Final 1-Year Results of the TUTOR Randomized Trial Comparing Carpal Tunnel Release with Ultrasound Guidance to Mini-open Technique.

Background: Studies comparing carpal tunnel release with ultrasound guidance (CTR-US) to mini-open CTR (mOCTR) are limited. This randomized trial compared the efficacy and safety of these techniques. Methods: In this multicenter randomized trial, patients were randomized (2:1) to unilateral CTR-US or mOCTR. Outcomes included Boston Carpal Tunnel Questionnaire Symptom Severity Scale (BCTQ-SSS) and Functional Status Scale (BCTQ-FSS), numeric pain scale (0-10), EuroQoL-5 Dimension 5-Level (EQ-5D-5L), scar outcomes, and complications over 1 year. Results: Patients received CTR-US (n = 94) via wrist incision (mean 6 mm) or mOCTR (n = 28) via palmar incision (mean 22 mm). Comparing CTR-US with mOCTR, the mean changes in BCTQ-SSS (-1.8 versus -1.8; P = 0.96), BCTQ-FSS (-1.0 versus -1.0; P = 0.75), numeric pain scale (-3.9 versus -3.8; P = 0.74), and EQ-5D-5L (0.13 versus 0.12; P = 0.79) over 1 year were comparable between groups. Freedom from scar sensitivity or pain favored CTR-US (95% versus 74%; P = 0.005). Complications occurred in 2.1% versus 3.6% of patients (P = 0.55), all within 3 weeks postprocedure. There was one revision surgery in the CTR-US group, and no revisions for persistent or recurrent symptoms in either group. Conclusions: CTR-US and mOCTR demonstrated similar improvement in carpal tunnel syndrome symptoms and quality of life with comparable low complication rates over 1 year of follow-up. CTR-US was performed with a smaller incision and associated with less scar discomfort.

Multicenter randomized trial of carpal tunnel release with ultrasound guidance versus mini-open technique.

BACKGROUND: Comparative studies of carpal tunnel release with ultrasound guidance (CTR-US) vs. mini-open CTR (mOCTR) are limited, prompting development of this randomized trial to compare efficacy and safety of these techniques. RESEARCH DESIGN AND METHODS: Patients were randomized (2:1) to CTR-US or mOCTR, treated by experienced hand surgeons (median previous cases: 12 CTR-US; 1000 mOCTR), and followed for 3 months. RESULTS: Among 149 randomized patients, 122 received CTR-US (n = 94) or mOCTR (n = 28). Mean incision length was 6 ± 2 mm in the wrist (CTR-US) vs. 22 ± 7 mm in the palm (mOCTR) (p < 0.001). Median time to return to daily activities (2 vs. 2 days; p = 0.81) and work (3 vs. 4 days; p = 0.61) were similar. Both groups reported statistically significant and clinically important improvements in Boston Carpal Tunnel Questionnaire Symptom Severity and Functional Status Scales, Numeric Pain Scale, and EuroQoL-5 Dimension 5-Level, with no statistical differences between groups. Freedom from wound sensitivity and pain favored CTR-US (61.1% vs. 17.9%; p < 0.001). Adverse event rates were low in each group (2.1% vs. 3.6%; p = 0.55). CONCLUSIONS: The efficacy and safety of CTR-US were comparable to mOCTR despite less previous surgical experience with CTR-US. The choice of CTR technique should be determined by shared decision-making between patient and physician. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT05405218.

Use of actigraphy and sleep diaries to assess sleep and academic performance in pharmacy students.

INTRODUCTION: Sleep parameters have been shown to correlate with academic performance. Current studies assessing sleep in doctor of pharmacy (PharmD) students rely on self-reported sleep parameters and academic performance. The objectives of this study were to describe and compare sleep parameters in pharmacy students using actigraphy and sleep diaries and to assess the correlation of sleep parameters with academic performance. METHODS: This prospective cohort study with convenience sampling assessed sleep parameters in pharmacy students. Thirty-five students completing the second year of a PharmD program participated in the study. Participants wore actigraph watches and maintained sleep diaries for seven consecutive days during the spring and fall semesters, while classes were in session, except for one week prior to exams and the week of exams. Academic performance was tracked during fall and spring semesters. RESULTS: Actigraphy and sleep diaries showed significant differences in sleep latency (SL), actual sleep time (AST), wake bouts, and sleep efficiency (SE). Actigraphy results indicated that the participants fell asleep faster (SL), slept a shorter duration (AST), had more wake bouts, and lower SE than results reported in the sleep diaries. SE and SL from the sleep diaries positively correlated with the fall semester pharmaceutical sciences course and overall spring semester academic performance. Actigraphy recorded AST correlated with performance in both semesters' clinical sciences courses. CONCLUSIONS: The results of actigraphy differed from the sleep diaries. More studies are needed to assess differences in detection of sleep parameters using sleep diaries and actigraphs.

