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The study aimed to evaluate salivary cortisol (SC) contamination and determine the associated factors in secondary adrenal insufficiency (SAI) patients treated with hydrocortisone (Hc). A randomized crossover trial involved SAI patients. SC was measured before the morning Hc dose, then at one, two, and four hours after. The procedure was performed twice on two days of a week: one day while taking Hc in tablet form (tablet set) and one day while taking Hc in capsule form (capsule set). Area under the curve (AUC) of SC levels over time was calculated in each participant for the two sets. SC contamination was defined as AUCtablet above the 95th percentile of AUCcapsule. Thirty-four patients (24 females and 10 males) with a median age of 48 years were enrolled. Post-Hc dose SC levels were higher in tablet than in capsule set, particularly at one hour. Prevalence and extent of SC contamination were estimated to 32% and 88%, respectively. In capsule set, SC measured two hours after Hc intake showed the strongest correlation with AUC (r=0.88, p<0.001). In multivariate analysis, serum potassium≥3.9 mEq/l was the only predictor for SC contamination [multi-adjusted OR (95% CI): 7.1 (1.4–36.1); p=0.018]. SC measured during the two hours after Hc intake is inaccurate for glucocorticoid replacement therapy assessment in SAI patients treated with Hc in tablet form. [ABSTRACT FROM AUTHOR]

Several therapies have been developed to reduce cognitive decline associated with aging. Aquatic exercises, which are widely used to enhance functional capacity, may play a role in stimulating cognitive functions. This study investigated the effects of a 3-month aquatic exercise program on cognitive functions in community-dwelling older adults. In this prospective, single-blinded, controlled clinical trial, 31 participants were allocated to either the experimental (aquatic exercises) or control (no-exercise) group. The intervention program consisted of exercises conducted twice a week in a 1.2 m deep indoor pool. The main outcome measures were cognitive functions, assessed using Raven's Progressive Matrices test and the Wisconsin Card Sorting Test. A repeated-measures analysis of variance was used to assess the impact of the exercise program. The effect sizes (η2p) were reported when a level of significance was achieved (p < 0.05). Compared with the control group, the participants who underwent aquatic exercises showed positive outcomes in Raven's Progressive Matrices test (p = 0.046; η2p = 0.131) and the Wisconsin Card Sorting Test (p = 0.001, η2p = 0.589). Complementary analyses of the Wisconsin Card Sorting Test indicated that the benefits of the aquatic exercise were observed in terms of the number of trials (p = 0.001, η2p = 0.478), number of errors (p = 0.001, η2p = 0.458), and number of non-perseverative errors (p = 0.001, η2p = 0.302). The results indicate that a period of three months of aquatic exercise was beneficial for stimulating specific aspects of the cognitive function of community-dwelling older individuals. Aquatic exercise should be prescribed to this population. [ABSTRACT FROM AUTHOR]

Background: This phase 2b/3, randomized, placebo‐controlled trial explored the efficacy and evaluated the safety of ensitrelvir. This trial involved individuals with asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and patients with mild symptoms of coronavirus disease 2019 (COVID‐19). Methods: The trial was conducted at 57 medical institutions in Japan, South Korea, and Vietnam (study period: January 6–August 14, 2022). Eligible participants were randomized (1:1:1) to the ensitrelvir 125‐mg, ensitrelvir 250‐mg, or placebo group, received the allocated intervention orally, and were followed up until Day 28. Participants self‐rated the severity of 14 typical COVID‐19 symptoms and recorded the data in an electronic diary. Results: In total, 572 participants (194, 189, and 189 in the ensitrelvir 125‐mg, ensitrelvir 250‐mg, and placebo groups, respectively) were included in the intention‐to‐treat population. Ensitrelvir 125‐mg group observed a 77% reduction in the risk of developing any of the 14 COVID‐19 symptoms or fever and a 29% reduction in the risk of worsening of such symptoms or fever versus placebo (statistically nonsignificant). The viral RNA, viral titer, and time to infectious viral clearance observed a statistically significant decrease versus placebo. Most treatment‐related adverse events (TEAEs) were mild to moderate in severity, and the most common TEAE observed across groups was a decrease in high‐density lipoprotein. Conclusions: Our exploratory results suggest a potential reduction in the risk of development or worsening of COVID‐19 symptoms with ensitrelvir. Ensitrelvir showed antiviral efficacy and was well tolerated. Trial Registration: Japan Registry of Clinical Trials identifier: jRCT2031210350. [ABSTRACT FROM AUTHOR]

Abstract 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].

Background: Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) have poor 5-year survival. Pharmacological ascorbate (P-AscH-, high dose, intravenous, vitamin C) has shown promise as an adjunct to chemotherapy. We hypothesized adding P-AscH- to gemcitabine and nab-paclitaxel would increase survival in patients with metastatic PDAC. Methods: Patients diagnosed with stage IV pancreatic cancer randomized 1:1 to gemcitabine and nab-paclitaxel only (SOC, control) or to SOC with concomitant P-AscH−, 75 g three times weekly (ASC, investigational). The primary outcome was overall survival with secondary objectives of determining progression-free survival and adverse event incidence. Quality of life and patient reported outcomes for common oncologic symptoms were captured as an exploratory objective. Thirty-six participants were randomized; of this 34 received their assigned study treatment. All analyses were based on data frozen on December 11, 2023. Results: Intravenous P-AscH- increased serum ascorbate levels from micromolar to millimolar levels. P-AscH- added to the gemcitabine + nab-paclitaxel (ASC) increased overall survival to 16 months compared to 8.3 months with gemcitabine + nab-paclitaxel (SOC) (HR = 0.46; 90 % CI 0.23, 0.92; p = 0.030). Median progression free survival was 6.2 (ASC) vs. 3.9 months (SOC) (HR = 0.43; 90 % CI 0.20, 0.92; p = 0.029). Adding P-AscH- did not negatively impact quality of life or increase the frequency or severity of adverse events. Conclusions: P-AscH− infusions of 75 g three times weekly in patients with metastatic pancreatic cancer prolongs overall and progression free survival without detriment to quality of life or added toxicity (ClinicalTrials.gov number NCT02905578).

Background: Oral care regimens can be explored to improve oral health in patients with gingivitis. This study aimed to evaluate the efficacy of a multicomponent oral care regimen with a dual zinc plus arginine (DZA) toothpaste and cetylpyridinium chloride with zinc lactate (CPC + Zn) mouthwash in reducing gingival bleeding in patients with gingivitis. Methods: This randomized clinical trial included 94 participants with gingivitis who were randomized into two groups: the DZA/CPC + Zn group, which used a 1450‐ppm fluoride toothpaste containing 0.96% zinc plus 1.5% arginine and a fluoride‐containing mouthwash with 0.075% CPC and 0.28% zinc lactate, and the control group, which used a 1450‐ppm fluoride toothpaste and a placebo mouthwash for 6 months. All participants were examined by a blinded examiner who measured the gingival index, plaque index, and gingival severity index. Data were analyzed using paired t test, independent t test, and analysis of covariance (ANCOVA). Results: Both groups presented statistically significant reductions in all clinical parameters compared to baseline. The DZA/CPC + Zn group exhibited significantly greater reductions in gingival index, gingival severity index, proximal gingival index, plaque index and proximal plaque index compared to the control group at 1, 3, and 6 months. Furthermore, DZA/CPC + Zn significantly decreased the percentage of patients with generalized gingivitis over a 6‐month follow‐up period. However, differences between the DZA/CPC + Zn and the control groups were not maintained after both groups established similar regimens with fluoride toothpaste. Conclusion: The multicomponent oral care regimen consisting of DZA toothpaste and CPC + Zn mouthwash is effective in reducing gingival inflammation and supragingival biofilm in patients with gingivitis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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]. [ABSTRACT FROM AUTHOR]

