Comparison of different methods of screening to identify intimate partner violence: A randomized controlled trial.

OBJECTIVE: Screening for intimate partner violence in the home is often challenging due to the lack of privacy. The aim of this study was to compare two different screening methods (paper-pencil vs. tablet) for identifying intimate partner violence during perinatal home visits. DESIGN: Randomized control trial. SAMPLE: Pregnant women (N = 416) in perinatal home visiting programs were randomized to either paper-pencil or computer assisted, intimate partner violence screening. MEASUREMENTS: The Abuse Assessment Screen was used to screen for physical and sexual IPV and Women's Experiences with Battering for emotional intimate partner violence. RESULTS: No significant differences in prevalence were found between the screening methods. Intimate partner violence prevalence rates for the year before and/or during pregnancy using paper-pencil was 21.8% versus 24.5% using tablets (p = .507). There were significant differences in prevalence among the three race/ethnic groups (Caucasian, 36.9%; African American, 26.7%; Hispanics, 10.6%; p < .001) and significant differences in rates across three geographical areas: urban 16.0%; rural 27.6%, suburban women 32.3% (p < .001). CONCLUSIONS: This study provides evidence that both methods are useful for identifying intimate partner violence during perinatal home visits.

Passport to Freedom: A Trauma-Informed Mindfulness Program for Previously Incarcerated Women.

Poly-victimization is often reported by formerly incarcerated women and leads to physical and mental health problems that interfere with daily functioning, sustained employment, and housing stability. Although reentry programs exist, few focus on the physical and emotional impact of multiple traumas. Passport to Freedom (P2F), a woman-centered, trauma-informed reentry program, was developed to support formerly incarcerated women. The pilot intervention, performed in 2017, focused on the connections between trauma and health, coping with symptoms, and managing one's own health. To examine the effectiveness and feasibility of the intervention, we performed the current mixed methods study with two phases: (1) focus groups, and (2) sessions combining mindfulness and health promotion activities with follow-up evaluations. Participants (N = 24) showed decreased symptoms of depression and concerns of everyday stressors after the intervention. Of participants, 84% (n = 16) reported practicing mindfulness and 63% (n = 8) stated that mindfulness exercises helped with daily stress management. The P2F program offers a promising approach to support formerly incarcerated women with health self-management. [Journal of Psychosocial Nursing and Mental Health Services, 62(6), 18-26.].

Influence of fine particle content in debris flows on alluvial fan morphology.

Alluvial fans are large-scale depositional structures commonly found at the base of mountain ranges. They are relatively soil-rich compared to the rocky terrains, or catchment areas, from which their material originates. When frequented by debris flows (massive, muddy, rocky flows) they contribute significantly to local hazards as they carry focused, collisional, fast-moving materials across alluvial fans, unpredictable in size, speed, and direction. We research how fine particle content in debris flows correlates with directional changes, i.e., debris flow avulsions. Toward this, we analyzed field data from two neighboring alluvial fans in the White Mountains (California, USA) that exhibit dramatically different topographies despite their proximity and associated similar long-term climates. Informed by these measurements, we performed long-term and incremental alluvial fan experiments built by debris flows with systematically-varied fine particle content. We found that (1) decreasing fine particle content increases the variability of fan slopes and associated channelization dynamics, and (2) for all mixtures longer-term continuous alluvial fan experiments form more complex surface channelizations than repeated flows for the same total time, indicating the importance of both particle sizes and timescales on alluvial fan surface morphology.

Clinical Implications of Climate Change on US Emergency Medicine: Challenges and Opportunities.

