Respiratory aspiration during treatment with clozapine and other antipsychotics: a literature search and a pharmacovigilance study in vigibase.

INTRODUCTION: Antipsychotics (APs), during treatment or overdose, may be associated with respiratory aspiration. AREAS COVERED: A PubMed search on 30 September 2022, provided 3 cases of respiratory aspiration during clozapine therapy and 1 case during an AP overdose. VigiBase records of respiratory aspiration associated with APs from inception until 5 September 2021, were reviewed. VigiBase, the World Health Organization's global pharmacovigilance database, uses a statistical signal for associations called the information component (IC). EXPERT OPINION: The ICs (and IC025) were 2.1 (and 2.0) for APs, 3.2 (and 3.0) for clozapine, 2.6 (and 2.4) for quetiapine, and 2.5 (and 2.2) for olanzapine. Cases of respiratory aspiration associated with APs included: 137 overdose/suicide cases (64 fatal) and 609 cases during treatment (385 fatal) including 333 taking clozapine (238 fatal). In logistic regression models of fatal outcomes, the odds ratios, OR, and (95% confidence intervals, CI) of significant independent variables were: a) 2.3-2.6 for clozapine in 3 samples of AP treatment of varying size, b) 1.9 (CI 1.0 to 3.5) for geriatric age in 284 patients on clozapine treatment, and c) 1.8 (CI 1.1-3.2) for antidepressant co-medication in 276 patients on non-clozapine APs. Multiple AP pharmacological mechanisms may explain respiratory aspiration.

Associations of muscle lipid content with physical function and resistance training outcomes in older adults: altered responses with metformin.

Preserving muscle mass and strength is critical for long-term health and longevity. Age-related muscle lipid accumulation has been shown to be detrimental to muscle health. In healthy older individuals, we sought to determine whether muscle lipid content, determined from computed tomography, is associated with self-reported physical function, laboratory-measured performance, and the response to progressive resistance training (PRT), and how metformin may alter these responses (N = 46 placebo, 48 metformin). Using multiple linear regression models adjusted for confounders in a large cohort, we show that intermuscular adipose tissue (IMAT) was not associated with baseline function or response to PRT, contrary to previous reports. On the other hand, thigh muscle density (TMD), as an indicator of intra- and extramyocellular lipid (IMCL and EMCL), remained strongly and independently positively associated with physical function and performance following adjustment. Baseline TMD was inversely associated with gains in strength, independent of muscle mass. Percent change in TMD was positively associated with improved chair stand and increased type II fiber frequency but was not associated with muscle hypertrophy or overall strength gain following PRT. For the first time, we show that metformin use during PRT blunted density and strength gains by inhibiting fiber type switching primarily in those with low baseline TMD. These results indicate that participants with higher muscle lipid content derive the most performance benefit from PRT. Our results further indicate that muscle density may be as influential as muscle size for strength, physical function, and performance in healthy older adults. ClinicalTrials.gov , NCT02308228, Registered on 25 November 2014.

Effect of necessity-concern framework and polypharmacy on treatment adherence in psychiatric patients. Comparing an Argentinian with a Spanish sample.

OBJECTIVE: We aimed to replicate a prior Spanish study of medication adherence where logistic regression models provided highly significant odds ratios (ORs) for three continuous scores: necessity, concern and the necessity-concern differential, and a dichotomous variable: skeptical attitude. Adherence ORs in the necessity-concern framework were very strong in patients taking five or six medications. METHODS: The sample comprised consecutive adult psychiatric outpatients in Mendoza, Argentina. The necessity-concerns framework was assessed using a subscale of the Beliefs about Medicines Questionnaire. Adherence (yes/no) to prescribed psychiatric medications was assessed by the Sidorkiewicz adherence tool. RESULTS: When compared with the Spanish sample, the Argentinian group (508 patients with 875 medications) was characterized by: (1) significantly stronger adherence ORs with the necessity-concern framework, (2) significantly lower number of medications per patient and percentage of patients with marked psychiatric polypharmacy (≥4 medications), (3) though a higher number of medications still was significantly associated with poor adherence. CONCLUSIONS: The Argentinian sample replicated the previous finding that patient beliefs regarding necessity and concern were associated with poor adherence to prescribed medications. Polypharmacy had an additive role decreasing adherence in both samples. In both samples, when prescribed ≥4 psychiatric medications, patients reported adherence to only two-third of the medications.

