The pharmacokinetics of single oral dose extended-release topiramate and adverse effects after multi-dose administration in healthy cats.

Current treatment options for feline epilepsy are limited to medications that require administration of multiple doses per day or administration of a capsule or large tablet. Expanding the current treatment options could improve patient and owner compliance and optimize seizure control. Topiramate has been used sparingly in veterinary medicine, and limited pharmacokinetic studies have focused on immediate release formulations in dogs. If effective and safe, topiramate extended-release (XR) could broaden the current treatment options for feline epilepsy. The aims of this two-phase study were to establish single-dose pharmacokinetics for topiramate XR in cats, identify a dosing regimen that maintains steady-state plasma drug concentrations within a reference range extrapolated from human medicine (5-20 µg/mL), and evaluate the safety of topiramate XR in cats following multidose administration. Topiramate XR administered orally at 10 mg/kg once daily for 30 days was sufficient to achieve the desired concentrations in all cats. While no clinically apparent adverse effects were observed, four out of eight cats developed subclinical anemia, calling into question the safety of topiramate XR with chronic administration. Further studies are necessary to better understand the potential adverse effects and overall efficacy of topiramate XR for the treatment of feline epilepsy.

Conceptualizing eating disorder psychopathology using an anxiety disorders framework: Evidence and implications for exposure-based clinical research.

Eating disorders (EDs) and anxiety disorders (ADs) evidence shared risk and significant comorbidity. Recent advances in understanding of anxiety-based disorders may have direct application to research and treatment efforts for EDs. The current review presents an up-to-date, behavioral conceptualization of the overlap between anxiety-based disorders and EDs. We identify ways in which anxiety presents in EDs, consider differences between EDs and ADs relevant to treatment adaptions, discuss how exposure-based strategies may be adapted for use in ED treatment, and outline directions for future mechanistic, translational, and clinical ED research from this perspective. Important research directions include: simultaneous examination of the extent to which EDs are characterized by aberrant avoidance-, reward-, and/or habit-based neurobiological and behavioral processes; improvement in understanding of how nutritional status interacts with neurobiological characteristics of EDs; incorporation of a growing knowledge of biobehavioral signatures in ED treatment planning; development of more comprehensive exposure-based treatment approaches for EDs; testing whether certain exposure interventions for AD are appropriate for EDs; and improvement in clinician self-efficacy and ability to use exposure therapy for EDs.

Predictors and moderators of treatment outcome in a randomized clinical trial for binge-eating disorder.

OBJECTIVE: The current study examined predictors and moderators of two interventions for binge-eating disorder (BED). METHOD: Participants were 112 adults with BED (Mage = 39.7 ± 13.4 years; MBMI = 35.1 ± 13.4 kg/m²; 82% female; 91% Caucasian) randomly assigned to integrative cognitive-affective therapy for BED (ICAT-BED) or guided self-help cognitive-behavioral therapy (CBTgsh). Generalized linear models examined predictors and moderators of objective binge-eating episode (OBE) frequency and OBE abstinence at end-of-treatment (EOT) and 6-month follow-up (FU). RESULTS: Lower levels of baseline dietary restraint and emotion regulation difficulties predicted greater reductions in OBE frequency at EOT and FU, respectively. At EOT, greater pretreatment self-control predicted greater reductions in OBE frequency in ICAT-BED than CBTgsh (ps < .05). In addition, low shape/weight overvaluation predicted greater reductions in OBE frequency in ICAT-BED than CBTgsh, whereas high shape/weight overvaluation predicted comparable reductions in OBE frequency across treatments at EOT (ps < .02). At EOT and FU, greater baseline actual-ideal self-discrepancy predicted significantly greater reductions in OBE frequency in ICAT-BED, than CBTgsh (ps < .02). No significant predictor or moderator effects were observed for models examining OBE abstinence. CONCLUSION: This study identified two general predictors and four moderators of BED treatment response. However, only one predictor (actual-ideal self-discrepancy) interacted with treatment type to differentially predict OBE frequencies at both EOT and FU. Altogether, findings suggest that ICAT-BED may confer specific and durable improvements in OBE frequencies among individuals with high actual-ideal self-discrepancy. Therefore, patients demonstrating these characteristics may be more likely to benefit from ICAT-BED. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Effectiveness of medication assisted treatment for opioid use in prison and jail settings: A meta-analysis and systematic review.

