Pain medication beliefs in individuals with headache.

OBJECTIVE: To evaluate pain medication beliefs in a community sample of individuals with headache. BACKGROUND: Previous studies of medication adherence for individuals with headache have identified a high rate of prescription nonfulfillment, frequent medication discontinuation, and widely varying levels of medication-related satisfaction. Still, there is a limited understanding of how these individuals view their medications and their relationships with health-care providers. Insight into these perceptions could prove useful in explaining medication adherence behaviors. METHODS: In this secondary analysis of a cross-sectional study, data from N = 215 adults with headache were analyzed. Participants completed the Pain Medication Attitudes Questionnaire (PMAQ), Center for Epidemiologic Studies Depression Scale (CES-D), State-Trait Anxiety Inventory Form Y-2, Weekly Stress Inventory Short Form, and Migraine Disability Scale. These participants also provided a list of their current pain medications. RESULTS: Using the PMAQ, participants could be characterized as having medication beliefs that were "trusting and unconcerned" (n = 83/215 [38.6%]), "skeptical and somewhat worried" (n = 99/215 [46.0%]), or "skeptical and concerned" (n = 33/215 [15.3%]). Individuals with skeptical and concerned beliefs expressed elevated concerns (z > 1.15) about side effects, scrutiny, perceived need, tolerance, withdrawal, and addiction. Individuals who were trusting and unconcerned expressed low levels (z < -0.40) of these beliefs. Increasing levels of mistrust and medication concerns were correlated with higher depression scores on the CES-D, with values ranging from r = 0.23 to r = 0.38. CONCLUSIONS: Subgroups of pain medication beliefs were identified, including two groups of patients with at least some concerns about their medical providers. Beliefs ranged from a lack of concern about using pain medications to worries about scrutiny and harm. It is unclear if poor experiences with pain medications cause these beliefs or if they prevent individuals from effectively utilizing medications. Additionally, more negative beliefs about pain medications were associated with more depressive symptoms.

Hispanic/Latino Ethnicity and Loss of Post-Surgery Independent Living: A Retrospective Cohort Study from a Bronx Hospital Network.

BACKGROUND: Black race is associated with postoperative adverse discharge to a nursing facility, but the effects of Hispanic/Latino ethnicity are unclear. We explored the Hispanic paradox, described as improved health outcomes among Hispanic/Latino patients on postoperative adverse discharge to nursing facility. METHODS: A total of 93,356 adults who underwent surgery and were admitted from home to Montefiore Medical Center in the Bronx, New York, between January 2016 and June 2021 were included. The association between self-identified Hispanic/Latino ethnicity and the primary outcome, postoperative adverse discharge to a nursing home or skilled nursing facility, was investigated. Interaction analysis was used to examine the impact of socioeconomic status, determined by estimated median household income and insurance status, on the primary association. Mixed-effects models were used to evaluate the proportion of variance attributed to the patient's residential area defined by zip code and self-identified ethnicity. RESULTS: Approximately 45.9% (42,832) of patients identified as Hispanic/Latino ethnicity and 9.7% (9074) patients experienced postoperative adverse discharge. Hispanic/Latino ethnicity was associated with lower risk of adverse discharge (relative risk [RRadj] 0.88; 95% confidence interval [CI], 00.82-0.94; P < .001), indicating a Hispanic Paradox. This effect was modified by the patient's socioeconomic status (P-for-interaction <.001). Among patients with a high socioeconomic status, the Hispanic paradox was abolished (RRadj 1.10; 95% CI, 11.00-1.20; P = .035). Furthermore, within patients of low socioeconomic status, Hispanic/Latino ethnicity was associated with a higher likelihood of postoperative discharge home with health services compared to non-Hispanic/Latino patients (RRadj 1.06; 95% CI, 11.01-1.12; P = .017). CONCLUSIONS: Hispanic/Latino ethnicity is a protective factor for postoperative adverse discharge, but this association is modified by socioeconomic status. Future studies should focus on postoperative discharge disposition and socioeconomic barriers in patients with Hispanic/Latino ethnicity.

High-Dose Inhaled Nitric Oxide in Acute Hypoxemic Respiratory Failure Due to COVID-19: A Multicenter Phase II Trial.

