Intravaginal Combination Therapy of Acetic and Lactic Acid in premenopausal women with recurrent vulvovaginal candidiasis: A randomized, double-blind placebo-controlled feasibility trial.

BACKGROUND: Recurrent vulvovaginal candidiasis management primarily entails azole therapy used as required or as an extended daily or weekly maintenance therapy for 6 months or more. Unfortunately, relapse within 3-6 months of ceasing maintenance therapy is experienced for more than half the patients, for whom indefinite treatment is required. OBJECTIVES: To explore the feasibility of trial design examining a prophylaxis treatment to prevent recurrent vulvovaginal candidiasis symptomatic episodes and reduce adverse effects. STUDY DESIGN: A double-blinded randomized controlled feasibility trial was conducted in Australia. Women with recurrent vulvovaginal candidiasis were enrolled. METHODS: An intravaginal prophylaxis application of lactic acid and acetic acid (Intravaginal Combination Therapy of Acetic and Lactic Acid) was compared with placebo. Primary outcomes comprised recruitment and retention, compliance to study medications and study assessments. Secondary outcomes included the reduction of symptomatic recurrence over the trial period and the acceptability, satisfaction, safety and tolerability of the intervention. The feasibility of quality-of-life measures was also explored. RESULTS: Fifteen participants were enrolled and randomized (active = 9, placebo = 6). Consent rate was 23.4%. Eight participants were lost to follow-up (active = 5, placebo = 3). Forty-seven per cent of participants (n = 7) were 100% compliant with the intervention, six of which completed the trial with good assessment compliance. The blinding process was effective. The study demonstrated a reduction in relapse in both active and placebo groups with only four participants across both groups reporting symptomatic episodes while enrolled. The intervention demonstrated good tolerability. Quality-of-life data showed minimal variance with a high quality-of-life measure. CONCLUSION: This trial assesses the feasibility of conducting a large-scale study exploring the efficacy of the Intravaginal Combination Therapy of Acetic and Lactic Acid intravaginal intervention and hints on the importance of psychological support through appropriate disease-specific communication and clinical attention. Consideration of the reported recruitment challenges, the inclusion of suitable quality-of-life measures and digital data collection is warranted for adaptation to a fully powered trial.

D-cycloserine-augmented one-session treatment of specific phobias in children and adolescents.

BACKGROUND: D-Cycloserine has potential to enhance exposure therapy outcomes. The current study presents a preliminary randomized, placebo-controlled double-blind pilot trial of DCS-augmented one-session treatment (OST) for youth (7-14 years) with specific phobia. A secondary aim of this pilot study was to explore the effects of youth age and within-session fear reduction as potential moderators of DCS outcomes in order to generate hypotheses for a larger trial. It was hypothesized that DCS would be associated with greater improvements than placebo, that children (7-10 years) would have greater benefits than adolescents (11-14 years), and that DCS effects would be stronger for participants with the greater within-session fear reduction during the OST. METHODS: Thirty-five children and adolescents were randomized to either OST combined with DCS (n = 17), or OST combined with placebo (PBO; n = 18) and assessed at 1 week, 1 month, and 3 month following treatment. RESULTS: There were no significant pre- to post-treatment or follow-up benefits of DCS relative to placebo. Secondary analyses of age indicated that relative to PBO, DCS was associated with greater improvements for children (but not adolescents) on measures of severity at 1-month follow-up. Children in the DCS condition also showed significantly greater improvement to 1 month on global functioning relative to other groups. Conversely, adolescents had significant post-treatment benefits in the PBO condition on symptom severity measures relative to DCS, and adolescents in the DCS condition had significantly poorer functioning at 3 months relative to all other groups. Finally, there was a trend for within-session fear reduction to be associated with moderating effects of DCS, whereby greater reduction in fear was associated with greater functioning at one-month follow-up for children who received DCS, relative to PBO. LIMITATIONS: The study sample was small and therefore conclusions are tentative and require replication. CONCLUSIONS: Age and within-session fear reduction may be important moderators of DCS-augmented one-session exposure therapy, which requires testing in a fully powered randomized controlled trial.

