A Matched-Cohort Analysis of Outcomes in Patients with Hereditary Hemochromatosis After Anterior Cervical Discectomy and Fusion.

BACKGROUND: Hereditary hemochromatosis (HH) is a common autosomal recessive disorder. This disease affects gut iron transport, leading to iron overload, which affects immune function, coagulation mechanics, and bone health. Within the spine, HH contributes to decreased bone mineral density and accelerated intervertebral disc degeneration. The purpose of this study was to discover the differences in the rates of common 90-day postoperative complications and 1-year and 2-year surgical outcomes in patients with and without HH after anterior cervical discectomy and fusion (ACDF). METHODS: Using the PearlDiver database, patients with active diagnoses of HH before ACDF were matched to patients without HH using a 1:5 ratio on the basis of age, sex, body mass index, and comorbidities. Postoperative complications were assessed at 90 days, and 1-year and 2-year surgical outcomes were assessed. All outcomes and complications were analyzed using multivariate logistic regression with significance achieved at P < 0.05. RESULTS: Patients with HH had significantly higher rates of 1-year and 2-year reoperation rates compared with patients without HH (29.19% vs. 3.94% and 37.1% vs. 5.93%, respectively; P < 0.001). The rates of 90-day postoperative complications significantly increased in patients with HH including dysphagia, pneumonia, cerebrovascular accident, deep vein thrombosis, acute kidney injury, urinary tract infection, hyponatremia, surgical site infection, iatrogenic deformity, emergency department visit, and hospital readmission. CONCLUSIONS: Patients with HH undergoing ACDF showed increased 90-day postoperative complications and significantly increased rates of 1-year and 2-year reoperation compared with patients without HH. These findings suggest that iron overload may contribute to adverse outcomes in patients with HH undergoing 1-level and 2-level ACDF.

Strategies to Make Telemedicine a Friend, Not a Foe, in the Provision of Accessible and Equitable Cancer Care.

Telemedicine has the potential to improve access to cancer care, particularly for patients with functional limitations, high symptom burdens, or financial or geographic constraints. However, there is also a risk that telemedicine can widen healthcare disparities among patients facing systemic disadvantages like those with technological barriers, poor digital literacy, older age, or non-English language preferences. To optimize telemedicine usage, we must implement practical strategies like video onboarding programs, user-friendly technology platforms, optimizing the clinician's environment, and best practices for using interpreters. Policy changes such as state licensing requirements, controlled substance prescribing requirements, and payment parity are also crucial. This Perspective highlights these practical strategies and policy recommendations to ensure accessible and equitable cancer care augmented by telemedicine.

Variable cardiac responses in rhesus macaque monkeys after discrete mediodorsal thalamus manipulations.

The control of some physiological parameters, such as the heart rate, is known to have a role in cognitive and emotional processes. Cardiac changes are also linked to mental health issues and neurodegeneration. Thus, it is not surprising that many of the brain structures typically associated with cognition and emotion also comprise a circuit-the central automatic network-responsible for the modulation of cardiovascular output. The mediodorsal thalamus (MD) is involved in higher cognitive processes and is also known to be connected to some of the key neural structures that regulate cardiovascular function. However, it is unclear whether the MD has any role in this circuitry. Here, we show that discrete manipulations (microstimulation during anaesthetized functional neuroimaging or localized cytotoxin infusions) to either the magnocellular or the parvocellular MD subdivisions led to observable and variable changes in the heart rate of female and male rhesus macaque monkeys. Considering the central positions that these two MD subdivisions have in frontal cortico-thalamocortical circuits, our findings suggest that MD contributions to autonomic regulation may interact with its identified role in higher cognitive processes, representing an important physiological link between cognition and emotion.

Validation of a Simulation-Based Resuscitation Curriculum for Maternal Cardiac Arrest.

