Sparsentan for Focal Segmental Glomerulosclerosis in the DUET Open-Label Extension: Long-term Efficacy and Safety.

Rationale & Objective: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist (DEARA) examined in the ongoing phase 2 DUET trial for focal segmental glomerulosclerosis (FSGS). In the DUET 8-week double-blind period, sparsentan resulted in greater proteinuria reduction versus irbesartan. We report the long-term efficacy and safety of sparsentan during the open-label extension over more than 4 years. Study Design: Patients were examined from their first sparsentan dose (double-blind period or open-label extension) through 4.6 years. Setting & Participants: Patients with FSGS, excluding secondary FSGS. Intervention: Sparsentan (200, 400, and 800 mg/d). Outcomes: Urinary protein-creatinine ratio, FSGS partial remission endpoint (urinary protein-creatinine ratio ≤1.5 g/g and >40% reduction from baseline), estimated glomerular filtration rate, and blood pressure approximately every 12 weeks. Treatment-emergent adverse events by year and cases/100 patient-years. Results: 109 patients were enrolled; 108 received ≥1 sparsentan dose; 103 entered the open-label extension (68 sparsentan, 35 irbesartan during the double-blind period). Sparsentan was ongoing in 45/108 patients (41.7%); median time to treatment discontinuation was 3.9 years (95% CI, 2.6-5.2). Mean percent proteinuria reduction from baseline was sustained through follow-up. Achieving partial remission within 9 months of first sparsentan dose (52.8% of patients) versus not achieving (47.2%) was associated with significantly slower rate of estimated glomerular filtration rate decline over the entire treatment period (-2.70 vs -6.56; P = 0.03) and in the first 2 years (-1.69 vs -6.46; P = 0.03). The most common treatment-emergent adverse events (>9 cases/100 patient-years) were headache, peripheral edema, upper respiratory infection, hyperkalemia, and hypotension. Peripheral edema and hypotension declined from year 1 (13.9% and 15.7% of patients, respectively) to ≤4% in years ≥2. There were no cases of heart failure and no patient deaths. Limitations: The open-label extension does not include a comparison group. Conclusions: Long-term sparsentan treatment showed sustained proteinuria reduction and a consistent safety profile.

There is substantial unmet clinical need for safe and effective treatments for focal segmental glomerulosclerosis (FSGS), a kidney lesion with varied causes. Sparsentan is being studied for treatment of FSGS and targets 2 important pathways (endothelin-1 and angiotensin II) that lead to the loss of kidney function. In the 8-week randomized, double-blind DUET study in patients with FSGS, sparsentan reduced the amount of protein in the urine better than irbesartan (a blood pressure medicine often used to treat FSGS). We examined long-term treatment with sparsentan over >4 years in the DUET open-label extension. We found sustained proteinuria reduction in patients who continued treatment with sparsentan and a consistent safety profile with no new or unexpected adverse effects.

Focal Segmental Glomerulosclerosis Patient Baseline Characteristics in the Sparsentan Phase 3 DUPLEX Study.

Introduction: The phase 3 DUPLEX trial is evaluating sparsentan, a novel, nonimmunosuppressive, single-molecule dual endothelin angiotensin receptor antagonist, in patients with focal segmental glomerulosclerosis (FSGS). Methods: DUPLEX (NCT03493685) is a global, multicenter, randomized, double-blind, parallel-group, active-controlled study evaluating the efficacy and safety of sparsentan 800 mg once daily versus irbesartan 300 mg once daily in patients aged 8 to 75 years (USA/UK) and 18 to 75 years (ex-USA/UK) weighing ≥20 kg with biopsy-proven FSGS or documented genetic mutation in a podocyte protein associated with FSGS, and urine protein-to-creatinine ratio (UP/C) ≥1.5 g/g. Baseline characteristics blinded to treatment allocation are reported descriptively. Results: The primary analysis population includes 371 patients (336 adult, 35 pediatric [<18 years]) who were randomized and received study drug (median age, 42 years). Patients were White (73.0%), Asian (13.2%), Black/African American (6.7%), or Other race (7.0%); and from North America (38.8%), Europe (36.1%), South America (12.7%), or Asia Pacific (12.4%). Baseline median UP/C was 3.0 g/g; 42.6% in nephrotic-range (UP/C >3.5 g/g [adults]; >2.0 g/g [pediatrics]). Patients were evenly distributed across estimated glomerular filtration rate (eGFR) categories corresponding to chronic kidney disease (CKD) stages 1 to 3b. Thirty-three patients (9.4% of 352 evaluable samples) had pathogenic or likely pathogenic (P/LP) variants of genes essential to podocyte structural integrity and function, 27 (7.7%) had P/LP collagen gene (COL4A3/4/5) variants, and 14 (4.0%) had high-risk APOL1 genotypes. Conclusions: Patient enrollment in DUPLEX, the largest interventional study in FSGS to date, will enable important characterization of the treatment effect of sparsentan in a geographically broad and clinically diverse FSGS population.