Since the 2017 Nobel Prize awarded to J. Hall, M. Rosbash and M.W. Young for their discoveries of molecular mechanisms behind the biological clock, circadian rhythm-based therapy, also known as chronotherapy, is receiving more attention in oncology and the number of anatomical sites of interest in this field is increasing. This observation is in line with the clinical evidence provided by trials on head and neck, lung, colorectal and cervical cancers, as well as the presently ongoing chronotherapy trials for breast and brain cancers. The aim of this review was to collate all randomized trials conducted on chronotherapy for various tumor sites and to appraise the evidence for chrono-oncology to advance personalized therapy. Relevant literature was collected from Pubmed/Medline databases and from clinicatrials.gov. Current randomized clinical trials offer a certain level of evidence for the potential of chronotherapy to personalize oncologic treatment. However, comparison of trial results is hindered by the differences in timing of radiation/chemotherapy, the absence of harmonized recommendations for treatment outcome evaluation and not ultimately, the general lack of considering gender as a matched variable in trials, which was found to be a powerful factor influencing response to treatment. [ABSTRACT FROM AUTHOR]

Background: For people with cognitive impairment, hospitalisation is challenging and associated with adverse events as well as negative outcomes resulting in a prolonged hospital stay. Person-centred care can improve the quality of care and the experience of people with cognitive impairment during hospitalisation. However, current care processes in German hospitals are rarely person-centred. To enable successful implementation of person-centred care on hospital wards, change agents within the interprofessional team are key. The aim of this study is to test the feasibility and initial effects of a newly developed complex person-centred care intervention for people with cognitive impairment provided by expanded practice nurses in acute care. Methods: We will conduct an exploratory non-randomised controlled clinical trial with accompanying process and cost evaluation with three intervention and three control wards at one university hospital. The person-centred care intervention consists of 14 components reflecting the activities of expanded practice nurses within the interprofessional team on the intervention wards. The intervention will be implemented over a six-month period and compared with optimised care on the control wards. We will include people aged 65 years and older with existing cognitive impairment and/or at risk of delirium. The estimated sample size is 720 participants. The primary outcome is length of hospital stay. Secondary outcomes include prevalence of delirium, prevalence of agitation, sleep quality, and person-centred care. We will collect patient level data at six time points (t1 admission, t2 day 3, t3 day 7, t4 day 14, t5 discharge, t6 30 days after discharge). For secondary outcomes at staff level, we will collect data before and after the intervention period. The process evaluation will examine degree and quality of implementation, mechanisms of change, and the context of the complex intervention. The economic evaluation will focus on costs from the hospital's perspective. Discussion: The ENROLE-acute study will provide insights into the effectiveness and underlying processes of a person-centred care intervention for people with cognitive impairment provided by expanded practice nurses on acute hospitals wards. Results may contribute to intervention refinement and evidence-based decision making. Trial registration: Current controlled trials: ISRCTN81391868. Date of registration: 12/06/2023. URL: https://doi.org/10.1186/ISRCTN81391868 [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) has gained popularity as a method of modulating cortical excitability in people with physical and mental disabilities. However, there is a lack of consensus on its effectiveness in older individuals. This study aimed to assess the efficacy of a 2-month tDCS program for improving physical and mental performance in community-dwelling older individuals. In this single-blinded, controlled clinical trial, forty-two participants were allocated to one of three groups: (1) the tDCS group, which received, twice a week, 20 min sessions of 2 mA electric current through electrodes placed on the dorsolateral prefrontal cortex; (2) the tDCS-placebo group, which underwent the same electrode placement as the tDCS group but without actual electric stimulation; and (3) the cognitive-control group, which completed crossword puzzles. Main outcome measures were cognition, mobility, and anxiety. Multivariate analyses of variance were employed. Significance was set at 5% (p < 0.05). Regarding the results, no significant benefits were observed in the tDCS group compared with the tDCS-placebo or cognitive-control groups for cognition (p = 0.557), mobility (p = 0.871), or anxiety (p = 0.356). Cognition exhibited positive oscillations during the assessments (main effect of time: p = 0.001). However, given that all groups showed similar variations in cognitive scores (main effect of group: p = 0.101; group × time effect: p = 0.557), it is more likely that the improvement reflects the learning response of the participants to the cognitive tests rather than the effect of tDCS. In conclusion, a 2-month tDCS program with two sessions per week appears to be ineffective in improving physical and mental performance in community-dwelling older individuals. Further studies are necessary to establish whether or not tDCS is effective in healthy older individuals. [ABSTRACT FROM AUTHOR]

Several therapies have been developed to reduce cognitive decline associated with aging. Aquatic exercises, which are widely used to enhance functional capacity, may play a role in stimulating cognitive functions. This study investigated the effects of a 3-month aquatic exercise program on cognitive functions in community-dwelling older adults. In this prospective, single-blinded, controlled clinical trial, 31 participants were allocated to either the experimental (aquatic exercises) or control (no-exercise) group. The intervention program consisted of exercises conducted twice a week in a 1.2 m deep indoor pool. The main outcome measures were cognitive functions, assessed using Raven’s Progressive Matrices test and the Wisconsin Card Sorting Test. A repeated-measures analysis of variance was used to assess the impact of the exercise program. The effect sizes (η2p) were reported when a level of significance was achieved (p < 0.05). Compared with the control group, the participants who underwent aquatic exercises showed positive outcomes in Raven’s Progressive Matrices test (p = 0.046; η2p = 0.131) and the Wisconsin Card Sorting Test (p = 0.001, η2p = 0.589). Complementary analyses of the Wisconsin Card Sorting Test indicated that the benefits of the aquatic exercise were observed in terms of the number of trials (p = 0.001, η2p = 0.478), number of errors (p = 0.001, η2p = 0.458), and number of non-perseverative errors (p = 0.001, η2p = 0.302). The results indicate that a period of three months of aquatic exercise was beneficial for stimulating specific aspects of the cognitive function of community-dwelling older individuals. Aquatic exercise should be prescribed to this population.

Purpose: The purpose of this study was to evaluate the feasibility of implementing the nursing intervention Breastfeeding Counseling (5244) in first‐time adolescent mothers and its effect on the knowledge and maintenance of exclusive breastfeeding in the first 6 months of life. Methods: Randomized, controlled feasibility study with 166 first‐time mothers between 14 and 19 years of age, from 20 to 30 weeks of gestation, assigned to an experimental group (nursing intervention: breastfeeding counseling) or a control group (usual education plus nursing intervention not related to breastfeeding). The rate of abandonment of exclusive breastfeeding and the level of knowledge about breastfeeding were evaluated. Findings: The inclusion was 91.7% (166/181), dropout during the intervention was 39.75% (n = 66), and loss in the follow‐up was 8.43% (n = 14). Compliance with the intervention protocol was 100%. The pregnant women and family members were satisfied with the intervention and perceived the health benefits for the mothers and their children. Outcome measures in the experimental group did not reveal a significant effect on breastfeeding abandonment rates at 2, 4, and 6 months postpartum, but they did manage to improve and maintain the level of knowledge about breastfeeding. Conclusions: It was found that it is feasible to implement the nursing intervention: "Breastfeeding counseling" in prenatal classes, achieving an increase in the level of knowledge about breastfeeding in adolescent mothers, but without a reduction in the rate of abandonment of breastfeeding. Nursing professionals need to know and address barriers to exclusive breastfeeding in adolescents. Implications for nursing practice: The nursing intervention "Breastfeeding counseling (5244)" and the outcome "Knowledge: Breastfeeding (1800)" supported the processes of education and knowledge assessment on breastfeeding in pregnant adolescents, which should be instituted in perinatal nursing care. [ABSTRACT FROM AUTHOR]

Aim: To compare, at different levels from the alveolar crest, the radiographic outcomes of equine‐derived collagenated xenogeneic bone blocks (CXBB) and autogenous bone blocks (ABB) used for lateral alveolar ridge augmentation. Materials and Methods: Sixty‐four patients with tooth gaps in atrophic alveolar ridges with ≤4 mm were randomly assigned to lateral augmentation using CXBB or ABB. The lateral bone thickness (LBT) was measured 2, 4, 6, 8, and 10 mm below the alveolar crest using CBCT scans obtained before augmentation surgery and at 30 weeks, prior to implant placement. Statistical analysis was performed using Shapiro–Wilk, Fisher's exact, Mann–Whitney, and Wilcoxon signed‐rank tests. Results: Both CXBB and ABB resulted in significant total and buccal LBT gains at 2, 4, 6, 8, and 10 mm. LBT gains were similar between CXBB‐ and ABB‐augmented sites, except for greater buccal LBT gains at 8 mm at CXBB‐augmented sites. While ABB‐augmented sites gained vertical bone height, CXBB‐treated sites suffered vertical bone loss (CXBB: −0.16 mm; ABB: 0.38 mm, p <.0009). Conclusions: CXBB and ABB were both associated with significant and similar LBT gains at 30 weeks. [ABSTRACT FROM AUTHOR]