OBJECTIVE: To assess the knowledge, skills, and self-efficacy of health care participants completing a simulation-based blended learning training curriculum on managing maternal medical emergencies and maternal cardiac arrest (Obstetric Life Support). METHODS: A formative assessment of the Obstetric Life Support curriculum was performed with a prehospital cohort comprising emergency medical services professionals and a hospital-based cohort comprising health care professionals who work primarily in hospital or urgent care settings and respond to maternal medical emergencies. The training consisted of self-guided precourse work and an instructor-led simulation course using a customized low-fidelity simulator. Baseline and postcourse assessments included multiple-choice cognitive test, self-efficacy questionnaire, and graded Megacode assessment of the team leader. Megacode scores and pass rates were analyzed descriptively. Pre- and post-self-confidence assessments were compared with an exact binomial test, and cognitive scores were compared with generalized linear mixed models. RESULTS: The training was offered to 88 participants between December 2019 and November 2021. Eighty-five participants consented to participation; 77 participants completed the training over eight sessions. At baseline, fewer than half of participants were able to achieve a passing score on the cognitive assessment as determined by the expert panel. After the course, mean cognitive assessment scores improved by 13 points, from 69.4% at baseline to 82.4% after the course (95% CI 10.9-15.1, P <.001). Megacode scores averaged 90.7±6.4%. The Megacode pass rate was 96.1%. There were significant improvements in participant self-efficacy, and the majority of participants (92.6%) agreed or strongly agreed that the course met its educational objectives. CONCLUSION: After completing a simulation-based blended learning program focused on managing maternal cardiac arrest using a customized low-fidelity simulator, most participants achieved a defensible passing Megacode score and significantly improved their knowledge, skills, and self-efficacy.

Acute administration of alprazolam, alcohol and their combination on cognitive performance and mood: A randomised, double-blind, placebo-controlled study.

BACKGROUND: Recreational co-consumption of benzodiazepines and alcohol is a common practise; yet, the cognitive effects of this combination remain poorly understood. This study aimed to investigate the acute cognitive effects of combining a 1 mg dose of alprazolam with a moderate dose of alcohol (target 0.04% blood alcohol concentration (BAC)) in a non-clinical population. METHODS: In this randomised, double-blind, placebo-controlled, crossover trial, participants completed computerised cognitive assessments and the brief biphasic alcohol effects scale (B-BAES) after consuming 1 mg of alprazolam, both with and without a moderate dose of alcohol (target 0.04% BAC). RESULTS: Among 20 healthy participants (mean age = 28.6, SD ± 4.0 years, 60% female), we found that a peak BAC of 0.03% had no significant impact on cognitive performance. Both the individual use of alprazolam and its combination with alcohol resulted in impaired reaction time, digit vigilance, and verbal, spatial and numeric working memory tasks, although an additive effect when alcohol and alprazolam were consumed together was not evident. The most pronounced cognitive effects occurred at 100 min after dosing, coinciding with increased alprazolam concentrations. Sedative effects were heightened with alcohol, alprazolam and their combination while no stimulative effects were reported. CONCLUSIONS: Our findings highlight the significant implications of a therapeutic dose of alprazolam on impairing cognitive performance. This is particularly relevant considering the frequency of non-medical alprazolam use. Future studies should explore different dosages, administration timings and long-term effects to inform the development of public health policies and guidelines regarding the combined use of alcohol and benzodiazepines.

Driving impairment and altered ocular activity under the effects of alprazolam and alcohol: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Alprazolam, also known by trade-name Xanax, is regularly detected along with alcohol in blood samples of drivers injured or killed in traffic collisions. While their co-consumption is principally legal, policy guidelines concerning fitness-to-drive are lacking and methods to index impairment are underdeveloped. METHODS: In this randomized, double-blind, placebo-controlled, crossover trial, we examined whether legally permissible levels of alcohol [target 0.04% blood alcohol concentration (BAC)], alprazolam (1mg), and their combination impacts driving performance, and whether driving impairment can be indexed by ocular activity. Participants completed a test battery consisting of a 40-minute simulated highway drive with ocular parameters assessed simultaneously, the Karolinska Sleepiness Scale, and a confidence to drive assessment following four separate treatment combinations. The predictive efficacy of ocular parameters to identify alcohol and alprazolam-related driving impairment was also examined. RESULTS: Among 21 healthy, fully licensed drivers (37% female, mean age 28.43, SD ± 3.96), driving performance was significantly impacted by alprazolam, alcohol, and their combination. Linear regression models revealed that the odds of an out-of-lane event occurring increased five-fold under the influence alprazolam alone and when combined with alcohol. An increase in gaze transition entropy (GTE) demonstrated the strongest association with the odds of an out-of-lane event occurring in the same minute, with both microsleeps and fixation rate achieving moderate accuracy across treatments. CONCLUSIONS: Alprazolam and alcohol, alone and in combination, impaired select aspects of vehicle control over time. GTE, microsleeps, and fixation rate show potential as real-time indicators of driving impairment and crash risk associated with alcohol and alprazolam consumption.

