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A dentoalveolar fracture requires thorough clinical and radiographic examination for an accurate diagnosis to guide appropriate treatment. Dentoalveolar fractures can be classified into the following 4 groups: (1) crown/root fractures, (2) luxation/displacement of teeth, (3) avulsion, and (4) alveolar fractures. Treatment can be divided into nonrigid fixation (splinting with wires and composite) and/or rigid fixation (Erich arch bars, Risdon cable wires) depending on the extent of dentoalveolar fractures. Special considerations must be made for primary teeth and mixed dentition to avoid injuring tooth buds and arising permanent dentition.

Background Post-operative hyponatraemia is common following arthroplasty. Clinical hyponatraemia guidelines lack detail on when treatment is necessary, and there is a paucity of literature to guide best practice. Methods Data were collected within retrospective service evaluations over two time periods in a single high throughput joint unit. The hospital’s electronic database identified 1000 patients who were admitted electively between February 2012 and June 2013 and again between November 2018 and April 2019 for primary total hip, total knee or uni-compartmental knee arthroplasty. Hyponatraemia and non-hyponatraemia groups were compared. Logistic regression analysis was used to identify independent predictors of post-operative hyponatraemia, length of stay (LOS), re-attendance or re-admission to hospital. Results Between 2012–2013 and 2018–2019, 32.1% and 25.7% of patients, respectively, developed post-operative hyponatraemia (serum sodium (s[Na]) ≤135 mmol/L). Those with post-operative hyponatraemia were significantly older, weighed less, were more comorbid and had lower pre-operative sodium. Multivariate analysis showed that increased age, knee surgery and lower pre-operative s[Na] independently predicted post-operative hyponatraemia. Post-operative hyponatraemia did not independently predict LOS, re-attendance or re-admission to hospital, within 90 days, in either cohort. Conclusion Post-operative hyponatraemia is common and may be a marker of pre-operative vulnerability. In these cohorts, it was not independently associated with LOS, re-attendance or re-admission to hospital. We suggest that otherwise well patients with mild hyponatraemia can be safely discharged earlier than is often the case and may not require extensive investigation. Further examination and research is required to develop a pre-operative approach to predict which patients will develop significant post-operative hyponatraemia.

A recurrent question is whether transient reactions to vaccines translate into better immune responses. Using clinical data from 2 large phase 3 studies of the recombinant zoster vaccine, we observed a small but statistically significant association between the intensity of a frequent side effect (pain) after vaccination and immune responses to vaccination. However, despite the statistical correlation, the impact on the immune response is so small, and the immune response in individuals without pain already sufficient, that pain cannot be a surrogate marker for an appropriate immune response. Reactogenicity cannot be used to predict immunity after vaccination.

OBJECTIVE To determine the prevalence and correlates of weight gain attempts in a pooled sample of adults aged 18 and older from Canada, Australia, the United Kingdom, the United States, and Mexico. METHOD Data collected during 2 years (2018 and 2019) of the International Food Policy Study (N = 42,108) were analyzed. Unadjusted 12-month prevalence of weight gain attempts was estimated based on body mass index (BMI; kg/m2 ), weight perception, country, survey year, and sex. Logistic regression analyses were estimated to determine the sociodemographic correlates (age, race/ethnicity, education, BMI, weight perception, weight perception accuracy, and self-rated mental health) of weight gain attempts among the pooled sample stratified by sex. RESULTS Men (10.4%) were significantly more likely than women (5.4%) to report weight gain attempts (p

OBJECTIVES: To evaluate the performance of 4-dimensional computed tomography (4D-CT) in assessing upper airway obstruction (UAO) in patients with Robin Sequence (RS) and compare the accuracy and reliability of 4D-CT and flexible fiberoptic laryngoscopy (FFL). STUDY DESIGN: Prospective survey of retrospective clinical data. SETTING: Single, tertiary care pediatric hospital. METHODS: At initial and 30-day timepoints, a multidisciplinary group of 11 clinicians who treat RS rated UAO severity in 36 sets of 4D-CT visualizations and FFL videos (dynamic modalities), and static CT images. Raters assessed UAO at the velopharynx and oropharynx (1-none to 5-complete) and noted confidence levels (LOC) of each rating. Intraclass correlation and Krippendorff’s Alpha were used to assess intra- and inter-rater reliability, respectively. Accuracy was assessed by comparing clinician ratings with Quantitative Percent Constriction (QPC) Ratings, calculated based on 4D-CT airway cross-sectional area. Results were compared using Wilcoxon rank-sum and signed-rank tests. RESULTS: 4D-CT and FFL demonstrated similar intra-rater agreement (moderate to substantial) and both demonstrated fair inter-rater agreement. Both modalities underestimated UAO severity, though 4D-CT ratings were significantly more accurate, as determined by QPC similarity, than FFL (−1.06 and −1.46 vs QPC Ratings, p=0.004). Overall LOC was similar for 4D-CT and FFL, but other specialists were significantly less confident in FFL ratings than were otolaryngologists (2.25 and 3.92, p

To determine the association between compulsive exercise and vaping among college students aged 18–26 years, and to characterize the type of vaping used among participants who report compulsive exercise. Cross-sectional, pooled data from two survey years (2018–2020; N = 2125) of the national (U.S.) Healthy Minds Study were analyzed. Compulsive exercise was measured based on number of occurrences in the past 28 days (analyzed continuously and among those who reported ≥ 1 and ≥ 20 occurrences). Vaping was measured based on reported use in the past 30 days. Most recent type of vaping was assessed only among participants who reported vaping. Logistic regression analyses were conducted to estimate the associations between compulsive exercise and vaping, while adjusting for covariates. For every additional occurrence of compulsive exercise reported by participants, their odds of also reporting vaping increased by 5% (95% CI 1.01–1.09). Participants who reported 20 or more occurrences of compulsive exercise in the past 28 days, a clinical threshold, had 3.71 (95% CI 1.28–10.76) higher odds of vaping in the past 30 days. Among participants who endorsed vaping, nicotine vaping was the most common recent type for those who reported any (76.2%) or 20 or more (50.2%) occurrences of compulsive exercise. Compulsive exercise is associated with vaping in a national, U.S. sample of college students, with nicotine vaping being the most common type used. Screening for both compulsive exercise and vaping, particularly if either is reported, among college-age young adults is necessary to implement prevention and intervention strategies. V, cross-sectional descriptive study.

SUMMARYAcute malignant catatonia with autonomic instability developed in a previously healthy man with PCR-verified SARS-CoV-2. CT and MRI were normal, EEG showed slowing and cerebrospinal fluid showed a subtle indication of inflammation. There were no signs of pathology in other organs.18F-FDG-PET conveyed high bilateral uptake in the striatum. While commercial tests were negative, immunohistochemical staining of mouse brain revealed anti-neuronal IgG antibodies against neuronal targets in the hippocampus, thalamus, striatum and cortex. Early treatment with plasmapheresis and corticosteroid reversed disease progression and may have prevented large-scale neurological damage. We are not aware of other types of encephalitis with such distinct pyramidal tract symptoms and raise the possibility that this may be a novel form of autoimmune encephalitis induced by infection with SARS-CoV-2.