Physical Function Measured Prior to Lung Transplantation Is Associated With Posttransplant Patient Outcomes.

INTRODUCTION: The primary objective of this study was to determine whether pretransplant physical function is correlated with posttransplantation outcomes. METHODS: We performed a retrospective study of patients that participated in pretransplantation screening and subsequently underwent lung transplantation. Pretransplant variables of interest included demographics, muscle mass, body composition, physical function, and physical frailty. Correlation tests were performed to assess relationships with significance set at 0.05. RESULTS: Twenty-five patients with a mean age of 57 ± 13 years (68% male) with pretransplant lung allocation score of 45 ± 14 were included. This cohort had a 3-year mortality rate of 32% (n = 8). Pretransplant 4-m gait speed was significantly related to performance on the Short Physical Performance Battery (r = 0.74, P = .02) and distance ambulated on the 6-minute walk test (r = 0.62, P = .07) at hospital discharge. Older age was associated with slower gait speed and worse performance on sit-to-stand testing at hospital discharge (r = -0.76, P = .01 and r = -0.75, P = .01, respectively). Statistically, only diagnosis of cystic fibrosis was associated with 3-year mortality. DISCUSSION: Our study demonstrates that demographic, clinical, and physical function assessed prior to lung transplantation may be indicators of functional recovery.

Physical therapy referral and medication for ankle sprain visits to physician offices: an analysis of the national ambulatory medical care survey.

OBJECTIVES: Supervised physical therapy is the recommended care for an ankle sprain. Yet, recent evidence indicates some ankle sprain patients may not receive the recommended care, and instead, prescribed medication to alleviate symptoms. Therefore, the purpose of this study is to describe the percentage of patients reporting to an office-based physician in the U.S. that were or were not referred to physical therapy. Secondly, to describe the percentage of ankle sprain patients with or without medication administered, supplied or ordered. METHODS: This was a secondary analysis of the cross-sectional National Ambulatory Medical Care Survey (NAMCS) from 2007 to 2016. The NAMCS is a multi-stage probability sample survey of visits to office-based physicians. The percentage and associated 95% confidence intervals (CI) were calculated for visits that had a physical therapy referral or a non-steroidal anti-inflammatory drug (NSAID), opioid and non-opioid analgesics administered, supplied or ordered. Sampled data were weighted to produce national-level estimates. RESULTS: A physical therapy referral was given for 16.8% (95% CI: 13.2, 21.2) of ankle sprain visits. Approximately 34.5% (95%CI: 30.5, 38.7) of all ankle sprain visits had a medication administered, supplied or ordered. NSAIDs (72.1%; 95% CI: 66.9,76.8) and opioids (21.0%; 95% CI: 16.3, 26.5) were the two most common types of medication. CONCLUSIONS: NSAIDs and opioid medication combined were administered, supplied or ordered more frequently than a referral to physical therapy. These findings provide evidence that suggests many ankle sprain patients reporting to an office-based physician are not receiving the recommended care; physical therapy. Rather, medication appears to be the primary type of care provided to patients. These data are important because it gives a focused area to improve the treatment of an ankle sprain by developing strategies that ensure all patients are provided the recommended care from the onset of entering the healthcare system.

Comparison between students' self-assessment, and visual and digital assessment techniques in dental anatomy wax-up grading.

