determinant of outcome. Results: Males had lower GAF scores than females, both at intake and at 1 year. Males comprised only 40% (12 out of 39) of the early remission group. For females only, early remission was strongly and positively correlated with bilateral lentiform and striatal volumes. For males, there was no such relationship. Conclusion: Larger striato-thalamic volume correlated with early remission in females only. These baseline MRI findings were unlikely to be confounded by antipsychotic treatment and chronicity. These brain morphological markers show gender dimorphism and may assist in the prediction of early remission in newly diagnosed schizophrenia.

Study Objectives: The STOP-Bang questionnaire is a concise and easy screening tool for obstructive sleep apnea (OSA). Using modified body mass index (BMI), we assessed the diagnostic performance of the STOP-Bang questionnaire in predicting OSA in ethnically different groups of patients undergoing surgery. Methods: This was a multicenter prospective cohort study involving patients with cardiovascular risk factors who were undergoing major noncardiac surgery. Patients underwent home sleep apnea testing. All patients completed the STOP-Bang questionnaire. The predictive parameters of STOP-Bang scores were calculated against the apnea-hypopnea index. Results: From 4 ethnic groups 1,205 patients (666 Chinese, 161 Indian, 195 Malay, and 183 Caucasian) were included in the study. The mean BMI ranged from 25 ± 4 to 30 ± 6 kg/m 2 and mean age ranged from 64 ± 8 to 71 ± 10 years. For the Chinese and Indian patients, diagnostic parameters are presented using BMI threshold of 27.5 kg/m 2 with the area under curve to predict moderate-to-severe OSA being 0.709 (0.665-0.753) and 0.722 (0.635-0.808), respectively. For the Malay and Caucasian, diagnostic parameters are presented using BMI threshold of 35 kg/m 2 with the area under curve for predicting moderate-to-severe OSA being 0.645 (0.572-0.720) and 0.657 (0.578-0.736), respectively. Balancing the sensitivity and specificity, the optimal STOP-Bang thresholds for the Chinese, Indian, Malay, and Caucasian groups were determined to be 4 or greater. Conclusions: For predicting moderate-to-severe OSA, we recommend BMI threshold of 27.5 kg/m 2 for Chinese and Indian patients and 35 kg/m 2 for Malay and Caucasian patients. The optimal STOP-Bang threshold for the Chinese, Indian, Malay and Caucasian groups is 4 or greater.

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Background The purpose of this study was to evaluate the association between single-nucleotide polymorphisms and chronic postsurgical pain. Methods Using GoldenGate genotyping assays, we genotyped 638 polymorphisms within 54 pain-related genes in 1,152 surgical patients who were enrolled in our Persistent Pain after Surgery Study. Patients were contacted by phone to determine whether they had chronic postsurgical pain at 12 months. Polymorphisms identified were validated in a matched cohort of 103 patients with chronic postsurgical pain and 103 patients who were pain free. The functions of targeted polymorphisms were tested in an experimental plantar incisional nociception model using knock-in mice. Results At 12 months after surgery, 246 (21.4%) patients reported chronic postsurgical pain. Forty-two polymorphisms were found to be associated with chronic postsurgical pain, 19 decreased the risk of pain, and 23 increased the risk of pain. Patients carrying allele A of rs6265 polymorphism in brain-derived neurotrophic factor (BDNF) had a lower risk of chronic postsurgical pain in the discovery and validation cohorts, with an adjusted odds ratio (95% CI) of 0.62 (0.43 to 0.90) and 0.57 (0.39 to 0.85), respectively. Age less than 65 yr, male sex, and prior history of pain syndrome were associated with an increased risk of pain. Genetic polymorphisms had higher population attributable risk (7.36 to 11.7%) compared with clinical risk factors (2.90 to 5.93%). Importantly, rs6265 is a substitution of valine by methionine at amino acid residue 66 (Val66Met) and was associated with less mechanical allodynia in BDNFMet/Met mice compared with BDNFVal/Val group after plantar incision. Conclusions This study demonstrated that genetic variant of BDNF rs6265G>A is associated with decreased risk of chronic postsurgical pain.