Adherence to a restrictive red blood cell transfusion strategy in critically ill patients: An observational study.

BACKGROUND: Randomized controlled trials relatively consistently show that restrictive red blood cell (RBC) transfusion strategies are safe and associated with similar outcomes compared to liberal transfusion strategies in critically ill patients. Based on these data, the general threshold for RBC transfusion was changed to 70 g/L at a 9-bed tertiary level intensive care unit in September 2020. Implementation measures included lectures, webinars and feedback during clinical practice. The aim of this study was to investigate how implementation of a restrictive transfusion strategy influenced RBC usage, haemoglobin trigger levels and adherence to prescribed trigger levels. METHODS: In this registry-based, observational study, critically ill adult patients without massive bleeding were included and divided into a pre-cohort, with admissions prior to the change of transfusion strategy, and a post-cohort, with admissions following the change of transfusion strategy. These cohorts were compared regarding key RBC transfusion-related variables. RESULTS: In total 5626 admissions were included in the analyses (pre-cohort n = 4373, post-cohort n = 1253). The median volume (interquartile range, IQR) of RBC transfusions per 100 admission days, in the pre-cohort was 6120 (4110-8110) mL versus 3010 (2890-4970) mL in the post-cohort (p < .001). This corresponds to an estimated median saving of 1128 € per 100 admission days after a restrictive RBC transfusion strategy was implemented. In total, 26% of the admissions in the pre-cohort and 19% in the post-cohort (p < .001) received RBC transfusion(s) during days 0-10. Both median (IQR) prescribed trigger levels (determined by intensivist) and actual haemoglobin trigger levels (i.e., levels prior to actual administration of transfusion) were higher in the pre- versus post-cohort (90 [80-100] vs. 80 [72-90] g/L, p < .001 and 89 [82-96] g/L vs. 83 [79-94], p < .001, respectively). Percentage of days without compliance with the prescribed transfusion trigger was higher in the pre-cohort than in the post-cohort (23% vs. 14%, p < .001). Sensitivity analyses, excluding patients with traumatic brain injury, ischemic heart disease and COVID-19 demonstrated similar results. CONCLUSIONS: Implementation of a restrictive transfusion trigger in a critical care setting resulted in lasting decreased RBC transfusion use and costs, decreased prescribed and actual haemoglobin trigger levels and improved adherence to prescribed haemoglobin trigger levels.

Audio podcast and procedural video use in anaesthesiology and intensive care: A nationwide survey of Swedish anaesthetists.

BACKGROUND: Digital modalities which enable asynchronous learning, such as audio podcasts and videos demonstrating procedures, may benefit acquisition and retention of knowledge and clinical skills. The main objective of this nationwide cross-sectional survey study was to evaluate key aspects and factors related to usage of audio podcasts and procedural videos in anaesthesiology and intensive care. METHODS: A 20-item multiple-choice-question online survey was created through a consensus process including pilot testing among residents and consultants. Data were collected over a 3-month period, September-November 2023. RESULTS: The survey was completed by 466 anaesthetists. More than a third reported using procedural videos ≥1 time per week, whereas fewer than one in four participants used audio podcasts at least once per week. Multivariable logistic regression analysis showed that working at a university hospital, male sex, and younger age were independently associated with podcast use ≥1 time per week, with the highest odds ratio (OR) for younger age (<40 years vs. ≥40 years old; OR 5.86 (95% confidence interval 3.55-9.67), p < .001). Younger age was also significantly associated with higher frequency of video use (OR 1.71 (1.13-2.58), p = .011), while working predominantly in intensive care was associated with a lower frequency of video use. Podcasts were often used during commuting (42.3%), household work (30.7%), and exercise (24.9%), indicating a role in multi-tasking. Approximately half of respondents expressed that audio podcast-based learning has a moderate to very large positive impact on acquisition of theoretical knowledge, as well as practical skills. A vast majority, 85.2%, reported that procedural videos have a moderate to very large impact on development of clinical skills. CONCLUSION: Audio podcasts and procedural videos are appreciated tools with potential to supplement more traditional didactic techniques in anaesthesiology and intensive care. Procedural video use is common, with perceived large effects on development of clinical skills. Further data are needed to fully understand learning outcomes, quality of peer-review processes, and potential sex-differences.

Influence of airway trolley organization on efficiency and team performance: A randomized, crossover simulation study.