Crack-cocaine dependence is a severe condition with a high mortality rate. This single case study report details the first deep brain stimulation (DBS) trial targeting the sub-thalamic nucleus (STN) for crack-cocaine dependence. The investigation aimed to assess the e ects of STN-DBS on cocaine craving and cocaine use, as well as STN-DBS safety and tolerance in this indication. In this pilot study, we performed double blind cross-over trials, with "ON-DBS" vs. "SHAM-DBS" for 1-month periods. STN-DBS failed to reduce cocaine craving and use. An episode of DBS-induced hypomania occurred after several weeks of cocaine intake at stimulation parameters previously well tolerated. Future research on cocaine dependence should be conducted after a prolonged abstinence period and/or explore novel types of stimulation patterns. [ABSTRACT FROM AUTHOR]

Non‐alcoholic Fatty Liver Disease (NAFLD) is a global health problem that can progress to steatohepatitis and cirrhosis. The aim of this study was to determine the effect of curcumin + piperine on cardiometabolic risk factors, as well as hepatic steatosis and fibrosis in NAFLD patients with moderate‐to‐high hepatic steatosis. Patients diagnosed with moderate‐to‐high NAFLD by liver sonography were randomized to either curcumin + piperine (500 mg/day curcumin plus 5 mg/day piperine) for 12 weeks (n = 30) or placebo groups (n = 30). Liver fibroscan, anthropometric measurements, dietary intake, physical activity, blood pressure, lipid profile, high‐sensitivity C‐reactive protein, fasting blood glucose (FBG), and liver enzymes were assessed at baseline and after 12 weeks of follow‐up. Intention‐to‐treat analysis was undertaken. Curcumin + piperine decreased waist circumference (p = 0.026), systolic blood pressure (p = 0.001), total cholesterol (p = 0.004), low‐density lipoprotein‐cholesterol (p = 0.006), FBG (p = 0.002), alanine transaminase (p = 0.007) and aspartate transaminase (p = 0.012) compared with placebo. However, fibroscan measurement did not differ between curcumin + piperine and placebo groups (p > 0.05). Fibroscan measurement as a marker of NAFLD improvement did not differ after 12 weeks of curcumin + piperine; however, curcumin + piperine may be considered as an adjunct therapy to improve anthropometric measures, blood pressure, lipid profile, blood glucose, and liver function in NAFLD patients. [ABSTRACT FROM AUTHOR]

Abstract Objectives To compare the clinical effectiveness of Hawley retainers (HRs) and modified vacuum-formed retainers (mVFRs) with palatal coverage in maintaining transverse expansion throughout a 24-month retention period and to assess the subjects’ perception toward the retainers. Materials and methods The trial accomplished blinding only by the outcome assessor and data analyst. Data were collected from post-orthodontic treatment patients who met the inclusion criteria. Thirty-five subjects were randomly allocated using a centralized randomization technique into either mVFR (n = 18) or HR group (n = 17). Dental casts of subjects were evaluated at debond (T0), 3-month (T1), 6-month (T2), 12-month (T3), and 24-month retention (T4). The intercanine width (ICW), interpremolar width (IPMW), interfirst molar mesiobuccal cusp width (IFMW1), and interfirst molar distobuccal cusp width (IFMW2) were compared between groups over time using Mixed ANOVA. A pilot-tested and validated questionnaire consisting of six items were given at T4. Subjects were instructed to rate their retainer in terms of fitting, speech, appearance, oral hygiene, durability, and comfort on a 100-mm Visual Analogue Scale (VAS). Results No statistically significant differences in arch width were found between the two groups at ICW (P = .83), IPMW (P = 0.63), IFMW1 (P = .22), and IFMW2 (P = .46) during the 24-month retention period. Also, no statistically significant differences were found between perception of both retainers in terms of fitting, speech, oral hygiene, durability, and comfort (P > .05) after 24-month wear. The appearance of mVFRs was rated significantly higher compared to HRs (P

Crack-cocaine dependence is a severe condition with a high mortality rate. This single case study report details the first deep brain stimulation (DBS) trial targeting the sub-thalamic nucleus (STN) for crack-cocaine dependence. The investigation aimed to assess the effects of STN-DBS on cocaine craving and cocaine use, as well as STN-DBS safety and tolerance in this indication. In this pilot study, we performed double blind cross-over trials, with “ON-DBS” vs. “SHAM-DBS” for 1-month periods. STN-DBS failed to reduce cocaine craving and use. An episode of DBS-induced hypomania occurred after several weeks of cocaine intake at stimulation parameters previously well tolerated. Future research on cocaine dependence should be conducted after a prolonged abstinence period and/or explore novel types of stimulation patterns.

Transcranial direct current stimulation (tDCS) has gained popularity as a method of modulating cortical excitability in people with physical and mental disabilities. However, there is a lack of consensus on its effectiveness in older individuals. This study aimed to assess the efficacy of a 2-month tDCS program for improving physical and mental performance in community-dwelling older individuals. In this single-blinded, controlled clinical trial, forty-two participants were allocated to one of three groups: (1) the tDCS group, which received, twice a week, 20 min sessions of 2 mA electric current through electrodes placed on the dorsolateral prefrontal cortex; (2) the tDCS-placebo group, which underwent the same electrode placement as the tDCS group but without actual electric stimulation; and (3) the cognitive-control group, which completed crossword puzzles. Main outcome measures were cognition, mobility, and anxiety. Multivariate analyses of variance were employed. Significance was set at 5% (p < 0.05). Regarding the results, no significant benefits were observed in the tDCS group compared with the tDCS-placebo or cognitive-control groups for cognition (p = 0.557), mobility (p = 0.871), or anxiety (p = 0.356). Cognition exhibited positive oscillations during the assessments (main effect of time: p = 0.001). However, given that all groups showed similar variations in cognitive scores (main effect of group: p = 0.101; group × time effect: p = 0.557), it is more likely that the improvement reflects the learning response of the participants to the cognitive tests rather than the effect of tDCS. In conclusion, a 2-month tDCS program with two sessions per week appears to be ineffective in improving physical and mental performance in community-dwelling older individuals. Further studies are necessary to establish whether or not tDCS is effective in healthy older individuals.

Rasagiline is a monoamine oxidase B (MAO-B) inhibitor with possible neuroprotective effects in patients with amyotrophic lateral sclerosis (ALS). We performed a randomized, double-blind, placebo-controlled trial of 80 ALS participants with enrichment of the placebo group with historical controls (n = 177) at 10 centers in the United States. Participants were randomized in a 3:1 ratio to 2 mg/day rasagiline or placebo. The primary outcome was average slope of decline on the ALS Functional Rating Scale-Revised (ALSFRS-R). Secondary measures included slow vital capacity, survival, mitochondrial and molecular biomarkers, and adverse-event reporting. There was no difference in the average 12-month ALSFRS-R slope between rasagiline and the mixed placebo and historical control cohorts. Rasagiline did not show signs of drug-target engagement in urine and blood biomarkers. Rasagiline was well tolerated with no serious adverse events. Rasagiline did not alter disease progression compared with controls over 12 months of treatment. Muscle Nerve 59:201-207, 2019.