This study examined the state of the literature on the effectiveness of medication assisted treatment (MAT; methadone, buprenorphine, naltrexone) delivered in prisons and jails on community substance use treatment engagement, opioid use, recidivism, and health risk behaviors following release from incarceration. Randomized controlled trials (RCTs) and quasi-experimental studies published through December 2017 that examined induction to or maintenance on methadone (n = 18 studies), buprenorphine (n = 3 studies), or naltrexone (n = 3 studies) in correctional settings were identified from PsycINFO and PubMed databases. There were a sufficient number of methadone RCTs to meta-analyze; there were too few buprenorphine or naltrexone studies. All quasi-experimental studies were systematically reviewed. Data from RCTs involving 807 inmates (treatment n = 407, control n = 400) showed that methadone provided during incarceration increased community treatment engagement (n = 3 studies; OR = 8.69, 95% CI = 2.46; 30.75), reduced illicit opioid use (n = 4 studies; OR = 0.22, 95% CI = 0.15; 0.32) and injection drug use (n = 3 studies; OR = 0.26, 95% CI = 0.12; 0.56), but did not reduce recidivism (n = 4 studies; OR = 0.93, 95% CI = 0.51; 1.68). Data from observational studies of methadone showed consistent findings. Individual review of buprenorphine and naltrexone studies showed these medications were either superior to methadone or to placebo, or were as effective as methadone in reducing illicit opioid use post-release. Results provide the first meta-analytic summary of MATs delivered in correctional settings and support the use of MATs, especially with regard to community substance use treatment engagement and opioid use; additional work is needed to understand the reduction of recidivism and other health risk behaviors.

Feasibility and Effectiveness of Continuing Methadone Maintenance Treatment During Incarceration Compared With Forced Withdrawal.

BACKGROUND: Methadone maintenance treatment (MMT) is underutilized in correctional settings, and those receiving MMT in the community often undergo withdrawal upon incarceration. Federal and state regulations present barriers to providing methadone in correctional facilities. For this investigation, a community provider administered methadone to inmates who had been receiving methadone prior to incarceration. We hypothesized that inmates continued on MMT would have improved behavior during incarceration and post-release. METHODS: This open-label quasi-experimental trial (n = 382) compared MMT continuation throughout incarceration (n = 184) to an administrative control group (ie, forced withdrawal; n = 198) on disciplinary tickets and other program attendance during incarceration. Post-release, re-engagement in community-based MMT and 6-month recidivism outcomes were evaluated. RESULTS: Inmates in the MMT continuation group versus controls were less likely to receive disciplinary tickets (odds ratio [OR] = 0.32) but no more likely to attend other programs while incarcerated. MMT continuation increased engagement with a community MMT provider within 1 day of release (OR  = 32.04), and 40.6% of MMT participants re-engaged within the first 30 days (vs 10.1% of controls). Overall, re-engagement in MMT was not associated with recidivism. However, among a subset of inmates who received MMT post-incarceration from the jail MMT provider (n = 69), re-engagement with that provider was associated with reduced risk of arrest, new charges, and re-incarceration compared with those who did not re-engage. CONCLUSIONS: Results support interventions that facilitate continuity of MMT during and after incarceration. Engagement of a community provider is feasible and can improve access to methadone in correctional facilities.

Impact of Cannabis Use on Treatment Outcomes among Adults Receiving Cognitive-Behavioral Treatment for PTSD and Substance Use Disorders.