The adverse influences of climate change are manifesting as health burdens relevant to clinical practice, affecting the very underpinnings of health and stressing the health care system. Emergency medicine is likely to bear a large burden, with its focus on urgent and emergency care, through its role as a safety-net provider for vulnerable populations and as a leader in disaster medicine. Clinically, climate change is affecting emergency medicine practice through the amplification of climate-related disease patterns and epidemiologic shifts for conditions diagnosed and treated in emergency departments (EDs), especially for vulnerable populations. In addition, climate-driven intensification of extreme weather is disrupting health care delivery in EDs and health care systems. Thus, there are significant opportunities for emergency medicine to lead the medical response to climate change through 7 key areas: clinical practice improvements, building resilient EDs and health care systems, adaptation and public health engagement, disaster preparedness, mitigation, research, and education. In the face of this growing health threat, systemwide preparation rooted in local leadership and responsiveness is necessary to efficiently and effectively care for our vulnerable communities.

Developing emergency care systems: a human rights-based approach.

The delivery of emergency care is an effective strategy to reduce the global burden of disease. Emergency care cross cuts traditional disease-focused disciplines to manage a wide range of the acute illnesses and injuries that contribute substantially to death and disability, particularly in low- and middle-income countries. While the universal health coverage (UHC) movement is gaining support, and human rights and health systems are integral to UCH, few concrete discussions on the human right to emergency care have been taken place to date. Furthermore, no rights-based approach to developing emergency care systems has been proposed. In this article, we explore key components of the right to health (that is, availability, accessibility, acceptability and quality of health facilities, goods and services) as they relate to emergency care systems. We propose the use of a rights-based framework for the fulfilment of core obligations of the right to health and the progressive realization of emergency care in all countries.

La prestation de soins d'urgence constitue une stratégie efficace pour réduire la charge mondiale de morbidité. Les soins d'urgence recoupent les disciplines traditionnelles centrées sur les maladies pour prendre en charge de nombreuses blessures et affections aiguës qui contribuent sensiblement aux décès et aux handicaps, en particulier dans les pays à revenu faible et intermédiaire. Alors que le mouvement pour la couverture sanitaire universelle prend de l'ampleur et que les droits de l'homme et les systèmes de santé en font partie intégrante, peu de discussions concrètes sur le droit à des soins d'urgence ont eu lieu à ce jour. En outre, aucune démarche fondée sur les droits et visant à développer des systèmes de soins d'urgence n'a été proposée. Dans cet article, nous nous intéressons aux composantes clés du droit à la santé (à savoir la disponibilité, l'accessibilité, l'acceptabilité et la qualité des établissements, des produits et des services de soins) pour ce qui est des systèmes de soins d'urgence. Nous proposons d'utiliser un cadre fondé sur les droits pour l'exécution des obligations essentielles du droit à la santé et la mise en place progressive de soins d'urgence dans tous les pays.

La prestación de atención de emergencia es una estrategia eficaz para reducir la carga mundial de morbilidad. La atención de emergencia trasciende las disciplinas tradicionales centradas en las enfermedades para tratar una amplia gama de enfermedades y lesiones agudas que contribuyen sustancialmente a la muerte y la discapacidad, en particular en los países de ingresos bajos y medianos. Si bien el movimiento de la cobertura sanitaria universal (CSU) está ganando apoyo, y los derechos humanos y los sistemas de salud son parte integral de la CSU, hasta la fecha se han llevado a cabo pocas discusiones concretas sobre el derecho humano a la atención de emergencia. Además, no se ha propuesto un enfoque basado en los derechos para desarrollar sistemas de atención de emergencia. En este artículo exploramos los componentes clave del derecho a la salud (es decir, disponibilidad, accesibilidad, aceptabilidad y calidad de las instalaciones, bienes y servicios sanitarios) en relación con los sistemas de atención de emergencia. Proponemos el uso de un marco basado en los derechos para el cumplimiento de las obligaciones básicas del derecho a la salud y la realización progresiva de la atención de emergencia en todos los países.

Phase I and Pharmacology Study of Ropidoxuridine (IPdR) as Prodrug for Iododeoxyuridine-Mediated Tumor Radiosensitization in Advanced GI Cancer Undergoing Radiation.

