Exploring the Minnesota Multiphasic Personality Inventory (MMPI)-3 in a transgender and gender diverse sample.

Comparisons of transgender and gender diverse (TGD) individuals' mental health functioning with that of cisgender individuals rely almost exclusively on screening measures. The limited research with TGD individuals and omnibus assessment measures has primarily used previous iterations of the Minnesota Multiphasic Personality Inventories (MMPIs). This study sought to examine the psychometric functioning of the MMPI-3 with a TGD community sample (n = 97) and compare mean scores across TGD and cisgender subsamples. We expected MMPI-3 substantive scale reliability to be comparable across all samples and subsamples. Individual MMPI-3 scales were expected to demonstrate appropriate convergent and discriminant validity with relevant criterion measures in the TGD sample. Results generally supported MMPI-3 scale score reliability and validity with TGD individuals. Next, three sets of mean score comparisons were conducted across all MMPI-3 substantive scales: (a) TGD individuals not currently in mental health treatment and the MMPI-3 normative sample, (b) TGD individuals not currently in mental health treatment and TGD individuals currently in mental health treatment, and (c) TGD individuals currently in mental health treatment and an outpatient mental health sample. Fewer differences were found between TGD individuals in our sample who were not currently in mental health treatment and the MMPI-3 normative sample compared to previous work. This initial study indicates that MMPI-3 scales largely have appropriate psychometric properties when administered to a TGD sample and that the test may be helpful in identifying mental health needs of TGD individuals. Needs and directions for further research are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

International practice variation in perioperative laboratory testing in glioblastoma patients-a retrospective cohort study.

PURPOSE: Although standard-of-care has been defined for the treatment of glioblastoma patients, substantial practice variation exists in the day-to-day clinical management. This study aims to compare the use of laboratory tests in the perioperative care of glioblastoma patients between two tertiary academic centers-Brigham and Women's Hospital (BWH), Boston, USA, and University Medical Center Utrecht (UMCU), Utrecht, the Netherlands. METHODS: All glioblastoma patients treated according to standard-of-care between 2005 and 2013 were included. We compared the number of blood drawings and laboratory tests performed during the 70-day perioperative period using a Poisson regression model, as well as the estimated laboratory costs per patient. Additionally, we compared the likelihood of an abnormal test result using a generalized linear mixed effects model. RESULTS: After correction for age, sex, IDH1 status, postoperative KPS score, length of stay, and survival status, the number of blood drawings and laboratory tests during the perioperative period were 3.7-fold (p < 0.001) and 4.7-fold (p < 0.001) higher, respectively, in BWH compared to UMCU patients. The estimated median laboratory costs per patient were 82 euros in UMCU and 256 euros in BWH. Furthermore, the likelihood of an abnormal test result was lower in BWH (odds ratio [OR] 0.75, p < 0.001), except when the prior test result was abnormal as well (OR 2.09, p < 0.001). CONCLUSIONS: Our results suggest a substantially lower clinical threshold for ordering laboratory tests in BWH compared to UMCU. Further investigating the clinical consequences of laboratory testing could identify over and underuse, decrease healthcare costs, and reduce unnecessary discomfort that patients are exposed to.

Predictors of thoracic and lumbar spine injuries in patients with TBI: A nationwide analysis.