BACKGROUND: Research has demonstrated a strong link between trauma, posttraumatic stress disorder PTSD and substance use disorders (SUDs) in general and cannabis use disorders in particular. Yet, few studies have examined the impact of cannabis use on treatment outcomes for individuals with co-occurring PTSD and SUDs. METHODS: Participants were 136 individuals who received cognitive-behavioral therapies for co-occurring PTSD and SUD. Multivariate regressions were utilized to examine the associations between baseline cannabis use and end-of-treatment outcomes. Multilevel linear growth models were fit to the data to examine the cross-lagged associations between weekly cannabis use and weekly PTSD symptom severity and primary substance use during treatment. RESULTS: There were no significant positive nor negative associations between baseline cannabis use and end-of-treatment PTSD symptom severity and days of primary substance use. Cross-lagged models revealed that as cannabis use increased, subsequent primary substance use decreased and vice versa. Moreover, results revealed a crossover lagged effect, whereby higher cannabis use was associated with greater PTSD symptom severity early in treatment, but lower weekly PTSD symptom severity later in treatment. CONCLUSION: Cannabis use was not associated with adverse outcomes in end-of-treatment PTSD and primary substance use, suggesting independent pathways of change. The theoretical and clinical implications of the reciprocal associations between weekly cannabis use and subsequent PTSD and primary substance use symptoms during treatment are discussed.

Guanfacine alters the effect of stress and smoking on heart rate variability in regular daily smokers.

BACKGROUND: We had previously demonstrated that guanfacine, an α2a-adrenergic agonist, attenuated the effect of stress on smoking-lapse behavior in regular daily smokers. Heart rate variability (HRV), a measure of vagal activity, may be a potential mechanism underlying the relationship between stress, smoking, and relapse. METHODS: We examined whether guanfacine (0 mg/day vs. 3 mg/day; n = 26) altered changes in high-frequency heart rate variability (HF-HRV) following stress and ad-lib smoking using a validated laboratory analogue of smoking-lapse behavior. All participants completed a parent study evaluating the effects of guanfacine on stress-precipitated smoking. Each subject completed two laboratory sessions assessing the effects of guanfacine on HF-HRV following stress imagery (vs. neutral imagery; order counterbalanced) and smoking. RESULTS: Results demonstrated that guanfacine did not increase tonic levels of HF-HRV relative to placebo. Following the stress versus neutral imagery manipulation (prior to ad-lib smoking), there were no significant changes in HF-HRV in the placebo group. In contrast, guanfacine increased phasic HF-HRV following stress imagery and decreased HF-HRV following neutral imagery. Ad libitum smoking following both the stress and neutral conditions decreased HF-HRV in the placebo group across both imagery conditions. In contrast, guanfacine attenuated stress- and smoking-related decreases in phasic HF-HRV relative to the neutral imagery condition. CONCLUSIONS: This is the first demonstration that a noradrenergic target altered dynamic changes in HF-HRV in response to stress and smoking, suggesting that guanfacine alters HF-HRV response to stress. Findings support current theories which suggest that phasic changes in HRV are an important marker of the stress response.

Utility of antigen testing for the diagnosis of ocular histoplasmosis in four cats: a case series and literature review.

Case series summary This case series describes the clinical utility of antigen testing for the diagnosis of feline ocular histoplasmosis. Four cats with suspected (n = 2) or confirmed (n = 2) ocular histoplasmosis are described: three from Oklahoma and one from California. In one case, serial urine antigen tests, as well as a serum antigen test for Histoplasma capsulatum, were negative; however, light microscopy identified microorganisms consistent with H capsulatum in ocular tissues at necropsy. In a further two cats with recurrent ocular histoplasmosis following long-term systemic antifungal therapy, Histoplasma species urine antigen concentrations were negative, but both cats improved clinically following systemic antifungal therapy and remained in apparent clinical remission after treatment cessation (9-16 months). The final cat displayed profound bilateral endophthalmitis; however, Histoplasma species antigen testing of vitreous humor and subretinal fluid from the left eye was negative. Intralesional organisms were detected on histopathology of both eyes, and H capsulatum was subsequently isolated and sequenced from tissue of one eye. Relevance and novel information These cases highlight the potential difficulty in definitively diagnosing ocular histoplasmosis in cats when conducting antigen testing of serum, urine and even ocular fluids. Although antigen testing has previously proven useful in the diagnosis of disseminated feline histoplasmosis, it may not be adequate in cats with only ocular signs.