Effect of Rural Trauma Team Development on the Outcomes of Motorcycle Accident-Related Injuries (Motor Registry Project): Protocol for a Multicenter Cluster Randomized Controlled Trial.

BACKGROUND: Injury is a global health concern, and injury-related mortality disproportionately impacts low- and middle-income countries (LMICs). Compelling evidence from observational studies in high-income countries shows that trauma education programs, such as the Rural Trauma Team Development Course (RTTDC), increase clinician knowledge of injury care. There is a dearth of such evidence from controlled clinical trials to demonstrate the effect of the RTTDC on process and patient outcomes in LMICs. OBJECTIVE: This multicenter cluster randomized controlled clinical trial aims to examine the impact of the RTTDC on process and patient outcomes associated with motorcycle accident-related injuries in an African low-resource setting. METHODS: This is a 2-arm, parallel, multi-period, cluster randomized, controlled, clinical trial in Uganda, where rural trauma team development training is not routinely conducted. We will recruit regional referral hospitals and include patients with motorcycle accident-related injuries, interns, medical trainees, and road traffic law enforcement professionals. The intervention group (RTTDC) and control group (standard care) will include 3 hospitals each. The primary outcomes will be the interval from the accident to hospital admission and the interval from the referral decision to hospital discharge. The secondary outcomes will be all-cause mortality and morbidity associated with neurological and orthopedic injuries at 90 days after injury. All outcomes will be measured as final values. We will compare baseline characteristics and outcomes at both individual and cluster levels between the intervention and control groups. We will use mixed effects regression models to report any absolute or relative differences along with 95% CIs. We will perform subgroup analyses to evaluate and control confounding due to injury mechanisms and injury severity. We will establish a motorcycle trauma outcome (MOTOR) registry in consultation with community traffic police. RESULTS: The trial was approved on August 27, 2019. The actual recruitment of the first patient participant began on September 01, 2019. The last follow-up was on August 27, 2023. Posttrial care, including linkage to clinical, social support, and referral services, is to be completed by November 27, 2023. Data analyses will be performed in Spring 2024, and the results are expected to be published in Autumn 2024. CONCLUSIONS: This trial will unveil how a locally contextualized rural trauma team development program impacts organizational efficiency in a continent challenged with limited infrastructure and human resources. Moreover, this trial will uncover how rural trauma team coordination impacts clinical outcomes, such as mortality and morbidity associated with neurological and orthopedic injuries, which are the key targets for strengthening trauma systems in LMICs where prehospital care is in the early stage. Our results could inform the design, implementation, and scalability of future rural trauma teams and trauma education programs in LMICs. TRIAL REGISTRATION: Pan African Clinical Trials Registry (PACTR202308851460352); https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=25763. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55297.

China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI) to Prevent Cognitive Decline: Study Design and Progress.

BACKGROUND: Alzheimer's disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately. MEDTODS: We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60-80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application. RESULTS: Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025. CONCLUSIONS: This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China.

Comparative Evaluation of the Effectiveness of Innovative Periorbital Eye Massager and Virtual Reality Eyeglasses for Reducing Dental Anxiety during Dental Restorative Procedures in Children.

Background: Many behavior management techniques are employed to reduce the anxiety associated with dental procedures in children. One of the most commonly used methods comprises audiovisual distraction using virtual reality (VR) eyeglasses. In this study, an innovative device, a periorbital eye massager (PEM), is compared with VR to evaluate dental anxiety in children. Materials and methods: in this study, 22 children were divided into two groups, that is, group I consisting of PEM and group II consisting of VR. The participants were instructed to wear the device and then subjected to dental restorative procedures. After completion of the procedure, anxiety was measured using a validated questionnaire by the children and by using the modified behavior pain scale by the second investigator. Also, physiological parameters like heart rate and oxygen saturation were evaluated before and after a dental procedure. Results: The results were statistically insignificant for group I and group II when a validated questionnaire and modified behavior pain scale were used to measure the dental anxiety of children. Also, the data also shows no significant difference in heart rate and oxygen saturation between the two groups. Conclusion: The innovative PEM can also be used as an effective behavior management tool in managing dental anxiety in children, as there was no statistically significant difference between PEM and VR. Clinical significance: As a pediatric dentist, the methods for administering a patient present a novel challenge because behavior management varies from patient to patient. As a result, the prospects for augmenting various techniques of behavior therapy for pediatric patients are limitless. How to cite this article: Gala UP, Kalaskar R. Comparative Evaluation of the Effectiveness of Innovative Periorbital Eye Massager and Virtual Reality Eyeglasses for Reducing Dental Anxiety during Dental Restorative Procedures in Children. Int J Clin Pediatr Dent 2024;17(1):48-53.