Rationale: The effects of high-dose inhaled nitric oxide on hypoxemia in coronavirus disease (COVID-19) acute respiratory failure are unknown. Objectives: The primary outcome was the change in arterial oxygenation (PaO2/FiO2) at 48 hours. The secondary outcomes included: time to reach a PaO2/FiO2.300mmHg for at least 24 hours, the proportion of participants with a PaO2/FiO2.300mmHg at 28 days, and survival at 28 and at 90 days. Methods: Mechanically ventilated adults with COVID-19 pneumonia were enrolled in a phase II, multicenter, single-blind, randomized controlled parallel-arm trial. Participants in the intervention arm received inhaled nitric oxide at 80 ppm for 48 hours, compared with the control group receiving usual care (without placebo). Measurements and Main Results: A total of 193 participants were included in the modified intention-to-treat analysis. The mean change in PaO2/FiO2 ratio at 48 hours was 28.3mmHg in the intervention group and 21.4mmHg in the control group (mean difference, 39.1mmHg; 95% credible interval [CrI], 18.1 to 60.3). The mean time to reach a PaO2/FiO2.300mmHg in the interventional group was 8.7 days, compared with 8.4 days for the control group (mean difference, 0.44; 95% CrI, 23.63 to 4.53). At 28 days, the proportion of participants attaining a PaO2/FiO2.300mmHg was 27.7% in the inhaled nitric oxide group and 17.2% in the control subjects (risk ratio, 2.03; 95% CrI, 1.11 to 3.86). Duration of ventilation and mortality at 28 and 90 days did not differ. No serious adverse events were reported. Conclusions: The use of high-dose inhaled nitric oxide resulted in an improvement of PaO2/FiO2 at 48 hours compared with usual care in adults with acute hypoxemic respiratory failure due to COVID-19.

Preoperative Heart Failure Treatment Prevents Postoperative Cardiac Complications in Patients With Lower Risk: A Retrospective Cohort Study.

OBJECTIVE: The objective of this study was to identify undertreated subgroups of patients with heart failure who would benefit from better perioperative optimization. SUMMARY OF BACKGROUND DATA: Patients with heart failure have increased risks of postoperative cardiac complications after noncardiac surgery. METHODS: In this analysis of hospital registry data of 130,677 patients undergoing noncardiac surgery, the exposure was preoperative history of heart failure. The outcome, cardiac complications, was defined as a composite of myocardial infarction, cardiac arrest, acute heart failure, and mortality within 30 postoperative days. RESULTS: History of heart failure (n = 10,256; 7.9%) was associated with increased risk of cardiac complications [8.1% vs 1.1%; adjusted odds ratio, 2.28 (95% CI, 2.02-2.56); P < 0.001). Patients with heart failure and who carried a lower risk profile had increased risks of postoperative cardiac complications secondary to heart failure [adjusted absolute risk difference, 1.7% (95% CI, 1.4%-2.0%, lower risk); P < 0.001 vs 0.5% (95% CI, -0.6% to 1.6%, higher risk); P = 0.38]. Patients with heart failure and lower risk received a lower level of health care utilization preoperatively, and less frequently received anti-heart failure medications (59% vs 72% and 61% vs 82%; both P < 0.001). These preventive therapies significantly decreased the risk of cardiac complications in patients with heart failure. CONCLUSIONS: In patients with heart failure who have a lower preoperative risk profile, clinicians often make insufficient attempts to optimize their clinical condition preoperatively. Preoperative preventive treatment reduces the risk of postoperative cardiac complications in these lower-risk patients with heart failure.

Learning headache triggers through experience: A laboratory study.

OBJECTIVE: To examine how individuals may learn headache trigger beliefs through sequential symbolic pairings of trigger candidates and headache attacks. BACKGROUND: Learning from experience may be a major source of information about headache triggers. Little is known about learning-based influences on the establishment of trigger beliefs. METHODS: This cross-sectional, observational study included N = 300 adults with headache who participated in a laboratory computer task. First, participants rated the chances (0%-100%) that encountering specific triggers would lead to experiencing a headache. Then, 30 sequential images with the presence or absence of a common headache trigger were presented alongside images representing the presence or absence of a headache attack. The primary outcome measure was the cumulative association strength rating (0 = no relationship to 10 = perfect relationship) between the trigger and headache using all previous trials. RESULTS: A total of N = 296 individuals completed 30 trials for each of three triggers, yielding 26,640 total trials for analysis. The median [25th, 75th] association strength ratings for each of the randomly presented headache triggers were 2.2 [0, 3] for the Color Green, 2.7 [0, 5] for Nuts, and 3.9 [0, 8] for Weather Changes. There was a strong association between the "true" cumulative association strength and corresponding ratings. A 1-point increase on the phi scale (i.e., no relationship to perfect relationship) was associated with a 1.20 (95% CI: 0.81 to 1.49, p < 0.0001) point increase in association strength rating. A participant's prior belief about the potency of a trigger affected their perceived rating of the accumulating evidence, accounting for 17% of the total variation. CONCLUSION: In this laboratory task, individuals appeared to learn trigger-headache associations through repeated exposures to accumulating symbolic evidence. Prior beliefs about the triggers appeared to influence ratings of the strength of relationships between triggers and headache attacks.

Information theory and headache triggers.