BACKGROUND: Failed management of unanticipated difficult airway situations contributes to significant anesthesia-related morbidity and mortality. Optimization of design and layout of difficult airway trolleys (DATs) may influence outcomes during airway emergencies. The main objective of the current study was to evaluate whether a difficult airway algorithm-based DAT with integrated cognitive aids improves efficiency and team performance in difficult airway scenarios. METHODS: In a crossover design, 16 teams (anesthetist, nurse anesthetist, assistant nurse) completed two high-fidelity simulated unanticipated difficult airway scenarios. Teams used both an algorithm-based DAT and a comparison, standard DAT, in the scenarios and were randomized to order of trolley type. Outcome measures included objective efficiency parameters, team performance assessment and subjective user-ratings. Linear mixed models ANOVA, including DAT type and order of condition as main factors, was utilized for the primary analyses of the team results. RESULTS: Usage of the algorithm-based DAT was associated with fewer departures from the difficult airway algorithm (p = .010), and reduced number of unnecessary drawer openings (p = .002), but no significant differences in time to retrieval of airway devices or time to first effective ventilation, compared to the standard DAT. There were no significant differences in team performance, although participants expressed strong preference for the algorithm-based DAT (all user-rated measures p < .0001). Higher percentage of female members of the team improved adherence to the difficult airway algorithm (p = .043). CONCLUSIONS: Algorithm-based DATs with integrated cognitive aids may improve efficiency in difficult airway situations, compared to traditional DATs. These findings have implications for improvement of anesthetic practice.

ABO and RhD blood group are not associated with mortality and morbidity in critically ill patients; a multicentre observational study of 29 512 patients.

BACKGROUND: The ABO and RhD blood group represent antigens on the surface of erythrocytes. The ABO blood group antigens are also present on multiple other cells. Interestingly, previous studies have demonstrated associations between the blood group and many types of disease. The present study aimed to identifying associations between the ABO blood group, the RhD blood group, and morbidity and mortality in a mixed cohort and in six pre-defined subgroups of critically ill patients. METHODS: Adult patients admitted to any of the five intensive care units (ICUs) in the Scania Region, Sweden, between February 2007 and April 2021 were eligible for inclusion. The outcomes were mortality analysed at 28- and 90-days as well as at the end of observation and morbidity measured using days alive and free of (DAF) invasive ventilation (DAF ventilation) and DAF circulatory support, including vasopressors or inotropes (DAF circulation), maximum Sequential Organ Failure Assessment score (SOFAmax) the first 28 days after admission and length of stay. All outcomes were analysed in separate multivariable regression models adjusted for age and sex. In addition, in a sensitivity analysis, five subgroups of patients with the main diagnoses sepsis, septic shock, acute respiratory distress syndrome, cardiac arrest and trauma were analysed using the same separate multivariable regression models. RESULTS: In total, 29,512 unique patients were included in the analyses. There were no significant differences for any of the outcomes between non-O blood groups and blood group O, or between RhD blood groups. In the sensitivity analysis of subgroups, there were no differences in mortality between non-O blood groups and blood group O or between the RhD blood groups. AB was the most common blood group in the COVID-19 cohort. CONCLUSIONS: The ABO and RhD blood group do not influence mortality or morbidity in a general critically ill patient population.

Decreased pain sensitivity and alterations of cerebrospinal fluid and plasma inflammatory mediators after total hip arthroplasty in patients with disabling osteoarthritis.

BACKGROUND: Proinflammatory mechanisms are implicated in pain states. Recent research indicates that patients with osteoarthritis (OA) with signs of central sensitization exhibit elevated cerebrospinal fluid (CSF) levels of interferon gamma-induced protein 10 (IP-10), Fms-related tyrosine kinase 1 (Flt-1), and monocyte chemoattractant protein 1 (MCP-1). METHODS: The current prospective cohort study, including 15 patients with OA, primarily aimed to evaluate associations among alterations in CSF IP-10, Flt-1, MCP-1, and pain sensitization following total hip arthroplasty (THA). Participants provided CSF and blood samples for analysis of 10 proinflammatory mediators, and underwent detailed clinical examination and quantitative sensory testing, immediately preoperative and 18 months after surgery. RESULTS: Neurophysiological measures of pain showed markedly reduced pain sensitivity long-term postoperative. Increases in remote site pressure pain detection thresholds (PPDTs) and decreased temporal summation indicated partial resolution of previous central sensitization. Compared to preoperative, CSF concentrations of IP-10 were increased (p = 0.041), whereas neither Flt-1 (p = 0.112) nor MCP-1 levels changed (p = 0.650). Compared to preoperative, plasma concentrations of IP-10 were increased (p = 0.006), whereas interleukin (IL)-8 was decreased (p = 0.023). Subjects who exhibited increases in arm PPDTs above median showed greater increases in CSF IP-10 compared to those with PPDT increases below median (p = 0.028). Analyses of plasma IP-10 and IL-8 indicated higher levels of peripheral inflammation were linked to decreased pressure pain thresholds (unadjusted ß = -0.79, p = 0.006, and ß = -118.1, p = 0.014, respectively). CONCLUSIONS: THA leads to long-term decreases in pain sensitivity, indicative of resolution of sensitization processes. Changes in CSF and plasma levels of IP-10, and plasma IL-8, may be associated with altered pain phenotype.