Efficacy and safety evaluation of Ginkgo biloba dropping pill (GBDP) on stable angina pectoris complicated with depression: A placebo-controlled, randomized, double-blind, multicenter study.

BACKGROUND: Stable angina pectoris (SAP) is a clinical condition characterized by reversible and temporary myocardial ischemia and hypoxia. A majority of SAP patients also experience depressive disorders, which adversely affect their disease prognosis and overall quality of life. However, the clinical utility of existing antidepressants is constrained by their side effects. Ginkgo biloba dropping pill (GBDP), a Chinese patented medication, has demonstrated efficacy in the treatment of both coronary heart disease and mental disorders. This prospective, randomized, double-blind, multicenter clinical trial aimed to assess the effectiveness and safety of GBDP as an adjuvant therapy for SAP complicated by depression. METHODS: Participants were randomly assigned in a 1:1 ratio to receive either GBDP or a placebo (5 pills, three times a day) in addition to standard therapy for a duration of 12 weeks. The Seattle Angina Questionnaire (SAQ) was administered every 4 weeks during the treatment, and angina event frequency was assessed weekly. The 36-item Short-Form (SF-36) and Hamilton Depression Scale (HAMD) scores were measured both before and after the treatment. RESULTS: Out of the 72 patients, 68 (n = 34 per group) completed the entire study. At the first visit (4 weeks ± 3 days), the SAQ-Angina Stability score in the GBDP group was significantly higher than that in the placebo group (p < 0.05). While the average weekly frequency of angina episodes in the placebo group notably increased after 12 weeks of treatment (p < 0.05), it displayed an improving trend in the GBDP group (p > 0.05). By the endpoint, each subcategory score of SF-36 in the GBDP group exhibited significant improvement compared to baseline (p < 0.05). The comparison of score improvement between the two groups revealed that the SF-PCS score of the GBDP group was higher than that of the placebo group (p < 0.05). HAMD scores in both groups significantly increased after treatment (p < 0.05). No discernible difference in the incidence of adverse reactions was observed between the two groups (p > 0.05). CONCLUSION: In patients with SAP complicated by depression, GBDP, when combined with standard treatment, rapidly and safely alleviates angina pectoris symptoms. It demonstrates therapeutic potential in enhancing the quality of life and alleviating depressive symptoms.

Transcutaneous auricular vagus nerve stimulation for post-stroke depression: A double-blind, randomized, placebo-controlled trial.

BACKGROUND: It is a well-established fact that post-stroke depression (PSD) is a prevalent condition that affects a significant proportion of individuals who have suffered a stroke. Hence, our research endeavors to explore the safety, efficacy and the potential molecular mechanism of transcutaneous auricular vagus nerve stimulation (ta-VNS) for the treatment of depression in PSD patients by conducting a double-blind, sham-controlled, randomized trial. METHODS: Patients who had experienced strokes and exhibited depressive symptoms, with a Hamilton Depression Scale (HAMD-17) score of ≥8 and met the DSM-IV criteria, were diagnosed with PSD. A volunteer sample of participants (N = 80) were randomly divided into either the ta-VNS group (which received ta-VNS in addition to conventional treatment) or the control group (which received conventional treatment only), in a 1:1 ratio. The effectiveness of the interventions was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD-17), Zung Self-Rating Depression Scale (SDS), and Barthel Index (BI) scores. Furthermore, Plasma BDNF, CREB1, and 5-HT levels were measured before and after treatment. RESULTS: The concomitant application of ta-VNS demonstrated a remarkable reduction in HAMD-17 and SDS scores, leading to noteworthy enhancements in patients' daily functioning, as evidenced by improved activities of daily living, at all assessed time points, in contrast to the control group (p < 0.0001). Notably, the ta-VNS group exhibited superior effects in modulating the measured neurotrophic biomarkers when compared to the control group (p < 0.05). CONCLUSIONS: The synergistic approach of combining ta-VNS with conventional treatment has demonstrated remarkable efficacy and tolerability in managing depression following a stroke.

Therapy effect of cochleural alternating acoustic beam therapy versus traditional sound therapy for managing chronic idiopathic tinnitus patients.