Differential Use of Outpatient Palliative Care by Demographic and Clinical Characteristics.

CONTEXT: Little is known about equity in utilization of outpatient palliative care (PC). OBJECTIVES: To explore whether patient-level factors are associated with completing initial and follow-up visits among patients referred to outpatient PC. METHODS: Using electronic health record data, we generated a cohort of all adults referred to outpatient PC at University of California, San Francisco October 2017-October 2021. We assessed whether demographic and clinical characteristics were associated with completion of 1) an initial PC visit and 2) at least one follow-up visit. RESULTS: Of patients referred to outpatient PC (N = 6,871), 60% completed an initial visit; 66% of those who established care returned for follow-up. In multivariable models, patients who were less likely to complete an initial visit were older (OR per decade 0.94; 95% confidence interval [CI] 0.89-0.98), Black (OR 0.71; 95% CI 0.56-0.90), Latinx (OR 0.69; 95% CI 0.57-0.83), unpartnered (OR 0.80; 95% CI 0.71-0.90), and had Medicaid (OR 0.82; 95% CI 0.69-0.97). Among patients who completed an initial visit, those less likely to complete a follow-up visit were older (OR 0.88; 95% CI 0.82-0.94), male (OR 0.83; 95% CI 0.71-0.96), preferred a language other than English (0.71; 95% CI 0.54-0.95), and had a serious illness other than cancer (OR 0.74; 95% CI 0.61-0.90). CONCLUSION: We found that Black and Latinx patients were less likely to complete an initial visit and those with a preferred language other than English were less likely to complete a follow-up visit. To promote equity in PC, these differences and their impact on outcomes must be explored.

An Increase in Same-day Discharge After Total Joint Arthroplasty During the COVID-19 Pandemic Does Not Influence Patient Outcomes: A Retrospective Cohort Analysis.

Background: The coronavirus disease 2019 (COVID-19) pandemic caused major transitions in total joint arthroplasty (TJA), notably with the increased utilization of same-day discharge (SDD) pathways. This study assessed the effect of accelerated discharge pathways following the resumption of elective cases during the COVID-19 pandemic on SDD rates, adverse events, and characteristics associated with successful SDD following total hip and total knee arthroplasty. Methods: This retrospective study split patients into cohorts: TJA prior to COVID-19 (pre-COVID, July 2019-December 2019) and TJA following the resumption of elective surgeries (post-COVID, July 2020-December 2020). Patient characteristics such as age, sex, body mass index, American Society of Anesthesiologists score, and pertinent comorbidities were analyzed, and length of stay, 30-day emergency department (ED) visit rates, readmissions, and reoperations were compared. Results: A total of 1333 patients met inclusion criteria that were divided into pre-COVID (692) and post-COVID (641) cohorts. The pre-COVID group had a median age of 69 years (interquartile range 63-76), and the post-COVID group had a median age of 68 years (interquartile range 61-75) (P = .024). SDD increased from 0.1% to 28.9% (P < .001), and length of stay decreased from 1.3 days to 0.89 days (P < .001). There was no change in 30-day ED visits, readmissions, or reoperations (P = .817, P = .470, and P = .643, respectively). There was no difference in ED visits, readmissions, or reoperations in SDD patients. The odds of SDD were associated with age (P < .001, odds ratio [OR] = 0.94), body mass index (P = .006, OR = 0.95), male sex (P < .001, OR = 1.83), and history of tobacco use (P < .001, OR = 1.87). Conclusions: At our institution, the COVID-19 pandemic accelerated the utilization of SDD pathways without increasing ED visits, readmissions, or reoperations.

A large-scale genetic screen identifies genes essential for motility in Agrobacterium fabrum.