Acute posterior reversible encephalopathy syndrome (PRES) in setting of interferon-beta use: case presentation with reduction of edema in 72 h after cessation of interferon-beta therapy with sub-clinical inflammation.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) represents a transient change in mental status with associated vasogenic edema of cortical and subcortical brain structures. It is often attributed to multifactorial etiology including hypertension and altered hemodynamics and disruption of vessel integrity. Patients with autoimmune disease and certain immune modulator therapies are at greater risk. CASE PRESENTATION: A 54-year-old female with past medical history of well-controlled multiple sclerosis on interferon-beta since 2013, presented with witnessed tonic colonic seizure. She also was noted to demonstrate left gaze deviation and left-sided hemiparesis. MRI fluid-attenuated inversion recovery sequence showed hyperintensity of the subcortical U fibers, concentrated in the occipital, parietal lobes and frontal lobes. Systolic blood pressure was 160 mmHg on arrival. The patient was started on seizure prophylxis and Interferon beta was discontinued. The patient's mentation, seizures and hemiapresis significantly improved in next 72 h with tight blood pressure control, and had notble improvement on MRI imaging and inflammatory markers. Lumbar puncture CSF results were devoid of infectious and autoimmune pathology. CONCLUSIONS: A middle-aged female with multiple sclerosis who was on chronic IFN-beta presented to the emergency room with a witnessed tonic-clonic seizure, with MRI T2 FLAIR imaging consistent with PRES. She had notable clinical improvement with decreased edema on imaging and improved inflammatory markers 72 h after cessation of IFN-beta therapy.

Availability and organization of difficult airway equipment in Swedish hospitals: A national survey of anaesthesiologists.

BACKGROUND: Airway complications account for almost one third of anaesthesia-related brain damage and death. Immediate access to equipment enabling rescue airway strategies is crucial for successful management of unanticipated difficult airway situations. METHODS: We conducted a nationwide survey of Swedish anaesthesiologists to analyse availability and organization of difficult airway trolleys (DATs), and multiple factors pertaining to difficult airway management, to highlight areas of potential improvement. RESULTS: Six hundred and thirty-nine anaesthesiologists completed the 14-item survey. Whereas DATs were almost ubiquitous (95%) in main operating departments of hospitals, prevalence was low in remote anaesthetizing locations (20.3%) and electroconvulsive therapy units (26.6%). Approximately 60% of emergency departments had a DAT. Immediate (within 60 seconds) access to videolaryngoscopes in all units where general anaesthesia is conducted was reported by 56.8%. Almost half of anaesthesiologists reported that all DATs at their workplace were standardized. Forty-six per cent reported that the DATs were organized according to a difficult airway algorithm; almost 90% believe that such an organization can impact the outcome of a difficult airway situation positively. Only 36.2% of DATs contained second-generation supraglottic airway devices exclusively. Most Swedish anaesthesiologists use the Swedish Society of Anaesthesiology and Intensive care Medicine difficult airway algorithm, but almost one fifth prefer the Difficult Airway Society algorithm. Less than half of respondents underwent formal difficult airway training annually. CONCLUSION: Our results motivate efforts to (a) increase availability of DATs in remote anaesthetizing locations, (b) increasingly standardize DATs and organize DATs according to airway algorithms, and (c) increase the frequency of difficult airway training.

Perioperative Pharmacological Sleep-Promotion and Pain Control: A Systematic Review.

BACKGROUND: Sleep macrostructure is commonly disturbed after surgery. Postoperative pain control remains challenging. Given the bidirectional interaction between sleep and pain, understanding the role of modulation of sleep during the perioperative period on postoperative pain is needed. METHODS: This was a systematic review. Controlled trials examining the effects of perioperative sleep-promoting pharmacological agents on postoperative pain and analgesic consumption were identified through a systematic search strategy utilizing multiple electronic databases. RESULTS: Fourteen studies (9 melatonin, 5 zolpidem) involving 921 patients (melatonin n = 586, zolpidem n = 335) were included. Compared to placebo, melatonin reduced postoperative pain scores by ≥30% and significantly decreased opioid consumption in 3 studies (postoperative day [POD] 1-2), whereas 4 studies reported no significant effect of melatonin on postoperative pain. Compared to placebo, zolpidem reduced postoperative pain scores during POD1-7/POD1-14 in 2 studies, but only 1 trial suggested clinically meaningful improvement (ie, relative reduction of pain score ≥ 30%). Whereas 3 zolpidem trials showed no significant differences regarding postoperative pain ratings, zolpidem treatment was associated with decreased analgesic consumption in 4 out of 5 trials. Several limitations of the included studies were identified; only 1 study out of 14 was deemed to be at low risk of bias, and heterogeneity of the study design and outcome assessment precluded meta-analysis. CONCLUSION: Perioperative addition of a sleep-promoting pharmacological agent may improve pain control, but underlying evidence is weak and results are inconsistent. Only 5 of the 14 studies objectively evaluated changes in sleep (polysomnography, 2 zolpidem studies; actigraphy, 3 melatonin studies), which complicates conclusions regarding links between perioperative sleep and pain.