PURPOSE: Iododeoxyuridine (IUdR) is a potent radiosensitizer; however, its clinical utility is limited by dose-limiting systemic toxicities and the need for prolonged continuous infusion. 5-Iodo-2-pyrimidinone-2'-deoxyribose (IPdR) is an oral prodrug of IUdR that, compared with IUdR, is easier to administer and less toxic, with a more favorable therapeutic index in preclinical studies. Here, we report the clinical and pharmacologic results of a first-in-human phase I dose escalation study of IPdR + concurrent radiation therapy (RT) in patients with advanced metastatic gastrointestinal (GI) cancers. PATIENTS AND METHODS: Adult patients with metastatic GI cancers referred for palliative RT to the chest, abdomen, or pelvis were eligible for study. Patients received IPdR orally once every day × 28 days beginning 7 days before the initiation of RT (37.5 Gy in 2.5 Gy × 15 fractions). A 2-part dose escalation scheme was used, pharmacokinetic studies were performed at multiple time points, and all patients were assessed for toxicity and response to Day 56. RESULTS: Nineteen patients were entered on study. Dose-limiting toxicity was encountered at 1,800 mg every day, and the recommended phase II dose is 1,200 mg every day. Pharmacokinetic analyses demonstrated achievable and sustainable levels of plasma IUdR ≥1 µmol/L (levels previously shown to mediate radiosensitization). Two complete, 3 partial, and 9 stable responses were achieved in target lesions. CONCLUSIONS: Administration of IPdR orally every day × 28 days with RT is feasible and tolerable at doses that produce plasma IUdR levels ≥1 µmol/L. These results support the investigation of IPdR + RT in phase II studies.

Characterization of potent and selective iodonium-class inhibitors of NADPH oxidases.

The NADPH oxidases (NOXs) play a recognized role in the development and progression of inflammation-associated disorders, as well as cancer. To date, several NOX inhibitors have been developed, through either high throughput screening or targeted disruption of NOX interaction partners, although only a few have reached clinical trials. To improve the efficacy and bioavailability of the iodonium class NOX inhibitor diphenylene iodonium (DPI), we synthesized 36 analogs of DPI, focusing on improved solubility and functionalization. The inhibitory activity of the analogs was interrogated through cell viability and clonogenic studies with a colon cancer cell line (HT-29) that depends on NOX for its proliferative potential. Lack of altered cellular respiration at relevant iodonium analog concentrations was also demonstrated. Additionally, inhibition of ROS generation was evaluated with a luminescence assay for superoxide, or by Amplex Red® assay for H2O2 production, in cell models expressing specific NOX isoforms. DPI and four analogs (NSCs 740104, 751140, 734428, 737392) strongly inhibited HT-29 cell growth and ROS production with nanomolar potency in a concentration-dependent manner. NSC 737392 and 734428, which both feature nitro functional groups at the meta position, had >10-fold higher activity against ROS production by cells that overexpress dual oxidase 2 (DUOX2) than the other compounds examined (IC50≈200-400nM). Based on these results, we synthesized and tested NSC 780521 with optimized potency against DUOX2. Iodonium analogs with anticancer activity, including the first generation of targeted agents with improved specificity against DUOX2, may provide a novel therapeutic approach to NOX-driven tumors.

Evaluating IPMN and pancreatic carcinoma utilizing quantitative histopathology.

Intraductal papillary mucinous neoplasms (IPMN) are pancreatic lesions with uncertain biologic behavior. This study sought objective, accurate prediction tools, through the use of quantitative histopathological signatures of nuclear images, for classifying lesions as chronic pancreatitis (CP), IPMN, or pancreatic carcinoma (PC). Forty-four pancreatic resection patients were retrospectively identified for this study (12 CP; 16 IPMN; 16 PC). Regularized multinomial regression quantitatively classified each specimen as CP, IPMN, or PC in an automated, blinded fashion. Classification certainty was determined by subtracting the smallest classification probability from the largest probability (of the three groups). The certainty function varied from 1.0 (perfectly classified) to 0.0 (random). From each lesion, 180 ± 22 nuclei were imaged. Overall classification accuracy was 89.6% with six unique nuclear features. No CP cases were misclassified, 1/16 IPMN cases were misclassified, and 4/16 PC cases were misclassified. Certainty function was 0.75 ± 0.16 for correctly classified lesions and 0.47 ± 0.10 for incorrectly classified lesions (P = 0.0005). Uncertainty was identified in four of the five misclassified lesions. Quantitative histopathology provides a robust, novel method to distinguish among CP, IPMN, and PC with a quantitative measure of uncertainty. This may be useful when there is uncertainty in diagnosis.