OBJECTIVES: This secondary analysis evaluated the information content exhibited by various measurement strategies of commonly perceived causes, or "triggers," of headache attacks. BACKGROUND: When evaluating triggers of primary headache attacks, the variation observed in trigger candidates must be measured to compare against the covariation in headache activity. Given the numerous strategies that could be used to measure and record headache trigger variables, it is useful to consider the information contained in these measurements. METHODS: Using previously collected data from cohort and cross-sectional studies, online data sources, and simulations, the Shannon information entropy exhibited by many common triggers was evaluated by analyzing available time-series or theoretical distributions of headache triggers. The degree of information, reported in bits, was compared across trigger variables, measurement strategies, and settings. RESULTS: A wide range of information content was observed across headache triggers. Due to lack of variation, there was little information, near 0.00 bits, in triggers like red wine and air conditioning. Most headache triggers exhibited more information when measured using an ordinal scale of presence/degree (e.g., absent, mild, moderate, severe) versus a present/absent binary coding. For example, the trigger "joy" exhibited 0.03 bits when assessed using binary coding but 1.81 bits when coded using an ordinal scale. More information was observed with the use of count data (0.86 to 1.75 bits), Likert rating scales (1.50 to 2.76 bits), validated questionnaires (3.57 to 6.04 bits), weather variables (0.10 to 8.00 bits), and ambulatory monitoring devices (9.19 to 12.61 bits). CONCLUSIONS: Although commonly used, all binary-coded measurements contain ≤1.00 bit of information. Low levels of information in trigger variables make associations with headache activity more difficult to detect. Assessments that balance information-rich measurements with reasonable participant burden using efficient formats (e.g., Likert scales) are recommended to enhance the evaluation of the association with headache activity.

Mechanisms of change in posttraumatic headache-related disability: A mediation model.

OBJECTIVE: To explore whether the association between change in headache management self-efficacy and posttraumatic headache-related disability is partially mediated by a change in anxiety symptom severity. BACKGROUND: Many cognitive-behavioral therapy treatments for headache emphasize stress management, which includes anxiety management strategies; however, little is currently known about mechanisms of change in posttraumatic headache-related disability. Increasing our understanding of mechanisms could lead to improvements in treatments for these debilitating headaches. METHODS: This study is a secondary analysis of veterans (N = 193) recruited to participate in a randomized clinical trial of cognitive-behavioral therapy, cognitive processing therapy, or treatment as usual for persistent posttraumatic headache. The direct relationship between headache management self-efficacy and headache-related disability, along with partial mediation through change in anxiety symptoms was tested. RESULTS: The mediated latent change direct, mediated, and total pathways were statistically significant. The path analysis supported a significant direct pathway between headache management self-efficacy and headache-related disability (b = -0.45, p < 0.001; 95% confidence interval [CI: -0.58, -0.33]). The total effect of change of headache management self-efficacy scores on change in Headache Impact Test-6 scores was significant with a moderate-to-strong effect (b = -0.57, p = 0.001; 95% CI [-0.73, -0.41]). There was also an indirect effect through anxiety symptom severity change (b = -0.12, p = 0.003; 95% CI [-0.20, -0.04]). CONCLUSIONS: In this study, most of the improvements in headache-related disability were related to increased headache management self-efficacy with mediation occurring through change in anxiety. This indicates that headache management self-efficacy is a likely mechanism of change of posttraumatic headache-related disability with decreases in anxiety explaining part of the improvement in headache-related disability.

Association of sugammadex reversal of neuromuscular block and postoperative length of stay in the ambulatory care facility: a multicentre hospital registry study.

BACKGROUND: Encapsulation of rocuronium or vecuronium with sugammadex can reverse neuromuscular block faster than neostigmine reversal. This pharmacodynamic profile might facilitate patient discharge after ambulatory surgery. METHODS: We included patients who underwent ambulatory surgery with general anaesthesia and neuromuscular block between 2016 and 2021 from hospital registries at two large academic healthcare networks in the USA. The primary outcome was postoperative length of stay in the ambulatory care facility (PLOS-ACF). We examined post hoc whether the type of reversal affects postoperative nausea and vomiting and direct hospital costs. RESULTS: Among the 29 316 patients included, 8945 (30.5%) received sugammadex and 20 371 (69.5%) received neostigmine for reversal. PLOS-ACF and costs were lower in patients who received sugammadex vs neostigmine (adjusted difference in PLOS-ACF: -9.5 min; 95% confidence interval [95% CI], -10.5 to -8.5 min; adjusted difference in direct hospital costs: -US$77; 95% CI, -$88 to -$66; respectively; P<0.001). The association was magnified in patients over age 65 yr, with ASA physical status >2 undergoing short procedures (<2 h) (adjusted difference in PLOS-ACF: -18.2 min; 95% CI, -23.8 to -12.4 min; adjusted difference in direct hospital costs: -$176; 95% CI, -$220 to -$128; P<0.001). Sugammadex use was associated with reduced postoperative nausea and vomiting (17.2% vs 19.6%, P<0.001), which mediated its effects on length of stay. CONCLUSIONS: Reversal with sugammadex compared with neostigmine was associated with a small decrease in postoperative length of stay in the ambulatory care unit. The effect was magnified in older and high-risk patients, and can be explained by reduced postoperative nausea and vomiting. Sugammadex reversal in ambulatory surgery may also help reduce cost of care.