Increased Central Nervous System Interleukin-8 in a Majority Postlaminectomy Syndrome Chronic Pain Population.

Background and Objectives: Multiple processes have been identified as potential contributors to chronic pain, with increasing evidence illustrating an association with aberrant levels of neuroimmune mediators. The primary objectives of the present study were to examine central nervous system cytokines, chemokines, and growth factors present in a chronic pain population and to explore patterns of the same mediator molecules over time. Secondary objectives explored the relationship of central and peripheral neuroimmune mediators while examining the levels of anxiety, depression, sleep quality, and perception of pain associated with the chronic pain patient experience. Methods: Cerebrospinal fluid (CSF) from a population of majority postlaminectomy syndrome patients (N = 8) was compared with control CSF samples (N = 30) to assess for significant differences in 10 cytokines, chemokines, and growth factors. The patient population was then followed over time, analyzing CSF, plasma, and psychobehavioral measures. Results: The present observational study is the first to demonstrate increased mean CSF levels of interleukin-8 (IL-8; P < 0.001) in a small population of majority postlaminectomy syndrome patients, as compared with a control population. Over time in pain patients, CSF levels of IL-8 increased significantly (P < 0.001). Conclusions: These data indicate that IL-8 should be further investigated and psychobehavioral components considered in the overall chronic pain paradigm. Future studies examining the interactions between these factors and IL-8 may identify novel targets for treatment of persistent pain states.

Reciprocal Relationship Between Sleep Macrostructure and Evening and Morning Cellular Inflammation in Rheumatoid Arthritis.

OBJECTIVE: This study examined the reciprocal associations between sleep macrostructure and levels of cellular inflammation in rheumatoid arthritis (RA) patients and controls. METHODS: RA patients (n = 24) and matched controls (n = 48) underwent all-night polysomnography, along with assessment of spontaneous- and Toll-like receptor-4-stimulated monocytic production of tumor necrosis factor α (TNF) and interleukin (IL)-6 at 11:00 PM and 8:00 AM. RESULTS: As compared with controls, RA patients showed lower levels of sleep efficiency (mean [standard deviation], 88.1 [6.1] versus 83.8 [7.0]), a higher percentage stage 3 sleep (9.3 [6.4] versus 13.1 [6.9]), and higher levels of percentage of monocytes either spontaneously expressing TNF at 11:00 PM (log transformed, 1.07 [0.28] versus 1.22 [0.17]), and higher Toll-like receptor-4-stimulated production of IL6 at 8:00 AM (log transformed, 3.45 [0.80] versus 3.83 [0.39]). Higher levels of stimulated production of TNF at 11:00 PM were associated with higher sleep efficiency (0.74). In turn, sleep efficiency had a countervailing relationship on TNF production at 8:00 AM (-0.64). Higher levels of spontaneous and stimulated production of IL6 at 11:00 PM were associated with more stage 3 (0.39), stage 4 (0.43), and slow-wave sleep (0.49), with evidence that stage 4 had a countervailing relationship on IL6 production at 8:00 AM (-0.60). CONCLUSIONS: RA patients show evidence of sleep fragmentation, greater sleep depth, and higher levels of cellular inflammation. Sleep maintenance and sleep depth show countervailing relationships with evening and morning levels of monocytic production of TNF and IL-6, respectively, which support the hypothesis of a feedback loop between sleep maintenance, slow-wave sleep, and cellular inflammation that is cytokine specific.

Neurophysiological and Clinical Effects of Laparoscopic Retroperitoneal Triple Neurectomy in Patients with Refractory Postherniorrhaphy Neuropathic Inguinodynia.