PURPOSE: To provide 5-year time trends in prevalence and demographic, substance use, and mental health correlates of compulsive exercise among a national sample of college men and women. METHODS: We analyzed 4 academic survey years (2016-2020; N = 8251) of the national (USA) Healthy Minds Study. Compulsive exercise was measured by self-report of any occurrence of "compulsive" exercise in the past 4 weeks. Unadjusted prevalence of compulsive exercise in the past 4 weeks was estimated across the 4 survey years by sex. Multiple logistic regression analyses were conducted among the pooled sample and stratified by sex to estimate the associations between compulsive exercise in the past 4 weeks and demographic, substance use, and mental health correlates. RESULTS: Among the pooled sample, 11% (95% confidence interval [CI] 9.60-12.42%) of men and 17% (95% CI 15.86-18.24%) of women reported compulsive exercise in the past 4 weeks. Prevalence across the 4 survey years remained stable among men and women. Higher body mass index was associated with greater odds of any compulsive exercise in the past 4 weeks among men, while any sports participation was associated with greater odds of any compulsive exercise in the past 4 weeks among women. Compulsive exercise in the past 4 weeks was associated with greater odds of all mental health symptoms and illicit drug use among men and women, and higher odds of alcohol use among women. CONCLUSION: Compulsive exercise is relatively common among college men and women and is associated with substance use behaviors and poor mental health symptoms. LEVEL OF EVIDENCE: V, cross-sectional descriptive study.

Delirium is an acute change in attention and cognition occurring in ~65% of severe SARS-CoV-2 cases. It is also common following surgery and an indicator of brain vulnerability and risk for the development of dementia. In this work we analyzed the underlying role of metabolism in delirium-susceptibility in the postoperative setting using metabolomic profiling of cerebrospinal fluid and blood taken from the same patients prior to planned orthopaedic surgery. Distance correlation analysis and Random Forest (RF) feature selection were used to determine changes in metabolic networks. We found significant concentration 2 differences in several amino acids, acylcarnitines and polyamines linking delirium-prone patients to known factors in Alzheimer’s disease such as monoamine oxidase B (MAOB) protein. Subsequent computational structural comparison between MAOB and angiotensin converting enzyme 2 as well as protein-protein docking analysis showed that there potentially is strong binding of SARS-CoV-2 spike protein to MAOB. The possibility that SARS-CoV-2 influences MAOB activity leading to the observed neurological and platelet-based complications of SARS-CoV-2 infection requires further investigation.

Surgical approaches to the head and maxillofacial area have been described and modified by many authors throughout history. It was, however, during the nineteenth and twentieth centuries when most of the techniques were described, mainly thanks to the advent of anesthesia and antibiotic therapy. Currently, a myriad of surgical techniques are employed to access the maxillofacial complex, with each of them having advantages and disadvantages. Although the approaches are the subject of textbooks and articles, most do not describe the circumstances or the historical context under which they were designed. In a series of three articles, we will provide a historical perspective of the most common surgical approaches to the head and face employed today. Descriptions contain advantages and disadvantages and modifications are provided. The purpose of the present article (3/3) is to review the approaches to the lower face.

Up to 23% of newly diagnosed, non-demented, Parkinson’s disease (PD) patients experience deficits in executive functioning (EF). In fact, EF deficits may occur up to 39-months prior to the onset of motor decline. Optimal EF requires working memory, attention, cognitive flexibility, and response inhibition underlying appropriate decision-making. The capacity for making strategic decisions requires inhibiting imprudent decisions and are associated with noradrenergic and dopaminergic signaling in prefrontal and orbitofrontal cortex. Catecholaminergic dysfunction and the loss of noradrenergic and dopaminergic cell bodies early in PD progression in the aforementioned cortical areas likely contribute to EF deficits resulting in non-strategic decision-making. Thus, detecting these deficits early in the disease process could help identify a significant portion of individuals with PD pathology (14–60%) before frank motor impairment. A task to evaluate EF in the domain of non-strategic decision-making might be useful to indicate the moderate loss of catecholamines that occurs early in PD pathology prior to motor decline and cognitive impairment. In this review, we focus on the potential utility of the Iowa Gambling Task (IGT) for this purpose, given significant overlap between in loss of dopaminergic and noradrenergic cells bodies in early PD and the deficits in catecholamine function associated with decreased EF. As such, given the loss of catecholamines already well-underway after PD diagnosis, we evaluate the potential utility of the IGT to identify the risk of therapeutic non-compliance and a potential companion approach to detect PD in premotor stages.

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in serum and cerebrospinal fluid (CSF) samples from 16 patients with coronavirus disease 2019 and neurological symptoms were assessed using 2 independent methods. Immunoglobulin G (IgG) specific for the virus spike protein was found in 81% of patients in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in 2 patients with negative serological findings. Levels of IgG in both serum and CSF were associated with disease severity (P

There has been an exponential increase in sexually transmitted infections (STIs) in the United States, causing the Centers for Disease Control and Prevention to declare an epidemic. Current evidence demonstrates that extragenital STIs of the oropharynx and rectum are often asymptomatic and may not be associated with concurrent positive urogenital infections. As a result, these infections are often missed in primary care. Furthermore, guidelines only recommend extragenital site testing in men who have sex with men, excluding oropharyngeal chlamydia, despite evidence that extragenital STIs are occurring in other high-risk populations as well. A case report is provided to enhance primary health care providers' knowledge of extragenital STIs and promote early recognition and testing to improve patient outcomes.

Introduction: Opioid prescribing occurs within almost every healthcare setting. Implementation of safe, effective opioid stewardship programs represents a critical but daunting challenge for medical leaders. This study sought to understand the barriers and aids to the routine use of clinical guidelines for opioid prescribing among healthcare professionals and to identify areas in need of additional education for prescribing providers, pharmacists, and nurses. Methods: Data collection and analysis in 2018-2019 employed a team of two trained facilitators who conducted 20 focus groups using a structured facilitation guide to explore operational, interpersonal, and patient care-related barriers to best practice adherence. Each professional group was interviewed separately, with similar care settings assigned together. Invitation to participate was based on a sampling methodology representing emergency, medical specialty, primary care, and surgical practice settings. Results: Key concerns among all groups reflected the inadequacy of available tools for staff to appropriately assess and treat patients’ pain. Tools and technology to support safe opioid prescribing were also cited as a barrier by all three professional groups. All groups noted that prescribers tend to rely upon default settings within the electronic medical record when issuing prescriptions. Both pharmacists and prescribers cited time and scheduling as a barrier to adherence. Conclusions: In spite of significant regulatory and public policy efforts to address the opioid crisis, healthcare organizations face significant challenges to improve adherence to best practice prescribing guidelines. These findings highlight several facilitators for change which could boost opioid stewardship initiatives to focus on critical systems’ factors for improvement.