Abstract Background Pressure injuries (PIs), especially in the sacral region are frequent, costly, and increase morbidity and mortality of patients in an intensive care unit (ICU). These injuries can occur as a result of prolonged pressure and/or shear forces. Neuromuscular electrical stimulation (NMES) can increase muscle mass and improve local circulation, potentially reducing the incidence of PI. Methods We performed a randomized controlled trial to assess the efficacy and safety of NMES in preventing PI in critically ill patients. We included patients with a period of less than 48 h in the ICU, aged ≥ 18 years. Participants were randomly selected (1:1 ratio) to receive NMES and usual care (NMES group) or only usual care (control group—CG) until discharge, death, or onset of a PI. To assess the effectiveness of NMES, we calculated the relative risk (RR) and number needed to treat (NNT). We assessed the muscle thickness of the gluteus maximus by ultrasonography. To assess safety, we analyzed the effects of NMES on vital signs and checked for the presence of skin burns in the stimulated areas. Clinical outcomes were assessed by time on mechanical ventilation, ICU mortality rate, and length of stay in the ICU. Results We enrolled 149 participants, 76 in the NMES group. PIs were present in 26 (35.6%) patients in the CG and 4 (5.3%) in the NMES group (p ˂ 0.001). The NMES group had an RR = 0.15 (95% CI 0.05–0.40) to develop a PI, NNT = 3.3 (95% CI 2.3–5.9). Moreover, the NMES group presented a shorter length of stay in the ICU: Δ = − 1.8 ± 1.2 days, p = 0.04. There was no significant difference in gluteus maximus thickness between groups (CG: Δ = − 0.37 ± 1.2 cm vs. NMES group: Δ = 0 ± 0.98 cm, p = 0.33). NMES did not promote deleterious changes in vital signs and we did not detect skin burns. Conclusions NMES is an effective and safe therapy for the prevention of PI in critically ill patients and may reduce length of stay in the ICU. Trial registration RBR-8nt9m4. Registered prospectively on July 20th, 2018, https://ensaiosclinicos.gov.br/rg/RBR-8nt9m4

Background: Assuming that the mechanisms inducing adaptation in healthy tendons yield similar responses in tendinopathic tendons, we hypothesized that a high-loading exercise protocol that increases tendon stiffness and cross-sectional area in male healthy Achilles tendons may also induce comparable beneficial adaptations in male tendinopathic Achilles tendons in addition to improving pain and function. Objectives: We investigated the effectiveness of high-loading exercise in Achilles tendinopathy in terms of inducing mechanical (tendon stiffness, maximum strain), material (Young's modulus), morphological (tendon cross-sectional area (CSA)), maximum voluntary isometric plantar flexor strength (MVC) as well as clinical adaptations (Victorian Institute of Sports Assessment—Achilles (VISA-A) score and pain (numerical rating scale (NRS))) as the primary outcomes. As secondary outcomes, drop (DJ) and counter-movement jump (CMJ) height and intratendinous vascularity were assessed. Methods: We conducted a controlled clinical trial with a 3-month intervention phase. Eligibility criteria were assessed by researchers and medical doctors. Inclusion criteria were male sex, aged between 20 and 55 years, chronic Achilles tendinopathy confirmed by a medical doctor via ultrasound-assisted assessment, and a severity level of less than 80 points on the VISA-A score. Thirty-nine patients were assigned by sequential allocation to one of three parallel arms: a high-loading intervention (training at ~ 90% of the MVC) (n = 15), eccentric exercise (according to the Alfredson protocol) as the standard therapy (n = 15) and passive therapy (n = 14). Parameters were assessed pre- and-post-intervention. Data analysis was blinded. Results: Primary outcomes: Plantar flexor MVC, tendon stiffness, mean CSA and maximum tendon strain improved only in the high-loading intervention group by 7.2 ± 9.9% (p = 0.045), 20.1 ± 20.5% (p = 0.049), 8.98 ± 5.8% (p < 0.001) and −12.4 ± 10.3% (p = 0.001), respectively. Stiffness decreased in the passive therapy group (−7.7 ± 21.2%; p = 0.042). There was no change in Young's modulus in either group (p > 0.05). The VISA-A score increased in all groups on average by 19.8 ± 15.3 points (p < 0.001), while pain (NRS) dropped by −0.55 ± 0.9 points (p < 0.001). Secondary outcomes: CMJ height decreased for all groups (−0.63 ± 4.07 cm; p = 0.005). There was no change in DJ height and vascularity (p > 0.05) in either group. Conclusion: Despite an overall clinical improvement, it was exclusively the high-loading intervention that induced significant mechanical and morphological adaptations of the plantar flexor muscle–tendon unit. This might contribute to protecting the tendon from strain-induced injury. Thus, we recommend the high-loading intervention as an effective (alternative) therapeutic protocol in Achilles tendinopathy rehabilitation management in males. Clinical Trials Registration Number: NCT02732782. [ABSTRACT FROM AUTHOR]

Tooth germ autotransplantation of open apices of the teeth exhibits high pulpal healing rates, whereas that of mature permanent teeth normally causes irreversible pulpal necrosis. Extraoral root-end resection (EORER) during transplantation may promote pulpal revascularization (PRV) in transplanted mature teeth and reduce endodontic treatment requirement. This study compared the primary outcomes of survival rates, PRV, and root resorption and determined relevant confounders in autotransplanted mature and immature teeth. The medical charts of consecutive patients who underwent tooth autotransplantation between January 2017 and March 2021 were evaluated. Teeth with a documented follow-up of at least 1 year were included. During the study period, 59 teeth were transplanted in 44 patients. Overall, 2 teeth were excluded owing to missing data; 57 teeth were analyzed, including 25 mature teeth additionally treated with EORER. After a mean follow-up of 21.2 ± 16.1 months, no significant differences in primary outcomes were detected. Fifty-five teeth remained in situ (96.5%), and radiological signs of root resorption were detected in 9/57 teeth (15.8%). PRV was positive in 54/57 teeth (94.7%). Surgical duration and PRV failure were significantly associated with high incidences of root resorption. Mature teeth autotransplantation with EORER yielded similar results to immature teeth autotransplantation and is a feasible treatment option. Long surgery and failed revascularization increased root resorption rates. More factors should be evaluated in larger trials with longer observation periods. [ABSTRACT FROM AUTHOR]

Abstract Background Caries prevalence has declined significantly since the introduction of fluoridated toothpaste. There have been several developments regarding specific active fluoride ingredients but not enough evidence to support one over the other. The purpose of this double-blind randomized controlled trial was to compare salivary fluoride concentrations of different fluoride formulations in the form of toothpaste with and without post-brushing water rinsing in adults. Methods The study included 120 participants who were randomly assigned to one of 12 groups (10 participants/group). The toothpaste formulas investigated included (1) fluoride-free (0 ppmF); (2) sodium fluoride (1450 ppmF); (3) sodium monofluorophosphate (1450 ppmF); (4) sodium fluoride and monofluorophosphate combined (1450 ppmF); (5) stannous fluoride and sodium fluoride combined (1450 ppmF); and (6) amine fluoride (1400 ppmF). Block randomisation was used to assign each participant to one of the 12 groups. Participants brushed with 1.0 g of one of the six different toothpaste formulations either with or without post-brushing water rinsing. Saliva was collected at six different times (baseline and at 1, 15, 30, 60, and 90 min/s post-brushing). Samples were analysed using a fluoride ion-specific sensitive electrode connected to an ion analyser. Results The demographic characteristics of the participants were not significantly different among the groups (P > 0.05). Time, toothpaste formulation, and post-brushing rinsing routines had significant effects on saliva fluoride retention (P

We set out to discern to what extent the media strategies adopted around the vaccines against COVID-19 during the first 15 months since the beginning of their application can be considered as a legitimate and coherent contributions to a better understanding about their performance and to what extent the elaborated discourses could respond to the economic interests of the corporations' elites. Once the most relevant elements that have shaped the predominant narratives from the moment the vaccines were conceived were compiled, several anomalies were identified that were to a greater or lesser extent invisibilized in the process of their approval and the results of their application. The most significant of these concern the handling of definitions, non-compliance with commitments and conflicts of interest that compromise the actions of vaccine marketing companies and regulatory bodies. Many elements related to corporative interests have influenced the narrative concerning vaccines. Among those that require a resignification are: their real preventive capacity against contagions, serious diseases and deaths, their efficacy against new variants, the duration of the immunity they confer, their side effects, the synergic role of acquired immunity, and the resources used by the companies to achieve a virtually market monopolistic predominance. [ABSTRACT FROM AUTHOR]