BACKGROUND: Chronic postherniorrhaphy inguinal pain (CPIP) is a complex, major health problem. In the absence of recurrence or meshoma, laparoscopic retroperitoneal triple neurectomy (LRTN) has emerged as an effective surgical treatment of CPIP. METHODS: This prospective pilot study evaluated the neurophysiological and clinical effects of LRTN. Ten consecutive adult CPIP patients with unilateral predominantly neuropathic inguinodynia underwent three comprehensive quantitative sensory testing (QST) assessments (preoperative, immediate postoperative, and late postoperative). Pain severity, health-related function, and sleep quality were assessed over the course of a 6-month follow-up period. RESULTS: QST revealed marked increases in mechanical, pressure, thermal, and pain thresholds in the areas with maximum pain prior to LRTN surgery for the immediate (P < 0.01; mean 160.9 minutes, range 103 to 255 minutes after extubation) and late postoperative (P < 0.05; mean 27.9 days, range 14 to 78 days after surgery) assessments compared to baseline. Wind-up phenomena were eliminated postoperatively. LRTN provided robust group-level improvements of all clinical measures. No preoperative QST variables were found to be predictive of surgical outcomes. The positive change in heat pain threshold (preoperative compared to late postoperative) showed significant positive correlations with improvements of pain scores and function. CONCLUSIONS: LRTN may produce immediate, profound, and consistent positive effects across multiple mechanical, pressure, and thermal QST variables, and marked improvements of clinical outcomes in selected CPIP patients. These data contribute to the understanding of mechanisms involved in the success of LRTN. Large, high-powered studies are warranted to determine whether preoperative or repeated longitudinal QST may guide patient selection and predict effectiveness of LRTN.

Cerebrospinal Fluid Cytokines and Neurotrophic Factors in Human Chronic Pain Populations: A Comprehensive Review.

Chronic pain is a prevalent and debilitating condition, conveying immense human burden. Suffering is caused not only by painful symptoms, but also through psychopathological and detrimental physical consequences, generating enormous societal costs. The current treatment armamentarium often fails to achieve satisfying pain relief; thus, research directed toward elucidating the complex pathophysiological mechanisms underlying chronic pain syndromes is imperative. Central neuroimmune activation and neuroinflammation have emerged as driving forces in the transition from acute to chronic pain, leading to central sensitization and decreased opioid efficacy, through processes in which glia have been highlighted as key contributors. Under normal conditions, glia exert a protective role, but in different pathological states, a deleterious role is evident--directly and indirectly modulating and enhancing pain transmission properties of neurons, and shaping synaptic plasticity in a dysfunctional manner. Cytokines and neurotrophic factors have been identified as pivotal mediators involved in neuroimmune activation pathways and cascades in various preclinical chronic pain models. Research confirming these findings in humans has so far been scarce, but this comprehensive review provides coherent data supporting the clear association of a mechanistic role of altered central cytokines and neurotrophic factors in a number of chronic pain states despite varying etiologies. Given the importance of these factors in neuropathic and inflammatory chronic pain states, prospective therapeutic strategies, and directions for future research in this emerging field, are outlined.

Quantitative somatosensory assessments in patients with persistent pain following groin hernia repair: A systematic review with a meta-analytical approach.

OBJECTIVES: Quantitative sensory testing (QST) provides an assessment of cutaneous and deep tissue sensitivity and pain perception under normal and pathological settings. Approximately 2-4% of individuals undergoing groin hernia repair (GHR) develop severe persistent postsurgical pain (PPSP). The aims of this systematic review of PPSP-patients were (1) to retrieve and methodologically characterize the available QST literature and (2) to explore the role of QST in understanding mechanisms underlying PPSP following GHR. METHODS: A systematic literature search was conducted from JAN-1992 to SEP-2022 in PubMed, EMBASE, and Google Scholar. For inclusion, studies had to report at least one QST-modality in patients with PPSP. Risk of bias assessment of the studies was conducted utilizing the Newcastle Ottawa Scale and Cochrane's Risk of Bias assessment tool 2.0. The review provided both a qualitative and quantitative analysis of the results. A random effects model was used for meta-analysis. RESULTS: Twenty-five studies were included (5 randomized controlled trials, 20 non-randomized controlled trials). Overall, risk of bias was low. Compared with the contralateral side or controls, there were significant alterations in somatosensory function of the surgical site in PPSP-patients. Following thresholds were significantly increased: mechanical detection thresholds for punctate stimuli (mean difference (95% CI) 3.3 (1.6, 6.9) mN (P = 0.002)), warmth detection thresholds (3.2 (1.6, 4.7) °C (P = 0.0001)), cool detection thresholds (-3.2 (-4.9, -1.6) °C (P = 0.0001)), and heat pain thresholds (1.9 (1.1, 2.7) °C (P = 0.00001)). However, the pressure pain thresholds were significantly decreased (-76 (-123, -30) kPa (P = 0.001)). CONCLUSION: Our review demonstrates a plethora of methods used regarding outcome assessments, data processing, and data interpretation. From a pathophysiological perspective, the most consistent findings were postsurgical cutaneous deafferentation and development of a pain generator in deeper connective tissues. TRIAL REGISTRATION: CRD42022331750.

Sleep disruption and activation of cellular inflammation mediate heightened pain sensitivity: a randomized clinical trial.