Objective To identify serum proteins associated with MS and affected by interferon beta treatment. Methods Plasma samples from 29 untreated relapsing-remitting MS patients and 15 healthy controls were investigated with a multiplexed panel containing 92 proteins related to inflammation. Follow-up samples were available from 13 patients at 1 and 3 months after initiation of treatment with interferon beta-1a. Results Ten proteins were differentially expressed in MS patients. Five of these were altered by treatment with IFN-β 1a: uPA, CX3CL1, CCL2, TRAIL and IL18. Conclusion CCL2 and TRAIL were confirmed to be modulated with interferon beta treatment in MS. As novel findings, we now report that uPA and CX3CL1 were differentially expressed in MS and increased after IFN-beta-1a treatment. Conflicting results have been reported on how interferon beta affects IL-18. Title in Web of Science: Urokinase, CX3CL1, CCL2, TRAIL and IL-18 induced by interferon-beta treatment

In two large clinical trials (ZOE-50 [NCT01165177] and ZOE-70 [NCT01165229]), two doses of the adjuvanted recombinant zoster vaccine (RZV) demonstrated >90% efficacy (VE) against herpes zoster (HZ) in adults ≥50 years of age (YOA). This post-hoc analysis assessed the VE against HZ and postherpetic neuralgia (PHN), in participants from Asian study sites enrolled in ZOE-50/70. Reactogenicity and safety were also assessed. Participants ≥50 YOA were randomized 1:1 to receive 2 doses of either RZV or placebo, 2 months apart. VE was evaluated for a median follow-up of 4 years post-vaccination overall and by age in the ZOE-50 Asian population ≥50 YOA and in the pooled ZOE-50/70 Asian population ≥70 YOA. Of the 2,729 participants included in the ZOE-50 Asian population ≥50 YOA, 3 RZV and 66 placebo recipients reported a confirmed HZ episode. Overall VE was 95.6% (95% confidence interval [CI]: 86.4–99.1) against HZ and 100% (95% CI: 35.44–100) against PHN. In the pooled ZOE-50/70 Asian population ≥70 YOA, 4 RZV and 75 placebo recipients out of the 2,723 participants reported a confirmed HZ episode. Overall VE was 94.7% (95% CI: 85.9–98.6) against HZ and 89.8% (95% CI: 28.39–99.77) against PHN. Pain and myalgia were the most frequent solicited local and general adverse events, respectively, in both populations. No safety concern was identified during the study periods. RZV is highly efficacious against HZ and PHN and has an acceptable safety profile in Asian populations ≥50 YOA, similar to what was observed in the general ZOE-50/70 populations. Trademark statement: Shingrix is a trademark owned by or licensed to the GSK group of companies.

Orbital floor blowout fractures can result in a variety of signs and symptoms depending on the severity of the bone defect. Large defects often result in enophthalmos and restriction of ocular movement; yet the timing of surgery can be delayed up to two weeks with good functional outcomes. In contrast, an orbital trapdoor defect with entrapment of the inferior rectus muscle usually elicits pain with marked restriction of the upward gaze and activation of the oculocardiac reflex without significant dystopia or enophthalmos. When autonomic cardiac derangement is diagnosed along with an orbital floor fracture, it has been suggested that the fracture should be treated immediately. Otherwise, it will result in continued hemodynamic instability and muscular injury and may require a second surgery. This article reports the management of an unusual presentation of a trapdoor blowout orbital floor fracture surgery with oculocardiac response in an adult, with emphasis on its pathophysiology, management, and differential diagnosis.

Background/objectives Frail participants are often under-represented in randomized trials, raising questions about outcomes of interventions in real-world settings. Frailty is strongly associated with vulnerability to illness and adverse health outcomes. We studied the impact of frailty on recombinant zoster vaccine (RZV) clinical outcomes. Design/setting Data from two previously conducted phase III randomized trials of RZV were pooled. These two parent trials were conducted concurrently at the same study sites using the same methods. Participants/intervention In the two parent studies, participants aged ≥50 years (ZOE-50 study) and ≥70 years (ZOE-70 study), respectively, were randomized 1:1 to receive two doses of RZV or placebo. Measurements In the current ZOE-Frailty study (NCT03563183), a frailty index was created using previously validated methods. Clinical outcomes assessed by frailty status included vaccine efficacy, immunogenicity, reactogenicity, and safety. Results Of 29,305 participants from the pooled ZOE-50 and ZOE-70 total vaccinated cohort, 92% were included in this study. Mean age was 68.8 years; 58.1% were women; 45.6% were pre-frail and 11.3% frail. The percentage of frail participants increased with age from 5.7% aged 50-59 years to 22.7% aged ≥80 years. RZV vaccine efficacy against herpes zoster was >90% for all frailty subgroups (non-frail: 95.8% (95% confidence interval = 91.6-98.2), pre-frail: 90.4% (84.4-94.4), frail: 90.2% (75.4-97.0)). The RZV group demonstrated robust anti-gE antibody and gE-specific CD42+ responses, with mean concentrations remaining above pre-vaccination levels at least 3 years post-dose two, in all frailty subgroups. In the RZV group, the percentage of participants reporting solicited adverse events tended to decrease with increasing frailty. Conclusion The relatively nonrestrictive inclusion/exclusion criteria in the parent ZOE studies resulted in a range of participants that included frail and pre-frail older adults. RZV significantly reduced the risk of herpes zoster across all frailty subgroups.

Objective: Anticholinergic burden refers to the cumulative effect of medications which contain anticholinergic properties. We assessed how anticholinergic burden and different types of anticholinergic medications influence mortality rates among people with dementia in Northern Ireland. Our secondary aim was to determine what demographic characteristics predict the anticholinergic burden of people with dementia. Methods: Data were extracted from the Enhanced Prescribing database for 25,418 people who were prescribed at least one dementia management medication between 2010 and 2016.Information was also extracted on the number of times each available anticholinergic drug was prescribed between 2010 and 2016, allowing the calculation of an overall anticholinergic burden. Cox proportional hazard models were used to determine how anticholinergic burden influenced mortality whilst multilevel model regression determined what demographic characteristics influence overall anticholinergic burden. Results: Of the 25,418 people with dementia, only 15% (n ¼ 3880) had no anticholinergic burden. Diazepam (42%) and risperidone (18%) were the two most commonly prescribed drugs. Unadjusted Cox proportional hazard models indicated that higher anticholinergic burden was associated with significantly higher mortality rates in comparison to people with dementia who had no anticholinergic burden (HR ¼ 1.59: 95% CI ¼ 1.07-2.36). In particular, urological (HR ¼ 1.20: 95%CI ¼ 1.05-1.38) and respiratory (HR ¼ 1.17: 95% CI ¼ 1.08-1.27) drugs significantly increased mortality rates. People with dementia living in areas with low levels of deprivation had significantly lower anticholinergic burden (HR=-.39: 95% CI=-.47:-30).Conclusions: Reducing anticholinergic burden is essential for people with dementia. Further research should address the unfavourable prognosis of people living with dementia in highly deprived areas.