INTRODUCTION: Digital technology has the potential to provide a bias-free evaluation instrument for practical examination grading. E4D Compare software was designed for teaching institutions to allow comparison between scanned models prepared by students and master models prepared by instructors. The aim of this study was to determine the tolerance value for the E4D compare software (E4D Technologies LLC, Richardson, TX, USA) that provides scores comparable with faculty grades for wax-ups #23 and #19. Additionally, this study sought to assess the correlation between students' self-assessments, visual and digital grades and the reliability of the software. METHODS: Student wax-ups (n = 112) were uploaded into the software and then compared with faculty-generated master wax-ups. Digital grading was performed at tolerances 200-800 µm in 50 µm increments and was repeated twice. RESULTS: A tolerance of 350 µm was the closest to faculty grades for #23 and 500 µm was the closest for #19. Visual and digital grades showed moderate to high correlation for both wax-ups. Correlations between students' self-assessments and visual and digital grades improved with #19 versus #23. A near-perfect correlation was found between grades at the first and second digital grading sessions. CONCLUSIONS: The tolerance that closely matches faculty grades differs according to the tooth type. The software provided consistent grades and correlated well with faculty grades. Students' self-assessment skills improved as they proceeded throughout the course. Further studies are necessary to ascertain the role of the software in improving students' self-assessment skills.

Visit Characteristics Associated With Opioids Administered or Prescribed During Emergency Department Visits for Ankle Sprain Between 2010 and 2015.

BACKGROUND: Recent research has demonstrated that patients with ankle sprain who are discharged from the emergency department (ED) are prescribed an opioid. Minimizing the exposure to opioids is important to help prevent future abuse and misuse of these medications. OBJECTIVE: Identify ED visit characteristics for an ankle sprain that are associated with an opioid given in the ED, prescribed at discharge, or both. DESIGN: Retrospective analysis of the National Hospital Ambulatory Medical Care Survey (NHAMCS). SETTING: Hospital. PARTICIPANTS: Isolated ankle sprain visits to a United States ED. MAIN OUTCOME MEASUREMENTS: The main outcome was an opioid given in the ED, prescribed at discharge, or both between 2010 and 2015. Explanatory variables included age, sex, race, attending physician or resident, and geographic location of the hospital. A multiple logistic regression was performed to assess the independent association between an opioid given in the ED, prescribed at discharge, or both, and all explanatory variables. The analysis accounted for the cluster, strata, and probability weights for each year of the NHAMCS. RESULTS: Ankle sprain visits for patients ≤17 years of age had a lower odds of an opioid being given in the ED, prescribed at discharge, or both, compared to visits for patients 18 to 24 years of age (adjusted odds ratio [aOR] = 0.26 [95% confidence interval (CI) = 0.1, 0.5]; P < .001). Visits in the West (aOR = 2.5 [95% CI = 1.2, 5.4]) or South (aOR = 2.9 [95% CI = 1.6, 5.4]; P = .010) had higher odds of an opioid being given in the ED, prescribed at discharge, or both, compared to visits in the Northeast. CONCLUSIONS: Ankle sprain visits for patients ≤17 years of age had a lower odds of an opioid compared to visits for patients 18 to 24 years of age. Ankle sprain visits in the South or West had a higher odds of an opioid compared to visits in the Northeast. These findings provide a direction for future work aimed at minimizing exposure to opioids after an ankle sprain.

Joint Fluid Proteome after Anterior Cruciate Ligament Rupture Reflects an Acute Posttraumatic Inflammatory and Chondrodegenerative State.

