Intranasal Oxytocin for Stimulant Use Disorder Among Male Veterans Enrolled in an Opioid Treatment Program: A Randomized Controlled Trial

The increasing prevalence of illicit stimulant use among those in opioid treatment programs poses a significant risk to public health, stimulant users have the lowest rate of retention and poorest outcomes among those in addiction treatment, and current treatment options are limited. Oxytocin administration has shown promise in reducing addiction-related behavior and enhancing salience to social cues. We conducted a randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin administered twice daily for 6 weeks to male Veterans with stimulant use disorder who were also receiving opioid agonist therapy and counseling (n = 42). There was no significant effect of oxytocin on stimulant use, stimulant craving, or therapeutic alliance over 6 weeks. However, participants receiving oxytocin (vs. placebo) attended significantly more daily opioid agonist therapy dispensing visits. This replicated previous work suggesting that oxytocin may enhance treatment engagement among individuals with stimulant and opioid use disorders, which would address a significant barrier to effective care.

The Gaseous Ozone Therapy as a Promising Antiseptic Adjuvant of Periodontal Treatment: A Randomized Controlled Clinical Trial

Background: the establishment of periodontitis is regulated by the primary etiological factor and several individual conditions including the immune response mechanism of the host and individual genetic factors. It results when the oral homeostasis is interrupted, and biological reactions favor the development and progression of periodontal tissues damage. Different strategies have been explored for reinforcing the therapeutic effect of non-surgical periodontal treatment of periodontal tissue damage. Gaseous ozone therapy has been recognized as a promising antiseptic adjuvant, because of its immunostimulating, antimicrobial, antihypoxic, and biosynthetic effects. Then, we hypothesized that the adjunct of gaseous ozone therapy to standard periodontal treatment may be leveraged to promote the tissue healing response. Methods: to test this hypothesis, we conducted a prospective randomized study comparing non-surgical periodontal treatment plus gaseous ozone therapy to standard therapy. A total of 90 healthy individuals with moderate or severe generalized periodontitis were involved in the study. The trial was conducted from September 2019 to October 2020. Forty-five patients were randomized to receive scaling and root-planning (SRP) used as conventional non-surgical periodontal therapy plus gaseous ozone therapy (GROUP A); forty-five were allocated to standard treatment (GROUP B). The endpoint was defined as the periodontal response rate after the application of the ozone therapy at 3 months and 6 months, defined as no longer meeting the criteria for active periodontitis. Statistical analysis was performed employing SPSS v.18 Chicago: SPSS Inc. Results: periodontal parameters differed significantly between patients treated with the two distinct procedures at 3 months (p ≤ 0.005); a statistically significant difference between groups was observed from baseline in the CAL (p ≤ 0.0001), PPD (p ≤ 0.0001) and BOP (p ≤ 0.0001) scores. Conclusions: The present study suggests that SRP combined with ozone therapy in the treatment of periodontitis revealed an improved outcome than SRP alone.

Aerosol Biologics for the Treatment of Eosinophilic Asthma

Asthma is a heterogeneous chronic airway disease comprising of distinct phenotypes characterized by different immunopathophysiologic pathways, clinical features, disease severity, and response to treatment. The phenotypes of asthma include eosinophilic, neutrophilic, mixed cellularity, and paucigranulocytic asthma. Eosinophilic asthma is principally a T helper type 2 (Th2)-mediated airway disease. However, several other immune and structural cells secrete the cytokines implicated in the pathogenesis of eosinophilic asthma. Innate type 2 lymphoid cells, mast cells, basophils, and eosinophils secrete Th2 cytokines, such as interleukin-4 (IL-4), IL-13, and IL-5. Additionally, airway epithelial cells produce alarmin cytokines, including IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). Alarmins are the key initiators of allergic inflammation at the sentinel mucosal surfaces. Innovative biotherapeutic research has led to the discovery of monoclonal antibodies which target and inhibit the immunopathological effects of the cytokines involved in the pathogenesis of eosinophilic asthma. Parenteral biologics targeting the inciting interleukins, include mepolizumab and reslizumab (anti-IL-5), benralizumab (anti-IL-5Rα), dupilumab (anti-4Rα), and tezelizumab (anti-TSLP). They have been shown to significantly reduce annualized exacerbation rates, improve asthma control, lung function, and quality of life. Currently, there are no pulmonary delivered aerosol biologics for topical treatment of asthma. CSJ117 is a potent neutralizing antibody Fab fragment against TSLP, formulated as a PulmoSol TM engineered powder, and is delivered to the lungs by a dry powder inhaler. Phase 2 placebo-controlled clinical trial evaluated the efficacy and safety of CSJ117. CSJ117 delivered as an inhaler attenuated the late asthmatic response (LAR), and the early asthmatic response (EAR) after allergen inhalation challenge (AIC) at day 84 of treatment. The maximum decrease in FVE1 from pre-AIC were significantly lower in the CSJ117 group compared to placebo (P = 029), during LAR. CSJ117 also significantly reduced fractional exhaled nitric oxide before AIC at day 83; and significantly reduced the allergen-induced increase in % sputum eosinophil count. Pulmonary delivery of biologics directly to the airway mucosal surface has several advantages over parenteral routes, particularly in treating airway diseases such as asthma. Inhaler delivered biologics, such as CSJ117 are innovative and attractive methods of future precision treatment of asthma, and other respiratory diseases.