Alcohol use disorder is a chronic disease characterized in part by repeated relapsing events. Exposure to environmental stimuli or cues that have previously been associated with the effects of alcohol can promote relapse through the triggering of craving for alcohol. Therefore, identifying and characterizing neuronal populations that may regulate these associations is of the upmost importance. Previous studies have implicated the centrally-projecting Edinger Westphal nucleus (EWcp) in this process, as the EWcp is both sensitive to, and can regulate alcohol intake. To date however, it is unclear if the EWcp is involved in the formation or expression of these alcohol-cue associations. As such, the present studies examined the involvement of the EWcp in male DBA/2J mice in the acquisition and expression of place preference for an alcohol-paired cue using the conditioned place preference (CPP) procedure. Pharmacological inhibition of the EWcp via the GABAA and GABAB receptor agonists muscimol and baclofen did not affect either the acquisition or the expression of CPP. Follow up studies did find however, that pharmacological inhibition of the EWcp increased body temperature and prevented alcohol-induced increases in c-Fos expression in the EWcp. When considered in light of previous studies, the present results indicate that the EWcp may be involved in the regulation of alcohol self-administration, and not conditioned alcohol-seeking. Additionally, the present studies provide further evidence for the involvement of the EWcp in thermoregulation and help elucidate the molecular mechanisms by which alcohol increases c-Fos in the EWcp.

Objective To elucidate factors that influence opioid prescribing behaviors of key stakeholders after major spine surgery, with a focus on barriers to optimized prescribing. Methods In-person semi-structured interviews were performed with 20 surgical and medical professionals (January 23, 2019 to June 11, 2019) at a large academic medical center, including resident physicians, midlevel providers, attending physicians, and clinical pharmacists. Interviews centered on perceptions of postoperative prescribing practices were coded and analyzed using a qualitative inductive approach. Results Several unique themes emerged. First, wide interprovider variation exists in the perceived role of opioid prescribing guidelines. Second, there are important relationships between clinical experience, time constraints, and postoperative opioid prescribing. Third, opioid tapering is a major area of inconsistency. Fourth, there are serious challenges in managing analgesic expectations, particularly in those with chronic pain. Finally, there is currently no process to facilitate the hand-off or transition of opioid prescribing responsibility between surgical and primary care teams, which represents a major area for practice optimization efforts. Conclusion Despite increased focus on postoperative opioid prescribing, there remain numerous areas for improvement. The development of tools and processes to address critical gaps in postoperative prescribing will be essential for our efforts to reduce long-term opioid use after major spine surgery and improve patient care.

Objective To determine the impact of a drug deactivation system to post-surgical patients on the rate of opioid prescription disposal. Patients and Methods Two hundred post-operative patients discharged after inpatient surgery at a large academic medical center. This study was conducted August 20, 2018, through November 30, 2018. Patients were provided with a drug deactivation system (DDS) and instruction sheet along with their opioid prescription. Three to 4 weeks after dismissal, patients were surveyed about quantity of opioids remaining, use of DDS or other disposal methods, and satisfaction with DDS if used. Results One hundred forty-nine of 200 (74.5%) patients were surveyed. One hundred six reported leftover opioids and 29 (27.3%) had disposed of these medications. By the time of survey, 23 (21.2%) participants with leftover opioids had used the DDS to destroy their remaining supply and an additional 33 (31.1%) participants reported plans to use the disposal bag on a future date. Of the 23 participants who used the DDS, 22 (96.0%) reported that they were very satisfied with the disposal process. Conclusion Participants are willing to use a DDS and are satisfied with the process; however, additional education is needed to ensure timely disposal.

Cisplatin is a widely used anti-cancer drug used to treat a variety of cancer types. One of the side effects of this life-saving drug is irreversible ototoxicity, resulting in permanent hearing loss in many patients. In order to understand why cisplatin is particularly toxic to the inner ear, we compared the hearing loss and cochlear uptake of cisplatin to that of two related drugs, carboplatin and oxaliplatin. These three drugs are similar in that each contains a core platinum atom; however, carboplatin and oxaliplatin are considered less ototoxic than cisplatin. We delivered these three drugs to mice using a 6-week cyclic drug administration protocol. We performed the experiment twice, once using equimolar concentrations of the drugs and once using concentrations of the drugs more proportional to those used in the clinic. For both concentrations, we detected a significant hearing loss caused by cisplatin and no hearing loss caused by carboplatin or oxaliplatin. Cochlear uptake of each drug was measured using inductively coupled plasma mass spectrometry (ICP-MS) to detect platinum. Cochlear platinum levels were highest in mice treated with cisplatin followed by oxaliplatin, while carboplatin was largely excluded from the cochlea. Even when the drug doses were increased, cochlear platinum remained low in mice treated with oxaliplatin or carboplatin. We also examined drug clearance from the inner ear by measuring platinum levels at 1 h and 24 h after drug administration. Our findings suggest that the reduced cochlear platinum we observed with oxaliplatin and carboplatin were not due to increased clearance of these drugs relative to cisplatin. Taken together, our data indicate that the differential ototoxicity among cisplatin, carboplatin, and oxaliplatin is attributable to differences in cochlear uptake of these three drugs.

Context.—Body fluid specimens are regularly submitted to the hematology laboratory for cell count and differential. Unless there is high clinical suspicion for malignancy, most cases lack concurrent cytology review and may not benefit from more focused examination for malignancy.Objective.—To compare rates of malignancy detection before and after fluid-focused training for hematology technologists as part of a quality improvement initiative.Design.—During an 8-week pretraining period, body fluids submitted to the cytology laboratory were correlated with concurrent hematology specimens. After slide review and training sessions for the hematology technologists, the same data were collected for a 4-week period. Discrepant cases were reviewed by hematology laboratory supervisors and pathologists.Results.—We collected 465 pretraining and 249 posttraining body fluids with concurrent cytology and hematology evaluation. In the pretraining cohort, 48 cases (10.3%) were diagnosed as malignant by cytology; of those, 33 were detected by hematology. In the posttraining cohort, 30 cases (12.0%) were diagnosed as malignant by cytology of which 27 were detected by hematology. Of the 18 discrepant cases (all carcinomas), hematology slide review showed definite features of malignancy in 15 and no tumor cells in 3. The malignancy detection rate by the hematology laboratory significantly improved after training (68.8% versus 90.0%, P = .01).Conclusions.—We demonstrate the comparatively lower malignancy detection rate for body fluid specimens processed in our hematology laboratory, particularly for carcinomas. Hematology technologist education/training improved the malignancy detection rate, an important quality improvement given the large proportion of body fluids undergoing hematology evaluation without concurrent cytology reviews.

Objective: To examine the effectiveness of an interdisciplinary pain rehabilitation program (IPRP) that incorporates medication tapering on improving pain-related and performance-based outcomes for older adults with chronic noncancer pain and determine the proportion who demonstrated reliable improvement in outcome. Patients and Methods: This 2-year retrospective clinical cohort study examined treatment outcomes of 134 older adult patients 65 years or older with chronic noncancer pain who completed a 3-week IPRP with physician-supervised medication tapering between January 1, 2015, and December 31, 2017. Pain, pain catastrophizing, depressive symptoms, and quality of life were assessed at pretreatment, posttreatment, and follow-up. Physical performance and medication use were assessed pre- and posttreatment. Outcomes were examined using a series of repeated-measures analyses of variance, examining effect size and reliable change. Results: Significant treatment effects (P

The use of buprenorphine, a mixed opioid agonist-antagonist, for the management of chronic pain and/or opioid use disorder is increasing. As such, medical providers will more frequently encounter patients on this therapy. In this paper, we synthesize existing knowledge (derived through keyword searches using MEDLINE databases) in a novel conceptual framework for patients on buprenorphine presenting with acute pain or for those requiring surgical or invasive procedures. This framework is based on three unique domains: the patient, the features of the acute pain insult, and the environment. We discuss important considerations regarding the unique aspects of buprenorphine formulations and dosing, and we describe the importance of multidisciplinary planning and multimodal analgesic strategies. We also highlight important differences in management strategies based upon the presence or absence of opioid use disorder. All medical providers must be prepared to guide the patient on buprenorphine safely through the acute care episode, which includes adequate treatment of acute pain and avoidance of iatrogenic harm, including both short-term complications (eg, respiratory depression) and long-term complications (eg, relapse to opioid use).

