Parallel-arm Trial Research Articles

Neuropharmacological Study of Posaconazole for Glioblastoma: A Phase 0 Clinical Trial Protocol.

Glioblastoma (GBM) is the most common malignant primary brain tumor with a universally poor prognosis. GBMs express elevated levels of hexokinase 2 (HK2), catalyzing the critical step in glycolysis and influencing several oncogenic pathways. Previous preclinical work has suggested a role for repurposed posaconazole (PCZ) in downregulating HK2 activity, reducing lactate and pyruvate production, interfering with tumor cell metabolism, and increasing mouse survival. To establish brain tumor penetrance, neuropharmacokinetic profile, and mechanistic effect on tumor cell metabolism of PCZ in adults with GBM. This is an open label, nonrandomized, parallel arm trial involving patients with GBM. Cohorts will receive PCZ (intervention, n = 5) or will not receive PCZ (control, n = 5), followed by tumor resection and microdialysis catheter placement. Dialysate, plasma, and tumor samples will be analyzed for lactate and pyruvate concentrations. Tumor samples will also be assessed for PCZ concentration, HK2 expression, angiogenesis, and apoptosis. PCZ's neuropharmacokinetics will be determined based on the concentration vs time profile and area under the curve 0 to 24 hours of PCZ concentration in the brain interstitium. (1) Increased PCZ concentration in contrast-enhancing brain regions compared with nonenhancing regions; (2) inverse correlation between lactate/pyruvate and PCZ concentrations in dialysate samples from treated patients, over time; and (3) decreased HK2 activity in PCZ-treated tumor samples. A successful trial will support the decision to proceed to advanced phase trials. Any tumor penetration by PCZ, with concomitant effect on glycolysis, warrants further in-depth analysis, as therapeutic options for these deadly tumors are currently limited.

Effect of Incorporating 1 Avocado Per Day Versus Habitual Diet on Visceral Adiposity: A Randomized Trial.

Background Excess visceral adiposity is associated with increased risk of cardiometabolic disorders. Short-term well-controlled clinical trials suggest that regular avocado consumption favorably affects body weight, visceral adiposity, and satiety. Methods and Results The HAT Trial (Habitual Diet and Avocado Trial) was a multicenter, randomized, controlled parallel-arm trial designed to test whether consuming 1 large avocado per day for 6 months in a diverse group of free-living individuals (N=1008) with an elevated waist circumference compared with a habitual diet would decrease visceral adiposity as measured by magnetic resonance imaging. Secondary and additional end points related to risk factors associated with cardiometabolic disorders were assessed. The primary outcome, change in visceral adipose tissue volume during the intervention period, was not significantly different between the Avocado Supplemented and Habitual Diet Groups (estimated mean difference (0.017 L [-0.024 L, 0.058 L], P=0.405). No significant group differences were observed for the secondary outcomes of hepatic fat fraction, hsCRP (high-sensitivity C-reactive protein), and components of the metabolic syndrome. Of the additional outcome measures, modest but nominally significant reductions in total and low-density lipoprotein cholesterol were observed in the Avocado Supplemented compared with the Habitual Diet Group. Changes in the other additional and post hoc measures (body weight, body mass index, insulin, very low-density lipoprotein concentrations, and total cholesterol:high-density lipoprotein cholesterol ratio) were similar between the 2 groups. Conclusions Addition of 1 avocado per day to the habitual diet for 6 months in free-living individuals with elevated waist circumference did not reduce visceral adipose tissue volume and had minimal effect on risk factors associated with cardiometabolic disorders. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT03528031.