Childhood adversity interacts with adult stressful events to predict reduced likelihood of smoking cessation among women but not men.

Research has documented important sex differences in associations between early stress, stress-sensitization, and psychiatric outcomes. The current study investigated whether sex differences in stress-sensitization extended to cigarette smoking cessation. Data were analyzed from the National Epidemiologic Survey on Alcohol and Related Conditions (waves 1 and 2), selecting for current daily and non-daily smokers at wave 1 (daily smokers: n=3,499 women, 3055 men; non-daily smokers: n=451 women, 501 men). Three-way interactions between sex, childhood adversity, and past year stressful life events were modeled in the prediction of smoking cessation. Among women, stressful life events were more strongly related to lower likelihood of smoking cessation for those with a history of childhood adversity than those without. This relationship was not found among men. The stress-sensitization model may be applicable to women with regards to smoking cessation, supporting further exploration of stress-sensitization as a prevention and clinical target for smoking cessation.

Stability of 1% voriconazole solution in a constant-rate infusion pump for topical ocular delivery to horses.

OBJECTIVE: To establish the effect of storage in a constant-rate infusion (CRI) pump on the sterility and stability of voriconazole 1% solution. PROCEDURE: Nine vials of voriconazole (Vfend(®) I.V.) 1% solution were prepared. Approximately half of each solution was used to prime a commercially available CRI pump with attached subpalpebral lavage system (CRI/SPL unit) with the remaining solution stored in the commercial glass vial. Three CRI/SPL units and their three corresponding vials were stored at one of three temperatures: 23 °C, 33 °C, and 40 °C. The CRI pumps ran for 7 days, and the vials were stored for 30 days. Fungal and aerobic bacterial cultures were performed on the first and last day of the storage period for each vessel. Samples were obtained at regular intervals for determination of voriconazole concentration using high-performance liquid chromatography. RESULTS: No bacterial or fungal contamination was identified in any solution at any time point. All solutions stored in the commercial glass vial remained stable throughout the study period. Multiple CRI/SPL units became blocked with crystallized voriconazole. There was a significant increase in voriconazole concentration after passage through the CRI/SPL units. CONCLUSIONS: Voriconazole 1% solution is not compatible for use in a CRI/SPL unit at temperatures between 23 and 40 °C. Voriconazole 1% solution is stable in the commercial glass vial when stored at controlled temperatures as high as 40 °C for up to 30 days.

Treatment of six cases of equine corneal stromal abscessation with intracorneal injection of 5% voriconazole solution.

OBJECTIVE: To describe a reproducible technique for intrastromal injection in the standing horse for treatment of corneal stromal abscessation. ANIMAL STUDIED: A retrospective clinical study addressing the history, treatment, and outcome of six equids (six eyes) that received intrastromal voriconazole injection. PROCEDURE: Equids having a deep stromal abscess suspected to be of fungal origin were administered intrastromal injection of 5% voriconazole solution under standing sedation in an effort to bring about enhanced resolution of clinical disease. RESULTS: Intracorneal administration of 5% voriconazole solution resulted in resolution of clinical disease, specifically stromal abscessation and secondary uveitis. All animals displayed decreased blepharospasm and no significant complications in the immediate postinjection period. Convalescent periods were subjectively shorter than anticipated with traditional medical therapy. All animals developed mild to moderate stromal fibrosis relative to the initial severity and depth of abscessation. CONCLUSIONS: Intrastromal injection of 5% voriconazole solution may provide a safe and effective treatment option for corneal stromal abscessation in horses. In all reported cases, administration of injection early in the treatment period appeared to contribute to rapid resolution of clinical disease without significant complications. The authors present this technique as an alternative to traditional surgical intervention, being more economical, having shorter treatment duration, and potentially resulting in less scar formation.