OBJECTIVE: The purpose of this study was to evaluate changes in the synovial fluid proteome following acute anterior cruciate ligament (ACL) injury. DESIGN: This study represents a secondary analysis of synovial fluid samples collected from the placebo group of a previous randomized trial. Arthrocentesis was performed twice on 6 patients with an isolated acute ACL tear at a mean of 6 and 14 days postinjury. Synovial fluid was analyzed by a highly multiplexed assay of 1129 proteins (SOMAscan version 3, SomaLogic, Inc., Boulder, CO). Pathway analysis using DAVID was performed; genes included met 3 criteria: significant change between the 2 study time points using a paired t test, significant change between the 2 study time points using a Mann-Whitney nonparametric test, and significant Benjamini post hoc analysis. RESULTS: Fifteen analytes demonstrated significant increases between time points. Five of the 15 have been previously associated with the onset and/or severity of rheumatoid arthritis, including apoliopoprotein E and isoform E3, vascular cell adhesion protein 1, interleukin-34, and cell surface glycoprotein CD200 receptor 1. Chondrodegenerative enzymes and products of cartilage degeneration all increased over time following injury: MMP-1 (P = 0.08, standardized response mean [SRM] = 1.00), MMP-3 (P = 0.05, SRM = 0.90), ADAM12 (P = 0.03, SRM = 1.31), aggrecan (P = 0.08, SRM = 1.13), and CTX-II (P = 0.07, SRM = 0.56). Notable pathways that were differentially expressed following injury were the cytokine-cytokine receptor interaction and osteoclast differentiation pathways. CONCLUSIONS: The proteomic results and pathway analysis demonstrated a pattern of cartilage degeneration, not only consistent with previous findings but also changes consistent with an inflammatory arthritogenic process post-ACL injury.

Medications Used in U.S. Emergency Departments for an Ankle Sprain: An Analysis of the National Hospital Ambulatory Medical Care Survey.

BACKGROUND: An ankle sprain is a common musculoskeletal injury treated in the emergency department. Rest, ice, compression, and elevation is the preferred method for managing the symptoms after an ankle sprain. However, many patients receive a medication, such as a nonsteroidal anti-inflammatory drug (NSAID) or an opioid. OBJECTIVES: We sought to quantify the type of medication(s) used for an ankle sprain and to examine those across age and sex. METHODS: This was a retrospective review of the publicly available data collected through the National Hospital Ambulatory Medical Care Survey from 2006-2015. All cases with an isolated diagnosis of an ankle sprain were identified. Medication listed for each case was classified based on its detailed category and further explored across all 10 years, age, and sex. RESULTS: An estimated 9,052,678 ankle sprain visits occurred in emergency departments from 2006-2015. NSAIDs (56.1%) and opioid analgesic combination (28.4%) were the 2 most common medications. Regardless of the type, most medications were prescribed at discharge. The use of NSAIDs appears to have increased while opioid analgesic combinations decreased in 2010. NSAIDs were the most common medication identified with each age cohort; however, there was no apparent trend in medication for sex. CONCLUSIONS: NSAIDs are the most common medication used for ankle sprain visits to the ED. Nevertheless, an opioid is also used at a relatively high rate for this injury. These findings provide awareness and opportunity to focus on strategies for reduction of opioid use.

Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double-blind, placebo-controlled, multicenter trial: The MASTERS trial.

Progressive resistance exercise training (PRT) is the most effective known intervention for combating aging skeletal muscle atrophy. However, the hypertrophic response to PRT is variable, and this may be due to muscle inflammation susceptibility. Metformin reduces inflammation, so we hypothesized that metformin would augment the muscle response to PRT in healthy women and men aged 65 and older. In a randomized, double-blind trial, participants received 1,700 mg/day metformin (N = 46) or placebo (N = 48) throughout the study, and all subjects performed 14 weeks of supervised PRT. Although responses to PRT varied, placebo gained more lean body mass (p = .003) and thigh muscle mass (p < .001) than metformin. CT scan showed that increases in thigh muscle area (p = .005) and density (p = .020) were greater in placebo versus metformin. There was a trend for blunted strength gains in metformin that did not reach statistical significance. Analyses of vastus lateralis muscle biopsies showed that metformin did not affect fiber hypertrophy, or increases in satellite cell or macrophage abundance with PRT. However, placebo had decreased type I fiber percentage while metformin did not (p = .007). Metformin led to an increase in AMPK signaling, and a trend for blunted increases in mTORC1 signaling in response to PRT. These results underscore the benefits of PRT in older adults, but metformin negatively impacts the hypertrophic response to resistance training in healthy older individuals. ClinicalTrials.gov Identifier: NCT02308228.