Acute Kinematic Changes as a Response to Barefoot Habituation Training Program

Context: Barefoot running has seen a lot of scientific interest in the running community over the last decade. However, there are conflicting claims to its efficacy in improving acute adaptations in the form of joint kinematics. Interventions to transition from shod running to barefoot running are limited in scope and implementation. Aim: The study investigated the kinematic differences between barefoot and habitually shod runners following 8 weeks of habituation training. It was hypothesized that the habituation phase with gradual increments in time spent barefoot would result in better kinematic changes in barefoot runners compared to habitual shod (in-shoe). Setting and Design: Randomized parallel arm trial conducted on professional runners. Methods and Materials: Thirty-two (n = 32) professional runners with a mean age of 21.5 ± 2.04 years with standing height measuring 1.69 ± 0.04 m and weighing 69 ± 3.55 kg were selected for the study. Participants were randomly allocated to experimental barefoot and control shod groups using computer-generated sequencing. The barefoot group received an transition plan in which the participants progressed from average time spent in walking and running barefoot. The control shod group was not required to do any changes to their traditional in-shoe training. Statistical analysis used: The primary outcome measures were joint kinematics at trunk, hip, knee and foot during the treadmill walk analyzed thorough independent T test and paired t test. The level of significance was set at P < 0.05. Results: The results indicated that the experimental barefoot group showed statistically significant (P < 0.01) changes to trunk flexion-extension during the preswing phase of running. Similarly, hip flexion-extension ranges were statistically significant (P < 0.01) in the habitual shod (in-shoe) group during the preswing to the terminal swing of running. Hip and knee flexion-extension ranges improved in the barefoot group with a statistical difference of P = 0.00 following 8 weeks of barefoot training. The mean difference for the change in hip and knee flexion ranges was of a higher magnitude for the barefoot group (26.88°) than the shod group (13.23°). Similarly, foot pronation-supination ranges improved for the barefoot group with P = 0.00. Conclusion: In conclusion, running barefoot was no different from shod running, although habitually in-shoe athletes, when transitioning to barefoot condition, were essentially better at adopting the natural running style for certain variables.

Addition of probenecid to oral β-lactam antibiotics: a systematic review and meta-analysis.

To explore the literature comparing the pharmacokinetic and clinical outcomes from adding probenecid to oral β-lactams. Medline and EMBASE were searched from inception to December 2021 for all English language studies comparing the addition of probenecid (intervention) with an oral β-lactam [flucloxacillin, penicillin V, amoxicillin (± clavulanate), cefalexin, cefuroxime axetil] alone (comparator). ROBINS-I and ROB-2 tools were used. Data on antibiotic therapy, infection diagnosis, primary and secondary outcomes relating to pharmacokinetics and clinical outcomes, plus adverse events were extracted and reported descriptively. For a subset of studies comparing treatment failure between probenecid and control groups, meta-analysis was performed. Overall, 18/295 (6%) screened abstracts were included. Populations, methodology and outcome data were heterogeneous. Common populations included healthy volunteers (9/18; 50%) and those with gonococcal infection (6/18; 33%). Most studies were crossover trials (11/18; 61%) or parallel-arm randomized trials (4/18; 22%). Where pharmacokinetic analyses were performed, addition of probenecid to oral β-lactams increased total AUC (7/7; 100%), Cmax (5/8; 63%) and serum t½ (6/8; 75%). Probenecid improved PTA (2/2; 100%). Meta-analysis of 3105 (2258 intervention, 847 control) patients treated for gonococcal disease demonstrated a relative risk of treatment failure in the random-effects model of 0.33 (95% CI 0.20-0.55; I2 = 7%), favouring probenecid. Probenecid-boosted β-lactam therapy is associated with improved outcomes in gonococcal disease. Pharmacokinetic data suggest that probenecid-boosted oral β-lactam therapy may have a broader application, but appropriately powered mechanistic and efficacy studies are required.

Design and rationale of the mobile health intervention for rural atrial fibrillation

Atrial fibrillation (AF) is a highly morbid condition which requires long-term adherence to oral anticoagulation and may be associated with adverse quality of life and health care utilization. We developed a relational agent-an interactive smartphone-based intervention accessible regardless of digital or health literacy-to assist individuals residing in rural, Western Pennsylvania, with AF with chronic disease self-management. The "Mobile health intervention for rural atrial fibrillation" is a single center, parallel-arm randomized clinical trial for adults with AF funded by the National Institute of Health's National Heart, Lung, and Blood Institute to enroll 264 participants. All participants receive a smartphone with data plan: The intervention is a 4 month relational agent coupled with the AliveCor Kardia for heart rate and rhythm monitoring provided by smartphone, and the control a pre-installed, smartphone-based application for health-related information (WebMD). The study uses remote recruitment and engagement to enroll individuals who would otherwise be unlikely to participate in clinical research due to rurality. The primary outcome of the trial is adherence to oral anticoagulation, determined by proportion of days covered, as measured at 12 months. The secondary outcomes are quality of life, both AF-specific and general, and health care utilization. The study entails a baseline visit, a 4 month intervention phase, and 8 and 12 month follow-up visits. This mobile health trial tests the effectiveness of a smartphone-based relational agent to improve clinical and patient-reported outcomes in rural-dwelling individuals.