The genetic and molecular basis of flagellar motility has been investigated for several decades, with innovative research strategies propelling advances at a steady pace. Furthermore, as the phenomenon is examined in diverse bacteria, new taxon-specific regulatory and structural features are being elucidated. Motility is also a straightforward bacterial phenotype that can allow undergraduate researchers to explore the palette of molecular genetic tools available to microbiologists. This study, driven primarily by undergraduate researchers, evaluated hundreds of flagellar motility mutants in the Gram-negative plant-associated bacterium Agrobacterium fabrum. The nearly saturating screen implicates a total of 37 genes in flagellar biosynthesis, including genes of previously unknown function.

Improvement of postural stability and gait velocity after cervical decompression surgery in patients with cervical spondylotic myelopathy.

OBJECTIVE: Cervical spondylotic myelopathy (CSM) is a progressive degenerative condition that can lead to significant neurological deficits, including gait instability. Biomechanical alterations of gait and its various components are poorly understood. The goal of the current study was to determine how spatiotemporal gait parameters, as well as postural and dynamic stability, change after surgery in CSM patients. METHODS: A total of 47 subjects were included, with 23 test subjects and 24 controls. Baseline measurements were made for both cohorts. In the CSM cohort, repeat measurements were made at 3 and 6 months postoperatively. To record spatiotemporal and dynamic stability parameters, subjects performed walking trials over force plates on a 15-m runway. To assess postural stability, standing balance trials were conducted on a floor-mounted force plate. Three-dimensional motion analysis cameras and gait modeling software were used to quantify and visually represent results. Statistical analysis was completed using repeated-measures ANOVA and paired t-tests. Significance was set at p < 0.05. RESULTS: CSM patients had significantly increased gait velocity at the 6-month follow-up (mean 0.948 ± 0.248 m/sec/leg length) versus baseline (mean 0.852 ± 0.257 m/sec/leg length) (p = 0.039). The tilted ellipse area was significantly decreased at the 6-month follow-up compared with baseline (mean 979.8 ± 856.7 mm2 vs 598.0 ± 391.1 mm2, p = 0.018). Angular momentum excursion was not significantly different between baseline and the 3- and 6-month follow-ups. CONCLUSIONS: CSM patients displayed significant improvement in gait velocity and postural stability parameters after decompressive surgery. Dynamic stability parameters did not change significantly during the study period.

Cortico-thalamocortical interactions for learning, memory and decision-making.

The thalamus and cortex are interconnected both functionally and anatomically and share a common developmental trajectory. Interactions between the mediodorsal thalamus (MD) and different parts of the prefrontal cortex are essential in cognitive processes, such as learning and adaptive decision-making. Cortico-thalamocortical interactions involving other dorsal thalamic nuclei, including the anterior thalamus and pulvinar, also influence these cognitive processes. Our work, and that of others, indicates a crucial influence of these interdependent cortico-thalamocortical neural networks that contributes actively to the processing of information within the cortex. Each of these thalamic nuclei also receives potent subcortical inputs that are likely to provide additional influences on their regulation of cortical activity. Here, we highlight our current neuroscientific research aimed at establishing when cortico-MD thalamocortical neural network communication is vital within the context of a rapid learning and memory discrimination task. We are collecting evidence of MD-prefrontal cortex neural network communication in awake, behaving male rhesus macaques. Given the prevailing evidence, further studies are needed to identify both broad and specific mechanisms that govern how the MD, anterior thalamus and pulvinar cortico-thalamocortical interactions support learning, memory and decision-making. Current evidence shows that the MD (and the anterior thalamus) are crucial for frontotemporal communication, and the pulvinar is crucial for frontoparietal communication. Such work is crucial to advance our understanding of the neuroanatomical and physiological bases of these brain functions in humans. In turn, this might offer avenues to develop effective treatment strategies to improve the cognitive deficits often observed in many debilitating neurological disorders and diseases and in neurodegeneration.

Standard Venipuncture vs a Capillary Blood Collection Device for the Prospective Determination of Abnormal Liver Chemistry.