Patients with co-morbid chronic pain and post-traumatic stress disorder (PTSD) pose significant treatment challenges. This study evaluated the effectiveness of an interdisciplinary pain rehabilitation program (IPRP) in improving pain and PTSD outcomes, as well as reducing medication use. In addition, the mediating effect of pain catastrophizing, which is theorized to underlie the pain and PTSD comorbidity, was examined. Participants included 83 completers of an IPRP with chronic pain and a provisional PTSD diagnosis. Significant improvements were found for pain outcomes, PTSD symptomatology, depressive symptoms, physical performance, and medication use (i.e., opioids and benzodiazepines). At discharge, 86.7% of participants reliably improved in at least one key measure of functioning and 50.6% demonstrated reliable improvement in PTSD symptomatology. Change in pain catastrophizing mediated improvements in pain interference and PTSD symptomatology. Results support the potential utility of an interdisciplinary pain treatment approach in the treatment of patients with comorbid pain and PTSD.

Herpes zoster (shingles) is a painful condition resulting from reactivation of latent varicella zoster virus (VZV). The Australian National Shingles Vaccination Program (commenced November 2016) provides free herpes zoster vaccination for eligible adults aged 70 years, with a 5-year catch-up program (until October 2021) for adults aged 71–79 years. Patterns and impact of the program were evaluated by analysis of vaccine distribution and delivery data and specific antiviral prescription data from the Pharmaceutical Benefits Scheme. During the first 2 years, uptake of funded live attenuated shingles vaccine ZOSTAVAX® (Zoster Virus Vaccine Live; ZVL) was high across the ongoing and catch-up programs. Before program implementation (2006–2016), herpes zoster coded antiviral prescription rates increased by 2.2% per year (95% CI: 1.5, 2.9) in the 70–79 years age group. In the two years since program launch, herpes zoster antiviral prescription rates declined substantially in this age group, by an average of 13.6% per year (95% CI: 1.5, 24.2). These results indicate that the National Shingles Vaccination Program has been highly successful in vaccinating a considerable proportion of Australian adults aged 70–79 years against herpes zoster and suggest that vaccine uptake was associated with decreased incidence of herpes zoster.

The opioid crisis is a major concern of most health care institutions, including our large academic center. In this article, an organized approach to managing the epidemic institutionally is discussed. An Opioid Stewardship Program was instituted at our tertiary-care center with multiple sites and states of practice, which included diverse membership and expertise. Charges of the program included reviewing current practice, workflows, and external and internal guidelines and evaluating and standardizing prescribing practices. The development of an Opioid Stewardship Program resulted in: (1) an understanding of our diverse prescribing practices and the formation of patient- and procedure-specific guidelines to manage them, (2) education tools for our patients and providers, and (3) workflows and practice advisories within the electronic health record to support appropriate prescribing and monitoring of patients. This ongoing work continues to evolve in response to the needs of our patients, changing regulatory environments, and our improved understanding of our practices.

Introduction: Hyponatremia due to elevated arginine vasopressin (AVP) secretion increases mortality in liver failure patients. No previous studies have addressed sex differences in hyponatremia in liver failure animal models. Objective: This study addressed this gap in our understanding of the potential sex differences in hyponatremia associated with increased AVP secretion. Methods: This study tested the role of sex in the development of hyponatremia using adult male, female, and ovariectomized (OVX) female bile duct-ligated (BDL) rats. Results: All BDL rats had significantly increased liver to body weight ratios compared to sham controls. Male BDL rats had hyponatremia with significant increases in plasma copeptin and FosB expression in supraoptic AVP neurons compared to male shams (all p < 0.05; 5–7). Female BDL rats did not become hyponatremic or demonstrate increased supraoptic AVP neuron activation and copeptin secretion compared to female shams. Plasma oxytocin was significantly higher in female BDL rats compared to female sham (p < 0.05; 6–10). This increase was not observed in male BDL rats. Ovariectomy significantly decreased plasma estradiol in sham rats compared to intact female sham (p < 0.05; 6–10). However, circulating estradiol was significantly elevated in OVX BDL rats compared to the OVX and female shams (p < 0.05; 6–10). Adrenal estradiol, testosterone, and dehydroepiandrosterone (DHEA) were measured to identify a possible source of circulating estradiol in OVX BDL rats. The OVX BDL rats had significantly increased adrenal estradiol along with significantly decreased adrenal testosterone and DHEA compared to OVX shams (all p < 0.05; 6–7). Plasma osmolality, hematocrit, copeptin, and AVP neuron activation were not significantly different between OVX BDL and OVX shams. Plasma oxytocin was significantly higher in OVX BDL rats compared to OVX sham. Conclusions: Our results show that unlike male BDL rats, female and OVX BDL rats did not develop hyponatremia, supraoptic AVP neuron activation, or increased copeptin secretion compared to female shams. Adrenal estradiol might have compensated for the lack of ovarian estrogens in OVX BDL rats.

Background This ongoing follow-up study evaluated the persistence of efficacy and immune responses for 6 additional years in adults vaccinated with the glycoprotein E (gE)-based adjuvanted recombinant zoster vaccine (RZV) at age ≥50 years in 2 pivotal efficacy trials (ZOE-50 and ZOE-70). The present interim analysis was performed after ≥2 additional years of follow-up (between 5.1 and 7.1 years [mean] post-vaccination) and includes partial data for year (Y) 8 post-vaccination. Methods Annual assessments were performed for efficacy against herpes zoster (HZ) from Y6 post-vaccination and for anti-gE antibody concentrations and gE-specific CD4[2+] T-cell (expressing ≥2 of 4 assessed activation markers) frequencies from Y5 post-vaccination. Results Of 7413 participants enrolled for the long-term efficacy assessment, 7277 (mean age at vaccination, 67.2 years), 813, and 108 were included in the cohorts evaluating efficacy, humoral immune responses, and cell-mediated immune responses, respectively. Efficacy of RZV against HZ through this interim analysis was 84.0% (95% confidence interval [CI], 75.9–89.8) from the start of this follow-up study and 90.9% (95% CI, 88.2–93.2) from vaccination in ZOE-50/70. Annual vaccine efficacy estimates were >84% for each year since vaccination and remained stable through this interim analysis. Anti-gE antibody geometric mean concentrations and median frequencies of gE-specific CD4[2+] T cells reached a plateau at approximately 6-fold above pre-vaccination levels. Conclusions Efficacy against HZ and immune responses to RZV remained high, suggesting that the clinical benefit of RZV in older adults is sustained for at least 7 years post-vaccination. Clinical Trials Registration. NCT02723773.