Blueberries Improve Endothelial Function in Postmenopausal Women With Above-Normal Blood Pressure via Reductions in Oxidative Stress

ObjectivesResearch suggests blueberries and their (poly)phenols may improve endothelial dysfunction, a major risk factor for cardiovascular disease (CVD). The objective of this study was to investigate the impact of consuming 22 g/day for 12 weeks of freeze-dried highbush blueberry powder on endothelial function and other measures of cardiovascular health, oxidative stress, and circulating (poly)phenol metabolites in postmenopausal women with above-normal blood pressure.MethodsWe performed a randomized, double-blind, placebo-controlled, parallel-arm trial in estrogen-deficient postmenopausal women aged 45–65 years with elevated blood pressure or stage 1-HTN. Endothelial function was assessed as brachial artery flow-mediated dilation (FMD) and normalized to individual shear rate area under the curve (FMD/SRAUC) to control for inter-individual variability in reactive hyperemia-induced shear stress. To assess whether improvements in FMD were mediated by reduced oxidative stress, FMD was assessed before and after intravenous infusion of a supra-physiologic dose of ascorbic acid. Blood pressure, arterial stiffness, and plasma (poly)phenol metabolites were also assessed.ResultsA total of 43 women completed the trial (n = 32 for endothelial function). Compliance in the Blueberry and Placebo groups were 93% and 91%, respectively. Mean total plasma (poly)phenol metabolite concentrations were increased at 4 (250,053 nmol/L, P < 0.05) and 8 (303,053 nmol/L, P < 0.05) weeks in the Blueberry group compared to baseline (125,798 nmol/L) with a strong trend at 12 weeks (227,971 nmol/L, P < 0.05), and no changes in Placebo. Blood pressure and arterial stiffness were unchanged with both treatments. At 12 weeks, FMD/SRAUC was increased by 96% from baseline (P < 0.05) in the Blueberry group but unchanged in Placebo, and changes in FMD/SRAUC from baseline to 12 weeks were higher (P < 0.05) than Placebo. The response in FMD/SRAUC to ascorbic acid infusion was lower (P < 0.05) at 12 weeks compared to baseline in the Blueberry group but not Placebo.ConclusionsThese findings suggest blueberries improve endothelial function, and is mediated, in part, by reduced oxidative stress in postmenopausal women with above-normal blood pressure, a high-risk population for developing CVD.Funding SourcesUS Highbush Blueberry Council and USDA National Institute of Food and Agriculture.

Efficacy of amoxicillin or amoxicillin and clavulanic acid in reducing infection rates after third molar surgery: a systematic review and meta-analysis.

The current review was designed to assess the efficacy of amoxicillin (AMX) and amoxicillin-clavulanic acid (AMX-CLA) for reducing infection rates after third molar surgery. PubMed, Embase, ScienceDirect, and Google Scholar were searched for double-blind randomized controlled trials (RCTs) assessing the efficacy of AMX/AMX-CLA for infection control after third molar surgery. 13 RCTs were included. Our meta-analysis demonstrated a statistically significant reduced risk of infections with AMX/AMX-CLA (RR: 0.29, 95% CI: 0.18, 0.45 I2=0% p<0.00001). The meta-analysis demonstrated that the risk of infections was significantly reduced only in parallel-arm trials but not in split-mouth trials. Sub-group analysis based on antibiotic type indicated that the risk of infections was reduced with both AMX and AMX-CLA. A subgroup analysis based on the timing of AMX/AMX-CLA administration indicated that the risk of infections was significantly reduced with both preoperative (RR: 0.41, 95% CI: 0.21, 0.81 I2=0% p=0.01) and postoperative (RR: 0.18, 95% CI: 0.09, 0.35 I2=0% p<0.00001) administration of AMX/AMX-CLA. Meta-analysis indicated no increased risk of adverse events with the use of AMX/AMX-CLA (RR: 1.47, 95% CI: 0.41, 5.22 I2=77% p=0.55). The use of AMX/AMX-CLA is associated with a significant reduction in the risk of infections after impacted third molar surgery. The risk of infections is reduced with both AMX and AMX-CLA. Our results also indicated that the infection risk was reduced with preoperative and postoperative antibiotic administration and there is no significant increase in the risk of antibiotic-related adverse events.