Idiopathic tinnitus is a common and complex disorder with no established cure. The CAABT (Cochleural Alternating Acoustic Beam Therapy CAABT), is a personalized sound therapy designed to target specific tinnitus frequencies and effectively intervene in tinnitus according to clinical tinnitus assessment. This study aimed to compare the effectiveness of the CAABT and Traditional Sound Therapy (TST) in managing chronic idiopathic tinnitus. This was a randomized, double-blind, parallel-group, single-center prospective study. Sixty adult patients with tinnitus were recruited and randomly assigned to the CAABT or TST group in a 1:1 ratio using a computer-generated randomization. The treatment lasted for 12 weeks, and participants underwent assessments using the tinnitus handicap inventory (THI), visual analog scale (VAS), tinnitus loudness measurements, and resting-state functional magnetic resonance imaging (rs-fMRI). Both groups showed significant reductions in THI scores, VAS scores, and tinnitus loudness after treatment. However, CAABT showed superiority to TST in THI Functional (p = 0.018), THI Emotional (p = 0.015), THI Catastrophic (p = 0.022), THI total score (p = 0.005) as well as VAS score (p = 0.022). More interesting, CAABT showed superiority to TST in the changes of THI scores, and VAS scores from baseline. The rs-fMRI results showed significant changes in the precuneus before and after treatment in both groups. Moreover, the CAABT group showed more changes in brain regions compared to the TST. No side effects were observed. These findings suggest that CAABT may be a promising treatment option for chronic idiopathic tinnitus, providing significant improvements in tinnitus-related symptoms and brain activity.Trial registration: ClinicalTrials.gov:NCT02774122.

Dynamic salivary cytokine profile of recurrent aphthous stomatitis patients in thalidomide maintenance treatment.

OBJECTIVE: To dynamically compare the longitudinal (time axis) and transverse (between groups) differences of the salivary cytokines during thalidomide maintenance treatment of recurrent aphthous stomatitis. METHODS: A randomized, controlled, clinical trial was performed. After the initial prednisone treatment, thalidomide (50 mg/d vs. 25 mg/d) was used as a maintenance drug for 4 or 8 weeks. The salivary IL-4, 5, 6, 10, TNF-α, and IFN-γ were dynamically detected with a cytometric bead array. RESULTS: Overall, the level of six elevated salivary cytokines after prednisone treatment was significantly downregulated, remained low during thalidomide maintenance, and rebounded at recurrence. The effect of 50 mg/d thalidomide on the salivary cytokines was not superior to 25 mg/d medication. The relapse-free period following drug withdrawal was the longest in the subgroup using 25 mg/d thalidomide for 8 weeks. The order of magnitude of IL-6 was the most obvious, and at week 8, only the level of IL-6 in the group (25 mg/d thalidomide for 8 weeks) continued to decline compared with the other groups. CONCLUSION: Thalidomide maintenance treatment can effectively sustain low levels of salivary IL-4, 5, 6, 10, TNF-α, and IFN-γ of recurrent aphthous stomatitis patients. IL-6 displayed a good correlation with the disease and is expected to become an index for diagnosis and follow-up. CLINICAL RELEVANCE: Low-dose long-term thalidomide maintenance treatment was supported for recurrent aphthous stomatitis. TRIAL REGISTRATION: Trial registration number of ChiCTR-IPR-16009759 at http://www.chictr.org/index.aspx .

Repeated local delivery of hyaluronic acid gel as adjunctive treatment of residual pockets in periodontitis patients undergoing supportive periodontal care. A randomized controlled clinical trial.

OBJECTIVES: To assess the effect of hyaluronic acid (HyA) application as adjunct to re-instrumentation of residual pockets in patients undergoing regular supportive periodontal care (SPC). METHODS: Chronic periodontitis patients (stage III and IV, grade B and C) with 4 interproximal residual pockets were randomly assigned to the test (HyA gel) or control (saline) group. After subgingival instrumentation, test or control substance was applied subgingivally, then daily supragingivally for 3 months, and if required a second time after subgingival re-instrumentation after 3 months. Clinical and patient reported outcome parameters were recorded every 3 months for 12 months. Pocket closure [probing pocket depth (PPD) ≤ 4mm with absence of bleeding on probing (BoP) at PPD = 4mm] was the main outcome parameter. RESULTS: Fifty-six patients (221 experimental sites) were analysed. Pocket closure was achieved in 56.8 and 46.6% of the experimental sites in the test and control group, respectively (p > 0.05), while median PPD and PPD distribution (< 5mm/5mm/ > 5mm) differed significantly between groups in favour of the test group, at 12 months. Further, significantly fewer sites in the HyA group required re-instrumentation at 3 months, and sites in the HyA group showed a tendency for lower odds to remain diseased compared to the control group (OR 0.48, 95%CI 0.22-1.06). The odds for a site to remain diseased after 12 months increased significantly in the presence of plaque (OR 7.94, 95%CI 4.12-15.28), but in general, decreased significantly over time (OR 0.48, 95%CI 0.28-0.81). CONCLUSION: Re-instrumentation of residual pockets in SPC patients, per se, leads to a significant increase in pocket closure over time; this was impeded by poor plaque control. Repeated local application of HyA results in fewer sites requiring re-instrumentation and might slightly improve the rate of pocket closure. (clinicaltrials.gov registration nr. NCT04792541). CLINICAL RELEVANCE: HyA gel is easy to apply, well accepted by patients, and may have some positive effect in terms of fewer sites requiring re-instrumentation at 3 months and higher pocket closure rate at 12 months.