Comparison of the effects of sugammadex versus neostigmine for reversal of neuromuscular block on hospital costs of care.

BACKGROUND: Sugammadex reversal of neuromuscular block facilitates recovery of neuromuscular function after surgery, but the drug is expensive. We evaluated the effects of sugammadex on hospital costs of care. METHODS: We analysed 79 474 adult surgical patients who received neuromuscular blocking agents and reversal from two academic healthcare networks between 2016 and 2021 to calculate differences in direct costs. We matched our data with data from the Healthcare Cost and Utilization Project-National Inpatient Sample (HCUP-NIS) to calculate differences in total costs in US dollars. Perioperative risk profiles were defined based on ASA physical status and admission status (ambulatory surgery vs hospitalisation). RESULTS: Based on our registry data analysis, administration of sugammadex vs neostigmine was associated with lower direct costs (-1.3% lower costs; 95% confidence interval [CI], -0.5 to -2.2%; P=0.002). In the HCUP-NIS matched cohort, sugammadex use was associated with US$232 lower total costs (95% CI, -US$376 to -US$88; P=0.002). Subgroup analysis revealed that sugammadex was associated with US$1042 lower total costs (95% CI, -US$1198 to -US$884; P<0.001) in patients with lower risk. In contrast, sugammadex was associated with US$620 higher total costs (95% CI, US$377 to US$865; P<0.001) in patients with a higher risk (American Society of Anesthesiologists physical status ≥3 and preoperative hospitalisation). CONCLUSIONS: The effects of using sugammadex on costs of care depend on patient risk, defined based on comorbidities and admission status. We observed lower costs of care in patients with lower risk and higher costs of care in hospitalised surgical patients with severe comorbidities.

Preliminary results from a randomized, controlled, cross-over trial of intrathecal oxytocin for neuropathic pain.

OBJECTIVE: Compare intrathecal oxytocin, 100 µg to placebo on ongoing neuropathic pain and mechanical hyperalgesia and allodynia. STUDY DESIGN: Randomized, controlled, double-blind cross-over. SETTING: Clinical research unit. SUBJECTS: Individuals aged 18 to 70 years with neuropathic pain for at least 6 months. METHODS: Individuals received intrathecal injections of oxytocin and saline, separated by at least 7 days, and ongoing pain in neuropathic area (VAS [visual analog scale]) and areas of hypersensitivity to von Frey filament and cotton wisp brushing were measured for 4 hours. Primary outcome was VAS pain in the first 4 hours after injection, analyzed by linear mixed effects model. Secondary outcomes were verbal pain intensity scores at daily intervals for 7 days and areas of hypersensitivity and elicited pain for 4 hours after injections. RESULTS: The study was stopped early after completion of 5 of 40 subjects planned due to slow recruitment and funding limitations. Pain intensity prior to injection was 4.75 ± 0.99 and modeled pain intensity decreased more after oxytocin than placebo to 1.61 ± 0.87 and 2.49 ± 0.87, respectively (P = .003). Daily pain scores were lower in the week following injection of oxytocin than saline (2.53 ± 0.89 vs 3.66 ± 0.89; P = .001). Allodynic area decreased by 11%, but hyperalgesic area increased by 18% after oxytocin compared to placebo. There were no study drug related adverse effects. CONCLUSION: Although limited by the small number of subjects studied, oxytocin reduced pain more than placebo in all subjects. Further study of spinal oxytocin in this population is warranted. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov on 03/27/2014 (NCT02100956). The first subject was studied on 06/25/2014.

Age-Dependent Electroencephalogram Features in Infants Under Spinal Anesthesia Appear to Mirror Physiologic Sleep in the Developing Brain: A Prospective Observational Study.

BACKGROUND: Infants under spinal anesthesia appear to be sedated despite the absence of systemic sedative medications. In this prospective observational study, we investigated the electroencephalogram (EEG) of infants under spinal anesthesia and hypothesized that we would observe EEG features similar to those seen during sleep. METHODS: We computed the EEG power spectra and spectrograms of 34 infants undergoing infraumbilical surgeries under spinal anesthesia (median age 11.5 weeks postmenstrual age, range 38-65 weeks postmenstrual age). Spectrograms were visually scored for episodes of EEG discontinuity or spindle activity. We characterized the relationship between EEG discontinuity or spindles and gestational age, postmenstrual age, or chronological age using logistic regression analyses. RESULTS: The predominant EEG patterns observed in infants under spinal anesthesia were slow oscillations, spindles, and EEG discontinuities. The presence of spindles, observed starting at about 49 weeks postmenstrual age, was best described by postmenstrual age ( P =.002) and was more likely with increasing postmenstrual age. The presence of EEG discontinuities, best described by gestational age ( P = .015), was more likely with decreasing gestational age. These age-related changes in the presence of spindles and EEG discontinuities in infants under spinal anesthesia generally corresponded to developmental changes in the sleep EEG. CONCLUSIONS: This work illustrates 2 separate key age-dependent transitions in EEG dynamics during infant spinal anesthesia that may reflect the maturation of underlying brain circuits: (1) diminishing discontinuities with increasing gestational age and (2) the appearance of spindles with increasing postmenstrual age. The similarity of these age-dependent transitions under spinal anesthesia with transitions in the developing brain during physiological sleep supports a sleep-related mechanism for the apparent sedation observed during infant spinal anesthesia.