Manubriosternal joint dislocation due to blunt force trauma.

A 35-year-old woman was involved in a motor vehicle collision and suffered a manubriosternal joint dislocation with posterior subluxation of the manubrium. She underwent open reduction and internal fixation with sternal plate reconstruction. This report highlights the mechanism and management of these rare traumatic chest wall injuries.

Correction: Loss of the BMP Antagonist, SMOC-1, Causes Ophthalmo-Acromelic (Waardenburg Anophthalmia) Syndrome in Humans and Mice.

[This corrects the article DOI: 10.1371/journal.pgen.1002114.].

Effects of chronic marijuana use on driving performance.

OBJECTIVES: The effects of marijuana on driving pose a significant public health concern. More studies on chronic marijuana use in driving are needed. The study objectives were to (1) assess differences in the Standardized Field Sobriety Test (SFST) and driving performance outcomes between chronic medical marijuana users and nonusers and (2) identify a cutoff tetrahydrocannabinol (THC) concentration above which chronic medical marijuana users demonstrate driving impairment. METHODS: This prospective cross-sectional study assessed 31 chronic marijuana users and 41 nonusers. Rapid Detect Saliva Drug Screen 10-panel was administered to all participants. Participants were given a simple visual reaction time test (SVRT) and SFST consisting of the horizontal gaze nystagmus (HGN), the one leg stand (OLS), and the walk and turn (WAT) tests. The STISIM Drive M100 driving simulator assessed driving performance. Driving parameters included standard deviation of speed (SDS), deviation of mean lane position, off-road accidents, collisions, pedestrians hit, and car-following modulus, delay, and coherence. Cannabinoid blood plasma was obtained from marijuana users. RESULTS: Marijuana users and nonusers did not differ in age (40.06 ± 13.92 vs. 41.53 ± 15.49, P = .6782). Marijuana users were more likely to fail the SFST (P = .005) and the WAT (P = .012) and HGN (P = .001) components. Marijuana users had slower SVRT (P = .031), less SDS (P = .039), and lower modulus (P = .003). Participants with THC >2 ng/mL (P = .017) and TCH >5 ng/mL (P = .008) had lower SDS. Participants with THC >2 ng/mL (P = .021) and THC >5 ng/mL (P = .044) had decreased modulus. CONCLUSION: Chronic marijuana users had slower reaction times, deviated less in speed, and had difficulty matching a lead vehicle's speed compared to nonusers. The effects on SDS and modulus were present at cutoffs of 2 and 5 ng/mL.

DISC1 regulates N-methyl-D-aspartate receptor dynamics: abnormalities induced by a Disc1 mutation modelling a translocation linked to major mental illness.

The neuromodulatory gene DISC1 is disrupted by a t(1;11) translocation that is highly penetrant for schizophrenia and affective disorders, but how this translocation affects DISC1 function is incompletely understood. N-methyl-D-aspartate receptors (NMDAR) play a central role in synaptic plasticity and cognition, and are implicated in the pathophysiology of schizophrenia through genetic and functional studies. We show that the NMDAR subunit GluN2B complexes with DISC1-associated trafficking factor TRAK1, while DISC1 interacts with the GluN1 subunit and regulates dendritic NMDAR motility in cultured mouse neurons. Moreover, in the first mutant mouse that models DISC1 disruption by the translocation, the pool of NMDAR transport vesicles and surface/synaptic NMDAR expression are increased. Since NMDAR cell surface/synaptic expression is tightly regulated to ensure correct function, these changes in the mutant mouse are likely to affect NMDAR signalling and synaptic plasticity. Consistent with these observations, RNASeq analysis of the translocation carrier-derived human neurons indicates abnormalities of excitatory synapses and vesicle dynamics. RNASeq analysis of the human neurons also identifies many differentially expressed genes previously highlighted as putative schizophrenia and/or depression risk factors through large-scale genome-wide association and copy number variant studies, indicating that the translocation triggers common disease pathways that are shared with unrelated psychiatric patients. Altogether, our findings suggest that translocation-induced disease mechanisms are likely to be relevant to mental illness in general, and that such disease mechanisms include altered NMDAR dynamics and excitatory synapse function. This could contribute to the cognitive disorders displayed by translocation carriers.

Population Pharmacokinetic/Pharmacodynamic Modeling of Depot Testosterone Cypionate in Healthy Male Subjects.