Electroacupuncture efficacy in diabetic polyneuropathy: Study protocol for a double-blinded randomized controlled multicenter clinical trial.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM); its diagnosis and treatment are based on symptomatic improvement. However, as pharmacological therapy causes multiple adverse effects, the implementation of acupunctural techniques, such as electroacupuncture (EA) has been suggested as an alternative treatment. Nonetheless, there is a lack of scientific evidence, and its mechanisms are still unclear. We present the design and methodology of a new clinical randomized trial, that investigates the effectiveness of EA for the treatment of DPN. METHODS: This study is a four-armed, randomized, controlled, multicenter clinical trial (20-week intervention period, plus 12 weeks of follow-up after concluding intervention). A total of 48 T2DM patients with clinical signs and symptoms of DPN; and electrophysiological signs in the Nerve Conduction Study (NCS); will be treated by acupuncture specialists in outpatient units in Mexico City. Patients will be randomized in a 1:1 ratio to one of the following four groups: (a) short fibre DPN with EA, (b) short fibre DPN with sham EA, (c) axonal DPN with EA and (d) axonal DPN with sham EA treatment. The intervention will consist of 32 sessions, 20 min each, per patient over two cycles of intervention of 8 weeks each and a mid-term rest period of 4 weeks. The primary outcome will be NCS parameters, and secondary outcomes will include DPN-related symptoms and pain by Michigan Neuropathy Screening Instrument (MNSI), Michigan Diabetic Neuropathy Score (MDNS), Dolour Neuropatique Score (DN-4), Semmes-Westein monofilament, Numerical Rating Scale (NRS) for pain assessment, and the 36-item Short Form Health Survey (SF-36). To measure quality of life and improve oxidative stress, the inflammatory response; and genetic expression; will be analysed at the beginning and at the end of treatment. DISCUSSION: This study will be conducted to compare the efficacy of EA versus sham EA combined with conventional diabetic and neuropathic treatments if needed. EA may improve NCS, neuropathic pain and symptoms, oxidative stress, inflammatory response, and genetic expression, and it could be considered a potential coadjutant treatment for the management of DPN with a possible remyelinating effect. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05521737 Registered on 30 August 2022. International Clinical Trials Registry Platform (ICTRP) ISRCTN97391213 Registered on 26 September 2022 [2b].

Randomized controlled multi-centre study comparing shorter dental implants (6 mm) to longer dental implants (11-15 mm) in combination with sinus floor elevation procedures: 10-year data.

AIM: To compare implant survival and complication rates between shorter and standard-length implants with sinus augmentation and restored with single crowns, at 10 years of loading. MATERIALS AND METHODS: One-hundred and one patients (137 implants) with a ridge height of 5-7 mm in the posterior maxilla were randomly assigned to two treatment modalities: shorter implants (6 mm) (group short [GS]) or standard-length implants (11-15 mm) with sinus grafting (group graft [GG]). Following the insertion of final restorations, patients were regularly recalled for up to 10 years. Assessed outcomes encompassed implant survival, marginal bone levels (MBLs), biological and technical parameters and patient-reported outcome measures (OHIP-49 = Oral Health Impact Profile). Non-parametric statistical analysis was used to analyse the data. RESULTS: For the 5- to 10-year follow-up period, 77 patients with 105 implants (GS: 36 patients/48 implants; GG: 41/57) were available for re-examination (drop-out rate 21%). Implant survival rates at the patient level were 96.0% (GS; 2 failures) and 100% (GG) (inter-group p = .24). Median MBLs amounted to 0.00 mm (min 0.00; max 3.25; GS) and 0.00 mm (min 0.00; max 4.55; GG) (inter-group p = .73). Technical complications predominantly occurred within the first 5 years (inter-group p > .05). Peri-implantitis rates were 4.2% (GS) and 13.3% (GG) (intergroup p = .37). Median OHIP-49 scores were 7.00 (0.00; 39.00; GS) and 9.00 (0.00; 196; GG) (inter-group p = .61) at 10 years. CONCLUSIONS: Based on similar 10-year implant survival rates, reduced patient morbidity and lower costs, the use of shorter dental implants might well serve as an alternative treatment concept to longer implants placed in conjunction with sinus grafting for patients with a limited ridge height in the posterior maxilla. Study register: https://clinicaltrials.gov/ct2/show/NCT01030523.

Statistical analysis plan for the Recovery-focused Community support to Avoid readmissions and improve Participation after Stroke randomised controlled clinical trial.