Dizziness and hearing loss are among the most common disabilities. Many forms of hereditary balance and hearing disorders are caused by abnormal development of stereocilia, mechanosensory organelles on the apical surface of hair cells in the inner ear. The deaf whirler mouse, a model of human Usher syndrome (manifested by hearing loss, dizziness, and blindness), has a recessive mutation in the whirlin gene, which renders hair cell stereocilia short and dysfunctional. In this study, wild-type whirlin cDNA was delivered to the inner ears of neonatal whirler mice using adeno-associated virus serotype 2/8 (AAV8-whirlin) by injection into the posterior semicircular canal. Unilateral whirlin gene therapy injection was able to restore balance function as well as improve hearing in whirler mice for at least 4 months. Our data indicate that gene therapy is likely to become a treatment option for hereditary disorders of balance and hearing.

"The Diseases of the Horny-coat of The Eye", known today as keratoconus, is a progressive, multifactorial, non-inflammatory ectatic corneal disorder that is characterized by steepening (bulging) and thinning of the cornea, irregular astigmatism, myopia, and scarring that can cause devastating vision loss. The significant socioeconomic impact of the disease is immeasurable, as patients with keratoconus can have difficulties securing certain jobs or even joining the military. Despite the introduction of corneal crosslinking and improvements in scleral contact lens designs, corneal transplants remain the main surgical intervention for treating keratoconus refractory to medical therapy and visual rehabilitation. To-date, the etiology and pathogenesis of keratoconus remains unclear. Research studies have increased exponentially over the years, highlighting the clinical significance and international interest in this disease. Hormonal imbalances have been linked to keratoconus, both clinically and experimentally, with both sexes affected. However, it is unclear how (molecular/cellular signaling) or when (age/disease stage(s)) those hormones affect the keratoconic cornea. Previous studies have categorized the human cornea as an extragonadal tissue, showing modulation of the gonadotropins, specifically luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Studies herein provide new data (both in vitro and in vivo) to further delineate the role of hormones/gonadotropins in the keratoconus pathobiology, and propose the existence of a new axis named the Hypothalamic-Pituitary-Adrenal-Corneal (HPAC) axis.

Chronic lymphocytic leukemia (CLL) is associated with immunocompromise and high risk of severe COVID-19 disease and mortality. Monoclonal B-Lymphocytosis (MBL) patients also have immune impairment. We evaluated humoral and cellular immune responses in 181 patients with CLL (160) and MBL (21) to correlate failed seroconversion (pppppp1000AU/mL. In a representative subset of 32 CLL patients, 80% had normal T-cell responses by IFNγ and IL-2 FluoroSpot assay. Failed seroconversion occurred in 36.6%% of treatment-naive patients, 52.9% treatment-naive with reduced IgM, 78.1% on therapy, and 85.7% on ibrutinib. Vaccination failure is very common in CLL, including early-stage disease.6 Key Novel FindingsComparison CLL vs MBL vs normal-45% of CLL and 9.5% of MBL fail to seroconvert with 2 doses of COVID-19 vaccineNeutralization assay-SARS CoV-2 IgG levels COVID-19-specific T-cell function by FluoroSpot IFN-g and IL-2 productionIgG, A, M class and IgG subclass:correlations by univariate and multivariate analysis-IgM (OR 7.29 pCorrelation withtherapy– ICT, targeted therapies, and those on Ig replacementHigh risk of vaccination failure for all CLL, including early-stage disease, and MBLKey PointsCLL and MBL show significantly impaired anti-spike antibody, viral neutralization, with cellular immune response to COVID-19 vaccinationFailure to seroconvert is associated with low IgM, IgG2, IgG3, and recent therapy; many CLL and MBL patients remain COVID-19 vulnerable

Delirium is a clinical syndrome occurring in heterogeneous patient populations. It affects 45–87% of critical care patients and is often associated with adverse outcomes including acquired dementia, institutionalisation, and death. Despite an exponential increase in delirium research in recent years, the pathophysiological mechanisms resulting in the clinical presentation of delirium are still hypotheses. Efforts have been made to categorise the delirium spectrum into clinically meaningful subgroups (subphenotypes), using psychomotor subtypes such as hypoactive, hyperactive, and mixed, for example, and also inflammatory and non-inflammatory delirium. Delirium remains, however, a constellation of symptoms resulting from a variety of risk factors and precipitants with currently no successful targeted pharmacological treatment. Identifying specific clinical and biological subphenotypes will greatly improve understanding of the relationship between the clinical symptoms and the putative pathways and thus risk factors, precipitants, natural history, and biological mechanism. This will facilitate risk factor mitigation, identification of potential methods for interventional studies, and informed patient and family counselling. Here, we review evidence to date and propose a framework to identify subphenotypes. Endotype identification may be done by clustering symptoms with their biological mechanism, which will facilitate research of targeted treatments. In order to achieve identification of delirium subphenotypes, the following steps must be taken: (1) robust records of symptoms must be kept at a clinical level. (2) Global collaboration must facilitate large, heterogeneous research cohorts. (3) Patients must be clustered for identification, validation, and mapping of subphenotype stability.

OBJECTIVE Emotion dysregulation is proposed as a key factor within eating disorder pathology. However, less is known about specific emotion regulation difficulties experienced by adolescents with varying levels of eating disorders symptoms. The present study examined the relationship between eating disorder behaviors and specific facets of emotion dysregulation, and differences in emotion dysregulation between eating disorder diagnostic groups. METHOD Participants were 2,783 adolescents, 11-19 years (M = 14 years, 9 months, SD = 1 year, 6 months), who completed self-report measures as part of the EveryBODY study. Adolescents were identified as not having eating disorder symptoms (n = 2,122) or meeting diagnostic criteria for symptoms of specific eating disorder, including: anorexia nervosa or atypical anorexia nervosa (n = 57), bulimia nervosa (n = 136), binge-eating disorder (n = 57), other specified feeding or eating disorder characterized by binge eating or purging (n = 381), and unspecified feeding or eating disorder (n = 30). RESULTS Binge eating, driven exercise, and fasting were each uniquely associated with emotion dysregulation, whereas purging was not. Similar findings were obtained within specific domains of emotion dysregulation. Findings from diagnostic groups showed a significant main effect of diagnosis on overall emotion dysregulation and most domains of emotion dysregulation. Adolescents with eating disorder symptoms consistently reported higher emotion dysregulation compared to those without these symptoms. DISCUSSION Findings indicate that emotion dysregulation is a key factor across eating disorder pathology, and potential treatment target across the spectrum of eating disorder diagnoses in adolescents.