Objectives: To compare the clinical effectiveness of Hawley retainers (HRs) and modified vacuum-formed retainers (mVFRs) with palatal coverage in maintaining transverse expansion throughout a 24-month retention period and to assess the subjects' perception toward the retainers. Materials and methods: The trial accomplished blinding only by the outcome assessor and data analyst. Data were collected from post-orthodontic treatment patients who met the inclusion criteria. Thirty-five subjects were randomly allocated using a centralized randomization technique into either mVFR (n = 18) or HR group (n = 17). Dental casts of subjects were evaluated at debond (T0), 3-month (T1), 6-month (T2), 12-month (T3), and 24-month retention (T4). The intercanine width (ICW), interpremolar width (IPMW), interfirst molar mesiobuccal cusp width (IFMW1), and interfirst molar distobuccal cusp width (IFMW2) were compared between groups over time using Mixed ANOVA. A pilot-tested and validated questionnaire consisting of six items were given at T4. Subjects were instructed to rate their retainer in terms of fitting, speech, appearance, oral hygiene, durability, and comfort on a 100-mm Visual Analogue Scale (VAS). Results: No statistically significant differences in arch width were found between the two groups at ICW (P =.83), IPMW (P = 0.63), IFMW1 (P =.22), and IFMW2 (P =.46) during the 24-month retention period. Also, no statistically significant differences were found between perception of both retainers in terms of fitting, speech, oral hygiene, durability, and comfort (P >.05) after 24-month wear. The appearance of mVFRs was rated significantly higher compared to HRs (P <.05). Conclusions: HR and mVFR have similar clinical effectiveness for retention of transverse expansion cases in a 24-month retention period. Both retainers were perceived to be equal in terms of fitting, speech, oral hygiene, durability, and comfort. Subjects in the mVFRs group found their retainers to be significantly more esthetic than those in HRs group. [ABSTRACT FROM AUTHOR]

Background: Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) have poor 5-year survival. Pharmacological ascorbate (P-AscH - , high dose, intravenous, vitamin C) has shown promise as an adjunct to chemotherapy. We hypothesized adding P-AscH - to gemcitabine and nab-paclitaxel would increase survival in patients with metastatic PDAC., Methods: Patients diagnosed with stage IV pancreatic cancer randomized 1:1 to gemcitabine and nab-paclitaxel only (SOC, control) or to SOC with concomitant P-AscH - , 75 g three times weekly (ASC, investigational). The primary outcome was overall survival with secondary objectives of determining progression-free survival and adverse event incidence. Quality of life and patient reported outcomes for common oncologic symptoms were captured as an exploratory objective. Thirty-six participants were randomized; of this 34 received their assigned study treatment. All analyses were based on data frozen on December 11, 2023., Results: Intravenous P-AscH - increased serum ascorbate levels from micromolar to millimolar levels. P-AscH - added to the gemcitabine + nab-paclitaxel (ASC) increased overall survival to 16 months compared to 8.3 months with gemcitabine + nab-paclitaxel (SOC) (HR = 0.46; 90 % CI 0.23, 0.92; p = 0.030). Median progression free survival was 6.2 (ASC) vs. 3.9 months (SOC) (HR = 0.43; 90 % CI 0.20, 0.92; p = 0.029). Adding P-AscH - did not negatively impact quality of life or increase the frequency or severity of adverse events., Conclusions: P-AscH - infusions of 75 g three times weekly in patients with metastatic pancreatic cancer prolongs overall and progression free survival without detriment to quality of life or added toxicity (ClinicalTrials.gov number NCT02905578)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

ABSTRACT Objective: To evaluate the effectiveness of the educational intervention through an informative manual in reducing anxiety, stress, and changes in vital signs in patients awaiting cardiac catheterization. Methods: Parallel, randomized, controlled, blind clinical trial. The study excluded patients waiting for cardiac catheterization; those who received the information manual were randomized to the intervention group, and those who received routine information from the unit went to the control group. The study used the State Anxiety Inventory and Perceived Stress Scale and the ANOVA test to analyze the outcomes between the groups. Clinical Trials NCT03369873. Results: There was no change concerning time, first and second moment (anxiety, P=0.225; and stress, P=0.696), interaction (anxiety, P=0.183; and stress, P=0.444), or groups, control, and intervention (anxiety, P=0.341; and stress, p=0.624). Conclusion: Although the educational intervention performed did not have an impact on the reduction of anxiety and stress, this type of intervention should be maintained for greater comfort and safety of patients and family members.

Background: Pressure injuries (PIs), especially in the sacral region are frequent, costly, and increase morbidity and mortality of patients in an intensive care unit (ICU). These injuries can occur as a result of prolonged pressure and/or shear forces. Neuromuscular electrical stimulation (NMES) can increase muscle mass and improve local circulation, potentially reducing the incidence of PI. Methods: We performed a randomized controlled trial to assess the efficacy and safety of NMES in preventing PI in critically ill patients. We included patients with a period of less than 48 h in the ICU, aged ≥ 18 years. Participants were randomly selected (1:1 ratio) to receive NMES and usual care (NMES group) or only usual care (control group—CG) until discharge, death, or onset of a PI. To assess the effectiveness of NMES, we calculated the relative risk (RR) and number needed to treat (NNT). We assessed the muscle thickness of the gluteus maximus by ultrasonography. To assess safety, we analyzed the effects of NMES on vital signs and checked for the presence of skin burns in the stimulated areas. Clinical outcomes were assessed by time on mechanical ventilation, ICU mortality rate, and length of stay in the ICU. Results: We enrolled 149 participants, 76 in the NMES group. PIs were present in 26 (35.6%) patients in the CG and 4 (5.3%) in the NMES group (p ˂ 0.001). The NMES group had an RR = 0.15 (95% CI 0.05–0.40) to develop a PI, NNT = 3.3 (95% CI 2.3–5.9). Moreover, the NMES group presented a shorter length of stay in the ICU: Δ = − 1.8 ± 1.2 days, p = 0.04. There was no significant difference in gluteus maximus thickness between groups (CG: Δ = − 0.37 ± 1.2 cm vs. NMES group: Δ = 0 ± 0.98 cm, p = 0.33). NMES did not promote deleterious changes in vital signs and we did not detect skin burns. Conclusions: NMES is an effective and safe therapy for the prevention of PI in critically ill patients and may reduce length of stay in the ICU. Trial registration RBR-8nt9m4. Registered prospectively on July 20th, 2018, https://ensaiosclinicos.gov.br/rg/RBR-8nt9m4 [ABSTRACT FROM AUTHOR]

Objective: To compare perioperative and long-term outcomes of robot-assisted minimally invasive esophagectomy (RAMIE) and conventional minimally invasive esophagectomy (MIE) in the treatment for patients with esophageal squamous cell carcinoma (ESCC). Summary Background Data: RAMIE has emerged as an alternative to traditional open or thoracoscopic approaches. Efficacy and safety of RAMIE and MIE in the surgical treatment for ESCC remains uncertain given the lack of high-level clinical evidence. Methods: The RAMIE trial was designed as a prospective, multicenter, randomized, controlled clinical trial that compares the efficacy and safety of RAMIE and MIE in the treatment of resectable ESCC. From August 2017 to December 2019, eligible patients were randomly assigned to receive either RAMIE or MIE performed by experienced thoracic surgeons from 6 high-volume centers in China. Intent-to-treat analysis was performed. Results: Significantly shorter operation time was taken in RAMIE (203.8 vs 244.9 min, P <0.001).> P = 0.016), as well as higher achievement rate of lymph node dissection along the left recurrent laryngeal nerve (79.5% vs 67.6%, P = 0.001). No difference was found in blood loss, conversion rate, and R0 resection. The 90-day mortality was 0.6% in each group. Overall complications were similar in RAMIE (48.6%) compared with MIE (41.8%) (RR, 1.16; 95% CI, 0.92-1.46; P = 0.196). Besides, the rate of major complications (Clavien-Dindo classification >= III) was also comparable (12.2% vs 10.2%, P = 0.551). RAMIE showed similar incidences of pulmonary complications (13.8% vs 14.7%; P = 0.812), anastomotic leakage (12.2% vs 11.3%; P = 0.801), and vocal cord paralysis (32.6% vs 27.1%, P = 0.258) to MIE. Conclusions: Early results demonstrate that both RAMIE and MIE are safe and feasible for the treatment of ESCC. RAMIE can achieve shorter operative duration and better lymph node dissection in patients who received neoadjuvant therapy. Long-term results are pending for further follow-up investigations. Trial Registration: ClinicalTrial.gov Identifier: NCT03094351. [ABSTRACT FROM AUTHOR]

