Stimulating prefrontal cortex facilitates training transfer by increasing representational overlap.

A recent hypothesis characterizes difficulties in multitasking as being the price humans pay for our ability to generalize learning across tasks. The mitigation of these costs through training has been associated with reduced overlap of constituent task representations within frontal, parietal, and subcortical regions. Transcranial direct current stimulation, which can modulate functional brain activity, has shown promise in generalizing performance gains when combined with multitasking training. However, the relationship between combined transcranial direct current stimulation and training protocols with task-associated representational overlap in the brain remains unexplored. Here, we paired prefrontal cortex transcranial direct current stimulation with multitasking training in 178 individuals and collected functional magnetic resonance imaging data pre- and post-training. We found that 1 mA transcranial direct current stimulation applied to the prefrontal cortex paired with multitasking training enhanced training transfer to spatial attention, as assessed via a visual search task. Using machine learning to assess the overlap of neural activity related to the training task in task-relevant brain regions, we found that visual search gains were predicted by changes in classification accuracy in frontal, parietal, and cerebellar regions for participants that received left prefrontal cortex stimulation. These findings demonstrate that prefrontal cortex transcranial direct current stimulation may interact with training-related changes to task representations, facilitating the generalization of learning.

Neurochemical Predictors of Generalized Learning Induced by Brain Stimulation and Training.

Methods of cognitive enhancement for humans are most impactful when they generalize across tasks. However, the extent to which such "transfer" is possible via interventions is widely debated. In addition, the contribution of excitatory and inhibitory processes to such transfer is unknown. Here, in a large-scale neuroimaging individual differences study with humans (both sexes), we paired multitasking training and noninvasive brain stimulation (transcranial direct current stimulation, tDCS) over multiple days and assessed performance across a range of paradigms. In addition, we varied tDCS dosage (1.0 and 2.0 mA), electrode montage (left or right prefrontal regions), and training task (multitasking vs a control task) and assessed GABA and glutamate concentrations via ultrahigh field 7T magnetic resonance spectroscopy. Generalized benefits were observed in spatial attention, indexed by visual search performance, when multitasking training was combined with 1.0 mA stimulation targeting either the left or right prefrontal cortex (PFC). This transfer effect persisted for ∼30 d post intervention. Critically, the transferred benefits associated with right prefrontal tDCS were predicted by pretraining concentrations of glutamate in the PFC. Thus, the effects of this combined stimulation and training protocol appear to be linked predominantly to excitatory brain processes.

Optimization of Radiofrequency Needle Placement in Percutaneous Cordotomy Using Electromyography in the Deeply Sedated Patient.

BACKGROUND AND OBJECTIVES: Cordotomy, the selective disconnection of the nociceptive fibers in the spinothalamic tract, is used to provide pain palliation to oncological patients suffering from intractable cancer-related pain. Cordotomies are commonly performed using a cervical (C1-2) percutaneous approach under imaging guidance and require patients' cooperation to functionally localize the spinothalamic tract. This can be challenging in patients suffering from extreme pain. It has recently been demonstrated that intraoperative neurophysiology monitoring by electromyography may aid in safe lesion positioning. The aim of this study was to evaluate the role of compound muscle action potential (CMAP) in deeply sedated patients undergoing percutaneous cervical cordotomy (PCC). METHODS: A retrospective analysis was conducted of all patients who underwent percutaneous cordotomy while deeply sedated between January 2019 and November 2022 in 2 academic centers. The operative report, neuromonitoring logs, and clinical medical records were evaluated. RESULTS: Eleven patients underwent PCC under deep sedation. In all patients, the final motor assessment prior to ablation was done using the electrophysiological criterion alone. The median threshold for evoking CMAP activity at the lesion site was 0.9 V ranging between 0.5 and 1.5 V (average 1 V ± 0.34 V SD). An immediate, substantial decrease in pain was observed in 9 patients. The median pain scores (Numeric Rating Scale) decreased from 10 preoperatively (range 8-10) to a median 0 (range 0-10) immediately after surgery. None of our patients developed motor deficits. CONCLUSION: CMAP-guided PCC may be feasible in deeply sedated patients without added risk to postoperative motor function. This technique should be considered in a group of patients who are not able to undergo awake PCC.