551-P: Effects of a Plant-Based Intensive Lifestyle Intervention in Adults with Type 2 Diabetes: A Randomized Controlled Trial

Background: The Republic of the Marshall Islands (RMI) has the highest rate of type 2 diabetes (T2D) in the world. Lifestyle interventions, including plant-based diets and exercise, have been shown to effectively manage T2D. Objective: We therefore conducted the largest plant-based lifestyle intervention in adults with T2D. The goal of this study was to determine whether a plant-based lifestyle intervention is more effective than the standard of care for treating type 2 diabetes. Methods: We conducted a parallel-arm randomized clinical trial in Majuro, RMI. Adults with T2D were randomized to either standard of diabetes care (SOC) or a plant-based lifestyle intervention (PB+Ex) for 24 weeks. The first 12 weeks of the intervention involved the provision of plant-rich meals, counselling, cooking classes, and group exercise sessions, which gradually decreased in frequency over the 12-week period. Thereafter, from Weeks 13-24, participants in the PB+Ex group were instructed to continue the lifestyle intervention on their own. The primary outcome was change in HbA1c. Secondary outcomes included fasting glucose, insulin, blood pressure, lipids, and medication use. Outcome data was collected at five time points and analyzed using linear mixed models. Results: One hundred thirty-eight adults with T2D started the intervention (mean ± SD; age: 54.3 ± 8.6 years, HbA1c: 10.3 ± 2.1%; 50.7% female) . PB+Ex reduced HbA1c by 1.3 ± 0.3% (lsmean ± SEM; p&amp;lt;0.001) and 0.7 ± 0.3% (p=0.01) at weeks 12 and 24, respectively, compared to SOC. PB+Ex also decreased BMI at weeks 12 and 24 (both -1.1 kg/m2; p&amp;lt;0.001) . Additionally, PB+Ex reduced C-reactive protein and waist circumference compared to SOC. Additional analyses on other fasting cardiometabolic endpoints and medication changes are underway. Conclusions: A plant-based intensive lifestyle intervention with exercise is more effective at improving glycemic control, BMI, and inflammatory markers than the standard of diabetes care. Disclosure C.Hanick: None. C.M.Peterson: None. J.Sabaté: None. B.C.Davis: None. J.W.Spence: None. J.Kelly: None. Funding Department of the Army (W81XWH-05-1-0547)

Effectiveness of Telemedicine in Reducing Hospitalizations in Patients Discharged from the Hospital Due to Heart Failure: A Randomized Clinical Trial Protocol

Fundament: Telemedicine for follow-up in heart failure (HF) patients is effective in reducing hospitalizations, total and cardiovascular mortality. However, few studies were conducted in low and middle income, where lower access to technology and illiteracy could impact the results. Objective: To assess the effectiveness of associating telemedicine strategies, when compared to usual care, in reducing hospitalizations related to HF in patients discharged from the hospital due to HF. Methods: Controlled, randomized, multicenter, parallel-arm clinical trial, with an allocation ratio [...]