Micronutrient Therapy for Violent and Aggressive Male Youth: An Open-Label Trial.

OBJECTIVES: Pharmacotherapy for problematic aggressive and violent behavior disorders in male children and adolescents is associated with significant adverse events. Treatments with more acceptable risk-benefit ratios are critically needed. Micronutrient intervention will be investigated as an alternative to bridge the therapeutic gap in the management of these behaviors. METHODS: Males aged 4-14 who displayed ongoing violent and aggressive behaviors received micronutrient intervention containing alpha-tocopherol (vitamin E), ascorbic acid (vitamin C), biotin, chromium, pyridoxal-5-phosphate (P5P), pyridoxine (vitamins B6), selenium, and zinc, in a 16-week open-label trial. Plasma zinc, plasma copper, copper/zinc ratio, and urinary hydroxyhemopyrroline-2-one (HPL) tests were conducted at baseline and endpoint. Participants were examined for changes in aggressive and violent behaviors measured using the Children's Aggression Scale (CAS) and the Modified Overt Aggression Scale (MOAS), improvements in family functioning measured using the Family Functioning Style Scale, improvements in health-related quality of life (HRQoL) measured using the Pediatric Quality of Life Inventory (PedsQL) at baseline, 8 weeks, endpoint, and at 4-6-month follow-up. RESULTS: Thirty-two male children and adolescents met inclusion criteria. Thirty-one (mean 8.35 ± standard deviation 2.93 years) completed the study, with one participant lost to follow-up. Micronutrient therapy significantly improved parent-reported aggressive and violent behaviors measured using the CAS for all domains except the use of weapons (p < 0.001 to p = 0.02) with medium to large effect size (Cohen's d = 0.72-1.43) and the MOAS (p < 0.001) with large effect size (Cohen's d = 1.26). Parent-reported HRQoL (p < 0.001; Cohen's d = -1.69) and family functioning (p = 0.03; Cohen's d = -0.41) also significantly improved. CONCLUSION: Micronutrient therapy appeared well tolerated, with a favorable side effect profile. It appeared effective in the reduction of parent-reported aggressive and violent behaviors, and showed improvement in family functioning and HRQoL in male youth after 16 weeks. Further research in the form of a double-blinded, randomized controlled trial is required to verify these initial positive observations.

Difficult-to-treat pediatric obsessive-compulsive disorder: feasibility and preliminary results of a randomized pilot trial of D-cycloserine-augmented behavior therapy.

BACKGROUND: This study examined the feasibility and preliminary effectiveness of d-cycloserine (DCS)-augmented cognitive behavioral therapy (CBT) for children and adolescents with difficult-to-treat Obsessive Compulsive Disorder, in a double-blind randomized controlled pilot trial (RCT). METHODS: Seventeen children and adolescents (aged 8-18 years) with a primary diagnosis of OCD, which was deemed difficult-to-treat, were randomly assigned to either nine sessions of CBT including five sessions of DCS-augmented exposure and response prevention (ERP) [ERP + DCS] or nine sessions of CBT including five sessions of placebo-augmented ERP [ERP + PBO]. Weight-dependent DCS or placebo doses (25 or 50 mg) were taken 1 hour before ERP sessions. RESULTS: At posttreatment, both groups showed significant improvements with 94% of the entire sample classified as responders. However, a greater improvement in the ERP + DCS relative to the ERP + PBO condition was observed at 1-month follow-up on clinician-rated obsessional severity and diagnostic severity, and parent ratings of OCD severity. There were no changes across time or condition from 1- to 3-month follow-up. CONCLUSIONS: In this preliminary study, DCS-augmented ERP produced significant improvements in OCD severity from posttreatment to 1-month follow-up, relative to a placebo control condition, in severe and difficult-to-treat pediatric OCD. The significant effect on obsessional severity suggests that DCS augmentation might be associated with enhanced modification of obsessional thoughts during ERP, and warrants further investigation.

Compounding solutions for exotic and nondomesticated fauna in australia: an investigative study.