ABSTRACT: Sleep loss heightens pain sensitivity, but the pathways underlying this association are not known. Given that experimental sleep disruption induces increases in cellular inflammation as well as selective loss of slow wave, N3 sleep, this study examined whether these mechanisms contribute to pain sensitivity following sleep loss in healthy adults. This assessor-blinded, cross-over sleep condition, single-site, randomized clinical trial enrolled 95 healthy adults (mean [SD] age, 27.8 [6.4]; female, 44 [53.7%]). The 2 sleep conditions were 2 nights of undisturbed sleep (US) and 2 nights of sleep disruption or forced awakening (FA, 8 pseudorandomly distributed awakenings and 200 minutes wake time during the 8-hour sleep opportunity), administered in a cross-over design after 2 weeks of washout and in a random order (FA-US; US-FA). Primary outcome was heat pain threshold (hPTH). Sleep architecture was assessed by polysomnography, and morning levels of cellular inflammation were evaluated by Toll-like receptor-4 stimulated monocyte intracellular proinflammatory cytokine production. As compared with US, FA was associated with decreases in the amount of slow wave or N3 sleep ( P < 0.001), increases in Toll-like receptor-4 stimulated production of interleukin-6 and tumor necrosis factor-α ( P = 0.03), and decreases in hPTH ( P = 0.02). A comprehensive causal mediation analysis found that FA had an indirect effect on hPTH by decreases in N3 sleep and subsequent increases in inflammation (estimate=-0.15; 95% confidence interval, -0.30 to -0.03; P < 0.05) with the proportion mediated 34.9%. Differential loss of slow wave, N3 sleep, and increases in cellular inflammation are important drivers of pain sensitivity after sleep disruption.Clinical Trials Registration: NCT01794689.

Analgesic efficacy of sleep-promoting pharmacotherapy in patients with chronic pain: a systematic review and meta-analysis.

Dysregulation of sleep heightens pain sensitivity and may contribute to pain chronification. Interventions which consolidate and lengthen sleep have the potential to improve pain control. The main objective of this systematic review was to examine the effects of sleep-promoting pharmacotherapy on pain intensity in patients with chronic pain. Multiple electronic databases were searched from inception to January 2022 to identify relevant randomized controlled trials (RCTs). Two independent reviewers screened titles, abstracts, and full-text articles; extracted data; and assessed risk of bias for each included study. The GRADE approach was used to determine the strength of evidence. The search identified 624 articles. After full-text screening, 10 RCTs (n = 574 randomized participants) involving 3 pharmacologic interventions (melatonin, zopiclone, and eszopiclone) and 7 different chronic pain populations were included. Minimum clinically significant pain reduction ≥30% was reported in 4 studies. There is low-quality evidence (downgraded due to inconsistency and imprecision) that 2 to 8 weeks treatment with a sleep-promoting medication alone or in combination with an analgesic (6 trials, n = 397) decreases pain intensity compared with placebo or the same analgesic treatment alone (SMD -0.58 [95% confidence interval -1.00, -0.17], P = 0.006). Analyses of associations between changes in sleep and pain outcomes were only provided in 2 articles, with inconsistent findings. Notably, pain-relieving effects were most consistent in melatonin trials. Only 3 studies implemented polysomnography to obtain objective sleep measures. Low-quality evidence indicates that pharmacologic sleep promotion may decrease pain intensity in chronic pain populations. More research is needed to fully understand the influence of sleep-targeting interventions on pain control.

Health Care Utilization and Associated Economic Burden of Postoperative Surgical Site Infection after Spinal Surgery with Follow-Up of 24 Months.

BACKGROUND: Surgical site infection (SSI) may lead to vertebral osteomyelitis, diskitis, paraspinal musculoskeletal infection, and abscess, and remains a significant concern in postoperative management of spinal surgery. SSI is associated with greater postoperative morbidity and increased health care payments. METHODS: We conducted a retrospective analysis using MarketScan to identify health care utilization payments and risk factors associated with SSI that occurs postoperatively. Known patient- or procedure-related risk factors were searched across those receiving spine surgery who developed postoperative infection. RESULTS: A total of 33,061 patients who developed infection after spinal surgery were identified in Marketscan. Overall payments at 6 months, including index hospitalization for those with infection, were $53,573 and $46,985 for the cohort with no infection. At 24 months, the infection group had overall payments of $83,280 and $66,221 for no infection. Risk factors with largest effect size most likely to contribute to infection versus no infection were depression (4.6%), diabetes (3.7), anemia (3.3%), two or more levels (2.8%), tobacco use (2.2%), trauma (2.1%), neoplasm (1.8%), congestive heart failure (1.3%), instrumentation (1.1%), renal failure (0.9%), intravenous drug use (0.8%), and malnutrition (0.5%). CONCLUSIONS: SSIs were associated with significant health care utilization payments at 24 months of follow-up. The following clinical and procedural risk factors appear to be predictive of postoperative SSI: depression, diabetes, anemia, two or more levels, tobacco use, trauma, neoplasm, congestive heart failure, instrumentation, renal failure, intravenous drug use, and malnutrition. Interpretation of modifiable and nonmodifiable risk factors for infection informs surgeons of expected postoperative course and preoperative risk for this most common and deleterious postoperative complication to spinal surgery.