Immunoassay Urine Drug Testing among Patients Receiving Opioids at a Safety-Net Palliative Medicine Clinic.

BACKGROUND: Few studies have examined the use of immunoassay urine drug testing of cancer patients in palliative care clinics. OBJECTIVES: We examined the frequency of immunoassay urine drug test (UDT) abnormalities and the factors associated with aberrancy at a safety-net hospital palliative medicine clinic. METHODS: A retrospective review of the electronic medical records of consecutive eligible patients seen at the outpatient palliative medicine clinic in a resource-limited safety-net hospital system was conducted between 1 September 2015 and 31 December 2020. We collected longitudinal data on patient demographics, UDT findings, and potential predictors of aberrant results. RESULTS: Of the 913 patients in the study, 500 (55%) underwent UDT testing, with 455 (50%) having the testing within the first three visits. Among those tested within the first three visits, 125 (27%) had aberrant UDT results; 44 (35%) of these 125 patients were positive for cocaine. In a multivariable regression model analysis of predictors for aberrant UDT within the first three visits, non-Hispanic White race (odds ratio (OR) = 2.13; 95% confidence interval (CI): 1.03-4.38; p = 0.04), history of illicit drug use (OR = 3.57; CI: 1.78-7.13; p < 0.001), and history of marijuana use (OR = 7.05; CI: 3.85-12.91; p < 0.001) were independent predictors of an aberrant UDT finding. CONCLUSION: Despite limitations of immunoassay UDT, it was able to detect aberrant drug-taking behaviors in a significant number of patients seen at a safety-net hospital palliative care clinic, including cocaine use. These findings support universal UDT monitoring and utility of immunoassay-based UDT in resource-limited settings.

Neural substrates of individual differences in learning generalization via combined brain stimulation and multitasking training.

A pervasive limitation in cognition is reflected by the performance costs we experience when attempting to undertake two tasks simultaneously. While training can overcome these multitasking costs, the more elusive objective of training interventions is to induce persistent gains that transfer across tasks. Combined brain stimulation and cognitive training protocols have been employed to improve a range of psychological processes and facilitate such transfer, with consistent gains demonstrated in multitasking and decision-making. Neural activity in frontal, parietal, and subcortical regions has been implicated in multitasking training gains, but how the brain supports training transfer is poorly understood. To investigate this, we combined transcranial direct current stimulation of the prefrontal cortex and multitasking training, with functional magnetic resonance imaging in 178 participants. We observed transfer to a visual search task, following 1 mA left or right prefrontal cortex transcranial direct current stimulation and multitasking training. These gains persisted for 1-month post-training. Notably, improvements in visual search performance for the right hemisphere stimulation group were associated with activity changes in the right hemisphere dorsolateral prefrontal cortex, intraparietal sulcus, and cerebellum. Thus, functional dynamics in these task-general regions determine how individuals respond to paired stimulation and training, resulting in enhanced performance on an untrained task.

Individual Differences in Decision Strategy Relate to Neurochemical Excitability and Cortical Thickness.

The speed-accuracy trade-off (SAT), whereby faster decisions increase the likelihood of an error, reflects a cognitive strategy humans must engage in during the performance of almost all daily tasks. To date, computational modeling has implicated the latent decision variable of response caution (thresholds), the amount of evidence required for a decision to be made, in the SAT. Previous imaging has associated frontal regions, notably the left prefrontal cortex and the presupplementary motor area (pre-SMA), with the setting of such caution levels. In addition, causal brain stimulation studies, using transcranial direct current stimulation (tDCS), have indicated that while both of these regions are involved in the SAT, their role appears to be dissociable. tDCS efficacy to impact decision-making processes has previously been linked with neurochemical concentrations and cortical thickness of stimulated regions. However, to date, it is unknown whether these neurophysiological measures predict individual differences in the SAT, and brain stimulation effects on the SAT. Using ultra-high field (7T) imaging, here we report that instruction-based adjustments in caution are associated with both neurochemical excitability (the balance between GABA+ and glutamate) and cortical thickness across a range of frontal regions in both sexes. In addition, cortical thickness, but not neurochemical concentrations, was associated with the efficacy of left prefrontal and superior medial frontal cortex (SMFC) stimulation to modulate performance. Overall, our findings elucidate key neurophysiological predictors, frontal neural excitation, of individual differences in latent psychological processes and the efficacy of stimulation to modulate these.SIGNIFICANCE STATEMENT The speed-accuracy trade-off (SAT), faster decisions increase the likelihood of an error, reflects a cognitive strategy humans must engage in during most daily tasks. The SAT is often investigated by explicitly instructing participants to prioritize speed or accuracy when responding to stimuli. Using ultra-high field (7T) magnetic resonance imaging (MRI), we found that individual differences in the extent to which participants adjust their decision strategies with instruction related to neurochemical excitability (ratio of GABA+ to glutamate) and cortical thickness in the frontal cortex. Moreover, brain stimulation to the left prefrontal cortex and the superior medial frontal cortex (SMFC) modulated performance, with the efficacy specifically related to cortical thickness. This work sheds new light on the neurophysiological basis of decision strategies and brain stimulation.