Veterinarians face many challenges during routine administration of medication to animals. This study investigated the nature of the problems that veterinarians encounter in practice and assessed the potential benefit of pharmaceutical compounding interventions for exotic and nondomesticated fauna. The research was conducted at three large wildlife theme parks on the Gold Coast, Australia, using a multi-method design of qualitative techniques including semi-structured interviews accompanied by field note observations. Themes identified through the data analysis related to: the enthusiasm of veterinarians towards pharmaceutical compounding; medicated foods commonly being employed in practice; a lack of suitable commercially available medications; time constraint problems and incompatibilities between feeding and dosing intervals. A decisive factor identified in the uptake of compounding in veterinary care was the net cost of the compounding procedure when compared to the figurative "value" of the animal. In conlusion, the study found that pharmaceutical compounding would be able to deliver more effective solutions than current techniques employed for a majority of veterinary medication problems in the area of exotic and nondomesticated veterinary practice. Pharmacists therefore have opportunity to diversify their business model while providing an important service to the community.

Stability of melatonin in an extemporaneously compounded sublingual solution and hard gelatin capsule.

This study examined the stability of melatonin in a 10-mg/mL oral sublingual solution stored at 4 deg C or 25 deg C and in 3-mg capsules stored at ambient (25 deg C; 60% relative humidity) and accelerated (40 deg C; 75% relative humidity) conditions over a period of 90 days. A sublingual solution of melatonin 10 mg/mL was preprared with glycerin, ethyl alcohol, stevia powder extract, and tutti-frutti flavor. Six identical solutions were prepared and stored in prescription amber glass bottles at 4 deg C or 25 deg C. Triplicate 1-mL samples from each of the six solutions were assayed immediately after preparation and after 7, 14, 28, 60, and 90 days with a stability-indicating high-performance liquid chromatographic method. Six batches of 100 melatonin 3-mg capsules were prepared with Methocel E4M and lactose anhydrous and stored in prescription amber glass bottles at ambient or accelerated conditions. A sample of 10 capsules from each batch was assayed immediately after preparation, and additional examples from each storage condition were assayed at 7, 14, 28, 60, and 90 days. The mean concentration of melatonin exceeded 98% of the initial concentration throughout th 90-day study period for the sublingual solution and capsules under all storage conditions. There were no detectable changes in color, odor, taste, or pH, and no visible microbial growth in any of the sublingual solution samples. Compendia requirements for content uniformity were met for the extemporaneously prepared capsules. Melatonin in an extemporaneously compounded sublingual solution (10 mg/mL) was stable for at least 90 days when stored in prescription amber glass bottles at 4 deg C or 25 deg C. Melatonin in extemporaneously prepared capsules (3 mg) was stable for at leaast 90 days when stored in prescription amber glass bottles at ambient or acclereated conditions.

Fabrication and biocompatibility of polypyrrole implants suitable for neural prosthetics.

Finding a conductive substrate that promotes neural interactions is an essential step for advancing neural interfaces. The biocompatibility and conductive properties of polypyrrole (PPy) make it an attractive substrate for neural scaffolds, electrodes, and devices. Stand-alone polymer implants also provide the additional advantages of flexibility and biodegradability. To examine PPy biocompatibility, dissociated primary cerebral cortical cells were cultured on PPy samples that had been doped with polystyrene-sulfonate (PSS) or sodium dodecylbenzenesulfonate (NaDBS). Various conditions were used for electrodeposition to produce different surface properties. Neural networks grew on all of the PPy surfaces. PPy implants, consisting of the same dopants and conditions, were surgically implanted in the cerebral cortex of the rat. The results were compared to stab wounds and Teflon implants of the same size. Quantification of the intensity and extent of gliosis at 3- and 6-week time points demonstrated that all versions of PPy were at least as biocompatible as Teflon and in fact performed better in most cases. In all of the PPy implant cases, neurons and glial cells enveloped the implant. In several cases, neural tissue was present in the lumen of the implants, allowing contact of the brain parenchyma through the implants.