Assessment of Gender-Affirming Hormone Therapy Requirements.

PURPOSE: There are currently no recommendations regarding the starting doses of hormone therapy for individuals with gender dysphoria. The purpose of this study was to assess the hormone dose needed to achieve target hormone levels in transgender men and transgender women, and whether body mass index (BMI) affects these doses. METHODS: A retrospective chart review of subjects seeking gender-affirming hormone therapy was performed. Height, weight, hormone doses, and serum hormone levels were collected from charts. Data were analyzed for a correlation between BMI and effective hormone dosing (dose that achieved hormone levels in the target range). RESULTS: Charts from 319 subjects were reviewed; however, only 84 transgender women and 71 transgender men had serum hormone levels available and only 40 transgender women and 54 transgender men had plasma hormone levels in the target range (normal range for affirmed gender). For transgender women, there was a significant negative correlation between BMI and effective estradiol dose (r = -0.337, p = 0.04). For transgender men, there was a positive correlation between BMI and effective testosterone dose (r = 0.409, p = 0.002). CONCLUSION: Increased BMI was associated with lower estrogen dose requirements in transgender women. In transgender men, an increase in BMI was associated with increased testosterone dose requirements. These results suggest that BMI may influence effective gender-affirming hormone dosing; however, further studies are needed to examine its utility in determining the initial hormone dose.

A guide for using NIH Image J for single slice cross-sectional area and composition analysis of the thigh from computed tomography.

Reports using computed tomography (CT) to estimate thigh skeletal muscle cross-sectional area and mean muscle attenuation are often difficult to evaluate due to inconsistent methods of quantification and/or poorly described analysis methods. This CT tutorial provides step-by-step instructions in using free, NIH Image J software to quantify both muscle size and composition in the mid-thigh, which was validated against a robust commercially available software, SliceOmatic. CT scans of the mid-thigh were analyzed from 101 healthy individuals aged 65 and older. Mean cross-sectional area and mean attenuation values are presented across seven defined Hounsfield unit (HU) ranges along with the percent contribution of each region to the total mid-thigh area. Inter-software correlation coefficients ranged from R2 = 0.92-0.99 for all specific area comparisons measured using the Image J method compared to SliceOmatic. We recommend reporting individual HU ranges for all areas measured. Although HU range 0-100 includes the majority of skeletal muscle area, HU range -29 to 150 appears to be the most inclusive for quantifying total thigh muscle. Reporting all HU ranges is necessary to determine the relative contribution of each, as they may be differentially affected by age, obesity, disease, and exercise. This standardized operating procedure will facilitate consistency among investigators reporting computed tomography characteristics of the thigh on single slice images. Trial Registration: ClinicalTrials.gov NCT02308228.

Ethnopsychopharmacology study of patients' beliefs regarding concerns about and necessity of taking psychiatric medications.

OBJECTIVE: The aim of this study was to examine whether or not cultural differences influence beliefs about the necessity of taking prescribed psychiatric drugs and concern about their adverse effects in psychiatric outpatients in Spain, Argentina, and Venezuela. METHODS: This cross-sectional study included 1,372 adult psychiatric outpatients using 2,438 psychotropic drugs and was designed to assess outpatients' beliefs about their prescribed medication. Patients completed sociodemographic, clinical questionnaires, and the Beliefs about Medicines Questionnaire Specific Scale and registered scores ranging from 1 to 5 on each of two subscales: concern and necessity. A "necessity-concern differential" was obtained by calculating the difference (range -4 to +4). RESULTS: The global score, including all drugs in the total sample, had a mean necessity score of 3.50 ± 0.95, a mean concern score of 2.97 ± 0.99, and a mean differential score of 0.54 ± 1.42. The concern and necessity mean scores varied significantly across these three culturally Hispanic countries, probably across drug classes, and were associated with treatment duration. On the other hand, age and education played a very limited role. CONCLUSIONS: Understanding the diverse effects of culture and society on these attitudes is highly relevant for the development of responsive mental health services in multicultural societies.