Antiplatelet and Wound Healing Implications of Immunotherapy and Targeted Cancer Therapies in the Perioperative Period.

The traditional paradigm of oncologic treatment centered on cytotoxic chemotherapy has undergone tremendous advancement during the last 15 yr with the advent of immunotherapy and targeted cancer therapies. These agents, including small molecule inhibitors, monoclonal antibodies, and immune-checkpoint inhibitors, are highly specific to individual tumor characteristics and can prevent cell growth and tumorigenesis by inhibiting specific molecular targets or single oncogenes. While generally better tolerated than traditional chemotherapy, these therapies are associated with unique constellations of adverse effects. Of particular importance in the perioperative and periprocedural settings are hematologic abnormalities, particularly antiplatelet effects with increased risk of bleeding, and implications for wound healing. This narrative review discusses targeted cancer therapies and provides recommendations for physicians managing these patients' care as it relates to procedural or surgical interventions.

Spatial and temporal variability of mercury in Upper and Lower Red Lake Walleye.

Mercury is a global pollutant that is released into our environment by natural and anthropogenic processes resulting in extensive studies of mercury cycling in aquatic ecosystems, and the issuance of human-health-based fish-consumption advisories. We examined total mercury concentrations in Walleye Sander vitreus from Upper and Lower Red Lakes, located in north central Minnesota, between 2019 and 2020. Sampled Walleye (n = 265) ranged from 158 to 610 mm in total length from an age range of young-of-the year to 16 years. Mercury concentrations within the Walleye ranged from 0.030 mg/kg to 0.564 mg/kg (x̄ = 0.179 ± 0.105 mg/kg; x̄ = mean ± sd, all fish-mercury concentrations expressed on wet-weight basis). The best supported model for predicting mercury concentrations in Red Lake Walleye included the independent variables: length, age, sex, and lake basin. This model indicated that there was a significant difference in mercury concentrations between Upper and Lower Red Lake (x̄ = 0.215 ± 0.117 and 0.144 ± 0.077 mg/kg, respectively), and also suggests that individuals who rely on fish for subsistence should target Walleye that are ≤ 400 mm from Lower Red Lake. Observed differences in mercury concentrations could be linked to wetland area influences, fish growth rates, and physicochemical parameters between the two basins. Given that our results illustrated a significant difference in fish-mercury concentrations between basins, future pollutant monitoring efforts should treat Upper and Lower Red Lake as separate lakes and not assume that data from one basin can apply to the other.

Primer on Machine Learning in Electrophysiology.

Artificial intelligence has become ubiquitous. Machine learning, a branch of artificial intelligence, leads the current technological revolution through its remarkable ability to learn and perform on data sets of varying types. Machine learning applications are expected to change contemporary medicine as they are brought into mainstream clinical practice. In the field of cardiac arrhythmia and electrophysiology, machine learning applications have enjoyed rapid growth and popularity. To facilitate clinical acceptance of these methodologies, it is important to promote general knowledge of machine learning in the wider community and continue to highlight the areas of successful application. The authors present a primer to provide an overview of common supervised (least squares, support vector machine, neural networks and random forest) and unsupervised (k-means and principal component analysis) machine learning models. The authors also provide explanations as to how and why the specific machine learning models have been used in arrhythmia and electrophysiology studies.