OBJECTIVE: Cervical spine injury screening is common practice for traumatic brain injury (TBI) patients. However, risk factors for concomitant thoracolumbar trauma remain unknown. We characterized epidemiology and clinical risk for concomitant thoracolumbar trauma in TBI. METHODS: We conducted a multi-center, retrospective cohort analysis of TBI patients in the National Trauma Data Bank from 2011-2014 using multivariable logistic regression. RESULTS: Out of 768,718 TBIs, 46,654 (6.1%) and 42,810 (5.6%) patients were diagnosed with thoracic and lumbar spine fractures, respectively. Only 11% of thoracic and 7% of lumbar spine fracture patients had an accompanying spinal cord injury at any level. The most common mechanism of injury was motor vehicle accident (67% of thoracic and 71% and lumbar fractures). Predictors for both thoracic and lumbar fractures included moderate (thoracic: OR 1.26, 95%CI 1.21-1.31; lumbar: OR 1.13, 95%CI 1.08-1.18) and severe Glasgow Coma Scale (GCS) score (OR 1.71, 95%CI 1.67-1.75; OR 1.17, 95%CI 1.13-1.20) compared to mild; epidural hematoma (OR 1.36, 95%CI 1.28-1.44; OR 1.1, 95%CI 1.04-1.19); lower extremity injury (OR 1.38, 95%CI 1.35-1.41; OR 2.50, 95%CI 2.45-2.55); upper extremity injury (OR 2.19, 95%CI 2.14-2.23; OR 1.15, 95%CI 1.13-1.18); smoking (OR 1.09, 95%CI 1.06-1.12; OR 1.12, 95%CI 1.09-1.15); and obesity (OR 1.39, 95%CI 1.34-1.45; OR 1.29, 95%CI 1.24-1.35). Thoracic injuries (OR 4.45; 95% CI 4.35-4.55) predicted lumbar fractures, while abdominal injuries (OR 2.02; 95% CI 1.97-2.07) predicted thoracic fractures. CONCLUSIONS: We identified GCS, smoking, upper and lower extremity injuries, and obesity as common risk factors for thoracic and lumbar spinal fractures in TBI.

Examining Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) scale scores in a transgender and gender diverse sample.

Transgender and gender diverse (TGD) individuals are at increased risk of various forms of psychopathology. Little research has been conducted with broadband measures of psychopathology and TGD individuals. The present study sought to examine how TGD individuals scored on Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) scales. This included MMPI-2-RF profiles from 85 TGD individuals; 37 were in mental health treatment and 48 of which were not. This study involved three sets of pairwise comparisons on MMPI-2-RF substantive scales via t-tests: (a) TGD individuals not in treatment versus the MMPI-2-RF normative sample, (v) TGD individuals not in treatment versus TGD individuals in treatment, and (c) TGD individuals in treatment versus a large outpatient clinical sample. Compared to the MMPI-2-RF normative sample, TGD individuals not in treatment scored significantly higher on 31 of the MMPI-2-RF substantive scales. Compared to those TGD individuals not in treatment, those in treatment had significantly higher scores on several MMPI-2-RF scales, primarily those of internalizing psychopathology. In the final comparison between TGD individuals in treatment and an outpatient clinical sample, the TGD individuals had some significantly higher and significantly lower scores on MMPI-2-RF substantive scales. Implications regarding minority stress and the current findings are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Effect of a Mobile Health App on Adherence to Physical Health Treatment: Retrospective Analysis.

BACKGROUND: Adherence to prescribed medical interventions can predict the efficacy of the treatment. In physical health clinics, not adhering to prescribed therapy can take the form of not attending a scheduled clinic visit (no-show appointment) or prematurely terminating treatment against the advice of the provider (self-discharge). A variety of interventions, including mobile phone apps, have been introduced for patients to increase their adherence to attending scheduled clinic visits. Limited research has examined the impact of a mobile phone app among patients attending chiropractic and rehabilitation clinic visits. OBJECTIVE: This study aims to compare adherence to prescribed physical health treatment among patients attending a chiropractic and rehabilitation clinic who did and did not choose to adopt a phone-based app to complement their treatment. METHODS: The medical records of new patients who presented for care during 2019 and 2020 at 5 community-based chiropractic and rehabilitation clinics were reviewed for the number of kept and no-show appointments and to determine whether the patient was provider-discharged or self-discharged. During this 24-month study, 36.28% (1497/4126) of patients seen in the targeted clinics had downloaded the Kanvas app on their mobile phone, whereas the remaining patients chose not to download the app (usual care group). The gamification component of the Kanvas app provided the patient with a point every time they attended their visits, which could be redeemed as an incentive. RESULTS: During both 2019 and 2020, the Kanvas app group was provider-discharged at a greater rate than the usual care group. The Kanvas app group kept a similar number of appointments compared with the usual care group in 2019 but kept significantly more appointments than the usual care group in 2020. During 2019, both groups exhibited a similar number of no-show appointments; however, in 2020, the Kanvas app group demonstrated more no-show appointments than the usual care group. When collapsed across years and self-discharged, the Kanvas app group had a greater number of kept appointments compared with the usual care group. When provider-discharged, both groups exhibited a similar number of kept appointments. The Kanvas app group and the usual care group were similar in the number of no-show appointments when provider-discharged, and when self-discharged, the Kanvas app group had more no-show appointments compared with the usual care group. CONCLUSIONS: Patients who did or did not have access to the Kanvas app and were provider-discharged exhibited a similar number of kept appointments and no-show appointments. When patients were self-discharged and received the Kanvas app, they exhibited 3.2 more kept appointments and 0.94 more no-show appointments than the self-discharged usual care group.