Effect of active and passive distraction techniques while administering local anaesthesia on the dental anxiety, behaviour and pain levels of children: a randomised controlled trial

PurposeThe aim of the study was to compare the effect of a stress ball, an active distraction technique with audio-visual eyeglasses, a passive distraction technique during local anaesthesia administration, on dental anxiety (primary outcome), behaviour and pain levels of children (secondary outcomes).MethodsIn this randomised controlled parallel arm trial involving 123 children aged 8–12 years, who required dental treatment under inferior alveolar nerve block, children were randomly allocated into the following three groups: Group 1: Stress ball, Group 2: Audio-visual eyeglasses, Group 3: Control group (basic behaviour guidance without distraction). Dental anxiety was measured using modified child dental anxiety scale and pulse rate, behaviour was rated using Venham’s scale and pain was measured by both self-reporting and observational scales.ResultsNo significant difference between the groups was observed for dental anxiety, but a significant decrease was seen in dental anxiety scores within all groups. No significant differences were seen between the groups for behaviour ratings and pain scores.ConclusionUse of active stress ball distraction or passive audio-visual eyeglasses during local anaesthesia administration decreased dental anxiety but did not result in a significant improvement in the dental anxiety, behaviour and pain levels when compared to basic behaviour guidance without distraction.Clinical trial registrationThe clinical trial was registered at Clinical Trials Registry–India (CTRI Reg no: CTRI/2019/04/018768, Dated 24 April 2019).

Practical considerations in utilizing cluster randomized controlled trials conducted in biopharmaceutical industry.

Cluster randomized controlled trials (cluster RCTs), also known as parallel-arm group-randomized trials, are trials in which the randomized units are groups of participants, as opposed to individual participants. These trials have largely been implemented to address broad public health issues, but with the growing interest in use of real-world data in the regulatory setting, this design may be increasingly considered for industry trials. The key difference between cluster RCTs and traditional RCTs is the intraclass correlation coefficient (ICC) that needs to be considered in cluster RCTs. In this article, we discuss some key practical considerations that are related to ICC in the design, conduct, analysis, and report stages of a cluster RCT. These key considerations related to ICC can lead to improvement in how we translate research findings from cluster RCTs into practices in the biopharmaceutical industry.

Comment on The Unbearable Lightness of Difference Between Statistical and Clinical Significance.

Comment on The Unbearable Lightness of Difference Between Statistical and Clinical Significance.

Effectiveness of Pediatric Teleconsultation to Prevent Skin Conditions in Infants and Reduce Parenting Stress in Mothers: Randomized Controlled Trial.

BackgroundIn Japan, eHealth for infants and mothers is currently an important aspect, but its effectiveness has rarely been examined. For infants, skin problems, including atopic dermatitis (AD), which is known to lead to other allergic diseases, are one of the most common conditions. Mothers of infants are prone to experiencing parenting stress, which adversely affects mothers’ and children’s well-being. Additionally, studies have reported that AD among offspring enhances parenting stress, and postnatal maternal psychological problems can increase the risk of AD in children.ObjectiveThis study evaluated the effectiveness of pediatric teleconsultation for preventing AD in infants and reducing parenting stress in mothers in Japan.MethodsThe study was an open-label, randomized, parallel-armed controlled trial. In total, 318 pairs of infants and mothers in the Yokohama City Sakae Ward were recruited when they submitted birth cards to the ward, received the explanation about the trial, and provided informed consent on the website for this trial. Eligible pairs of infants and mothers were randomly assigned to the intervention group (n=140) or the control group (n=138). Participants in the intervention and control groups received routine postnatal care from local government services. In addition, participants in the intervention group had the option to combine routine pediatric services with teleconsultation and email newsletters without charge from the date of registration until the infant turned 4 months. Primary outcomes were (1) the prevalence of AD in infants diagnosed based on the United Kingdom Working Party criteria and (2) parenting stress and mental status of mothers assessed using the Parenting Stress Index-Short Form (PSI-SF) and General Health Questionnaire-12 (GHQ-12). Data were collected by the ward office staff and researcher during the 4-month checkup.ResultsThe prevalence of AD in infants was significantly lower in the intervention group than in the control group during the 4-month checkup (20% vs 33%, P=.02; relative risk ratio, 0.709 [95% CI 0.519-0.969]). No significant differences were observed in the PSI-SF and GHQ-12 scores between the 2 groups. There was a significant difference in the prevalence of AD between participants who used teleconsultation services and email newsletters, participants who did not use teleconsultation services but received email newsletters, and participants who neither received nor used either service (18% vs 22% vs 33%, P=.048).ConclusionsThis is the first randomized controlled trial demonstrating that routine pediatric care combined with teleconsultation and email newsletters was effective in reducing the prevalence of AD in infants. The findings highlight the potential of pediatric eHealth to become a useful new strategy for preventing AD.Trial RegistrationUniversity Hospital Medical Information Network Clinical Trials Registry UMIN000029774; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034022