Adherence to Opioid Patient Prescriber Agreements at a Safety Net Hospital.

Patient prescriber agreements, also known as opioid contracts or opioid treatment agreements, have been recommended as a strategy for mitigating non-medical opioid use (NMOU). The purpose of our study was to characterize the proportion of patients with PPAs, the rate of non-adherence, and clinical predictors for PPA completion and non-adherence. This retrospective study covered consecutive cancer patients seen at a palliative care clinic at a safety net hospital between 1 September 2015 and 31 December 2019. We included patients 18 years or older with cancer diagnoses who received opioids. We collected patient characteristics at consultation and information regarding PPA. The primary purpose was to determine the frequency and predictors of patients with a PPA and non-adherence to PPAs. Descriptive statistics and multivariable logistic regression models were used for the analysis. The survey covered 905 patients having a mean age of 55 (range 18-93), of whom 474 (52%) were female, 423 (47%) were Hispanic, 603 (67%) were single, and 814 (90%) had advanced cancer. Of patients surveyed, 484 (54%) had a PPA, and 50 (10%) of these did not adhere to their PPA. In multivariable analysis, PPAs were associated with younger age (odds ratio [OR] 1.44; p = 0.02) and alcohol use (OR 1.72; p = 0.01). Non-adherence was associated with males (OR 3.66; p = 0.007), being single (OR 12.23; p = 0.003), tobacco (OR 3.34; p = 0.03) and alcohol use (OR 0.29; p = 0.02), contact with persons involved in criminal activity (OR 9.87; p < 0.001), use for non-malignant pain (OR 7.45; p = 0.006), and higher pain score (OR 1.2; p = 0.01). In summary, we found that PPA non-adherence occurred in a substantial minority of patients and was more likely in patients with known NMOU risk factors. These findings underscore the potential role of universal PPAs and systematic screening of NMOU risk factors to streamline care.

Socioeconomic factors, perceived stress, and social support effect on neonatal nurse burnout in China: a cross-sectional study.

BACKGROUND: Neonatal nurses' working environments are highly stressful, and burnout is common. This study examines the effect of socioeconomic factors, perceived stress, and social support on neonatal nurse burnout. METHODS: A total of 311 neonatal nurses participated in this study. They were administered a validated Maslach Burnout Inventory. The study employed a 14-item perceived stress scale (PSS-14) and a social support rate scale (SSRS) to examine stress, socioeconomic factors, and lifestyles. RESULTS: Of the neonatal nurses, 40.19% had burnout, 89.60% had mild burnout, and 10.40% had moderate burnout; no neonatal nurse experienced severe burnout. Young nurses and those with low technical skills, poor interpersonal relationships, irregular diet, and insufficient rest were exposed to burnout (all p < 0.05).Most burnout nurses experienced moderate-severe perceived stress, and their PSS-14 scores were higher (all p < 0.05).The scores for objective social support, subjective social support, utilization of social support, total SSRS scores, and the level of social support were all lower in burnout nurses (all p < 0.05). Perceived stress was correlated positively and significantly with emotional exhaustion and personal accomplishment (all p < 0.05). Social support correlated significantly with and reduced personal accomplishments (p < 0.05). Age, poor interpersonal relationships, perceived stress, and social support were all independent factors associated with neonatal nurse burnout (all p < 0.05). CONCLUSION: The prevalence of burnout in neonatal nurses was higher than average. Socioeconomic factors, higher perceived stress, and lower social support contribute to neonatal nurse burnout. Nursing managers should pay attention to socioeconomic factors, perceived stress, and social support among neonatal nurses and employ strategies to reduce neonatal nurse burnout.

Individual variation in the avian gut microbiota: The influence of host state and environmental heterogeneity.