Prevention of Incident and Recurrent Major Depression in Older Adults With Insomnia: A Randomized Clinical Trial.

Importance: Older adults with insomnia have a high risk of incident and recurrent depression. Depression prevention is urgently needed, and such efforts have been neglected for older adults. Objective: To examine whether treatment of insomnia disorder with cognitive behavioral therapy for insomnia (CBT-I) compared with an active comparator condition, sleep education therapy (SET), prevents major depressive disorder in older adults. Design, Setting, and Participants: This assessor-blinded, parallel-group, single-site randomized clinical trial assessed a community-based sample of 431 people and enrolled 291 adults 60 years or older with insomnia disorder who had no major depression or major health events in past year. Study recruitment was performed from July 1, 2012, to April 30, 2015. The trial protocol was modified to extend follow-up from 24 to 36 months, with follow-up completion in July 2018. Data analysis was performed from March 1, 2019, to March 30, 2020. Interventions: Participants were randomized to 2 months of CBT-I (n = 156) or SET (n = 135). Main Outcomes and Measures: The primary outcome was time to incident major depressive disorder as diagnosed by interview and Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria. Secondary outcome was sustained remission of insomnia disorder before depression event or duration of follow-up. Results: Among 291 randomized participants (mean [SD] age, 70.1 [6.7] years; 168 [57.7%] female; 7 [2.4%] Asian, 32 [11.0%] Black, 3 [1.0%] Pacific Islander, 241 [82.8%] White, 6 [2.1%] multiracial, and 2 [0.7%] unknown), 156 were randomized to CBT-I and 135 to SET. A total of 140 participants (89.7%) completed CBT-I and 130 (96.3%) participants completed SET (χ2 = 4.9, P = .03), with 114 (73.1%) completing 24 months of follow-up in the CBT-I group and 117 (86.7%) in the SET group (χ2 = 8.4, P = .004). After protocol modification, 92 (59.0%) of the CBT-I participants and 86 (63.7%) of the SET participants agreed to extended follow-up (χ2 = 0.7, P = .41), with 81 (51.9%) of the CBT-I participants and 77 (57.0%) of the SET group completing 36 months of follow-up (χ2 = 0.8; P = .39). Incident or recurrent major depression occurred in 19 participants (12.2%) in the CBT-I group and in 35 participants (25.9%) in the SET group, with an overall benefit (hazard ratio, 0.51; 95%, CI 0.29-0.88; P = .02) consistent across subgroups. Remission of insomnia disorder continuously sustained before depression event or during follow-up was more likely in CBT-I participants (41 [26.3%]) compared with the SET participants (26 [19.3%], P = .03). Those in the CBT-I group with sustained remission of insomnia disorder had an 82.6% decreased likelihood of depression (hazard ratio, 0.17; 95%, CI 0.04-0.73; P = .02) compared with those in the SET group without sustained remission of insomnia disorder. Conclusions and Relevance: The findings of this randomized clinical trial indicate that treatment of insomnia with CBT-I has an overall benefit in the prevention of incident and recurrent major depression in older adults with insomnia disorder. Community-level screening for insomnia concerns in older adults and wide delivery of CBT-I-based treatment for insomnia could substantially advance public health efforts to treat insomnia and prevent depression in this vulnerable older adult population. Trial Registration: ClinicalTrials.gov Identifier: NCT01641263.

Central nervous system monoaminergic activity in hip osteoarthritis patients with disabling pain: associations with pain severity and central sensitization.