A randomized, double-blind clinical trial was conducted to investigate long-term abuse effects of testosterone cypionate (TC). Thirty-one healthy men were randomized into a dose group of 100, 250, or 500 mg/wk and received 14 weekly injections of TC. A pharmacokinetic/pharmacodynamic (PK/PD) model was developed to characterize testosterone concentrations and link exposure to change in luteinizing hormone and spermatogenesis following long-term TC administration. A linear one-compartment model best described the concentration-time profile of total testosterone. The population mean estimates for testosterone were 2.6 kL/day for clearance and 14.4 kL for volume of distribution. Weight, albumin, and their changes from baseline were identified as significant covariates for testosterone. The estimated potency of total testosterone (tT) with respect to suppression of luteinizing hormone (LH) synthesis was 9.33 ng/mL. Simulation based on the indirect response model suggests the suppression of endogenous testosterone secretion, LH synthesis, and spermatogenesis was more severe and of greater duration in the 250 mg and the 500 mg dose groups.

Characterizing Predictors and Severity of Vasoplegia Syndrome After Heart Transplantation.

BACKGROUND: Vasoplegia is characterized as a severe vasodilatory shock after cardiac surgery, and can be associated with substantial morbidity. Increased systemic inflammation and endothelial dysfunction, often related to prolonged cardiopulmonary bypass times, anesthesia, or mechanical circulatory support have been shown to be associated with the development of vasoplegia. We sought to identify risk factors and the impact of various degrees of vasoplegia after heart transplantation. METHODS: A retrospective review was conducted of 244 consecutive patients who underwent heart transplantation over a 3-year period. Patients were divided into three groups: no vasoplegia, mild vasoplegia (requiring one vasopressor), and moderate/severe vasoplegia (more than two vasopressors). One-year survival, freedom from rejection, and postoperative complication rates were assessed. Risk factors for vasoplegia subgroups were retrospectively identified. RESULTS: Vasoplegia syndrome was observed in 34.3% of patients after heart transplantation (mild, 74.1%; moderate/severe, 25.9%). Cardiopulmonary bypass time was significantly longer and pretransplant creatinine was significantly higher in the moderate/severe vasoplegia group. There was a strong trend toward greater use of mechanical circulatory support among moderate/severe vasoplegia patients compared with mild and no vasoplegia patients. After heart transplantation, 1-year survival, freedom from rejection, and need for hemodialysis were not significantly different between groups. CONCLUSIONS: Vasoplegia syndrome is common after heart transplantation. Risk factors for increased severity include longer cardiopulmonary bypass times and elevated preoperative creatinine. Although higher rates of mortality or graft rejection were not detected, vasoplegia was associated with prolonged intubation, greater blood product usage, and lengthened hospital stay. Further studies involving larger cohorts are warranted.

Ethanol Forensic Toxicology.

Ethanol abuse can lead to negative consequences that oftentimes result in criminal charges and civil lawsuits. When an individual is suspected of driving under the influence, law enforcement agents can determine the extent of intoxication by measuring the blood alcohol concentration (BAC) and performing a standardized field sobriety test. The BAC is dependent on rates of absorption, distribution, and elimination, which are influenced mostly by the dose of ethanol ingested and rate of consumption. Other factors contributing to BAC are gender, body mass and composition, food effects, type of alcohol, and chronic alcohol exposure. Because of individual variability in ethanol pharmacology and toxicology, careful extrapolation and interpretation of the BAC is needed, to justify an arrest and assignment of criminal liability. This review provides a summary of the pharmacokinetic properties of ethanol and the clinical effects of acute intoxication as they relate to common forensic questions. Concerns regarding the extrapolation of BAC and the implications of impaired memory caused by alcohol-induced blackouts are discussed.

Relationship Between Grit with Academic Performance and Attainment of Postgraduate Training in Pharmacy Students.

Objective. To determine if Grit-S scores correlate with academic success in a doctor of pharmacy (PharmD) program, as well as the pursuit and attainment of pharmacy postgraduate (residency or fellowship) training. Methods. A 28-item survey was administered to third- and fourth-year (P3 and P4) pharmacy students. Variables queried included Grit-S score, demographics, pharmacy experience prior to the PharmD program, and factors that may affect academic performance during didactic coursework. Didactic coursework GPA was used as a surrogate for academic success. Information about pursuit and attainment of a postgraduate training position was also documented and used in the analyses. Results. There was no significant correlation between Grit-S scores and variables related to academic success. However, students were more likely to pursue postgraduate training with higher academic success and higher Grit-S. Lastly, students with higher Grit-S were also more likely to obtain a postgraduate training position. Conclusion. Grit-S scores correlated with the pursuit and successful attainment of postgraduate training, but not with academic success during the didactic years of a PharmD program.