BACKGROUND: Abnormal liver function is a common manifestation of human disease and may also occur in approved and investigational medications as drug-induced liver injury (DILI). Capillary blood collection devices may allow for more frequent and convenient measurement outside of the clinic. Validation of such approaches is lacking. METHODS: This prospective, biospecimens collection study evaluated the Tasso+ in patients with abnormal liver tests (NCT05259618). The primary objective was to define the concordance of alanine aminotransferase (ALT) obtained via Tasso+ compared to standard venipuncture. Secondary objectives included measurement of 14 other analytes and patient surveys. At the time of venipuncture, 2 Tasso+ samples were collected: one was centrifuged and shipped, and the other was refrigerated and shipped as whole blood. RESULTS: Thirty-six patients with elevated ALT values were enrolled. In total, 100 venipuncture, 50 Tasso+ centrifuged, and 48 Tasso+ whole blood samples were obtained. Tasso+ centrifuged samples demonstrated concordance correlation coefficients (CCC) of >0.99 for ALT, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and total bilirubin and CCC >0.95 for albumin, chloride, enzymatic creatinine, serum glucose, magnesium, and phosphorus. Tasso+ whole blood showed CCC of >0.99 for AST, bilirubin total, and enzymatic creatinine and CCC >0.95 for ALT, ALP, albumin, magnesium, and phosphorus. Hemolysis was comparable across the 3 sample types, but its impact was reflected in the Tasso+ potassium data. Patient feedback indicated a very favorable patient experience. CONCLUSIONS: The capillary blood collection device, Tasso+, showed substantial to almost perfect concordance to standard venipuncture for measurement of abnormal liver function. Studies are ongoing to validate longitudinal sampling outside of the clinic. Clinicaltrials.gov Registration Number: NCT05259618.

The impact of break duration, time of break onset, and prior shift duration on the amount of sleep between shifts in heavy vehicle drivers.

This study aimed to examine the impact of break duration between consecutive shifts, time of break onset, and prior shift duration on total sleep time (TST) between shifts in heavy vehicle drivers (HVDs), and to assess the interaction between break duration and time of break onset. The sleep (actigraphy and sleep diaries) and work shifts (work diaries) of 27 HVDs were monitored during their usual work schedule for up to 9 weeks. Differences in TST between consecutive shifts and days off were assessed. Linear mixed models (followed by pairwise comparisons) assessed whether break duration, prior shift duration, time of break onset, and the interaction between break duration and break onset were related to TST between shifts. Investigators found TST between consecutive shifts (mean [SD] 6.38 [1.38] h) was significantly less than on days off (mean [SD] 7.63 [1.93] h; p < 0.001). Breaks starting between 12:01 and 8:00 a.m. led to shorter sleep (p < 0.05) compared to breaks starting between 4:01 and 8:00 p.m. Break durations up to 7, 9, and 11 h (Australian and European minimum break durations) resulted in a mean (SD) of 4.76 (1.06), 5.66 (0.77), and 6.41 (1.06) h of sleep, respectively. The impact of shift duration prior to the break and the interaction between break duration and time of break were not significant. HVDs' sleep between workdays is influenced independently by break duration and time of break onset. This naturalistic study provides evidence that current break regulations prevent sufficient sleep duration in this industry. Work regulations should evaluate appropriate break durations and break onset times to allow longer sleep opportunities for HVDs.

Developing Medical Students as Educators: A Course Applying Teaching and Learning Theory to Question Writing.

There is a need for formal students-as-teachers education with authentic application. We report on a course that teaches and models effective educational theory. Students applied theory by writing questions with answer explanations which were incorporated into an online educational platform used by first-year medical students.

A modified Delphi approach to determine current treatment advances for the development of a resuscitation program for maternal cardiac arrest.

OBJECTIVE: Maternal cardiac arrest is a rare and complex process requiring pregnancy-specific responses and techniques. The goals of this study were to (1) identify, evaluate, and determine the most current best practices to treat this patient population and (2) establish a standardized set of guidelines to serve as a foundation for a future educational simulation-based curriculum. STUDY DESIGN: We used a three-step modified Delphi process to achieve consensus. Twenty-two healthcare experts from across North America agreed to participate in the expert panel. In round 1, 12 pregnancy-specific best practice statements were distributed to the expert panel. Panelists anonymously ranked these using a 7-point Likert scale and provided feedback. Round 2 consisted of a face-to-face consensus meeting where statements that had not already achieved consensus were discussed and then subsequently voted upon by the panelists. RESULTS: Through two rounds, we achieved consensus on nine evidence-based pregnancy-specific techniques to optimize response to maternal cardiac arrest. Round one resulted in one of the 12 best practice statements achieving consensus. Round two resulted in six of the remaining 12 gaining consensus. Best practice techniques involved use of point-of care ultrasound, resuscitative cesarean delivery, cardiopulmonary resuscitation techniques, and the use of extracorporeal cardiopulmonary resuscitation. CONCLUSION: The results of this study provide the foundation to develop an optimal, long-term strategy to treat cardiac arrest in pregnancy. We propose these nine priorities for standard practice, curricula, and guidelines to treat maternal cardiac arrest and hope they serve as a foundation for a future educational curriculum.