Antibacterial Efficacy of Herbal Toothpaste Containing Bamboo Salt: A Randomized Controlled Clinical Trial

Background: The inclusion of herbal antibacterial agents in the composition of toothpastes is becoming increasingly popular, due to lower side effects. The present study intended to investigate the antibacterial efficacy of a herbal toothpaste containing Bamboo salt on cariogenic oral bacteria. Methods: The present double-blinded parallel randomized controlled clinical trial was conducted on 60 dental students (age range: 18-30). Following the baseline saliva sampling, the participants were randomly assigned into the case and control groups, to use the Bamboo salt herbal toothpaste and conventional non-herbal toothpaste, respectively. They were instructed to brush their teeth twice a day using the Bass technique. Saliva sampling was repeated after four weeks. The salivary counts of Streptococcus mutans and Lactobacillus at baseline and 4-week follow-up were determined and presented as the logarithm of colony-forming units per milliliter (log CFU/mL). statistical analysis was performed using independent samples t-test and paired sample t-test (P<0.05). Results: A significant decrease in salivary Streptococcus mutans and Lactobacillus was observed using both toothpastes (*P<0.001). The difference between the antibacterial efficacy of two toothpaste types on Streptococcus mutans and Lactobacillus was not statistically significant (P=0.530, and P=0.137, respectively). Conclusion: Due to the comparable efficacy of the investigated herbal toothpaste with conventional toothpaste, it potentially qualifies as a complementary agent for self-care oral hygiene procedures. Trial registration: This trial was registered in the “Iranian Registry of Clinical Trials” (IRCT20210414050964N1) on 21/06/2021.

Cost-Effectiveness of Upper Extremity Dry Needling in Chronic Stroke

Introduction: Dry needling is a non-pharmacological approach that has proven to be effective in different neurological conditions. Objective: The aim of this study was to evaluate the cost-effectiveness of a single dry needling session in patients with chronic stroke. Methods: A cost-effectiveness analysis was performed based on a randomized controlled clinical trial. The results obtained from the values of the EuroQol-5D questionnaire and the Modified Modified Ashworth Scale were processed in order to obtain the percentage of treatment responders and the quality-adjusted life years (QALYs) for each alternative. The cost analysis was that of the hospital, clinic, or health center, including the equipment and physiotherapist. The cost per respondent and the incremental cost-effectiveness ratio of each alternative were assessed. Results: Twenty-three patients with stroke were selected. The cost of DN treatment was EUR 14.96, and the data analysis showed a favorable cost-effectiveness ratio of both EUR/QALY and EUR/responder for IG, although the sensitivity analysis using limit values did not confirm the dominance (higher effectiveness with less cost) of the dry needling over the sham dry needling. Conclusions: Dry needling is an affordable alternative with good results in the cost-effectiveness analysis—both immediately, and after two weeks of treatment—compared to sham dry needling in persons with chronic stroke.