Automating Clinical Chart Review: An Open-Source Natural Language Processing Pipeline Developed on Free-Text Radiology Reports From Patients With Glioblastoma.

PURPOSE: The aim of this study was to develop an open-source natural language processing (NLP) pipeline for text mining of medical information from clinical reports. We also aimed to provide insight into why certain variables or reports are more suitable for clinical text mining than others. MATERIALS AND METHODS: Various NLP models were developed to extract 15 radiologic characteristics from free-text radiology reports for patients with glioblastoma. Ten-fold cross-validation was used to optimize the hyperparameter settings and estimate model performance. We examined how model performance was associated with quantitative attributes of the radiologic characteristics and reports. RESULTS: In total, 562 unique brain magnetic resonance imaging reports were retrieved. NLP extracted 15 radiologic characteristics with high to excellent discrimination (area under the curve, 0.82 to 0.98) and accuracy (78.6% to 96.6%). Model performance was correlated with the inter-rater agreement of the manually provided labels (ρ = 0.904; P < .001) but not with the frequency distribution of the variables of interest (ρ = 0.179; P = .52). All variables labeled with a near perfect inter-rater agreement were classified with excellent performance (area under the curve > 0.95). Excellent performance could be achieved for variables with only 50 to 100 observations in the minority group and class imbalances up to a 9:1 ratio. Report-level classification accuracy was not associated with the number of words or the vocabulary size in the distinct text documents. CONCLUSION: This study provides an open-source NLP pipeline that allows for text mining of narratively written clinical reports. Small sample sizes and class imbalance should not be considered as absolute contraindications for text mining in clinical research. However, future studies should report measures of inter-rater agreement whenever ground truth is based on a consensus label and use this measure to identify clinical variables eligible for text mining.

Apical sodium-dependent bile acid transporter inhibition with volixibat improves metabolic aspects and components of non-alcoholic steatohepatitis in Ldlr-/-.Leiden mice.

Interruption of bile acid recirculation through inhibition of the apical sodium-dependent bile acid transporter (ASBT) is a promising strategy to alleviate hepatic cholesterol accumulation in non-alcoholic steatohepatitis (NASH), and improve the metabolic aspects of the disease. Potential disease-attenuating effects of the ASBT inhibitor volixibat (5, 15, and 30 mg/kg) were investigated in high-fat diet (HFD)-fed Ldlr-/-.Leiden mice over 24 weeks. Plasma and fecal bile acid levels, plasma insulin, lipids, and liver enzymes were monitored. Final analyses included liver histology, intrahepatic lipids, mesenteric white adipose tissue mass, and liver gene profiling. Consistent with its mechanism of action, volixibat significantly increased the total amount of bile acid in feces. At the highest dose, volixibat significantly attenuated the HFD-induced increase in hepatocyte hypertrophy, hepatic triglyceride and cholesteryl ester levels, and mesenteric white adipose tissue deposition. Non-alcoholic fatty liver disease activity score (NAS) was significantly lower in volixibat-treated mice than in the HFD controls. Gene profiling showed that volixibat reversed the inhibitory effect of the HFD on metabolic master regulators, including peroxisome proliferator-activated receptor-γ coactivator-1ß, insulin receptor, and sterol regulatory element-binding transcription factor 2. Volixibat may have beneficial effects on physiological and metabolic aspects of NASH pathophysiology.