An Interprofessional Primary Palliative Care Curriculum for Health Care Trainees and Practicing Clinicians.

Background: Equipping all interprofessional clinicians with foundational palliative care competencies is essential to address the complex needs of the growing number of adults living with chronic, progressive, or life-threatening serious illness. There is a paucity of high-quality, open-access primary palliative care curricula and to the best of our knowledge, none designed interprofessionally. Objective: As an interprofessional team, we aimed at designing and evaluating an interactive primary palliative care education curriculum for interprofessional clinicians and trainees. Design: We developed a curriculum that includes nine 55-minute interactive modules facilitated by two interprofessional clinicians in small groups of 8-12 interprofessional learners. Setting/Subjects: Thirty-two practicing interprofessional clinicians from the San Francisco Bay Area enrolled in the pilot. Measurements: Pilot curriculum evaluation included electronic surveys pre- and post-module and at completion of the full curriculum. Results: The final evaluation response rate was 44%. Ninety-three percent of survey respondents rated the curriculum's quality as "very good" or "excellent"; 86% of respondents felt the curriculum was "extremely" or "very useful" to their clinical practice. Comparing pre- and post-module survey data, statistically significant (p < 0.01) improvements in learner confidence were seen for each of the 25 curriculum learning objectives with an average improvement of 2.8 points. Conclusions: The curriculum was well received and was associated with an increase in learner confidence. This novel, flexible, and tuition-free curriculum fills an important educational gap and can be used to equip frontline, interprofessional clinicians with the core palliative care knowledge, skills, and attitudes to take the best possible care of seriously ill patients and families.

Mediodorsal Thalamus Is Critical for Updating during Extradimensional Shifts But Not Reversals in the Attentional Set-Shifting Task.

Cognitive flexibility, attributed to frontal cortex, is vital for navigating the complexities of everyday life. The mediodorsal thalamus (MD), interconnected to frontal cortex, may influence cognitive flexibility. Here, male rats performed an attentional set-shifting task measuring intradimensional (ID) and extradimensional (ED) shifts in sensory discriminations. MD lesion rats needed more trials to learn the rewarded sensory dimension. However, once the choice response strategy was established, learning further two-choice discriminations in the same sensory dimension, and reversals of the reward contingencies in the same dimension, were unimpaired. Critically though, MD lesion rats were impaired during the ED shift, when they must rapidly update the optimal choice response strategy. Behavioral analyses showed MD lesion rats had significantly reduced correct within-trial second choice responses. This evidence shows that transfer of information via the MD is critical when rapid within-trial updates in established choice response strategies are required after a rule change.

Success of Feather Margin Preparation for Full Metal Prosthodontic Crowns in the Canine Teeth in 84 Pet and Working Dogs (2005-2017).

Medical and dental records of Veterinary Dental Specialties and Oral Surgery were searched to identify dogs that received full metal prosthodontic crowns on canine teeth, using a feather or knife edge preparation between 2005 and 2017. A total of 160 teeth in 84 dogs were included in the study. Current follow-up by telephone, electronic mail, or electronic messaging was conducted, in addition to thorough record review for in-person recheck examinations. Treatment was considered successful if the prosthodontic crown was in place and no further or additional injury to the tooth had occurred at the time of reexamination, owner contact, or patient death. Tooth fracture apical to the prosthodontic crown occurred in 2 (1.25%) cases, bond failure between the tooth and the cement or the cement and the crown occurred in a single case (0.625%), and one metal crown required replacement after 3 years due to wear (0.625%), for an overall failure rate of 2.5%. These results suggest that feather preparation of the margin is at least as, if not more, successful as the more commonly accepted and performed chamfer margin, and thus is a successful, practical and durable option for prosthodontic crown treatment in dog canine teeth.