Association Between Postoperative Delirium and Long-Term Subjective Cognitive Decline in Older Patients Undergoing Cardiac Surgery: A Secondary Analysis of the Minimizing Intensive Care Unit Neurological Dysfunction with Dexmedetomidine-Induced Sleep Trial.

OBJECTIVES: This study aimed to evaluate whether a measure of subjective cognitive decline (SCD), the Patient-Reported Outcomes Measurement Information System (PROMIS) Applied Cognition-Abilities questionnaire, was associated with postoperative delirium. It was hypothesized that delirium during the surgical hospitalization would be associated with a decrease in subjective cognition up to 6 months after cardiac surgery. DESIGN: This was a secondary analysis of data from the Minimizing Intensive Care Unit Neurological Dysfunction with Dexmedetomidine-induced Sleep randomized, placebo-controlled, parallel-arm superiority trial. SETTING: Data from patients recruited between March 2017 and February 2022 at a tertiary medical center in Boston, Massachusetts were analyzed in February 2023. PARTICIPANTS: Data from 337 patients aged 60 years or older who underwent cardiac surgery with cardiopulmonary bypass were included. INTERVENTIONS: Patients were assessed preoperatively and postoperatively at 30, 90, and 180 days using the subjective PROMIS Applied Cognition-Abilities and telephonic Montreal Cognitive Assessment. MEASUREMENT AND MAIN RESULTS: Postoperative delirium occurred within 3 days in 39 participants (11.6%). After adjusting for baseline function, participants who developed postoperative delirium self-reported worse cognitive function (mean difference [MD] -2.64 [95% CI -5.25, -0.04]; p = 0.047) up to 180 days after surgery, as compared with nondelirious patients. This finding was consistent with those obtained from objective t-MoCA assessments (MD -0.77 [95% CI -1.49, -0.04]; p = 0.04). CONCLUSIONS: In this cohort of older patients undergoing cardiac surgery, in-hospital delirium was associated with SCD up to 180 days after surgery. This finding suggested that measures of SCD may enable population-level insights into the burden of cognitive decline associated with postoperative delirium.

Preoperative Treatment of Severe Diabetes Mellitus and Hypertension Mitigates Healthcare Disparities and Prevents Adverse Postoperative Discharge to a Nursing Home.

OBJECTIVE: To evaluate whether patients of Black race are at higher risk of adverse postoperative discharge to a nursing home, and if a higher prevalence of severe diabetes mellitus and hypertension are contributing. BACKGROUND: It is unclear whether a patient's race predicts adverse discharge to a nursing home after surgery, and if preexisting diseases are contributing. METHODS: A total of 368,360 adults undergoing surgery between 2007 and 2020 across 2 academic healthcare networks in New England were included. Patients of self-identified Black or White race were compared. The primary outcome was postoperative discharge to a nursing facility. Mediation analysis was used to examine the impact of preexisting severe diabetes mellitus and hypertension on the primary association. RESULTS: In all, 10.3% (38,010/368,360) of patients were Black and 26,434 (7.2%) patients were discharged to a nursing home. Black patients were at increased risk of postoperative discharge to a nursing facility (adjusted absolute risk difference: 1.9%; 95% confidence interval: 1.6%-2.2%; P <0.001). A higher prevalence of preexisting severe diabetes mellitus and hypertension in Black patients mediated 30.2% and 15.6% of this association. Preoperative medication-based treatment adherent to guidelines in patients with severe diabetes mellitus or hypertension mitigated the primary association ( P -for-interaction <0.001). The same pattern of effect mitigation by pharmacotherapy was observed for the endpoint 30-day readmission. CONCLUSIONS: Black race was associated with postoperative discharge to a nursing facility compared to White race. Optimized preoperative assessment and treatment of diabetes mellitus and hypertension improves surgical outcomes and provides an opportunity to the surgeon to help eliminate healthcare disparities.

Mechanical Power during General Anesthesia and Postoperative Respiratory Failure: A Multicenter Retrospective Cohort Study.