The gut microbiota have important consequences for host biological processes and there is some evidence that they also affect fitness. However, the complex, interactive nature of ecological factors that influence the gut microbiota has scarcely been investigated in natural populations. We sampled the gut microbiota of wild great tits (Parus major) at different life stages allowing us to evaluate how microbiota varied with respect to a diverse range of key ecological factors of two broad types: (1) host state, namely age and sex, and the life history variables, timing of breeding, fecundity and reproductive success; and (2) the environment, including habitat type, the distance of the nest to the woodland edge, and the general nest and woodland site environments. The gut microbiota varied with life history and the environment in many ways that were largely dependent on age. Nestlings were far more sensitive to environmental variation than adults, pointing to a high degree of flexibility at an important time in development. As nestlings developed their microbiota from one to two weeks of life, they retained consistent (i.e., repeatable) among-individual differences. However these apparent individual differences were driven entirely by the effect of sharing the same nest. Our findings point to important early windows during development in which the gut microbiota are most sensitive to a variety of environmental drivers at multiple scales, and suggest reproductive timing, and hence potentially parental quality or food availability, are linked with the microbiota. Identifying and explicating the various ecological sources that shape an individual's gut bacteria is of vital importance for understanding the gut microbiota's role in animal fitness.

Role of lower dose hepatitis B immune globulin prophylaxis in liver transplantation: A single center perspective.

Background and Aim: Prevention of hepatitis B virus (HBV) reinfection is important for long-term outcomes following liver transplantation (LT). Hepatitis B immunoglobulin (HBIG) is used among recipients who have (i) native HBV disease, (ii) hepatitis B core antibody positivity (HBcAb positivity), or (iii) received HBcAb positive organs. Nucleos(t)ide analogue (NA) monotherapy is emerging for treating patients in this setting. There is no generalized consensus on the ideal dosage of HBIG. The aim of this study was to evaluate the efficacy of low-dose HBIG (1560 international unit [IU]) for post-LT HBV prevention. Materials and Methods: HBcAb positive patients who received either HBcAb positive or hepatitis B core antibody negative (HBcAb negative) organs and HBcAb negative patients who received HBcAb positive organs between January 2016 and December 2020 were reviewed. Pre-LT HBV serologies were collected. HBV-prophylaxis strategy included NA with/without HBIG. HBV recurrence was defined as HBV deoxyribonucleic acid (DNA) positivity during the 1-year, post-LT follow-up. No HBV surface antibody titers were followed. Results: A total of 103 patients with a median age of 60 years participated in the study. Hepatitis C virus was the most common etiology. Thirty-seven HBcAb negative recipients and 11 HBcAb positive recipients with undetectable HBV DNA received HBcAb positive organs and underwent prophylaxis with 4 doses of low-dose HBIG and NA. None of the recipients in our cohort had a recurrence of HBV at 1 year. Conclusion: Low-dose HBIG (1560 IU) × 4 days and NA, for HBcAb positive recipients and HBcAb positive donors, appear to be effective in preventing HBV reinfection during the post-LT period. Further trials are needed to confirm this observation.

Donor BMI and Post-living Donor Liver Transplantation Outcomes: A Preliminary Report.

Living liver donor obesity has been considered a relative contraindication to living donation given the association with hepatic steatosis and potential for poor donor and recipient outcomes. We investigated the association between donor body mass index (BMI) and donor and recipient posttransplant outcomes. Methods: We studied 66 living donors and their recipients who underwent living donor liver transplant at our center between 2013 and 2020. BMI was divided into 3 categories (<25, 25-29.9, and ≥30 kg/m2). Magnetic resonance imaging-derived proton density fat fraction was used to quantify steatosis. Donor outcomes included length of stay (LOS), emergency department visits within 90 d, hospital readmissions within 90 d, and complication severity. Recipient outcomes included LOS and in-hospital mortality. The Student t test was used to compare normally distributed variables, and Kruskal-Wallis tests were used for nonparametric data. Results: There was no difference in donor or recipient characteristics based on donor BMI. There was no significant difference in mean magnetic resonance imaging fat percentage among the 3 groups. Additionally, there was no difference in donor LOS (P = 0.058), emergency department visits (P = 0.64), and hospital readmissions (P = 0.66) across BMI category. Donor complications occurred in 30 patients. There was no difference in postdonation complications across BMI category (P = 0.19); however, there was a difference in wound complications, with the highest rate being seen in the highest BMI group (0% versus 16% versus 37%; P = 0.041). Finally, there was no difference in recipient LOS (P = 0.83) and recipient in-hospital mortality (P = 0.29) across BMI category. Conclusions: Selecting donors with BMI ≥30 kg/m2 can result in successful living donor liver transplantation; however, they are at risk for perioperative wound complications. Donor counseling and perioperative strategies to mitigate wound-related issues should be used when considering obese living donors.