Psychotic-like experiences, symptom expression, and cognitive performance in combat veterans with posttraumatic stress disorder.

Apparent psychotic symptoms are often associated with posttraumatic stress disorder (PTSD), but these symptoms are poorly understood. In a sample of 30 male Vietnam combat veterans with severe and chronic PTSD, we conducted detailed assessments of psychotic symptom endorsement, insight, symptom severity, neurocognitive function, and feigning. Two thirds of the subjects endorsed a psychotic item but did not believe that the experiences were real. Those endorsing psychotic items were higher in PTSD severity, general psychopathology, and dissociation but not depression, functional health, cognitive function, or feigned effort. Severity of psychotic symptoms correlated with dissociation, combat exposure, and attention but not PTSD, depression, or functional health. Those endorsing psychotic items scored higher on a screen but not on a detailed structured interview for malingering. Endorsement of psychotic experiences by combat veterans with PTSD do not seem to reflect psychotic symptoms or outright malingering.

First-in-human phase 0 trial of oral 5-iodo-2-pyrimidinone-2'-deoxyribose in patients with advanced malignancies.

PURPOSE: Iododeoxyuridine (IdUrd), a halogenated nucleoside analog, produced clinical responses when administered as a radiosensitizer via continuous intravenous (c.i.v.) infusion over the course of radiotherapy. We conducted a phase 0 trial of 5-iodo-2-pyrimidinone-2'-deoxyribose (IPdR), an oral prodrug of IdUrd, in patients with advanced malignancies to assess whether the oral route was a feasible alternative to c.i.v. infusion before embarking on large-scale clinical trials. Plasma concentrations of IPdR, IdUrd, and other metabolites were measured after a single oral dose of IPdR. EXPERIMENTAL DESIGN: Eligible patients had advanced refractory malignancies. A single oral dose of IPdR was administered per patient and patients were followed for 14 days for safety assessments; dose escalations were planned (150, 300, 600, 1,200, and 2,400 mg) with one patient per dose level and 6 patients at the highest dose level. Blood sampling was conducted over a 24-hour period for pharmacokinetic analysis. RESULTS: There were no drug-related adverse events. Plasma concentrations of IdUrd generally increased as the dose of IPdR escalated from 150 to 2,400 mg. All patients at the 2,400 mg dose achieved peak IdUrd levels of (mean ± SD) 4.0 µmol/L ± 1.02 µmol/L at 1.67 ± 1.21 hours after IPdR administration. CONCLUSIONS: Adequate plasma levels of IdUrd were obtained to justify proceeding with a phase I trial of IPdR in combination with radiation. This trial shows the ability of a small, phase 0 study to provide critical information for decision-making regarding future development of a drug.

Differences in natural history between breast cancers in BRCA1 and BRCA2 mutation carriers and effects of MRI screening-MRISC, MARIBS, and Canadian studies combined.