BACKGROUND: Unplanned hospital presentations may occur post-stroke due to inadequate preparation for transitioning from hospital to home. The Recovery-focused Community support to Avoid readmissions and improve Participation after Stroke (ReCAPS) trial was designed to test the effectiveness of receiving a 12-week, self-management intervention, comprising personalised goal setting with a clinician and aligned educational/motivational electronic messages. Primary outcome is as follows: self-reported unplanned hospital presentations (emergency department/admission) within 90-day post-randomisation. We present the statistical analysis plan for this trial. METHODS/DESIGN: Participants are randomised 1:1 in variable block sizes, with stratification balancing by age and level of baseline disability. The sample size was 890 participants, calculated to detect a 10% absolute reduction in the proportion of participants reporting unplanned hospital presentations/admissions, with 80% power and 5% significance level (two sided). Recruitment will end in December 2023 when funding is expended, and the sample size achieved will be used. Logistic regression, adjusted for the stratification variables, will be used to determine the effectiveness of the intervention on the primary outcome. Secondary outcomes will be evaluated using appropriate regression models. The primary outcome analysis will be based on intention to treat. A p-value ≤ 0.05 will indicate statistical significance. An independent Data Safety and Monitoring Committee has routinely reviewed the progress and safety of the trial. CONCLUSIONS: This statistical analysis plan ensures transparency in reporting the trial outcomes. ReCAPS trial will provide novel evidence on the effectiveness of a digital health support package post-stroke. TRIAL REGISTRATION: ClinicalTrials.gov ACTRN12618001468213. Registered on August 31, 2018. SAP version 1.13 (October 12 2023) Protocol version 1.12 (October 12, 2022) SAP revisions Nil.

The efficacy of hypnosis compared with the tell/show/do technique for the reduction of anxiety/pain in children undergoing pulpotomies: a randomized controlled trial.

Anxiety/pain is a combined experience that can hinder dental treatment in children and lead to the development of negative behaviours in any form of surgical treatment. Hypnosis is a suitable option with which to reduce anxiety and pain during dental treatment. In this study, we aimed to evaluate the efficacy of hypnosis compared to the tell/show/do technique for the reduction of anxiety and pain as measured by Face, Legs, Activity, Crying, Consolability (FLACC) scale in children undergoing pulpotomies. We performed a randomized and controlled clinical trial involving 60 children aged 5 to 7 years without previous dental experiences but with clinical and radiographic indications for pulpotomy in the primary mandibular right or left first or second molar. The children were divided into two groups: a control group (treated by conventional behaviour management techniques) and an experimental group (treated by hypnosis). The FLACC scale was used to evaluate anxiety/pain during preoperative, transoperative and postoperative pulpotomy treatment; we also analysed variations in heart rate and skin conductance. The trial was registered at ClinicalTrials.gov (NCT03739346). Statistical analysis was performed in R Studio version 1.2.1335. The FLACC scale was significantly lower in the experimental group (p = 0.022) throughout the entire treatment duration. In addition, heart rate and global skin conductance were both significantly lower in the experimental group when measured at different times (p = 0.005 and p = 0.032, respectively). When compared to conventional behavioural management techniques, the FLACC scale demonstrated that hypnosis was associated with significant reductions in heart rate, skin conductance and anxiety/pain throughout the entire duration of treatment. decreases anxiety/pain during the entire operative procedure. There was clear improvements in anxiety and pain control in patients receiving hypnotic therapy.

Effect of denture adhesives on masticatory performance: Multicenter randomized controlled trial.

PURPOSE: The purpose of this study is to investigate the effects of denture adhesives on masticatory performance via a 10-center, parallel, randomized, controlled trial of complete denture wearers in Japan. METHODS: The trial was conducted between September 2013 and October 2016. The inclusion criteria were complete edentulism, willingness to undergo new complete denture treatment, and willingness to return for recall treatment. The exclusion criteria were age 90 years or older, presence of severe systemic illness, inability to understand the questionnaires, wearing metal base complete dentures, denture adhesive user, wearing prosthetics for maxillofacial defects, wearing complete dentures with tissue conditioners, and severe xerostomia. Randomization of the powder-type denture adhesive (powder), cream-type denture adhesive (cream), and control (saline) groups was performed using a sealed envelope system. Masticatory performance was measured using color-changeable chewing gum. Intervention blinding was not feasible. RESULTS: Sixty-seven control, 69 powder, and 64 cream participants are analyzed using the intention-to-treat principle. The participants in all groups show significantly improved masticatory performance at post-intervention (paired t-test with Bonferroni correction P < 0.0001). However, no significant difference in masticatory performance is detected among the three groups (one-way analysis of variance). A significant negative correlation between pre- and post-changes in masticatory performance and intraoral condition scores is observed (Pearson's correlation coefficient, P < 0.0001). CONCLUSIONS: Although denture adhesives improved the masticatory performance of complete denture wearers, their clinical effects are comparable to those of saline solution. The use of denture adhesives is more effective in complete denture wearers with unsatisfactory intraoral conditions.

Impact of loading protocol of a mandibular single implant-supported complete denture on oral health-related quality of life over a period of 5 years: A randomized controlled trial.