High Coronary Artery Calcium Score Is Associated With Increased Major Adverse Cardiac Events After Liver Transplantation.

Liver transplantation (LT) candidates frequently have multiple cardiovascular risk factors, and cardiovascular disease is a major cause of morbidity and mortality after LT. Coronary artery calcium (CAC) scores are a noninvasive assessment of coronary artery disease using computed tomography. This study examines CAC scores and cardiac risk factors and their association with outcomes after LT. Methods: Patients who underwent LT between January 2010 and June 2019 with a pretransplant CAC score were included in this study. Patients were divided by CAC score into 4 groups (CAC score 0, CAC score 1-100, CAC score 101-400, CAC score >400). Major adverse cardiovascular events (MACEs) were defined as myocardial infarction, stroke, revascularization, heart failure, atrial fibrillation, and cardiovascular death. Associations between CAC score and MACE or all-cause mortality within the 5-y post-LT follow-up period were analyzed using Cox regression. Statistical significance was defined as P < 0.05. Results: During the study period, 773 adult patients underwent their first LT, and 227 patients met our study criteria. The median follow-up time was 3.4 (interquartile range 1.9, 5.3) y. After 5 y, death occurred in 47 patients (20.7%) and MACE in 47 patients (20.7%). In multivariable analysis, there was no difference in death between CAC score groups. There was significantly higher risk of MACE in the CAC score >400 group, with a hazard ratio 2.58 (95% confidence interval 1.05, 6.29). Conclusions: CAC score was not associated with all-cause mortality. Patients with CAC score >400 had an increase in MACEs within the 5-y follow-up period compared with patients with a CAC score = 0. Further research with larger cohorts is needed to examine cardiac risk stratification in this vulnerable patient population.

Dorsal Versus Ventral Intrathecal Catheter Tip Location and Effect on Dose Escalation and Opioid Use in Patients With Cancer Pain.

OBJECTIVES: In the practice of intrathecal drug delivery, consensus exists regarding the cephalad to caudad location of the catheter tip relative to dermatomal distribution of pain. However, data are lacking on the importance of dorsal vs ventral tip location relative to the spinal cord. We hypothesize that a dorsally placed catheter tip improves efficacy because of closer proximity to nociceptive pathways. MATERIALS AND METHODS: A retrospective review of 298 patients with cancer with intrathecal drug delivery systems implanted at the Huntsman Cancer Institute from May 2014 to June 2020 was performed. Patients were stratified by catheter tip location zones based on available radiographic studies. Patient-controlled intrathecal medication dose requirements and rate of change were compared with catheter zone and other variables, including the presence of adjuncts such as bupivacaine and ziconotide. RESULTS: A total of 158 patients were suitable for analysis demonstrating a dorsal tip in 63.9% (n = 101) and ventral tip in 36.1% (n = 57), with a median follow-up of 17 days (interquartile range [IQR], 10-24). There was no difference in daily dose change from implant to discharge between the dorsal group 8.2% (IQR, 0.0-41.5) and ventral group 20.8% (IQR, 0.0-66.7; p = 0.12). Daily dose change from discharge to follow-up was 2.6% (IQR, 0.0-7.1) in the dorsal group and 1.8% (IQR, 0.0-5.7) in the ventral group (p = 0.92). Catheter tip location had no impact on systemic opioid use. CONCLUSIONS: We did not find significant associations between dorsal vs ventral catheter tip location and measures of pain relief, including change in intrathecal dose or systemic opioid use.

Management of Cancer-Related Pain With Intrathecal Drug Delivery: A Systematic Review and Meta-Analysis of Clinical Studies.