Background: Caries prevalence has declined significantly since the introduction of fluoridated toothpaste. There have been several developments regarding specific active fluoride ingredients but not enough evidence to support one over the other. The purpose of this double-blind randomized controlled trial was to compare salivary fluoride concentrations of different fluoride formulations in the form of toothpaste with and without post-brushing water rinsing in adults. Methods: The study included 120 participants who were randomly assigned to one of 12 groups (10 participants/group). The toothpaste formulas investigated included (1) fluoride-free (0 ppmF); (2) sodium fluoride (1450 ppmF); (3) sodium monofluorophosphate (1450 ppmF); (4) sodium fluoride and monofluorophosphate combined (1450 ppmF); (5) stannous fluoride and sodium fluoride combined (1450 ppmF); and (6) amine fluoride (1400 ppmF). Block randomisation was used to assign each participant to one of the 12 groups. Participants brushed with 1.0 g of one of the six different toothpaste formulations either with or without post-brushing water rinsing. Saliva was collected at six different times (baseline and at 1, 15, 30, 60, and 90 min/s post-brushing). Samples were analysed using a fluoride ion-specific sensitive electrode connected to an ion analyser. Results: The demographic characteristics of the participants were not significantly different among the groups (P > 0.05). Time, toothpaste formulation, and post-brushing rinsing routines had significant effects on saliva fluoride retention (P < 0.05). Amine fluoride-containing toothpaste was the only formula that showed statistically significantly higher concentrations of salivary fluoride at 90 min in both the rinsing and non-rinsing groups. Sodium monofluorophosphate toothpaste did not result in a significant difference compared to the control group at any time point, in both rinsing and non-rinsing groups. Conclusions: Based on the results from this study, no rinsing after toothbrushing in adults can be recommended when sodium monofluorophosphate containing toothpaste formula is used. It also concludes that amine fluoride resulted in a significantly higher saliva fluoride concentration at 90 min in both the rinsing and non-rinsing groups compared to other fluoride toothpaste formulations. Registry: Protocol Registration and Results System (ClinicalTrials.gov). Clinical trial registration number: NCT02740803 (15/04/2016). [ABSTRACT FROM AUTHOR]

Objective: This study aims to assess the effectiveness of a 12‐weeks self‐management and exercise intervention to improve self‐efficacy in older individuals with knee osteoarthritis (KOA) Design: Randomised Controlled Trial. Setting: Four different community settings. Subjects: Eighty individuals aged 60 years or over with clinical and radiographic knee osteoarthritis. Intervention: The subjects were randomly assigned to (1) a combined self‐management and exercise programme (treatment group) and (2) an educational programme (control group). Main Measures: The primary outcome was self‐efficacy and secondary outcomes were physical activity, health‐related quality of life and skill‐related physical fitness measures. Results: Sixty‐seven participants, mean age 69.1 (5.8) years, completed the study: 32 in the control group and 35 in the treatment group. A significant group effect favourable to the treatment group was observed in the following variables: self‐efficacy (F[2,64] = 9.2, p = 0.003), physical activity (F[2,64] = 43.6, p < 0.001) and balance for most painful knee (F(2,64) = 4.87, p = 0.031) and less painful knee (F[2,64] = 6.94, p = 0.010). No improvements regarding health‐related quality of life, gait speed and agility were found. This study supports the importance of a combined self‐management and exercise intervention to improve self‐efficacy and physical activity in KOA individuals. [ABSTRACT FROM AUTHOR]

To compare the clinical effectiveness of Hawley retainers (HRs) and modified vacuum-formed retainers (mVFRs) with palatal coverage in maintaining transverse expansion during a 12-month retention period. Data were collected from postorthodontic treatment patients who met the inclusion criteria. A total of 35 patients were randomly allocated using a centralized randomization technique into either mVFR (n = 18) or HR group (n = 17). The outcome assessor and data analyst were blinded to the retention method. Dental casts of patients were evaluated at debond, 3 months, 6 months, and 12 months of retention. Intercanine width (ICW), interpremolar width (IPMW), interfirst molar mesiobuccal cusp width 1 (IFMW1), and interfirst molar distobuccal cusp width 2 (IFMW2) were compared between groups over time using mixed analysis of variance. No statistically significant differences were found between the two groups for ICW (P =.76), IPMW (P =.63), IFMW1 (P =.16), and IFMW2 (P =.40) during the 12-month retention period. The null hypothesis could not be rejected. HR and mVFR had similar clinical effectiveness in the retention of transverse expansion cases during a 12-month retention period. [ABSTRACT FROM AUTHOR]

Background. To evaluate the efficacy of short-term lurasidone in antipsychotic treatment-naïve (TN) adolescents with schizophrenia versus those treated previously (TP) with antipsychotics. Methods. Patients aged 13–17 with schizophrenia, and a Positive and Negative Symptom Scale (PANSS) score ≥ 70 and < 120, were randomized to 6 weeks of double-blind treatment with lurasidone (40 or 80 mg/day) or placebo. In a post-hoc, pooled-dose analysis, efficacy was evaluated for TN (criteria: never received antipsychotic treatment) versus TP at the time of the study. Treatment response criteria: ≥20% reduction in PANSS total score. Results. Altogether, 57 TN and 269 TP patients enrolled in the 6-week DB study. Mean endpoint change in PANSS total score was significantly greater for lurasidone versus placebo in both the TN group (−25.0 vs. -14.4; p < 0.02; effect size = 0.75), and in the TP group (−17.3 vs. -10.0; p < 0.001; effect size = 0.45); and responder rates were higher for lurasidone versus placebo in both the TN group 84.6% versus 38.9%; number needed to treat [NNT] = 3 and in the TP group (60% vs. 42%; NNT = 6). Rates of treatment-emergent adverse events, and mean changes in body weight and metabolic parameters were similar for the TN and TP groups. Conclusions. In a 6-week, placebo-controlled trial, lurasidone demonstrated significant efficacy in adolescents with schizophrenia regardless of previous antipsychotic therapy status; however, the effect size was notably larger in the TN patient group. In both the TN and TP groups, minimal effects were noted on weight, metabolic parameters, or prolactin. [ABSTRACT FROM AUTHOR]

Background Calcific uraemic arteriolopathy (CUA; calciphylaxis) is a rare disease seen predominantly in patients receiving dialysis. Calciphylaxis is characterized by poorly healing or non-healing wounds, and is associated with mortality, substantial morbidity related to infection and typically severe pain. In an open-label Phase 2 clinical trial, SNF472, a selective inhibitor of vascular calcification, was well-tolerated and associated with improvement in wound healing, reduction of wound-related pain and improvement in wound-related quality of life (QoL). Those results informed the design of the CALCIPHYX trial, an ongoing, randomized, placebo-controlled, Phase 3 trial of SNF472 for treatment of calciphylaxis. Methods In CALCIPHYX, 66 patients receiving haemodialysis who have an ulcerated calciphylaxis lesion will be randomized 1:1 to double-blind SNF472 (7 mg/kg intravenously) or placebo three times weekly for 12 weeks (Part 1), then receive open-label SNF472 for 12 weeks (Part 2). All patients will receive stable background care, which may include pain medications and sodium thiosulphate, in accordance with the clinical practices of each site. A statistically significant difference between the SNF472 and placebo groups for improvement of either primary endpoint at Week 12 will demonstrate efficacy of SNF472: change in Bates-Jensen Wound Assessment Tool-CUA (a quantitative wound assessment tool for evaluating calciphylaxis lesions) or change in pain visual analogue scale score. Additional endpoints will address wound-related QoL, qualitative changes in wounds, wound size, analgesic use and safety. Conclusions This randomized, placebo-controlled Phase 3 clinical trial will examine the efficacy and safety of SNF472 in patients who have ulcerated calciphylaxis lesions. Patient recruitment is ongoing. [ABSTRACT FROM AUTHOR]