OBJECTIVES: The aim of the present study was to assess the long-term course of OHRQoL and the impact of the loading protocol in patients receiving a single mandibular implant supporting a complete denture over a period of five years. METHODS: In this multicenter RCT, a total of 158 edentulous patients were initially included and were randomly allocated immediately after placement of a mandibular midline implant to either immediate loading (IL) or to conventional loading (CL) with submerged healing. The assessment of OHRQoL was performed with the 49-item Oral Health Impact Profile (OHIP) at baseline and 1, 4, 12, 24, and 60 months after loading. At 5-year follow-up, 100 patients (mean age: 69.2 years; 45.0% female) with completed OHIP were available for analyses. A mixed-effects model with patients as random effect and an unstructured covariance matrix was developed to address repeated outcome measurement. RESULTS: The OHRQoL improved substantially after loading, indicated by a decrease of mean OHIP summary scores from 51.0 points at baseline, by 14.2 (95%-CI: 9.4 - 19.1; p<0.001) points to 37.2 points at 1-month follow-up, and by continuous improvement to 20.4 OHIP points at final follow-up. Considering constant treatment effects, the loading protocol had no significant effect on OHIP scores (-3.7, 95%-CI: -9.4 - 2.2; p = 0.204). Time effect was statistically significant with -0.21 (95%-CI: -0.28 - -0.15; p<0.001) points per month. CONCLUSION: Both the immediate and conventional loading of a single mandibular midline implant supporting a complete denture offer long-lasting high levels of OHRQoL, with no significant or clinically relevant long-term differences. CLINICAL SIGNIFICANCE: The study firstly presents long-term data for OHRQoL by investigating the loading protocol of single mandibular implant-supported complete dentures. Since immediate loading has been associated with a reduced implant survival rate for this concept, information on patient benefits is essential for evidence-based decision making.

Effects of a workplace-based exercise program on shoulder pain and function in fruit workers: A randomized controlled trial.

BACKGROUND: Shoulder pain affects millions of workers worldwide and is considered one of the leading causes of absenteeism and presenteeism. Therefore, using exercises in the work environment emerges as a strategy to prevent or reduce shoulder pain. OBJECTIVE: The objective of this study was to evaluate the effects of a workplace-based exercise program on shoulder pain and function in fruit workers. METHODS: This was an 8-week parallel two-arm randomized controlled trial. Forty-four fruit workers who reported chronic shoulder pain were randomized to an Experimental Group (EG) or Control Group (CG). The EG was submitted to a program of resistance and stretching exercises for eight weeks, twice a week. The CG received a booklet with muscle stretching and mobility exercises. The primary outcome was shoulder pain intensity; the secondary outcomes were Shoulder Pain and Disability Index (SPADI) and perceived global effect. RESULTS: Both groups showed reductions in pain intensity EG: 4.26 (95% CI 2.78-5.74) and CG: 3.74 (95% CI 1.98-5.50) points. The SPADI results showed an average reduction of 17.76 (CI 95% 3.10-32.43) for the EG and 18.39 (CI 95% 3.66-33.13) for the CG. The mean value of the perceived global effect for the CG was 3.45±2.01, and for the EG, the mean was 4.13±1.24. No differences were observed between groups in any outcome analyzed. CONCLUSION: Both groups showed significant changes in the analyzed outcomes. However, the workplace-based exercise program was not superior to the exercise booklet.

Clinical and cost-effectiveness of PCF versus ACD in the treatment of cervical brachialgia (FORVAD trial).

BACKGROUND: Cervical radiculopathy occurs when a nerve root is compressed in the spine, if symptoms fail to resolve after 6 weeks surgery may be indicated. Anterior Cervical Discectomy (ACD) is the commonest procedure, Posterior Cervical Foraminotomy (PCF) is an alternative that avoids the risk of damage to anterior neck structures. This prospective, Phase III, UK multicentre, open, individually randomised controlled trial was performed to determine whether PCF is superior to ACD in terms of improving clinical outcome as measured by the Neck Disability Index (NDI) 52 weeks post-surgery. METHOD: Following consent to participate and collection of baseline data, subjects with cervical brachialgia were randomised to ACD or PCF in a 1:1 ratio on the day of surgery. Clinical outcomes were assessed on day 1 and patient reported outcomes on day 1 and weeks 6, 12, 26, 39 and 52 post-operation. A total of 252 participants were planned to be randomised. Statistical analysis was limited to descriptive statistics. Health economic outcomes were also described. RESULTS: The trial was closed early (n = 23). Compared to baseline, the median (interquartile range (IQR)) NDI score at 52 weeks reduced from 44.0 (36.0, 62.0) to 25.3 (20.0, 42.0) in the PCF group and increased from 35.6 (34.0, 44.0) to 45.0 (20.0, 57.0) in the ACD group. ACD may be associated with more swallowing, voice and other complications and was more expensive; neck and arm pain scores were similar. CONCLUSIONS: The trial was closed early, therefore no definitive conclusions on clinical or cost-effectiveness could be made.