BACKGROUND: It is recommended that BRCA1/2 mutation carriers undergo breast cancer screening using MRI because of their very high cancer risk and the high sensitivity of MRI in detecting invasive cancers. Clinical observations suggest important differences in the natural history between breast cancers due to mutations in BRCA1 and BRCA2, potentially requiring different screening guidelines. METHODS: Three studies of mutation carriers using annual MRI and mammography were analyzed. Separate natural history models for BRCA1 and BRCA2 were calibrated to the results of these studies and used to predict the impact of various screening protocols on detection characteristics and mortality. RESULTS: BRCA1/2 mutation carriers (N = 1,275) participated in the studies and 124 cancers (99 invasive) were diagnosed. Cancers detected in BRCA2 mutation carriers were smaller [80% ductal carcinoma in situ (DCIS) or ≤10 mm vs. 49% for BRCA1, P < 0.001]. Below the age of 40, one (invasive) cancer of the 25 screen-detected cancers in BRCA1 mutation carriers was detected by mammography alone, compared with seven (three invasive) of 11 screen-detected cancers in BRCA2 (P < 0.0001). In the model, the preclinical period during which cancer is screen-detectable was 1 to 4 years for BRCA1 and 2 to 7 years for BRCA2. The model predicted breast cancer mortality reductions of 42% to 47% for mammography, 48% to 61% for MRI, and 50% to 62% for combined screening. CONCLUSIONS: Our studies suggest substantial mortality benefits in using MRI to screen BRCA1/2 mutation carriers aged 25 to 60 years but show important clinical differences in natural history. IMPACT: BRCA1 and BRCA2 mutation carriers may benefit from different screening protocols, for example, below the age of 40.

High-throughput screening of a diversity collection using biodefense category A and B priority pathogens.

One of the objectives of the National Institutes of Allergy and Infectious Diseases (NIAID) Biodefense Program is to identify or develop broad-spectrum antimicrobials for use against bioterrorism pathogens and emerging infectious agents. As a part of that program, our institution has screened the 10 000-compound MyriaScreen Diversity Collection of high-purity druglike compounds against three NIAID category A and one category B priority pathogens in an effort to identify potential compound classes for further drug development. The effective use of a Clinical and Laboratory Standards Institute-based high-throughput screening (HTS) 96-well-based format allowed for the identification of 49 compounds that had in vitro activity against all four pathogens with minimum inhibitory concentration values of ≤16 µg/mL. Adaptation of the HTS process was necessary to conduct the work in higher-level containment, in this case, biosafety level 3. Examination of chemical scaffolds shared by some of the 49 compounds and assessment of available chemical databases indicates that several may represent broad-spectrum antimicrobials whose activity is based on novel mechanisms of action.

The decreased expression of Beclin-1 correlates with progression to esophageal adenocarcinoma: the role of deoxycholic acid.

Beclin-1 has a central role in the regulation of autophagy. Barrett's esophagus (BE) is associated with a significantly increased risk for the development of esophageal adenocarcinoma (EAC). In the current study, we evaluated the role of Beclin-1 and autophagy in the EAC. Biopsies obtained from patients with BE and EAC, tissues from a rat model of BE and EAC, and esophageal cell lines were evaluated for the expression of Beclin-1 by immunohistochemistry, immunoblotting, or RT-PCR. Since reflux of bile acids is important in EAC, we also evaluated the effect of exposure to deoxycholic acid (DCA) on autophagy and Beclin-1 expression. Beclin-1 expression was high in squamous epithelium and nondysplastic BE, whereas its expression was low in dysplastic BE and EAC. The same pattern of expression was observed in rat tissues and in esophageal cell lines. Normal esophageal epithelium and HET-1A cells (derived from normal squamous epithelium) show high levels of Beclin-1, but lower levels of Beclin-1 were found in BE and EAC cell lines (CP-A, CP-C, and OE33). Acute exposure to DCA led to increased Beclin-1 expression and increased autophagy as evaluated by electron microscopy and counting percentage of GFP-LC3-positive BE cells with punctate pattern. In contrast, chronic exposure to DCA did not result in the alteration of Beclin-1 levels or autophagy. In summary, these data suggest that autophagy is initially activated in response to bile acids, but chronic exposure to bile acids leads to decreased Beclin-1 expression and autophagy resistance.

The Na+/H+ exchanger controls deoxycholic acid-induced apoptosis by a H+-activated, Na+-dependent ionic shift in esophageal cells.