BACKGROUND: Mechanical power during ventilation estimates the energy delivered to the respiratory system through integrating inspiratory pressures, tidal volume, and respiratory rate into a single value. It has been linked to lung injury and mortality in the acute respiratory distress syndrome, but little evidence exists regarding whether the concept relates to lung injury in patients with healthy lungs. This study hypothesized that higher mechanical power is associated with greater postoperative respiratory failure requiring reintubation in patients undergoing general anesthesia. METHODS: In this multicenter, retrospective study, 230,767 elective, noncardiac adult surgical out- and inpatients undergoing general anesthesia between 2008 and 2018 at two academic hospital networks in Boston, Massachusetts, were included. The risk-adjusted association between the median intraoperative mechanical power, calculated from median values of tidal volume (Vt), respiratory rate (RR), positive end-expiratory pressure (PEEP), plateau pressure (Pplat), and peak inspiratory pressure (Ppeak), using the following formula: mechanical power (J/min) = 0.098 × RR × Vt × (PEEP + ½[Pplat - PEEP] + [Ppeak - Pplat]), and postoperative respiratory failure requiring reintubation within 7 days, was assessed. RESULTS: The median intraoperative mechanical power was 6.63 (interquartile range, 4.62 to 9.11) J/min. Postoperative respiratory failure occurred in 2,024 (0.9%) patients. The median (interquartile range) intraoperative mechanical power was higher in patients with postoperative respiratory failure than in patients without (7.67 [5.64 to 10.11] vs. 6.62 [4.62 to 9.10] J/min; P < 0.001). In adjusted analyses, a higher mechanical power was associated with greater odds of postoperative respiratory failure (adjusted odds ratio, 1.31 per 5 J/min increase; 95% CI, 1.21 to 1.42; P < 0.001). The association between mechanical power and postoperative respiratory failure was robust to additional adjustment for known drivers of ventilator-induced lung injury, including tidal volume, driving pressure, and respiratory rate, and driven by the dynamic elastic component (adjusted odds ratio, 1.35 per 5 J/min; 95% CI, 1.05 to 1.73; P = 0.02). CONCLUSIONS: Higher mechanical power during ventilation is statistically associated with a greater risk of postoperative respiratory failure requiring reintubation.

Atogepant - an orally-administered CGRP antagonist - attenuates activation of meningeal nociceptors by CSD.

BACKGROUND: This study investigated the mechanism of action of atogepant, a small-molecule CGRP receptor antagonist recently approved for the preventive treatment of episodic migraine, by assessing its effect on activation of mechanosensitive C- and Aδ-meningeal nociceptors following cortical spreading depression. METHODS: Single-unit recordings of trigeminal ganglion neurons (32 Aδ and 20 C-fibers) innervating the dura was used to document effects of orally administered atogepant (5 mg/kg) or vehicle on cortical spreading depression-induced activation in anesthetized male rats. RESULTS: Bayesian analysis of time effects found that atogepant did not completely prevent the activation of nociceptors at the tested dose, but it significantly reduced response amplitude and probability of response in both the C- and the Aδ-fibers at different time intervals following cortical spreading depression induction. For C-fibers, the reduction in responses was significant in the early phase (first hour), but not delayed phase of activation, whereas in Aδ-fibers, significant reduction in activation was apparent in the delayed phase (second and third hours) but not early phase of activation. CONCLUSIONS: These findings identify differences between the actions of atogepant, a small molecule CGRP antagonist (partially inhibiting both Aδ and C-fibers) and those found previously for fremanezumab, a CGRP-targeted antibody (inhibiting Aδ fibers only) and onabotulinumtoxinA (inhibiting C-fibers only)- suggesting that these agents differ in their mechanisms for the preventive treatment of migraine.

Efficacy of preemptive analgesia treatments for the management of postoperative pain: a network meta-analysis.

BACKGROUND: Preemptive analgesia may improve postoperative pain management, but the optimal regimen is unclear. This study aimed to compare the effects and adverse events of preemptive analgesia on postoperative pain and opioid consumption. METHODS: In this network meta-analysis, 19 preemptive analgesia regimens were compared. Two authors independently searched databases, selected studies, and extracted data. Primary outcomes were the intensity of postoperative pain and opioid consumption. Secondary outcomes included the time to first analgesia rescue and incidence of postoperative nausea or vomiting (PONV). RESULTS: In total, 188 studies were included (13 769 subjects). Ten of 19 regimens reduced postoperative pain intensity compared with placebo, with mean differences 100-point scale ranging from -4.79 (95% confidence interval [CI]: -8.61 to -0.96.) for gabapentin at 48 h to -21.99 (95% CI: -36.97 to -7.02) for lornoxicam at 6 h. Eight regimens reduced opioid consumption compared with placebo, with mean differences ranging from -0.48 mg (95% CI: -0.89 to -0.08) i.v. milligrams of morphine equivalents (IMME) for acetaminophen at 12 h to -2.27 IMME (95% CI: -3.07 to -1.46) for ibuprofen at 24 h. Five regimens delayed rescue analgesia from 1.75 (95% CI: 0.59-2.91) h for gabapentin to 7.35 (95% CI: 3.66-11.04) h for epidural analgesia. Five regimens had a lower incidence of PONV compared with placebo, ranging from an odds ratio of 0.22 (95% CI: 0.11-0.42) for ibuprofen to 0.59 (95% CI: 0.40-0.87) for pregabalin. CONCLUSIONS: Use of preemptive analgesia reduces postoperative pain, opioid consumption, and postoperative nausea or vomiting, and delays rescue analgesia. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42021232593.