Arming an Oncolytic Herpes Simplex Virus Type 1 with a Single-chain Fragment Variable Antibody against PD-1 for Experimental Glioblastoma Therapy.

PURPOSE: Glioblastoma (GBM) is resistant to standard of care. Immune checkpoints inhibitors (such as anti-PD-1 mAbs) efficiently restore antitumor T-cell activity. We engineered a new oncolytic herpes simplex virus (oHSV) expressing a single-chain antibody against PD-1 (scFvPD-1) to evaluate its efficacy in mouse models of GBM. EXPERIMENTAL DESIGN: NG34scFvPD-1 expresses the human GADD34 gene transcriptionally controlled by the Nestin promoter to allow replication in GBM cells and a scFvPD-1 cDNA transcriptionally controlled by the CMV promoter. ELISA assays were performed to detect binding of scFvPD-1 to mouse and human PD-1. In vitro cytotoxicity and replication assays were performed to measure NG34scFvPD-1 oncolysis, and scFvPD-1 expression and secretion were determined. In vivo survival studies using orthotopic mouse GBM models were performed to evaluate the therapeutic potency of NG34scFvPD-1. RESULTS: NG34scFvPD-1-infected GBM cells express and secrete scFvPD-1 that binds mouse PD-1. The introduction of the scFvPD-1 sequence in the viral backbone does not alter the oncolytic properties of NG34scFvPD-1. In situ NG34scFvPD-1 treatment improved the survival with a tail of durable survivorship in 2 syngeneic immunocompetent mouse models of GBM. Mice that survived the first GBM challenge rejected the second challenge of GBM when implanted in the contralateral hemisphere. However, this was not true when athymic mice were employed as the recipients of the second challenge, consistent with the need for an intact immune system to obtain a memory response. CONCLUSIONS: NG34scFvPD-1 treatment induces a durable antitumor response in 2 preclinical mouse models of GBM with evidence for antitumor memory.

The mechanics of corneal deformation and rupture for penetrating injury in the human eye.

Penetrating eye injuries are surgical emergencies with guarded visual prognosis. The purpose of the current study was to determine the force required to rupture the cornea with a penetrating object, and to study how this force is affected by the object geometry. Thirty-six human cadaveric eyes from donors of various ages were characterized for diameter, axial length, and pre-test intraocular pressure. In order to investigate the effects of specimen storage time on the tissue response, half of the specimens were tested within two weeks of donor expiration, and half of the specimens were stored at -4°C for 12-18 months. Indenters of three different diameters (1.0, 1.5, and 2.0mm) were lowered into the apex of the cornea until rupture. Resistance to displacement (stiffness), displacement at failure, and the force at failure were determined. Multi-variable regression analysis was used to determine associations of the input variables (indenter size, test speed, and tissue postmortem time) on the mechanics of the tissue response. Twenty-nine of the 36 specimens failed at the indenter location in the cornea, four failed at the limbus, and three failed in the sclera near sites of muscle attachment. The average force at failure caused by the 1.0mm, 1.5mm, and 2.0mm indenters increased from 30.5±5.5N to 40.5±8.3N to 58.2±14.5N, respectively (p<0.002). The force at failure was associated with the donor age (p<0.001), and globe diameter (p<0.041), but was not associated with pre-test intraocular pressure, tissue postmortem time, axial length, or speed of the indenter. This study has quantified the force-displacement and failure response of a large series of human cadaveric eyes subjected to penetrating indentation loads on the cornea. The results provide useful data for characterizing the relationship between corneal rupture and the geometry of a penetrating object.

Finite element analysis and experimental evaluation of penetrating injury through the cornea.