Neurodegenerative diseases cause severe impairments in cognitive and motor function. With an increasing aging population and the onset of these diseases between 50 and 70 years, the consequences are bound to be devastating. While age and longevity are the main risk factors for neurodegenerative diseases, sex is also an important risk factor. The characteristic of sex is multifaceted, encompassing sex chromosome complement, sex hormones (estrogens and androgens), and sex hormone receptors. Sex hormone receptors can induce various signaling cascades, ranging from genomic transcription to intracellular signaling pathways that are dependent on the health of the cell. Oxidative stress, associated with aging, can impact the health of the cell. Sex hormones can be neuroprotective under low oxidative stress conditions but not in high oxidative stress conditions. An understudied sex hormone receptor that can induce activation of oxidative stress signaling is the membrane androgen receptor (mAR). mAR can mediate nicotinamide adenine dinucleotide-phosphate (NADPH) oxidase (NOX)-generated oxidative stress that is associated with several neurodegenerative diseases, such as Alzheimer disease. Further complicating this is that aging can alter sex hormone signaling. Prior to menopause, women experience more estrogens than androgens. During menopause, this sex hormone profile switches in women due to the dramatic ovarian loss of 17β-estradiol with maintained ovarian androgen (testosterone, androstenedione) production. Indeed, aging men have higher estrogens than aging women due to aromatization of androgens to estrogens. Therefore, higher activation of mAR-NOX signaling could occur in menopausal women compared with aged men, mediating the observed sex differences. Understanding of these signaling cascades could provide therapeutic targets for neurodegenerative diseases.

Background Hyponatraemia, defined as a serum sodium [Na] concentration below 135 mmol/L, is common following surgery. As inpatient peri-operative stays shorten, there is a need to recognise pre-operative risk factors for post-operative hyponatraemia and complications associated with a peri-operative drop in Na. This audit aimed to investigate the prevalence of, risk factors for, and complications associated with hyponatraemia following elective primary hip and knee arthroplasty. Methods Data were collected within a retrospective audit of inpatient complications and unplanned reattendance or readmission at hospital in consecutive elective primary hip and knee arthroplasty patients in a single high throughput elective primary joint unit. The hospital’s electronic database identified 1000 patients who were admitted electively between February 2012 and June 2013 under the care of a single consultant orthopaedic surgeon for either total hip arthroplasty, total knee arthroplasty, or uni-compartmental knee arthroplasty. Groups were compared using appropriate tests, including chi-square analysis (or Fisher’s exact test), Mann-Whitney U test, Kruskal-Wallis test, and Wilcoxin signed-rank test. Logistic regression analysis was used to determine factors associated with hyponatraemia. Results Of the total 1000 patients, 217 (21.7%) developed post-operative hyponatraemia. Of these, 177 (81.6%) had mild (Na 130–134 mmol/L), 37 (17.1%) had moderate (Na 125–129 mmol/L), and 3 (1.4%) had severe (Na < 125 mmol/L) hyponatraemia. In multivariate analysis, age, pre-operative Na, and fasting glucose on day 1 remained significantly associated with having hyponatraemia post-operatively. There were no significant differences in reattendance at emergency departments and/or readmission within 90 days between those who had post-operative hyponatraemia whilst in hospital (39/217 = 18.0%) and those who did not (103/783 = 13.2%), or between those who were discharged with hyponatraemia (18/108 = 16.7%) and those discharged with normal Na (124/880 = 14.1%). Conclusion Approximately one fifth of elective joint arthroplasty patients had post-operative hyponatraemia. In these patients, older age, lower pre-operative Na and higher fasting glucose predicted post-operative hyponatraemia. We found no evidence that those discharged with hyponatraemia had more reattendance at emergency departments or readmission to hospital. We suggest that otherwise well patients with mild hyponatraemia can safely be discharged and followed up in the community.

Our understanding of the challenges and the broader role of spouses of expatriates is extremely limited. This study examined the impact of spousal work restrictions on expatriates' work life and overall life satisfaction using qualitative and quantitative analyses based on data from a sample of 409 Indian Information Technology professionals working in USA. Furthermore, hypothesised conditional process model (tested with PROCESS analysis tool) was supported, showing that spousal work restrictions created complications in personal lives of expatriates, which interfered with work lives resulting in lower overall life satisfaction. We identified six core classes of challenges faced by spouses of expatriates: wasted skills, financial issues, boredom, social isolation, quality time and domestic tension. Our mixed method approach also helps to provide a more comprehensive picture of these complications. This study may help organisational leaders and policy makers to more fully consider the implications of visa-related policy changes on expatriate families.

Public acceptability, and ultimately acceptance, of automated vehicles (AVs) is critical in order to ensure that drivers utilise them and thus realise their predicted safety and other benefits. The aim of this study was to gauge public acceptability and opinions of AVs within an Australian context, for which there is currently a scarcity of empirical research. The study employed a national sample of 5089 respondents who responded to a large online survey (including 45 items specifically targeting aspects of AV acceptability). Survey items gauged demographic and other sample characteristics, and probed responses to questions on key issues including (a) the perceived benefits of AVs, (b) sources, and degree, of concerns regarding AV-related issues, and (c) willingness to pay for AV technology. Overall, it was found that, even though Australian respondents tended to agree with many of the potential benefits of AVs probed in the survey, they have considerable concerns regarding many AV-related issues. Furthermore, a majority of Australians are currently not willing to pay any more for a fully autonomous vehicle than for a manually operated vehicle. Results also showed that a number of sample demographic and characteristic variables (e.g., gender, self-classification as an early vs. late adopter of technology) have unique associations with aspects of AV acceptability. Important theoretical and practical implications of these findings are discussed.

Herpes zoster is common in older and immune suppressed persons due to diminished VZV-specific cellular immunity. A recombinant herpes zoster vaccine (RZV) consisting of a single VZV glycoprotein and an adjuvant system stimulates robust and persistent VZV-specific antibody and CD4+ T cell responses in these high-risk populations. VZV-specific immune responses induced by RZV, including the generation of polyfunctional T cells, are driven by the synergistic actions of the components of the vaccine adjuvant system. RZV provides unprecedented protection against herpes zoster in older adults regardless of age at vaccination and is efficacious in immune suppressed populations. Adjuvanted subunit antigens may represent a general strategy for vaccines in the elderly and other individuals typically considered immunologically resistant to vaccination.

Background Laboratory tests to assist in the diagnosis and monitoring of neuroinflammatory diseases are scarce. The soluble form of the CD27 molecule (sCD27) is shed in high concentrations by activated T cells and can be detected in the cerebrospinal fluid. The aim of this study was to investigate whether CSF quantitation of sCD27 could discriminate between inflammatory and non-inflammatory neurological diseases. Methods The concentration of sCD27 was measured using a commercially available ELISA in 803 well-defined subjects from a study cohort comprised of 338 patients with neuroinflammatory disease, 338 with non-inflammatory neurological disease and 127 controls without neurological disease. Results The median value of cerebrospinal fluid sCD27 was 64 pg/mL (IQR 0–200) in controls, 58 pg/mL (IQR 0–130) in patients with non-inflammatory disease and 740 pg/mL (IQR 230–1800) in patients with inflammatory disease. The likelihood ratio of having an inflammatory disease was 10 (sensitivity 74% and specificity 93%) if the sCD27 concentration was >250 pg/mL. In patients with a known inflammatory condition, the likelihood ratio of having an infection was 10 (sensitivity 40% and specificity 96%) if the sCD27 concentration was >2500 pg/mL. Conclusions The likelihood of having an inflammatory neurological condition is increased with elevated concentrations of sCD27 in cerebrospinal fluid. Rapid tests of sCD27 should be developed to assist clinicians in diagnosis of neuroinflammatory disease.