Apoptosis resistance is a hallmark of cancer cells. Typically, bile acids induce apoptosis. However during gastrointestinal (GI) tumorigenesis the cancer cells develop resistance to bile acid-induced cell death. To understand how bile acids induce apoptosis resistance we first need to identify the molecular pathways that initiate apoptosis in response to bile acid exposure. In this study we examined the mechanism of deoxycholic acid (DCA)-induced apoptosis, specifically the role of Na(+)/H(+) exchanger (NHE) and Na(+) influx in esophageal cells. In vitro studies revealed that the exposure of esophageal cells (JH-EsoAd1, CP-A) to DCA (0.2 mM-0.5 mM) caused lysosomal membrane perturbation and transient cytoplasmic acidification. Fluorescence microscopy in conjunction with atomic absorption spectrophotometry demonstrated that this effect on lysosomes correlated with influx of Na(+), subsequent loss of intracellular K(+), an increase of Ca(2+) and apoptosis. However, ethylisopropyl-amiloride (EIPA), a selective inhibitor of NHE, prevented Na(+), K(+) and Ca(2+) changes and caspase 3/7 activation induced by DCA. Ouabain and amphotericin B, two drugs that increase intracellular Na(+) levels, induced similar changes as DCA (ion imbalance, caspase3/7 activation). On the contrary, DCA-induced cell death was inhibited by medium with low a Na(+) concentrations. In the same experiments, we exposed rat ileum ex-vivo to DCA with or without EIPA. Severe tissue damage and caspase-3 activation was observed after DCA treatment, but EIPA almost fully prevented this response. In summary, NHE-mediated Na(+) influx is a critical step leading to DCA-induced apoptosis. Cells tolerate acidification but evade DCA-induced apoptosis if NHE is inhibited. Our data suggests that suppression of NHE by endogenous or exogenous inhibitors may lead to apoptosis resistance during GI tumorigenesis.

Characterization of squamous esophageal cells resistant to bile acids at acidic pH: implication for Barrett's esophagus pathogenesis.

Barrett's esophagus (BE) is a premalignant condition, where normal squamous epithelium is replaced by intestinal epithelium. BE is associated with an increased risk of developing esophageal adenocarcinoma (EAC). However, the BE cell of origin is not clear. We hypothesize that BE tissue originates from esophageal squamous cells, which can differentiate to columnar cells as a result of repeated exposure to gastric acid and bile acids, two components of refluxate implicated in BE pathology. To test this hypothesis, we repeatedly exposed squamous esophageal HET1A cells to 0.2 mM bile acid (BA) cocktail at pH 5.5 and developed an HET1AR-resistant cell line. These cells are able to survive and proliferate after repeated 2-h treatments with BA at pH 5.5. HET1AR cells are resistant to acidification and express markers of columnar differentiation, villin, CDX2, and cytokeratin 8/18. HET1AR cells have increased amounts of reactive oxygen species, concomitant with a decreased level and activity of manganese superoxide dismutase compared with parental cells. Furthermore, HET1AR cells express proteins and activate signaling pathways associated with inflammation, cell survival, and tumorigenesis that are thought to contribute to BE and EAC development. These include STAT3, NF-κB, epidermal growth factor receptor (EGFR), cyclooxygenase-2, interleukin-6, phosphorylated mammalian target of rapamycin (p-mTOR), and Mcl-1. The expression of prosurvival and inflammatory proteins and resistance to cell death could be partially modified by inhibition of STAT3 signaling. In summary, our study shows that long-term exposure of squamous cells to BA at acidic pH causes the cells to display the same characteristics and markers as BE.

Breast cancer-related preferences among women with and without BRCA mutations.

Preference ratings are used to quantify quality of life in analyses used for health care policy making. Subjects indicated how many years of their life expectancy they would trade to avoid BRCA mutations, breast/ovarian cancer, and five preventive measures including prophylactic surgery, annual mammograms, and annual magnetic resonance imaging (MRI). Among 243 respondents, both the 83 women with mutations and the 160 controls rated mammography highest (most favorably), MRI next highest, having a child with a mutation lowest, and ovarian cancer next lowest. Controls rated prophylactic surgery higher than cancer (P < 0.01), but women with mutations did not. In logistic regression, controls were twice as willing as women with mutations to trade time except for screening modalities; younger, lower-income, and non-white women were more willing to trade time than older, higher-income, and white women. Our findings support the use of average-risk individuals' time trade-off preference ratings for health care policy development.