BACKGROUND: Despite increased attention paid to assessment and management, pain continues to be a prevalent and undertreated symptom in patients with cancer. Intrathecal drug delivery (IDD) is a therapeutic option that allows targeted delivery of analgesics to the intrathecal space. OBJECTIVE: The aim of this review was to examine the efficacy of managing cancer-related pain with IDD. Secondary objectives included the effects of IDD on systemic opioid use and infection rates. EVIDENCE REVIEW: A systematic search of the literature published between 1990 and 2019 was performed to identify studies evaluating the efficacy and/or safety of IDD with external or implanted pumps in patients with cancer-related pain. Data were extracted and meta-analyses performed to determine the mean changes in pain levels at short-, mid-, and long-term intervals; changes in opioid (oral morphine equivalent [OME]) daily dose; and infection rates. Changes were assessed compared with baseline. FINDINGS: Pain levels were decreased from baseline: On a 0 to 10 scale, mean differences were -4.34 (95% CI [-4.93 to -3.75], p < 0.001) at 4 to 5 weeks; -4.34 (95% CI [-5.07 to -3.62], p < 0.001) at 6 to 12 weeks; and -3.32 (95% CI [-4.60 to -2.04], p < 0.001) at >6 months. Weighted mean OME consumption was reduced by 308.24 (SE = 22.72) mg/d. Weighted mean infection rates were ∼3% for external and implanted pumps. CONCLUSIONS: Meta-analyses show a statistically significant and sustained decrease in cancer pain with IDD, compared with baseline. Systemic opioid consumption was reduced on average by >50% after IDD. Infection rates were comparable with other indications.

Comprehensive quality initiative leads to immediate postoperative extubation following liver transplant.

BACKGROUND: Immediate postoperative extubation (IPE) can reduce perioperative complications and length of stay (LOS), however it is performed variably after liver transplant across institutions and has historically excluded high-risk recipients from consideration. In late 2012, we planned and implemented a single academic institution structured quality improvement (QI) initiative to standardize perioperative care of liver transplant recipients without exceptions. We hypothesized that such an approach would lead to a sustained increase in IPE after primary (PAC) and delayed abdominal closure (DAC). METHODS: We retrospectively studied 591 patients from 2013 to 2018 who underwent liver transplant after initiative implementation. We evaluated trends in incidence of IPE versus delayed extubation (DE), and reintubation, LOS, and mortality. RESULTS: Overall, 476/591 (80.5%) recipients underwent PAC (278 IPE, 198 DE) and 115/591 (19.5%) experienced DAC (39 IPE, 76 DE). When comparing data from 2013 to data from 2018, the incidence of IPE increased from 9/67 (13.4%) to 78/90 (86.7%) after PAC and from 1/12 (8.3%) to 16/23 (69.6%) after DAC. For the same years, the incidence of IPE after PAC for recipients with MELD scores ≥30 increased from 0/19 (0%) to 12/17 (70.6%), for recipients who underwent simultaneous liver-kidney transplant increased from 1/8 (12.5%) to 4/5 (80.0%), and for recipients who received massive transfusion (>10 units of packed red blood cells) increased from 0/17 (0%) to 10/13 (76.9%). Reintubation for respiratory considerations <48 h after IPE occurred in 3/278 (1.1%) after PAC and 1/39 (2.6%) after DAC. IPE was associated with decreased intensive care unit (HR of discharge: 1.92; 95% CI: 1.58, 2.33; P < 0.001) and hospital LOS (HR of discharge: 1.45; 95% CI: 1.20, 1.76; P < 0.001) but demonstrated no association with mortality. CONCLUSION: A structured QI initiative led to sustained high rates of IPE and reduced LOS in all liver transplant recipients, including those classified as high risk.

Controversies in intrathecal drug delivery for cancer pain.

Pain and suffering related to cancer are challenging issues that continue to deserve consideration for treatment optimization. Advances in analgesic management and control of the underlying cancer have improved symptom management, yet many patients still suffer from uncontrolled pain. Intrathecal drug delivery has an established role in the management of refractory cancer pain, but there are significant knowledge gaps in our understanding and application of this therapy. This review addresses several areas of controversy, including the importance of intrathecal catheter tip location, the necessity of an intrathecal trial and the role of intrathecal ziconotide and local anesthetics. In each area, the evidence is discussed, with an emphasis on presenting practical clinical guidance and highlighting deficiencies in our knowledge that are worthy of future investigation.