Summary Background Indocyanine green angiography (ICGA) reduces ischemic complications by assessing mastectomy flap perfusion intraoperatively. However, outcomes of ICGA can be surgeon-dependent due to its relative novelty. We aimed to determine whether patient outcomes improved with the adoption of ICGA over time. Methods We conducted a single-institution retrospective study of mastectomy patients between March 2012 (date of ICGA introduction) and October 2016. We included patients who underwent immediate expander-based reconstruction with intraoperative ICGA, followed by second-stage permanent implant placement. Patients were chronologically sorted into 3 groups, of 45 patients each, based on the date of ICGA. Complications and reconstruction wait times (time between initial expander placement and subsequent final reconstruction) amongst the 3 groups were evaluated. Using the Cochran–Armitage test for trend, we tested the change in median adjusted expander fill volumes (expander fill volume in milliliter per gram of breast removed) over time. Results We identified 135 patients. Rates of ischemic complications significantly decreased (Group 1, 36%; Group 2, 22%; Group 3, 11%; p = 0.03), despite significantly increasing median adjusted expander fill volumes (Group 1, 0.46 mL/g; Group 2, 0.63 mL/g; Group 3, 0.76 mL/g; p = 0.003) over time. The rates of unexpected returns to the operating room across the 3 groups were not significantly different. The median reconstruction wait time was significantly reduced in the later groups (Group 1, 146 days; Group 2, 122 days; Group 3, 87 days; p = 0.01). Conclusions Outcomes for mastectomy with immediate expander-based reconstruction were found to improve with increasing case volume after implementation of ICGA.

PurposeTransformational leadership has been shown to have a positive impact on a host of employee level and organizational performance indicators. However, little research has sought to understand some of the antecedents of this style of leadership. The purpose of this paper is to examine the link between having a post-secondary education and perceptions of transformational leadership.Design/methodology/approachData were collected from two surveys issued in a mid-sized energy company located on the eastern seaboard of North America. One-way ANOVA comparing employees’ perceptions of transformational leadership exhibited by their supervisors that either did or did not have a post-graduate degree demonstrated a strong, positive relationship between the attainment of a Master’s degree and perceived levels of transformational leadership qualities.FindingsThe findings of this quasi-experimental field study demonstrated a strong, positive relationship between the attainment of a Master’s degree and perceived levels of transformational leadership qualities.Originality/valueThis study is the first of its kind to demonstrate that more educated managers are generally perceived to be more transformational in their leadership style.

Purpose Childhood trauma in an important public health concern, and there is a need for brief and easily administered assessment tools. The Early Trauma Inventory (ETI) is one such instrument. The aim of this paper is to test the psychometric properties of the Swedish translation of the short, self-rated version (ETISR-SF), and to further validate the instrument. Materials and methods In this cross-sectional study, 243 psychiatric patients from an open care unit in Sweden and 56 controls were recruited. Participants were interviewed and thereafter completed the ETISR-SF. Internal consistency was calculated using Cronbach's alpha, a confirmatory factor analysis (CFA) was performed and goodness-of-fit was determined. Intra Class Correlation (ICC) was used to calculate test-retest reliability. Discriminant validity between groups was gauged using the Mann-Whitney U-test. Results Cronbach's alpha varied between 0.55 and 0.76, with higher values in clinical samples than in controls. Of the four domains, general trauma showed a lower alpha than the other domains. The CFA confirmed the four-factor model previously seen and showed good to acceptable fit. The ICC value was 0.93, indicating good test-retest reliability. According to the Mann-Whitney U-test, the non-clinical sample differed significantly from the clinical sample, as did those with PTSD or borderline diagnosis from those without these diagnoses. Conclusions The Swedish translation of the ETISR-SF was found to have similar psychometric properties as both the original version and translations. ETISR-SF scores could also distinguish between different diagnostic groups associated with various degrees of trauma, which supports its discriminant validity.

Among children with FGFR2-associated Pfeiffer syndrome, those with the W290C pathogenic variant (PV) are reported to have the worst clinical outcomes. Mortality is high, and severe neurocognitive impairment has been reported in all surviving patients. However, it is unclear whether these poor outcomes are an unavoidable consequence of the PV itself, or could be improved with a genotype-specific treatment approach. The purpose of this report is to describe the more intensive surgical approach used for each of the three patients with W290C PV in FGFR2 at our center, all of whom survived and have normal neurocognitive functioning. Retrospective chart review. In contrast to other patients with Pfeiffer syndrome at our center, all three patients who were subsequently found to have a W290C PV required a similar and more aggressive approach based on early cephalocranial disproportion. In contrast to previously reported W290C cases, each of our three patients survived and demonstrate normal neurocognitive functioning. While previously reported outcomes in W290C-associated Pfeiffer syndrome have been extremely poor, we present three patients who underwent an intensive surgical approach and have normal development. This suggests that a personalized and aggressive surgical approach for children with W290C PV may dramatically improve clinical outcome.

Otilonium bromide is a poorly absorbed oral medication used to control irritable bowel syndrome. It is thought to act as a muscle relaxant in the intestine. Here, we show that otilonium bromide has broad-spectrum antibacterial and antifungal activity, including against multidrug-resistant strains. Our results suggest otilonium bromide acts on enteric pathogens and may offer a new scaffold for poorly absorbed intestinal antimicrobial therapy.

Objectives/hypothesis A tracheal cartilaginous sleeve (TCS) is a rare anomaly characterized by anterior fusion of tracheal cartilages. TCS is associated with syndromic craniosynostoses including Apert, Crouzon and Pfeiffer syndromes and FGFR2, FGFR3, and TWIST1 variants. This study presents a 30-year review of patients with syndromic craniosynostosis and TCS and describes diagnostic methods, genetic variants, surgical interventions, and long-term outcomes. Study design Retrospective, single-institution review. Methods This review included patients with syndromic craniosynostosis and TCS treated at Seattle Children's Hospital from 1990 to 2020. Tracheostomy, genetic variants, and additional surgery were primary measures. Fisher's exact test compared need for tracheostomy in patients with proposed high-risk (FGFR2 p.W290 or FGFR2 p.C342) versus low-risk genetic variants. Results Thirty patients with TCS were identified. Average age at diagnosis was 12 months (range 2-weeks to 7.9-years; standard deviation 19.8 months). Syndromes included Pfeiffer (37%), Apert (37%), and Crouzon (26%). Severe obstructive sleep apnea was present in 76% of patients. Tracheostomy was performed in 17 patients (57%); five were successfully decannulated. Additional interventions included adenotonsillectomy (57%), nasal (20%), laryngeal (17%), and craniofacial skeletal surgery (87%). All patients with Pfeiffer syndrome and FGFR2 p.W290C variants and 83% of patients with FGFR2 p.C342 variants required tracheostomy, differing from other variants (P = .02, odds ratio 33, 95% confidence interval 1.56-697.96). One patient (3%) died. Conclusion TCS contributes to multilevel airway obstruction in patients with syndromic craniosynostosis. Genetic testing in patients with FGFR2-related syndromic craniosynostoses may identify those at risk of TCS and facilitate early intervention. A better understanding of this patient population may foster individualized airway management strategies and improve outcomes. Level of evidence 4 Laryngoscope, 2021.