A Food-Based Intervention in a Military Dining Facility Improves Blood Fatty Acid Profile.

Enhancing dietary omega-3 highly unsaturated fatty acids (n-3 HUFA) intake may confer neuroprotection, brain resiliency, improve wound healing and promote cardiovascular health. This study determined the efficacy of substituting a few common foods (chicken meat, chicken sausage, eggs, salad dressings, pasta sauces, cooking oil, mayonnaise, and peanut butter) lower in omega-6 polyunsaturated fatty acids (n-6 PUFA) and higher in n-3 HUFA in a dining facility on blood fatty acid profile. An eight-week prospective, between-subjects (n = 77), repeated measures, parallel-arm trial was conducted. Participants self-selected foods consumed from conventionally produced foods (control), or those lower n-6 PUFA and higher n-3 HUFA versions (intervention). Changes in blood omega-3 index, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), n-6 PUFA, lipid profile, and food satisfaction were main outcomes. Between-group differences over time were assessed using a linear mixed model to measure the effect of diet on blood serum fatty acids and inflammatory markers. The intervention group achieved a higher omega-3 index score (3.66 ± 0.71 vs. 2.95 ± 0.77; p < 0.05), lower total n-6 (10.1 ± 4.6 vs. 15.3 ± 6.7 µg/mL; p < 0.05), and higher serum concentration of EPA (5.0 ± 1.31 vs. 4.05 ± 1.56 µg/mL; p < 0.05) vs. controls. Satisfaction in intervention foods improved or remained consistent. Substitution of commonly eaten dining facility foods with like-items higher in DHA and EPA and lower in n-6 PUFA can favorably impact fatty acid status and the omega-3 index.

Spillover Effects of a Family-Based Childhood Weight-Management Intervention on Parental Nutrient Biomarkers and Cardiometabolic Risk Factors

ABSTRACTBackgroundParental involvement has been shown to favorably affect childhood weight-management interventions, but whether these interventions influence parental diet and cardiometabolic health outcomes is unclear.ObjectivesThe aim was to evaluate whether a 1-y family-based childhood weight-management intervention altered parental nutrient biomarker concentrations and cardiometabolic risk factors (CMRFs).MethodsSecondary analysis from a randomized-controlled, parallel-arm clinical trial (NCT00851201). Families were recruited from a largely Hispanic population and assigned to either standard care (SC; American Academy of Pediatrics overweight/obesity recommendations) or SC + enhanced program (SC+EP; targeted diet/physical activity strategies, skill building, and monthly support sessions). Nutrient biomarkers (plasma carotenoids and fat-soluble vitamins, RBC fatty acid profiles) and CMRFs (BMI, blood pressure, glucose, insulin, lipid profile, inflammatory and endothelial dysfunction markers, adipokines) were measured in archived samples collected from parents of participating children at baseline and end of the 1-y intervention.ResultsParents in both groups (SC = 106 and SC+EP = 99) had significant reductions in trans fatty acid (–14%) and increases in MUFA (2%), PUFA n–6 (ɷ-6) (2%), PUFA n–3 (7%), and β-carotene (20%) concentrations, indicative of lower partially hydrogenated fat and higher vegetable oil, fish, and fruit/vegetable intake, respectively. Significant reductions in high-sensitivity C-reactive protein (hsCRP; –21%) TNF-α (–19%), IL-6 (–19%), and triglycerides (–6%) were also observed in both groups. An additional significant improvement in serum insulin concentrations (–6%) was observed in the SC+EP parents. However, no major reductions in BMI or blood pressure and significant unfavorable trajectories in LDL-cholesterol and endothelial dysfunction markers [P-selectin, soluble intercellular adhesion molecule (sICAM), thrombomodulin] were observed. Higher carotenoid, MUFA, and PUFA (n–6 and n–3) and lower SFA and trans fatty acid concentrations were associated with improvements in circulating glucose and lipid measures, inflammatory markers, and adipokines.ConclusionsThe benefits of a family-based childhood weight-management intervention can spill over to parents, resulting in apparent healthier dietary shifts that are associated with modest improvements in some CMRFs.