Penetration injuries of the eye are among the most frequent causes of permanent visual impairment resulting from trauma. The purpose of this study was to determine the peak strain at which rupture occurs in the cornea due to a penetrating object. Probes of varying diameters (1.0, 1.5, and 2.0mm) were pressed into the apex of the cornea of 36 human cadaveric eye specimens until perforation or rupture of the specimen at the cornea, limbus, or sclera occurred. An axisymmetric finite element model of the human globe was created to replicate the experimental set-up. The models were used to map the force-displacement response of the experiments and quantitatively determine a peak strain at which the eye ruptures. For the experiments, the average force at failure increased from the smallest to largest probe (p<0.002). The average forces at failure are as follows: 30.5±5.5N (1.0mm probe); 40.5±8.3N (1.5mm probe); 58.2±14.5N (2.0mm probe). The force-displacement responses of the finite element models of all three probe sizes bounded and tracked the experimental data. In all cases, the peak strain at failure in the cornea was located on the posterior surface of the cornea, directly adjacent to the corneal apex. This strain was in the range of 29% to 33% for all models analyzed. In addition to determining an objective failure strain of corneal tissue, the model developed in this study can provide quantitative information for understanding the risk of penetrating eye injuries.

Which Domain of the PSY-5 Is Most Relevant to Substance Use?

Substance use has generally been related to lower levels of agreeableness and conscientiousness, but has evidenced relationships with other personality trait domains as well, including impulsivity. This study was conducted to determine which trait domain of personality is most related to substance use from the perspective of the Personality Psychopathology Five model (Harkness & McNulty, 1994 ). Archival data were used from 2 clinical settings: 1 outpatient community mental health center and 1 inpatient Veteran's Affairs hospital. The outpatient sample was mostly female (58.9%), White (78.7%), and had a mean age of 33.01 (SD = 10.26). The inpatient sample was entirely male, predominantly White (91.5%), and had a mean age of 48.03 (SD = 13.88). Correlations were conducted to identify the Minnesota Multiphasic Personality Inventory-2-Restructured Form Personality Psychopathology Five scales (Ben-Porath & Tellegen, 2008 ; Harkness et al., 2013 ) that were significantly related to variables measuring substance use. Subsequent regression analyses revealed that Disconstraint was the only significant predictor in the majority (89%) of analyses. In the event Disconstraint was not the only significant predictor, it continued to exhibit the largest unique predictive impact in the regression models. These results suggest that Disconstraint is the Personality Psychopathology-Five dimension most relevant to substance use.

A Vertically Integrated Online Radiology Curriculum Developed as a Cognitive Apprenticeship: Impact on Student Performance and Learning.

RATIONALE AND OBJECTIVES: The principles of Collins' cognitive apprenticeship model were used to design a radiology curriculum in which medical students practice radiological skills using online case-based modules. The modules are embedded within clinical third-year clerkships, and students are provided with personalized feedback from the instructors. We describe the development of the vertical online radiology curriculum and evaluate its impact on student achievement and learning process using a mixed method approach. MATERIALS AND METHODS: The curriculum was developed over a 2-year period. Student participation was voluntary in the first year and mandatory in the second year. For quantitative curriculum evaluation, student metrics for voluntary versus mandatory groups were assessed using independent sample t tests and variable entry method regression analysis. For qualitative analysis, responses from a survey of students about the value of the curriculum were organized into defined themes using consensus coding. RESULTS: Mandatory participation significantly improved (p = .001) the mean radiology examination score (82 %) compared to the voluntary group (73%), suggesting that mandatory participation had a beneficial effect on student performance. Potential preexisting differences in underlying general academic performance were accounted for by including mean basic science grades as the first variable in the regression model. The significant increase in R(2) from .16 to .28 when number of radiology cases completed was added to the original model, and the greater value of the standardized beta for this variable, suggest that the curriculum made a significant contribution to students' radiology examination scores beyond their baseline academic performance. Five dominant themes about curricular characteristics that enhanced student learning and beneficial outcomes emerged from consensus coding. These themes were (1) self-paced design, (2) receiving feedback from faculty, (3) clinical relevance of cases, (4) gaining confidence in interpreting radiological images, and (5) transfer of conceptual knowledge to actual practice. CONCLUSIONS: The vertically integrated online radiology curriculum can positively impact student performance and learning process in the context of the cognitive apprenticeship model.