Effects of Oral Cryotherapy on Anticipatory, and Acute Nausea and Vomiting in Patients With Breast Cancer Undergoing Adjuvant Chemotherapy: A Randomized Controlled Clinical Trial.

PURPOSE: To determine the effects of oral cryotherapy (OC) on the anticipatory, and acute nausea and vomiting of patients with breast cancer who are receiving adjuvant chemotherapy. PATIENTS AND METHODS: Seventy eligible patients with breast cancer were assigned to 2 groups by stratified randomization. This parallel grouped, randomized, clinical trial used the ice application protocol. OC application for an intervention group (IG, n = 35) was performed in 3 stages: i) instructions on by the investigator at the hospital; ii) the implementation accompanied by the investigator at the hospital; iii) the individual application of at home by patients. The IG had been doing the application for 12 weeks. The patients in the control group (CG, n = 35) received standard care. Additionally, Rhodes Index of Nausea Vomiting, and Retching, and EORTC QLQ-C30 Life Quality Index were conducted on the first (T1 = cycle 1 day 0), second (T2 = cycle 2 day 21), third (T3 = cycle 3 day 42), and fourth (T4 = cycle 4 day 63) cycles of adjuvant chemotherapy. RESULTS: The anticipatory nausea scores in the T2 and T4, IG were significantly lower than the CG (P < .05). In the T3, all symptom sub-dimensions except symptom occurrence (t = -0,48; P = .63) of the IG were significantly lower than those of the CG (P < .05). In the T1, T2, T3, and T4, acute nausea, acute vomiting, acute retching, and anticipatory retching scores, were significantly lower than the CG (P < .05). CONCLUSION: OC alone was effective and safe for the treatment of nausea and vomiting. The results of this study showed the clinical applicability of OC in the management of nausea and vomiting.

Eficacia y seguridad del supositorio Proctokinasa® en el tratamiento de la enfermedad inflamatoria pélvica aguda

Introducción: La enfermedad inflamatoria pélvica aguda es una entidad frecuente en mujeres jóvenes en edad reproductiva, y constituye la causa principal de infertilidad. La búsqueda de un tratamiento antiinflamatorio eficaz y seguro que alivie el dolor, evite complicaciones y secuelas, es una prioridad para su tratamiento. Objetivo: Evaluar la eficacia y seguridad del tratamiento con Proctokinasa® en la enfermedad inflamatoria pélvica aguda grados I y II. Materiales y métodos: Se desarrolló un ensayo clínico, controlado, abierto, de enero de 2017 a enero de 2018, que incluyó 76 pacientes con diagnóstico de enfermedad inflamatoria pélvica aguda en la atención primaria de salud, quienes fueron asignadas aleatoriamente a dos grupos de tratamiento: grupo principal Proctokinasa®, que recibió una unidad/8 h por 2 días, y el grupo Piroxicam, un supositorio de 20 mg/24 h por 7 días. La antibioticoterapia oral recomendada se inició simultáneamente. Se evaluó la respuesta clínica y ecográfica al tratamiento. Los eventos adversos fueron evaluados. Resultados: Se constató respuesta clínica a partir de las 72 horas de tratamiento en más del 50 % de las pacientes en ambos grupos, y fue del 100 % de los casos para el grupo Proctokinasa® en las dos últimas evaluaciones realizadas (días 10 y 15). Se evidenció la remisión de las alteraciones ecográficas en el 96,9 % del grupo Proctokinasa®. Los eventos adversos fueron escasos y leves. Conclusiones: El empleo de Proctokinasa® resultó eficaz y seguro en el tratamiento de la enfermedad inflamatoria pélvica aguda grados I y II.

Introduction: Acute pelvic inflammatory disease is a common entity in young women of reproductive age and it is a leading cause of infertility. The search for an effective and safe anti-inflammatory treatment that relieves pain, avoids complications and sequels, it is priority for its treatment. Objective: To evaluate the efficacy and safety of the treatment with Proctokinasa® in acute pelvic inflammatory disease grades I and II. Materials and methods: An open, controlled clinical trial was carried out from January 2017 to January 2018 which included 76 patients diagnosed with acute pelvic inflammatory disease in primary health care; they were randomize assigned to two treatment groups: Proctokinasa® main group, who received one unity/8h for 2 days, and the Piroxican group, 1 suppository of 20 mg/24h per 7 days. The recommended oral antibiotic therapy was started simultaneously. Clinical and ultrasound response to treatment were evaluated. Adverse events were evaluated. Results: Clinical response was stated after 72 hours of treatment inmore than 50% of the patients in both groups, and it was 100% for the Proctokinasa® group in the last two evaluations (days 10 and 15). Remission of ultrasound alterations was evident in 96.9% of the Proctokinasa® group. Adverse events were few and mild. Conclusions: The use of Proctokinasa® was effective and safe in the treatment of acute pelvic inflammatory disease grades I and II.