“I feel like the worst mother in the world”: Neoliberal subjectivity in Indigenous Australian oral health

Neoliberalism gained popularity during the post-Cold War period as a set of dominating ideologies, practices and policies that underpinned the movement towards globalisation. Neoliberalism champions competitive private markets, deregulation that facilitates economic activity, personal responsibility, and reduced public expenditure on infrastructure. A decade after the initial rise of neoliberalism, health inequities became concerns on the global stage. Oral health inequities aptly reflect social injustices due to the unique relation between material circumstances, access to health services and structural inequities. In Australia, Indigenous children experience early childhood caries at alarmingly higher rates than non-Indigenous children. Recently, neoliberalism has been suggested as an overwhelming contributor to Indigenous oral health disparities. This qualitative research is an extension of a single-blind parallel-arm randomised control trial that aimed to identify factors related to the increased occurrence of dental caries in Indigenous children. The objective of this constructivist grounded theory study was to generate an understanding of how neoliberal subjectivity exists for Indigenous peoples in the context of oral health in Australia. Experiences of ownership, guilt, failure, embarrassment, shame, and judgment were key in participants’ experiences of neoliberal subjectivity; these feelings were exacerbated by experiences of bullying, financial limitations, and institutional racism. We argue that individual responsibility for health, as a tenet of neoliberal ideologies, furthers Indigenous oral health inequities and that neoliberalism as a societal discourse perpetuates colonial values by benefitting the privileged and further oppressing the disadvantaged. Trial registrationAustralian New Zealand Clinical Trial Registry ACTRN12611000111976; registered February 01, 2011.

Video self-confrontation as a therapeutic tool in schizophrenia: A randomized parallel-arm single-blind trial

BackgroundLack of insight is a barrier to treating psychosis. Preliminary studies have suggested that showing people videos of their psychotic behaviour may improve personal insight. This clinical trial aimed to assess the effect of video self-confrontation. MethodsInpatients between 18 and 65 years old with schizophrenia or schizoaffective disorder were filmed upon admission to two psychiatric hospitals while experiencing acute psychosis. After stabilization, individuals were randomized 1:1 to the “self-video” group where they watched their own video or to the “no video” control group. The primary outcome was the Scale to assess Unawareness of Mental Disorder (SUMD) at 48 h by a blinded assessor. Secondary objectives included psychotic and depressive symptoms, medication adherence and functioning using the Functional Remission of General Schizophrenia. Patients were followed up for four months. Results60 participants were randomized and the level of insight did not differ between groups at 48 h (p = 0.98). There was no impact on SUMD subscores or the other insight questionnaires at any timepoint, nor on psychopathology or medication adherence. At one month, the level of functioning of those in the “self-video” group (n = 23) was higher (61.8 vs 53.5, p = 0.02), especially concerning “Treatment” and “Daily life”. No adverse effects were reported. After video self-confrontation, people expressed more positive than negative emotions and were less lost to follow-up. ConclusionVideo self-confrontation did not change levels of insight, but may have a therapeutic impact nonetheless, by improving levels of self-care and adherence to care, indicating that this innovative therapeutic tool requires further study.Trial Registration Number: NCT02664129

The Design and Rationale of a Phase 2b, Randomized, Double-Blinded, and Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Lomecel-B in Older Adults with Frailty