Vasoplegia after heart transplantation: outcomes at 1 year.

OBJECTIVES: Vasoplegia syndrome is a potentially life-threatening condition that can occur following cardiopulmonary bypass. Heart transplantation is a recognized risk factor for developing this vasodilatory state. The objective of this study was to determine the effects of vasoplegia syndrome on 1-year heart transplant outcomes. METHODS: A retrospective review of orthotopic heart transplants at a single institution between November 2010 and December 2014 was performed. Of the 347 consecutive adult patients, 107 patients (30.8%) met criteria for vasoplegia syndrome. Preoperative factors and intraoperative variables were collected and compared between vasoplegia and non-vasoplegia cohorts. The incidence of postoperative complications, transplant rejection and patient survival within 1 year were evaluated. RESULTS: Demographics and preoperative medication profiles were similar in both groups, while mechanical circulatory support device use was associated with vasoplegia syndrome (30.8% vs 20.0%; P = 0.039). Perioperative characteristics such as longer cardiopulmonary bypass [165.0 (interquartile range [IQR] 74) min vs 140.0 (IQR 42.7) min; P < 0.001] and increased blood product usage (24.7 ± 17.2 units vs 17.7 ± 14.3 units; P < 0.001) were associated with vasoplegia. Non-vasoplegia patients were more likely to be extubated [42.9 (IQR 37.3) h vs 66.8 (IQR 50.2) h; P < 0.001] and discharged earlier [10.0 (IQR 6) days vs 14.0 (IQR 11.5) days; P < 0.001]. One-year patient survival (92.0% vs 88.6%; P = 0.338) and any-treated rejection rates (82.7% vs 84.3%; P = 0.569) were not significantly different between groups. CONCLUSIONS: Although vasoplegia syndrome was associated with an increase in perioperative morbidity, including greater mechanical ventilation time and hospital length of stay, no significant differences in survival or allograft rejection at 1 year was demonstrated.

Polypharmacy, Infectious Diseases, Sexual Behavior, and Psychophysical Health Among Anabolic Steroid-Using Homosexual and Heterosexual Gym Patrons in San Francisco's Castro District.

BACKGROUND: Limited studies based in England and Australia reported misuse of anabolic-androgenic steroids (AAS) among homosexual men to enhance body image. Anecdotally, AAS are also being misused by homosexual men in the United States. Since many AAS and certain performance enhancing drugs (PEDs) are administered via injection, this poses a potential vector for the spread of infectious disease in an already at-risk population. OBJECTIVES: This study compared and contrasted homosexual and heterosexual male gym clients regarding use of AAS and PEDs, use of alcohol and illicit drugs, seroprevalence of infectious disease, engagement in risky injection practices and sexual behaviors, and presence of psychiatric conditions. METHODS: Recruitment and data collection occurred outside four exercise gyms in the San Francisco Castro District area between October 25, 2014 and March 10, 2015. Two hundred and twenty homosexual men and 73 heterosexual men completed the 114-item cross-sectional survey. RESULTS: Ten percent of homosexual men reported lifetime AAS use. Homosexual men had almost four times more sexual partners and were over 14 times more likely to knowingly have unprotected intercourse with a known HIV positive person than heterosexual men. In addition, a quarter of homosexual men who injected drugs admitted to sharing used syringes or needles with another person. Conclusions/Importance: The current study is the first to confirm AAS use among homosexual men in the United States. Homosexual men partook in high-risk sexual behaviors and injection practices which may place them at greater risks for contracting and spreading HIV and other infectious diseases.

Novel application of a percutaneous left ventricular assist device as a bridge to transplant in a paediatric patient with severe heart failure due to viral myocarditis.

A 13-year obese female with suspected viral myocarditis presented with acute decompensated heart failure. Due to her body habitus, she was a poor candidate for immediate heart transplantation. A peripherally inserted left ventricular assist device (LVAD) was implanted via the right axillary artery. Following device insertion the patient experienced rapid improvement in symptoms. The LVAD provided effective left ventricular unloading for 50 days, promoting myocardial recovery and maintaining excellent patient performance status. The device placement strategy allowed for a high level of activity including completion of school-work and participation in a weight loss program. The patient achieved a 28-pound weight loss, thus improving candidacy for transplantation. Removal of the device was well tolerated and post-removal echocardiography revealed an improvement in the left ventricular ejection fraction (LVEF) from 21% at baseline to 38% after device removal. This case represents a successful application of a peripherally inserted LVAD as a bridge to transplant in a pediatric patient with severe heart failure due to suspected viral myocarditis. For select patients with this condition, a transaxillary LVAD should be considered as a therapeutic option as it is well tolerated and provides effective left ventricle unloading to promote myocardial recovery and maintain performance status.