Association Between Intraoperative Arterial Hypotension and Postoperative Delirium After Noncardiac Surgery: A Retrospective Multicenter Cohort Study.

BACKGROUND: It is unclear whether intraoperative arterial hypotension is associated with postoperative delirium. We hypothesized that intraoperative hypotension within a range frequently observed in clinical practice is associated with increased odds of delirium after surgery. METHODS: Adult noncardiac surgical patients undergoing general anesthesia at 2 academic medical centers between 2005 and 2017 were included in this retrospective cohort study. The primary exposure was intraoperative hypotension, defined as the cumulative duration of an intraoperative mean arterial pressure (MAP) <55 mm Hg, categorized into and short (<15 minutes; median [interquartile range {IQR}], 2 [1-4] minutes) and prolonged (≥15 minutes; median [IQR], 21 [17-31] minutes) durations of intraoperative hypotension. The primary outcome was a new diagnosis of delirium within 30 days after surgery. In secondary analyses, we assessed the association between a MAP decrease of >30% from baseline and postoperative delirium. Multivariable logistic regression adjusted for patient- and procedure-related factors, including demographics, comorbidities, and markers of procedural severity, was used. RESULTS: Among 316,717 included surgical patients, 2183 (0.7%) were diagnosed with delirium within 30 days after surgery; 41.7% and 2.6% of patients had a MAP <55 mm Hg for a short and a prolonged duration, respectively. A MAP <55 mm Hg was associated with postoperative delirium compared to no hypotension (short duration of MAP <55 mm Hg: adjusted odds ratio [ORadj], 1.22; 95% confidence interval [CI], 1.11-1.33; P < .001 and prolonged duration of MAP <55 mm Hg: ORadj, 1.57; 95% CI, 1.27-1.94; P < .001). Compared to a short duration of a MAP <55 mm Hg, a prolonged duration of a MAP <55 mm Hg was associated with greater odds of postoperative delirium (ORadj, 1.29; 95% CI, 1.05-1.58; P = .016). The association between intraoperative hypotension and postoperative delirium was duration-dependent (ORadj for every 10 cumulative minutes of MAP <55 mm Hg: 1.06; 95% CI, 1.02-1.09; P =.001) and magnified in patients who underwent surgeries of longer duration (P for interaction = .046; MAP <55 mm Hg versus no MAP <55 mm Hg in patients undergoing surgery of >3 hours: ORadj, 1.40; 95% CI, 1.23-1.61; P < .001). A MAP decrease of >30% from baseline was not associated with postoperative delirium compared to no hypotension, also when additionally adjusted for the cumulative duration of a MAP <55 mm Hg (short duration of MAP decrease >30%: ORadj, 1.13; 95% CI, 0.91-1.40; P = .262 and prolonged duration of MAP decrease >30%: ORadj, 1.19; 95% CI, 0.95-1.49; P = .141). CONCLUSIONS: In patients undergoing noncardiac surgery, a MAP <55 mm Hg was associated with a duration-dependent increase in odds of postoperative delirium. This association was magnified in patients who underwent surgery of long duration.

Continuous updating of individual headache forecasting models using Bayesian methods.

OBJECTIVE: To illustrate the benefits of deploying individual headache forecasting models using continuous updating with Bayesian methods. BACKGROUND: The ability to reliably forecast headache attacks within an individual over time would enhance the study of attacks and allow preemptive treatment. However, deploying a suitable forecasting model in a clinical setting will likely involve several unique challenges related to heterogeneity in the predictor weights, limited or sparse data, and the need for a quick "warm-up." The use of Bayesian methods offers solutions to each of these specific challenges. METHODS: This was a post hoc analysis of a cohort study of individuals with episodic migraine attacks. Individuals completed daily diaries that allowed the estimation of several forecasting models, each using different types of ancillary information incorporated into formal prior probability distributions. An in silico analysis was conducted that mimicked the deployment of these models in a clinical-like setting where the parameters of the models were continuously updated and evaluated each day using root mean square error (RMSE). RESULTS: Individuals (N = 95) were followed for 50 days and contributed 3359 days of nonmissing diary data. During the observation period, there were 1293/3359 (38.5%) days with a headache attack. Self-reported baseline headache frequency was associated with the corresponding predicted probability of future attacks, r = 0.15-0.39. At Day 25, the correlation between baseline information and predicted attack likelihood was r = 0.29 (95% CI: 0.09-0.47). Additionally, the use of prior probability distributions for model parameters improved the model fit, especially early in the deployment of the models (e.g., Day 5 RMSE 0.45 vs. 0.43). Models using informative prior probability distributions outperformed the models estimated without this information during the first 42 days of observation, although performance became more similar as more data were collected. CONCLUSIONS: This analysis demonstrates the value of Bayesian methods in using additional available information to improve forecasting model performance, especially early in the deployment of a forecasting model. To obtain the full value of such models or to apply any model in clinical settings, a model with adequate discrimination and calibration will be needed.