BackgroundFrailty in older adults is a rapidly growing unmet medical need. It is an aging-related syndrome characterized by physical decline leading to higher risk of adverse health outcomes.ObjectivesTo evaluate the efficacy of Lomecel-B, an allogeneic medicinal signaling cell (MSC) formulation, in older adults with frailty. DESIGN: This multicenter, randomized, parallel-arm, double-blinded, and placebo-controlled phase 2b trial is designed to evaluate doserange effects of Lomecel-B for frailty on physical functioning, patient-reported outcomes (PROs), frailty status, and biomarkers.SettingEight enrolling clinical research centers, including the Miami Veterans Affairs Medical Center.ParticipantsTarget enrollment is 150 subjects aged 70–85 years of any race, ethnicity, or gender. Enrollment criteria include a Clinical Frailty Score of 5 (“mild”) or 6 (“moderate”), a 6MWT of 200–400 m, and serum tumor necrosis factor-alpha (TNF-α) ≥2.5 pg/mL.InterventionA single intravenous infusion of Lomecel-B (25, 50, 100, or 200 million cells) or placebo (N=30/arm). Patients are followed for 365 days for safety, and the efficacy assessments performed at 90, 180, and 270 days.MeasurementsThe primary endpoint is change in 6MWT in the Lomecel-B-treated arms versus placebo at 180 days post-infusion. Secondary and exploratory endpoints include change in: 6MWT and other physical function measures at all time points; PROs; frailty status; cognitive status; and an inflammatory biomarkers panel. A pre-specified sub-study examines vascular/endothelial biomarkers. Safety is evaluated throughout the trial.ResultsThe trial is conducted under a Food and Drug Administration Investigational New Drug (IND), with Institutional Review Board approval, and monitoring by an NIH-appointed independent Data Safety Monitoring Board.ConclusionThis clinical trial investigates the use of a regenerative medicine strategy for frailty in older adults. The results will further the understanding of the potential for Lomecel-B in the geriatric condition of frailty.

Effects of short-term sugary beverage consumption on glucose control and cardiovascular disease risk factors: A randomized controlled parallel-arm trial

Objective To determine differences in glucose control and cardiovascular disease risk factors following three weeks of added soda, 100% fruit juice, or water in apparently healthy, college-aged adults. Participants Thirty-six adults (18 males; 18 females) between the ages of 18 and 30 years of age. Methods A 3-arm randomized controlled parallel-arm trial; at baseline and after three weeks consuming the assigned beverage, participants completed glucose control and cardiovascular disease risk factor assessments. Results There were no significant differences between beverage conditions for glucose control or cardiovascular disease risk factors (ps > 0.05). There were no significant changes in caloric intake or differences in caloric intake between conditions, p = 0.17. Conclusions In healthy, young adults, under free-living conditions, short-term consumption of two commercially packaged servings of SBs did not lead to significant glucose control or cardiovascular disease risk factor changes, indicating potential compensation and/or resilience to negative short-term effects.

Treatment of residual pockets using an oscillating chitosan device versus regular curettes alone-A randomized, feasibility parallel-arm clinical trial.

A brush made of chitosan has shown to be an effective and harmless device for non-surgical treatment of mild to moderate peri-implantitis. To date, no study has evaluated the use of a chitosan brush in the non-surgical treatment of residual pockets in periodontal treatment. Seventy-eight patients with periodontitis were included in this multicenter, randomized, examiner-blind clinical trial of 6 months duration. Patients with residual probing pocket depth (PPD) of ≥5mm and ≤7mm following previous active periodontal treatment were included. Patients were assigned either subgingival treatment with curettes (control) or an oscillating chitosan brush (test). Changes in bleeding on probing (BoP) and PPD between baseline and terminal evaluation at 6 months were evaluated. A significant reduction in both PPD and BoP was seen within both groups. There was no significant difference in BoP between test and control groups after 6 months, but the reduction in PPD was significantly improved in the test group (P≤0.01). The combined outcome of no BOP and PPD ≤4mm was significantly better in the test group (P≤0.01). No adverse reactions were seen. Treatment of residual periodontal pockets (PPD=5 to 7mm) with a chitosan brush disclosed equal or better clinical results as compared to regular curettes. This study supports that a chitosan brush can be used for subgingival biofilm removal and soft tissue curretage in the treatment of periodontitis.