Erythropoietin in Acute Kidney Injury (EAKI): a Pragmatic Randomized Clinical Trial

Background Treatment with erythropoietin is well established for anemia in chronic kidney disease patients but not well studied in acute kidney injury.MethodsThis is a multicenter, randomized, pragmatic controlled clinical trial. It included 134 hospitalized patients with anemia defined as hemoglobin <11 g/dL and acute kidney injury defined as an increase of serum creatinine of 0.3 mg/dL within 48 hours or 1.5 times baseline. One arm received recombinant human erythropoietin 4000 UI subcutaneously every other day (intervention; n=67) and the second received standard of care (control; n=67) during the hospitalization until discharge or death. The primary outcome was the need for transfusion; secondary outcomes were death, renal recovery, need for dialysis.ResultsThere was no statistically significant difference in transfusion need (RR=1.05, 95%CI 0.65,1.68; p=0.855), in renal recovery full or partial (RR=0.96, 95%CI 0.81,1.15; p=0.671), in need for dialysis (RR=11.00, 95%CI 0.62, 195.08; p=0.102) or in death (RR=1.43, 95%CI 0.58,3.53; p=0.440) between the erythropoietin and the control group. ConclusionsErythropoietin treatment had no impact on transfusions, renal recovery or mortality in acute kidney injury patients with anemia. The trial was registered on ClinicalTrials.gov (NCT03401710, 17/01/2018).

Granisetron Augmentation of Sertraline in Obsessive-Compulsive Disorder: A Double-Blind Placebo-Controlled, Randomized Clinical Trial

Background: Medications currently recommended for the treatment of Obsessive-Compulsive Disorder (OCD) usually relieve the severity of symptoms by as much as 20–30%, and satisfactory treatment is obtained in 40–60% of patients with OCD. Nevertheless, the remaining symptoms continue to impair the patients’ function. Therefore, it is necessary to investigate possible strategies to improve the mitigation of symptoms.In this study, the main objective was to examine and investigate the effectiveness of granisetron, which is a serotonin 5-hydroxytryptamine receptor type 3 (5-HT3) antagonist, as an adjunct therapy to selective serotonin reuptake inhibitors, for the purpose of ameliorating OCD symptoms. Methods: fifty-eight patients diagnosed with OCD, based on Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, who had a Yale-Brown obsessive-compulsive scale (Y-BOCS) score of more than 21 were recruited in a double-blinded, parallel-group, placebo-controlled, clinical trial of 10 weeks to receive either granisetron (1 mg twice daily) and sertraline (100 mg daily initially followed by 200 mg daily after week 4) or placebo and sertraline. The primary outcome was OCD symptoms measured by the Y-BOCS.Results: Y-BOCS total score significantly dropped in both groups (28.9 to 17.7 for granisetron and 27.5 to 19.3 for placebo group with a slightly greater drop for granisetron group), while the granisetron group experienced a significantly greater reduction in obsession scores (Greenhouse-Geisser F(2.32,97.57)=4.52,p-value=0.01). Moreover, in comparison with the placebo group, the proportion of the patients showing complete response was considerably higher among the granisetron group (P-value <0.01). No major adverse effects were observed in any of the groups. Conclusion: The results suggest that granisetron augmentation of sertraline may increase the rate of response in patients with moderate to severe non-refractory OCD. Further studies are suggested in this regard.Trial registration: The trial was registered at the Iranian Registry of Clinical Trials on 27/03/2019 (www.irct.ir; IRCT ID: IRCT20170123032145N3).

Prebiotic Galacto-Oligosaccharides Impact Stool Frequency and Fecal Microbiota in Self-Reported Constipated Adults: A Randomized Clinical Trial

Constipation is a major issue for 10–20% of the global population. In a double-blind randomized placebo-controlled clinical trial, we aimed to determine a dose-response effect of galacto-oligosaccharides (GOS) on stool characteristics and fecal microbiota in 132 adults with self-reported constipation according to Rome IV criteria (including less than three bowel movements per week). Subjects (94% females, aged: 18–59 years) received either 11 g or 5.5 g of BiotisTM GOS, or a control product, once daily for three weeks. Validated questionnaires were conducted weekly to study primarily stool frequency and secondary stool consistency. At base- and endline, stool samples were taken to study fecal microbiota. A trend towards an increased stool frequency was observed after the intervention with 11 g of GOS compared to control. While during screening everybody was considered constipated, not all subjects (n = 78) had less than three bowel movements per week at baseline. In total, 11 g of GOS increased stool frequency compared to control in subjects with a low stool frequency at baseline (≤3 bowel movements per week) and in self-reported constipated adults 35 years of age or older. A clear dose-response of GOS was seen on fecal Bifidobacterium, and 11 g of GOS significantly increased Anaerostipes hadrus. In conclusion, GOS seems to be a solution to benefit adults with a low stool frequency and middle-aged adults with self-reported constipation.