Patterns of Perceived Stress Throughout the Migraine Cycle: A Longitudinal Cohort Study Using Daily Prospective Diary Data.

OBJECTIVES: To describe patterns of perceived stress across stages of the migraine cycle, within and between individuals and migraine episodes as defined for this study. METHODS: Individuals with migraine aged ≥18 years, who were registered to use the digital health platform N1-HeadacheTM , and completed 90 days of daily data entry regarding migraine, headache symptoms, and lifestyle factors were eligible for inclusion. Perceived stress was rated once a day at the participant's chosen time with a single question, "How stressed have you felt today?" with response options graded on a 0-10 scale. Days were categorized into phases of the migraine cycle: Ppre  = pre-migraine headache (the 2 days prior to the first day with migraine headache), P0  = migraine headache days, Ppost  = post-migraine headache (the 2 days following the last migraine day with migraine headache), and Pi  = interictal days (all other days). Episodes, defined as discrete occurrences of migraine with days in all 4 phases, were eligible if there was at least 1 reported daily perceived stress value in each phase. Individuals with ≥5 valid episodes, and ≥75% compliance (tracking 90 days in 120 calendar days or less) were eligible for inclusion in the analysis. RESULTS: Data from 351 participants and 2115 episodes were included in this analysis. Eighty-six percent of the sample (302/351) were female. The mean number of migraine days per month was 6.1 (range 2-13, standard deviation = 2.3) and the mean number of episodes was 6.0 (range 5-10, standard deviation = 1.0) over the 90-day period. Only 8 (8/351, 2.3%) participants had chronic migraine (defined as 15 or more headache days per month with at least 8 days meeting criteria for migraine). Cluster analysis revealed 3 common patterns of perceived stress variation across the migraine cycle. For cluster 1, the "let down" pattern, perceived stress in the interictal phase (Pi ) falls in the pre-headache phase (Ppre ) and then decreases more in the migraine phase (P0 ) relative to Pi . For cluster 2, the "flat" pattern, perceived stress is relatively unchanging throughout the migraine cycle. For cluster 3, the "stress as a trigger/symptom" pattern, perceived stress in Ppre increases relative to Pi , and increases further in P0 relative to Pi . Episodes were distributed across clusters as follows: cluster 1: 354/2115, 16.7%; cluster 2: 1253/2115, 59.2%, and cluster 3: 508/2115, 24.0%. Twelve participants (12/351, 3.4%) had more than 50% of their episodes fall into cluster 1, 216 participants (216/351, 61.5%) had more than 50% of their episodes fall into cluster 2, and 25 participants (25/351, 7.1%) had more than 50% of their episodes fall into cluster 3. There were 40 participants with ≥90% of their episodes in cluster 2, with no participants having ≥90% of their episodes in cluster 1 or 3. CONCLUSIONS: On an aggregate level, perceived stress peaks during the pain phase of the migraine cycle. However, on an individual and episode basis, there are 3 dominant patterns of perceived stress variation across the migraine cycle. Elucidating how patterns of perceived stress vary across the migraine cycle may contribute insights into disease biology, triggers and protective factors, and provide a framework for targeting individualized treatment plans.

Persistent posttraumatic headaches and functioning in veterans: Injury type can matter.

OBJECTIVE: To characterize the relationship between head trauma types (blast injury, blunt injury, combined blast+blunt injury) with subsequent headache presentations and functioning. BACKGROUND: Posttraumatic headaches (PTHs), the most common sequelae of traumatic brain injury (TBI), are painful and disabling. More than 400,000 veterans report having experienced a TBI, and understanding the predictors of PTHs may guide treatment developments. METHODS: This study used a nested-cohort design analyzing baseline data from a randomized clinical trial of cognitive behavioral therapy for PTH (N = 190). Participants had PTH (from blast and/or blunt head trauma) and symptoms of posttraumatic stress disorder (PTSD). The Structured Diagnostic Interview for Headache-Revised and Ohio State University Traumatic Brain Injury Identification Method were used to phenotype headaches and head injury histories, respectively. RESULTS: Individuals with persistent PTHs after a combined blast and blunt head trauma were more likely (OR =3.45; 95% CI [1.41, 8.4]) to experience chronic (vs. episodic) PTHs compared with the blunt trauma only group (23/33, 70% vs. 26/65, 40%, respectively); and they were more likely (OR =2.51; 95% CI [1.07, 5.9]) to experience chronic PTH compared with the blast trauma only group (44/92, 48%). There were no differences between head injury type on headache-related disability, depression symptoms, or severity of PTSD symptoms. CONCLUSION: The combination of blast and blunt injuries was associated with headache chronicity, but not headache disability. Considering the refractory nature of chronic headaches, the potential added and synergistic effects of distinct head injuries warrant further study.