Effective intra-S checkpoint responses to UVC in primary human melanocytes and melanoma cell lines.

The objective of this study was to assess potential functional attenuation or inactivation of the intra-S checkpoint during melanoma development. Proliferating cultures of skin melanocytes, fibroblasts, and melanoma cell lines were exposed to increasing fluences of UVC and intra-S checkpoint responses were quantified. Melanocytes displayed stereotypic intra-S checkpoint responses to UVC qualitatively and quantitatively equivalent to those previously demonstrated in skin fibroblasts. In comparison with fibroblasts, primary melanocytes displayed reduced UVC-induced inhibition of DNA strand growth and enhanced degradation of p21Waf1 after UVC, suggestive of enhanced bypass of UVC-induced DNA photoproducts. All nine melanoma cell lines examined, including those with activating mutations in BRAF or NRAS oncogenes, also displayed proficiency in activation of the intra-S checkpoint in response to UVC irradiation. The results indicate that bypass of oncogene-induced senescence during melanoma development was not associated with inactivation of the intra-S checkpoint response to UVC-induced DNA replication stress.

Responding to the challenge of untreatable gonorrhea: ETX0914, a first-in-class agent with a distinct mechanism-of-action against bacterial Type II topoisomerases.

With the diminishing effectiveness of current antibacterial therapies, it is critically important to discover agents that operate by a mechanism that circumvents existing resistance. ETX0914, the first of a new class of antibacterial agent targeted for the treatment of gonorrhea, operates by a novel mode-of-inhibition against bacterial type II topoisomerases. Incorporating an oxazolidinone on the scaffold mitigated toxicological issues often seen with topoisomerase inhibitors. Organisms resistant to other topoisomerase inhibitors were not cross-resistant with ETX0914 nor were spontaneous resistant mutants to ETX0914 cross-resistant with other topoisomerase inhibitor classes, including the widely used fluoroquinolone class. Preclinical evaluation of ETX0914 pharmacokinetics and pharmacodynamics showed distribution into vascular tissues and efficacy in a murine Staphylococcus aureus infection model that served as a surrogate for predicting efficacious exposures for the treatment of Neisseria gonorrhoeae infections. A wide safety margin to the efficacious exposure in toxicological evaluations supported progression to Phase 1. Dosing ETX0914 in human volunteers showed sufficient exposure and minimal adverse effects to expect a highly efficacious anti-gonorrhea therapy.

Validity of Minnesota Multiphasic Personality Inventory ­ 2 ­ Restructured Form (MMPI-2-RF) scores as a function of gender, ethnicity, and age of bariatric surgery candidates.

BACKGROUND: Presurgical psychological screening is used to identify factors that may impact postoperative adherence and surgical outcomes in bariatric surgery candidates. Minnesota Multiphasic Personality Inventory - 2 Restructured Form (MMPI-2-RF) findings have demonstrated utility for this task. OBJECTIVES: To explore whether there are clinically meaningful gender, ethnicity, or age differences in presurgical MMPI-2-RF scores and the validity of these scores in bariatric surgery candidates. METHODS: The sample was composed of 872 men and 2337 women. Ethnicity/race groups included 2,204 Caucasian, 744 African American, and 96 Hispanic individuals. A sample of 165 were not included in the ethnicity/race analyses because they were of another descent. Ages groups included 18-35 year olds (n = 454), 36-49 year olds (n = 1154), 50-64 year olds, (n = 1246), and 65 years old or older (n = 355). Validity data, obtained via a retrospective chart review, were available for a subset patients (n = 1,268) who were similarly distributed. Step-down hierarchical regression analyses were conducted to assess for differential validity. RESULTS: Bariatric surgery candidates produced comparable MMPI-2-RF scores in all subsamples, indicating that the test norms generalize across demographic groups. Validity findings were also generally comparable, indicating that MMPI-2-RF scores have the same interpretive implications in demographically diverse subgroups of bariatric surgery candidates. CONCLUSIONS: The MMPI-2-RF can assist in presurgical psychological screening of demographically diverse bariatric surgery candidates.