Objective: Spironolactone (C24H32O4S), a potent mineralocorticoid receptor (MR) inhibitor, is a potassium-sparing diuretic that is traditionally used to treat fluid build-up in the body or for its anti-androgenic properties. This study is a double-blind, placebo-controlled, randomized clinical trial assessing the beneficial effects of spironolactone in addition to risperidone in improving negative symptoms of schizophrenia. Method: 40 patients with chronic schizophrenia, aged 18-60 years, were assigned to two groups: risperidone + spironolactone or risperidone + placebo. Risperidone was administered to both the spironolactone and placebo groups with a dose up to 6 mg/day throughout the trial. Spironolactone (C24H32O4S) was ordered 100 mg/day for the full 8- week course of the study. Patients were rated on the Positive and Negative Syndrome Scale (PANSS) at four time points: baseline, weeks two, four, and eight. The PANSS negative subscale score was the main objective. Results: PANSS negative, positive, and total scores showed significantly greater improvements in the spironolactone relative to the placebo group from baseline to the trial endpoint (P (Cohen's d): 0.004 (0.96), 0.007 (0.90), and 0.042 (0.66), respectively). Similarly, ANOVA also presented significant time x treatment interaction effect for spironolactone on PANSS negative (F = 9.04; ηp2 = 0.19; df = 1.38; P = 0.002), positive (F = 3.43; ηp2 = 0.08; df = 2.72; P = 0.023), and total (F = 3.94; ηp2 = 0.09; df = 2.05; P = 0.022) scores. However, spironolactone did not cause significant decrease in the general psychiatric pathology score of PANSS. Conclusion: Our findings suggest the efficacy and safety of spironolactone as an adjunctive therapy to risperidone in improving the symptoms of schizophrenia. [ABSTRACT FROM AUTHOR]

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What is known and objective: The discussion about health equity in the United States frequently involves concerns over racial and ethnic minority under‐representation in clinical trials and particularly in trials conducted in support of product approvals. The FDA has long worked to encourage diverse participation in clinical trials and through its Drug Trials Snapshots (DTS) program, the U.S. Food and Drug Administration (FDA) has moved to make trial demographic data more accessible and transparent. We conducted a demographic study of U.S. participants in clinical trials for FDA‐approved new drugs (new molecular entities [NMEs], and original Biologics License Applications [BLAs]) from 2015 to 2019, as reported in DTS database with a purpose of understanding the extent to which U.S.‐based trials used to support product approvals represent the racial and ethnic diversity of the U.S. population by therapeutic area. Methods: Participant‐level trial data were collected by accessing the FDA electronic common technical document (eCTD), for the applications used to publish each Snapshot. The therapeutic area (TA) for each drug was determined by review division assignment. The demographic data were analysed and compared to U.S. census data. Results and discussion: We examined 102,596 U.S. participants in trials of new drugs that were approved and presented in Drug Trials Snapshots between 2015 and 2019. White participation ranged from 51% in psychiatric trials to 90% in cardiovascular (CV) trials; Black or African American participation ranged from 5% in medical imaging to 45% in psychiatric trials; Asian participation ranged from 0.75% in CV to 4% in dermatologic trials; and Hispanic or Latino participation ranged from 1% in medical imaging to 22% in infectious diseases and gastroenterology trials. What is new and conclusion: Our data showed variable representation of racial and ethnic minorities across therapeutic areas at the U.S. sites. Blacks or African Americans were represented at or above U.S. census estimates across most therapeutic areas, while Asians and American Indian or Alaska Natives were consistently underrepresented. Hispanic or Latino participation across most therapeutic areas was below U.S. census estimates, however, more variable, and a sizable proportion of data was missing. The next step is a comparison of trial participation based on disease prevalence and epidemiology, which is a more accurate assessment of trial diversity. [ABSTRACT FROM AUTHOR]

The SPRINT (Systolic Blood Pressure Intervention Trial) results have influenced clinical practice but have also generated discussion regarding the validity, generalizability, and importance of the findings. Following the SPRINT primary results manuscript in 2015, additional results and analyses of the data have addressed these concerns. The primary objective of this article is to respond to key questions that have been raised. [ABSTRACT FROM AUTHOR]

Background/Aims: Ensuring verum and placebo cannot be visually distinguished from each other is a critical aspect of blinded controlled clinical trials. Our objective was to propose a rational approach to the visual evaluation of placebo matching candidates. Methods: Verum and placebo samples were prepared in clear clinical ancillary supplies (intravenous bags, syringes and administration lines) covered at different levels using opaque sleeves. Triangle and tetrad tests, two sensory discriminative testing methods widely used in the food industry, were applied to assess visual differences between verum and placebo. Results: Triangle and tetrad test results allowed defining the level of opaque coverage required to ensure blinding for three biological drug molecules of therapeutic interest. While the limited number of panelists did not allow a statistically sound comparison of triangle and tetrad test methodologies, tetrad test has a theoretical higher power than triangle test, meaning fewer panelists are needed to reach the same statistical conclusion. Conclusion: Tetrad test offers a rational approach to define a blinding strategy for ancillary supplies used in a controlled clinical trial. [ABSTRACT FROM AUTHOR]

Background Ebola virus RNA persists in the semen of male Ebola survivors for months to years after the acute infection, and male-to-female sexual transmission of the virus is well documented. We investigated whether remdesivir can safely reduce persistence of seminal Ebola virus RNA. Methods We recruited men with persistent seminal Ebola RNA in Liberia and Guinea. Participants were randomized 1:1 to receive intravenous remdesivir (GS-5734; Gilead Sciences) or matching placebo administered once daily by intravenous infusion over 1 hour on 5 consecutive days. Stratification was by country and number of positive (1 or 2) preenrollment semen tests. We evaluated the difference in mean assay negativity rate (ANR), that is, the proportion of negative tests for each participant in each group in the treatment (days 1–28) and follow-up (months 2–6) phases on an intention-to-treat basis. Results We enrolled 38 men from July 2016 through June 2018. The mean treatment phase ANRs were 85% (standard deviation [SD] = 24%) and 76% (SD = 30%) in the remdesivir and placebo arms, respectively (P  = .270). The mean follow-up phase ANRs were 96% (SD = 10%) and 81% (SD = 29%) in the remdesivir and placebo arms, respectively (P  = .041). The 5-day remdesivir regimen was well tolerated with no safety concerns. Conclusions In this small trial, remdesivir 100 mg/day for 5 days safely reduced the presence of Ebola virus RNA in the semen of Ebola survivors 2 to 6 months after administration. A larger follow-up study is necessary to confirm results. Clinical Trials Registration. NCT02818582 [ABSTRACT FROM AUTHOR]

Ahmad Zare Javid,1,2 Leila Maghsoumi-Norouzabad,1,2 Hadi Bazyar,1,3 Vahideh Aghamohammadi,4 Pejman Alavinejad5 1Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 2Department of Nutrition, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 3Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 4Department of Nutrition, Khalkhal University of Medical Sciences, Khalkhal, Iran; 5Alimentary Tract Research Center, Imam Khomeini Hospital Clinical Research Development Unit, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranCorrespondence: Vahideh AghamohammadiDepartment of Nutrition, Khalkhal University of Medical Sciences, Khalkhal, IranTel +989143529145Email v_agamohammadi@yahoo.comBackground: It seems alternative treatments such as antioxidant intervention and anti-inflammatory intervention adjuvant to antibiotic regimens may enhance cancer prevention approaches and decrease adverse side effects related to therapeutic antibiotic regimens. So, we will evaluate the effects of concurrent omega-3 and cranberry juice supplementation along with standard antibiotic therapy on the eradication of Helicobacter pylori, gastrointestinal symptoms, some serum inflammatory and oxidative stress markers in adults with HP infection.Methods: We will conduct a 4-week double-blinded randomized clinical trial. The subjects will be randomly stratified according to sex and BMI using a permuted block randomization procedure by Random Allocation Software (RAS). They will be assigned to one of the four study groups: (1) cranberry juice fortified with omega-3 Intervention (n=23), (2) cranberry juice intervention group (n=23), (3) placebo beverage fortified with omega-3 intervention group (n=23), and (4) placebo beverage intervention (control group) (n=23). All statistical analyses will be performed using IBM SPSS Statistics software.Discussion: A combination of alternative therapies may have a synergistic effect compared to a single approach. It could potentially be more effective in promoting the efficacy of standard antibiotic therapy in eradicating HP infection.Trial Registration: Iranian Registry of Clinical Trials (IRCT20151128025274N3, www.irct.ir/trial/28997).Trial Status: This study is in the early stages of sampling.Keywords: controlled clinical trial, cranberry juice, fatty acids, omega-3, Helicobacter pylori, inflammation mediators, oxidative stress, vaccinium macrocarpon