Driving performance comparing older versus younger drivers.

OBJECTIVES: A cross-sectional study was conducted at the Touro University California campus to compare differences in reaction times and driving performance of younger adult drivers (18-40 years) and older adult drivers (60 years and older). Each test group consisted of 38 participants. METHODS: A Simple Visual Reaction Test (SVRT) tool was used to measure reaction times. The STISIM Drive M100 driving simulator was used to assess driving parameters. Driving performance parameters included mean lane position, standard deviation of mean lane position measured, mean speed, standard deviation of mean speed, car-following delay, car-following modulus, car-following coherence, off-road accidents, collisions, pedestrians hit, and traffic light tickets. RESULTS: Compared to younger participants, older drivers experienced significantly slower reaction times (510.0 ± 208.8 vs. 372.4 ± 96.1 ms, P =.0004), had more collisions (0.18 ± 0.39 vs. none, P =.0044), drove slower (44.6 ± 6.6 vs. 54.9 ± 11.7 mph, P <.0001), deviated less in speed (12.6 ± 4.3 vs. 16.8 ± 6.3, P =.0011), and were less able to maintain a constant distance behind a pace car (0.42 ± 0.23 vs. 0.59 ± 0.24; P =.0025). CONCLUSIONS: Differences exist in driving patterns of older and younger drivers as measured by reaction times and driving simulator outcomes. These results are the first to compare these 2 specific adult age groups' driving performance as measured by a standardized driving simulator scenario. Identifying these differences is essential in addressing them and preventing future traffic injuries.

Effects of valerian on subjective sedation, field sobriety testing and driving simulator performance.

INTRODUCTION: The availability of herbal medicines over-the-counter (OTC) has increased the use of natural products for self-treatment. Valerian has been used to effectively treat generalized anxiety disorder and insomnia. Studies suggest that valerenic acid may increase gamma-aminobutyric acid (GABA) modulation in the brain. Benzodiazepines have a similar mechanism of action and have been linked to an increased risk of hospitalizations due to traffic accidents. Despite the risk of somnolence, the safety of driving while under the influence of valerian remains unknown. PURPOSE: The purpose of the study was to determine the effects of a one-time valerian 1600mg dose on subjective sedation effects, standardized field sobriety testing (SFST) and driving simulator performance parameters. METHODS: The study design was a randomized, placebo-controlled, double-blind, cross-over trial. For each session, participants received either a dose of valerian or placebo. The outcome measures included a simple visual reaction test (SVRT), subjective sleepiness scales, SFST performance scores, and driving simulator performance parameters. RESULTS: There were no significant differences in the SVRT or sleepiness scales between placebo and valerian exposures, but the study may have been underpowered. SFST total and individual test failure rates were not significantly different between the two exposures. The driving simulator performance parameters were equivalent between the two exposure conditions. CONCLUSIONS: A one-time valerian 1600mg dose, often used to treat insomnia, does not appear to impair driving simulator performance after acute ingestion.

Valproic acid-induced hyperammonemia and minimal hepatic encephalopathy prevalence among psychiatric inpatients.

BACKGROUND: Our purpose was to evaluate the relationship between valproic acid (VPA)-induced hyperammonemia (HA) and the prevalence of minimal hepatic encephalopathy (MHE) cognitive impairment among psychiatric inpatients. METHODS: Fifty-two psychiatric inpatients prescribed VPA were tested for MHE impairment after achieving steady-state VPA and ammonia concentrations during hospitalization between December 2013 and June 2014. The relationship between steady-state VPA and ammonia concentration was tested by correlation coefficient. Patients completed a battery of 5 psychometric tests that determined a Psychometric Hepatic Encephalopathy Score (PHES), which was used to test the association between a PHES <-4 cutoff for MHE impairment and HA exposure (ammonia >50 µmol/L) by chi-square testing. RESULTS: Steady-state VPA plasma concentration was not correlated significantly with ammonia concentration (r = 0.24, P = .093). The patients with HA did not have a higher proportion of MHE cognitive impairment than patients with normal ammonia exposure (43.8% vs 66.7% respectively, P = .806). CONCLUSIONS: Steady-state VPA concentration was not correlated with ammonia concentration and VPA-induced HA was not associated with a greater prevalence of MHE impairment. This suggests that the MHE impairment PHES cutoff might not detect VHE in psychiatric inpatients without cirrhosis, especially because inpatients could experience cognitive impairment related to acute mental illness.