INTRODUCTION: Monoaminergic activity modulates nociceptive transmission in the central nervous system (CNS). Although pain is the most disabling symptom of osteoarthritis (OA), limited knowledge exists regarding the CNS mechanisms that amplify pain and drive sensitization processes in humans. OBJECTIVES: The main objective of this study was to evaluate associations between cerebrospinal fluid (CSF) monoamine metabolites, pain severity, and central sensitization in patients with OA undergoing total hip arthroplasty (THA). METHODS: Patients with OA (n = 52) and pain-free controls (n = 30) provided CSF samples for measurement of serotonin (5-hydroxyindoleacetic acid [5-HIAA]), noradrenaline (3-methoxy-4-hydroxyphenylglycol [HMPG]), and dopamine (homovanillic acid [HVA]) monoamine metabolites. Patients with OA completed longitudinal evaluation of pain using clinical measures and quantitative sensory testing. RESULTS: Patients with OA had higher HMPG levels when compared with controls (P = 0.036). Within patients with OA undergoing THA, higher 5-HIAA and HVA levels were consistently associated with higher preoperative pain severity. Higher concentrations of 5-HIAA and HVA were also associated with lower conditioned pain modulation levels, whereas higher HMPG levels were linked to more efficient conditioned pain modulation. Patients with higher levels of CSF HVA exhibited increased pressure pain sensitivity (arm pressure pain detection threshold < 250 kPa vs ≥ 250 kPa, P = 0.042). Higher preoperative levels of CSF 5-HIAA predicted poorer pain control 6 months postoperatively (brief pain inventory pain severity; adjusted ß = 0.010, 95% CI 0.001-0.019). CONCLUSIONS: In OA patients with disabling pain, higher CSF levels of serotonin and dopamine metabolites are associated with increased pain severity and central sensitization. Increased noradrenergic activity may be associated with more efficient pain inhibitory capacity.

90-Day Bundled Payment Simulation, Health Care Utilization, and Complications following Craniopharyngioma Resection in Adult Patients.

Context Bundled payment and health care utilization models inform cost optimization and surgical outcomes. Economic analysis of payment plans for craniopharyngioma resection is unknown. Objective This study aimed to identify impact of endocrine and nonendocrine complications (EC and NEC, respectively) on health care utilization and bundled payments following craniopharyngioma resection. Design This study is presented as a retrospective cohort analysis (2000-2016) with 2 years of follow-up. Setting The study included national inpatient hospitalization and outpatient visits. Patients Patients undergoing craniopharyngioma resection were divided into the following four groups: group 1, no complications (NC); group 2, only EC; group 3, NEC; and group 4, both endocrine and nonendocrine complications (ENEC). Interventions This study investigated transphenoidal or subfrontal approach for tumor resection. Main Outcome Hospital readmission, health care utilization up to 24 months following discharge, and 90-day bundled payment performances are primary outcomes of this study. Results Median index hospitalization payments were significantly lower for patients in NC cohort ($28,672) compared with those in EC ($32,847), NEC ($36,259), and ENEC ($32,596; p < 0.0001). Patients in ENEC incurred higher outpatient services and overall median payments at 6 months (NC: 38,268; EC: 49,844; NEC: 68,237; and ENEC: 81,053), 1 year (NC: 46,878; EC: 58,210; NEC: 81,043; and ENEC: 94,768), and 2 years (NC: 58,391; EC: 70,418; NEC: 98,838; and ENEC: 1,11,841; p < 0.0001). The 90-day median bundled payment was significantly different among the cohorts with the highest in ENEC ($60,728) and lowest in the NC ($33,089; p < 0.0001). Conclusion ENEC following surgery incurred almost two times the overall median payments at 90 days, 6 months, 1 year. and 2 years compared with those without complications. Bundled payment model may not be a feasible option in this patient population. Type of complications and readmission rates should be considered to optimize payment model prediction following craniopharyngioma resection.

Sex Differences, Sleep Disturbance and Risk of Persistent Pain Associated With Groin Hernia Surgery: A Nationwide Register-Based Cohort Study.

Persistent pain after groin hernia repair is a major health problem. Sleep disturbance is associated with heightened pain sensitivity. The main objective of this study was to examine the role of sleep disturbance in the development and long-term maintenance of chronic postherniorrhaphy inguinal pain (CPIP), with exploration of sex differences. From 2012 to 2017, a national cohort of patients with prior groin hernia repair (n = 2084;45.8% females) were assessed for the development of CPIP 12 months after surgery. Patients then underwent long-term (median 5.0 years) follow-up to evaluate the contribution of sex and sleep disturbance on the maintenance of CPIP. Associations between pre- and postoperative sleep problems (assessed at long-term follow-up) and CPIP were tested using logistic regression. Females had higher rates of CPIP with negative impact on daily activities 12 months after surgery as compared to males (14.6 vs 9.2%, P < .0005), and were more likely to have moderate-severe CPIP in the long-term (3.1 vs 1.2%, P = .003). Preoperative sleep problems predicted development of CPIP 12 months after surgery (adjusted odds ratio [aOR] 1.76 [95%CI 1.26-2.46], P = .001) and CPIP in the long-term (aOR 2.20 [1.61-3.00] , P < .0001). CPIP was associated with insomnia and depression. Sleep disturbance may increase the risk for CPIP, and contribute to maintenance of postsurgical pain. PERSPECTIVE: Females are at heightened risk for CPIP as compared to males. Increased severity of pain symptoms are linked to poorer sleep and psychiatric morbidity. Given the robust associations between sleep disturbance and CPIP, interventions which consolidate and promote sleep, especially in females, may improve long-term pain control.