Liquid Chromatographic Determination of NSC 737664 (ABT-888: an Inhibitor of Poly(ADP-ribose) Polymerase (PARP)) in Plasma and Urine in a Phase 0 Clinical Trial.

A gradient reversed-phase high performance liquid chromatographic method was developed for determining NSC 737664 (2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide; ABT-888) in human plasma and urine. Chromatographic separation used a mobile phase composed of 0.1% formic acid in water and 0.1% formic acid in acetonitrile, and a C18 column (150 mm × 4.6 mm, 5µ). Quantitation was performed using UV detection at 300 nm. Chromatographic peak identity was confirmed using positive-ion electrospray ionization mass spectrometry. The method was shown to be specific, accurate and reproducible, and thereby appropriate for monitoring plasma and urine levels of the agent in support of a phase 0 clinical study.

A randomized, double-blind, placebo-controlled trial of augmentation topiramate for chronic combat-related posttraumatic stress disorder.

BACKGROUND: Topiramate, a novel anticonvulsant, has been reported to rapidly reduce symptoms of posttraumatic stress disorder (PTSD) in an open-label trial. The present study was designed as a test of topiramate's efficacy as adjunctive therapy in a 7-week, randomized, double-blind, placebo-controlled trial. METHODS: Forty male veterans with PTSD in a residential treatment program were randomized to flexible-dose topiramate or placebo augmentation. The primary outcome measures were PTSD symptom severity and global symptom improvement. RESULTS: Baseline Clinician-Administered PTSD Scale scores were 62.1 +/- 13.9 for placebo and 61.0 +/- 22.2 for topiramate. There was a high dropout rate from the study (55% topiramate; 25% placebo), with 40% of topiramate and 10% of placebo dropping because of adverse events (AEs). No significant treatment effects of topiramate versus placebo were observed for the primary treatment outcomes. Subjects reporting central nervous system-related AEs and with higher baseline severity of depression were more likely to discontinue because of AEs. CONCLUSIONS: Primary outcome measures failed to demonstrate a significant effect for topiramate over placebo; however, high dropout rate in the treatment group prohibits definitive conclusions about the efficacy of topiramate in this population.

Design, synthesis, and evaluation of in vivo potency and selectivity of epoxysuccinyl-based inhibitors of papain-family cysteine proteases.

The papain-family cathepsins are cysteine proteases that are emerging as promising therapeutic targets for a number of human disease conditions ranging from osteoporosis to cancer. Relatively few selective inhibitors for this family exist, and the in vivo selectivity of most existing compounds is unclear. We present here the synthesis of focused libraries of epoxysuccinyl-based inhibitors and their screening in crude tissue extracts. We identified a number of potent inhibitors that display selectivity for endogenous cathepsin targets both in vitro and in vivo. Importantly, the selectivity patterns observed in crude extracts were generally retained in vivo, as assessed by active-site labeling of tissues from treated animals. Overall, this study identifies several important compound classes and highlights the use of activity-based probes to assess pharmacodynamic properties of small-molecule inhibitors in vivo.

Therapeutic efficacy of a therapeutic cooking group from the patients' perspective.

The purpose of this study was to evaluate the therapeutic efficacy of the cooking group from the burn survivors' perspective. By incorporating concepts of kitchen skills, energy conservation, and desensitization techniques, the cooking group can assist patients with the functional use of their hands, standing tolerance, return to former vocational activities, and socialization with other patients. A questionnaire was developed based on commonly expressed benefits of cooking group. Areas of interest included decreasing anxiety in the kitchen, distraction from their burns, socializing with other burn survivors, and the physical benefits of participating in the group. The results of this study indicate that participants regard the therapeutic cooking group as a valuable treatment modality that effectively combines functional activities with socialization to decrease burn related anxiety and increase motion in a supportive environment for patients with burns.