Associations between formative practice quizzes and summative examination outcomes in a medical anatomy course.

Formative practice quizzes have become common resources for self-evaluation and focused reviews of course content in the medical curriculum. We conducted two separate studies to (1) compare the effects of a single or multiple voluntary practice quizzes on subsequent summative examinations and (2) examine when students are most likely to use practice quizzes relative to the summative examinations. In the first study, providing a single on-line practice quiz followed by instructor feedback had no effect on examination average grades compared to the previous year or student performances on similar questions. However, there were significant correlations between student performance on each practice quiz and each summative examination (r = 0.42 and r = 0.24). When students were provided multiple practice quizzes with feedback (second study), there were weak correlations between the frequency of use and performance on each summative examination (r = 0.17 and r = 0.07). The frequency with which students accessed the practice quizzes was greatest the day before each examination. In both studies, there was a decline in the level of student utilization of practice quizzes over time. We conclude that practice quizzes provide some predictive value for performances on summative examinations. Second, making practice quizzes available for longer periods prior to summative examinations does not promote the use of the quizzes as a study strategy because students appear to use them mostly to assess knowledge one to two days prior to examinations.

Compounded drugs of value in outpatient hospice and palliative care practice.

A compounded preparation is needed when no commercially manufactured medication is available to adequately address a patient's medical needs. Among the greatest therapeutic challenges faced by both patients and caregivers is the treatment required by individuals who have a terminal condition. It is difficult to find evidence-based studies on the management of end-of-life situations because each patient's medical case is unique. In addition, maintaining a controlled environment for such patients is difficult. End-of-life care is multifaceted; it does not lend itself to "cookbook medicine," and people with a terminal illness are among the most vulnerable patients in need of effective and compassionate care. When those patients suffer in spite of commercially available therapies, the innovation and experience of clinicians and compounding pharmacists can often yield a solution to the most challenging treatment problems. In this article, we discuss some of the most often prescribed compounds used in outpatient hospice and palliative care to treat common conditions (wounds, pain and dyspnea, intractable cough, nausea and vomiting, depression, bladder infections caused by an indwelling catheter, rectal pain). The effectiveness of the preparations we describe is substantiated in the medical literature and by our personal experience, which together encompasses nearly 100 years of clinical practice. The medications described in this report have been shown over time to be effective. Formulations for the preparations presented in this article are provided on the International Journal of Pharmaceutical Compounding website at www.ijpc.com/webcontent.

Novel DNA gyrase inhibiting spiropyrimidinetriones with a benzisoxazole scaffold: SAR and in vivo characterization.

The compounds described herein with a spirocyclic architecture fused to a benzisoxazole ring represent a new class of antibacterial agents that operate by inhibition of DNA gyrase as corroborated in an enzyme assay and by the inhibition of precursor thymidine into DNA during cell growth. Activity resided in the configurationally lowest energy (2S,4R,4aR) diastereomer. Highly active compounds against Staphylococcus aureus had sufficiently high solubility, high plasma protein free fraction, and favorable pharmacokinetics to suggest that in vivo efficacy could be demonstrated, which was realized with compound (-)-1 in S. aureus mouse infection models. A high drug exposure NOEL on oral dosing in the rat suggested that a high therapeutic margin could be achieved. Importantly, (-)-1 was not cross-resistant with other DNA gyrase inhibitors such as fluoroquinolone and aminocoumarin antibacterials. Hence, this class shows considerable promise for the treatment of infections caused by multidrug resistant bacteria, including S. aureus.