Description of the Services, Activities, and Interventions Within School-Based Physical Therapist Practices Across the United States.

Background: Students with disabilities receive school-based physical therapy services under the Individuals with Disabilities Education Improvement Act of 2004. Little research exists regarding therapy services in schools. Objective: This study explored the school-based services that students received and the activities and interventions that physical therapists implemented, and determined if services differed based on the student's functional gross motor ability and age. Design: This was a prospective observational cohort study using a practice-based evidence design. Methods: Data were collected by 109 physical therapists for 296 students, aged 5 to 12 years, receiving school-based physical therapy. Physical therapists completed the School-Physical Therapy Interventions for Pediatrics data form for 20 weeks during 1 school year. This evaluation included the type of service delivery, the amount of time spent on each student (consultation/documentation), minutes spent in activities, the specific interventions implemented, and the student's level of participation. The Gross Motor Function Classification System (GMFCS) was used to describe the students' functional ability. Results: Physical therapists provided an average of 26.7 min/wk (standard deviation [SD] = 15.1) of direct services and 13.1 min/wk (SD = 7.7) of services on behalf of the student. Primary activities were physical education/recreation (7.7 min/wk, SD = 8.2), mobility (6.7 min/wk, SD = 7.9), and sitting/standing/transitions (6.3 min/wk, SD = 8.1). Primary interventions were neuromuscular (32.5 counts per student, SD = 15.9), mobility (15.3 counts per student, SD = 14.65), and musculoskeletal (14.4 counts per student, SD = 10.3). Differences existed based on GMFCS but not student age. Limitations: Physical therapists reported School-Physical Therapy Interventions for Pediatrics data weekly, not necessarily after each therapy session. The GMFCS was used as a proxy of students' functional gross motor ability. Conclusions: Our description of services is provided to encourage physical therapists to reflect on the services they provide and to foster future examinations of service effectiveness.

School-based physical therapy services and student functional performance at school.

AIM: We explored relationships of school-based physical therapy to standardized outcomes of students receiving physical therapy. METHOD: Using a practice-based evidence research design, School Function Assessment (SFA) outcomes of 296 students with disabilities (mean age 7y 4mo [standard deviation 2y]; 166 males, 130 females), served by 109 physical therapists, were explored. After training, therapists completed 10 SFA scales on students at the beginning and end of the school year. Therapists collected detailed weekly data on services (activities, interventions, types, student participation) using the School-Physical Therapy Interventions for Pediatrics (S-PTIP) system. Stepwise linear regressions were used to investigate S-PTIP predictors of SFA outcomes. RESULTS: Predictors of SFA section outcomes varied in strength, with the coefficient of determination (R2 ) for each outcome ranging from 0.107 to 0.326. Services that correlated positively with the SFA outcomes included mobility, sensory, motor learning, aerobic/conditioning, functional strengthening, playground access interventions, and higher student participation during therapy (standardized ß=0.11-0.26). Services that correlated negatively with the SFA outcomes included providing services within student groups, within school activity, with students not in special education, during recreation activities, and with positioning, hands-on facilitation, sensory integration, orthoses, and equipment interventions (standardized ß=-0.14 to -0.22). INTERPRETATION: Consideration of outcomes is prudent to focus services. Overall results suggest we should emphasize active mobility practice by using motor learning interventions and engaging students within therapy sessions. WHAT THIS PAPER ADDS: No specific interventions predicted positively on all School Function Assessment (SFA) outcomes. Active movement practice seems related to overall better SFA outcomes. Active mobility practice improved SFA participation, mobility, recreation, and activities of daily living. Engaging students in therapy activities and interventions improved outcomes.