AbstractBackgroundTo evaluate the efficacy of short-term lurasidone in antipsychotic treatment-naïve (TN) adolescents with schizophrenia versus those treated previously (TP) with antipsychotics.MethodsPatients aged 13–17 with schizophrenia, and a Positive and Negative Symptom Scale (PANSS) score ≥ 70 and < 120, were randomized to 6 weeks of double-blind treatment with lurasidone (40 or 80 mg/day) or placebo. In a post-hoc, pooled-dose analysis, efficacy was evaluated for TN (criteria: never received antipsychotic treatment) versus TP at the time of the study. Treatment response criteria: ≥20% reduction in PANSS total score.ResultsAltogether, 57 TN and 269 TP patients enrolled in the 6-week DB study. Mean endpoint change in PANSS total score was significantly greater for lurasidone versus placebo in both the TN group (−25.0 vs. -14.4; p < 0.02; effect size = 0.75), and in the TP group (−17.3 vs. -10.0; p < 0.001; effect size = 0.45); and responder rates were higher for lurasidone versus placebo in both the TN group 84.6% versus 38.9%; number needed to treat [NNT] = 3 and in the TP group (60% vs. 42%; NNT = 6). Rates of treatment-emergent adverse events, and mean changes in body weight and metabolic parameters were similar for the TN and TP groups.ConclusionsIn a 6-week, placebo-controlled trial, lurasidone demonstrated significant efficacy in adolescents with schizophrenia regardless of previous antipsychotic therapy status; however, the effect size was notably larger in the TN patient group. In both the TN and TP groups, minimal effects were noted on weight, metabolic parameters, or prolactin.

Objective: Spironolactone (C24H32O4S), a potent mineralocorticoid receptor (MR) inhibitor, is a potassium-sparing diuretic that is traditionally used to treat fluid build-up in the body or for its anti-androgenic properties. This study is a double-blind, placebo-controlled, randomized clinical trial assessing the beneficial effects of spironolactone in addition to risperidone in improving negative symptoms of schizophrenia. Method: 40 patients with chronic schizophrenia, aged 18–60 years, were assigned to two groups: risperidone + spironolactone or risperidone + placebo. Risperidone was administered to both the spironolactone and placebo groups with a dose up to 6 mg/day throughout the trial. Spironolactone (C24H32O4S) was ordered 100 mg/day for the full 8-week course of the study. Patients were rated on the Positive and Negative Syndrome Scale (PANSS) at four time points: baseline, weeks two, four, and eight. The PANSS negative subscale score was the main objective. Results: PANSS negative, positive, and total scores showed significantly greater improvements in the spironolactone relative to the placebo group from baseline to the trial endpoint (P (Cohen’s d): 0.004 (0.96), 0.007 (0.90), and 0.042 (0.66), respectively). Similarly, ANOVA also presented significant time × treatment interaction effect for spironolactone on PANSS negative (F = 9.04; ηp2 = 0.19; df = 1.38; P = 0.002), positive (F = 3.43; ηp2 = 0.08; df = 2.72; P = 0.023), and total (F = 3.94; ηp2 = 0.09; df = 2.05; P = 0.022) scores. However, spironolactone did not cause significant decrease in the general psychiatric pathology score of PANSS. Conclusion: Our findings suggest the efficacy and safety of spironolactone as an adjunctive therapy to risperidone in improving the symptoms of schizophrenia.

Objectives: The objective of this prospective study was to compare the clinical outcomes of coronally advanced flap (CAF) using two different surgical strategies in the treatment of multiple gingival recessions. Method and Materials: Ten patients presenting with a total of 81 Miller class I gingival recessions were included. Recessions were randomly treated according to a split-mouth design by means of CAF with oblique interdental incisions (OBL technique), or CAF with horizontal interdental incisions (HOR technique). Marginal gingival recession (REC), clinical attachment level (CAL), pocket probing depth (PPD), height of keratinized tissue (PIKT), and thickness of keratinized tissue (TKT) were measured at baseline, and 3 and 6 months after treatment. Patient-centered outcomes concerning morbidity and improvement in the esthetic appearance were recorded using a visual analog scale (VAS). Results: Both groups showed significant reductions in REC and gains in CAL throughout the study (P < .05). At 3 months, OBL-treated sites showed greater root coverage than HOR-treated sites (P < .05), although no intergroup differences were observed at 6 months (P > .05). There was an increase in HKT only in the OBL group at 6 months from baseline (P< .05). No differences between therapies were revealed concerning morbidity (P> .05), whereas a higher satisfaction with the esthetic appearance was reported for the OBL technique 6 months postsurgery (P c .05). Conclusion: Although both surgical approaches may provide satisfactory root coverage, use of the OBL technique promoted additional benefits in terms of esthetic perception after the management of multiple gingival recessions. [ABSTRACT FROM AUTHOR]

Effects of sex on the incidence of cardiac tamponade after catheter ablation of atrial fibrillation: results from a worldwide survey in 34 943 atrial fibrillation ablation procedures. Keywords: Editorials; ablation techniques; anti-arrhythmia agents; atrial fibrillation; comorbidity; controlled clinical trial; stroke EN Editorials ablation techniques anti-arrhythmia agents atrial fibrillation comorbidity controlled clinical trial stroke 848 850 3 09/15/22 20220913 NES 220913 Atrial fibrillation (AF) serves as an independent predictor of decreased quality of life, morbidity, and mortality in select patient populations.[1] As the most common arrhythmia, AF affects an estimated 46.3 million individuals worldwide, and diagnoses of new AF have become increasingly frequent owing to improved public health awareness and enhanced detection from ambulatory electrocardiographic monitoring.[2],[3] The medical field has met the growing AF population with the creation and refinement of the armamentarium of AF therapies. Editorials, atrial fibrillation, comorbidity, controlled clinical trial, stroke, anti-arrhythmia agents, ablation techniques. [Extracted from the article]

Background: Even on optimal therapy, many patients with heart failure and atrial fibrillation experience cardiovascular complications. Additional treatments are needed to reduce these events, especially in patients with heart failure and preserved left ventricular ejection fraction.Methods: This prespecified subanalysis of the randomized EAST-AFNET4 trial (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) assessed the effect of systematic, early rhythm control therapy (ERC; using antiarrhythmic drugs or catheter ablation) compared with usual care (allowing rhythm control therapy to improve symptoms) on the 2 primary outcomes of the trial and on selected secondary outcomes in patients with heart failure, defined as heart failure symptoms New York Heart Association II to III or left ventricular ejection fraction [LVEF] <50%.Results: This analysis included 798 patients (300 [37.6%] female, median age 71.0 [64.0, 76.0] years, 785 with known LVEF). The majority of patients (n=442) had heart failure and preserved LVEF (LVEF≥50%; mean LVEF 61±6.3%), the others had heart failure with midrange ejection fraction (n=211; LVEF 40%-49%; mean LVEF 44 ± 2.9%) or heart failure with reduced ejection fraction (n=132; LVEF<40%; mean LVEF 31±5.5%). Over the 5.1-year median follow-up, the composite primary outcome of cardiovascular death, stroke, or hospitalization for worsening of heart failure or for acute coronary syndrome occurred less often in patients randomly assigned to ERC (94/396; 5.7 per 100 patient-years) compared with patients randomly assigned to usual care (130/402; 7.9 per 100 patient-years; hazard ratio, 0.74 [0.56-0.97]; P=0.03), not altered by heart failure status (interaction P value=0.63). The primary safety outcome (death, stroke, or serious adverse events related to rhythm control therapy) occurred in 71 of 396 (17.9%) patients with heart failure randomly assigned to ERC and in 87 of 402 (21.6%) patients with heart failure randomly assigned to usual care (hazard ratio, 0.85 [0.62-1.17]; P=0.33). LVEF improved in both groups (LVEF change at 2 years: ERC 5.3±11.6%, usual care 4.9±11.6%, P=0.43). ERC also improved the composite outcome of death or hospitalization for worsening of heart failure.Conclusions: Rhythm control therapy conveys clinical benefit when initiated within 1 year of diagnosing atrial fibrillation in patients with signs or symptoms of heart failure. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01288352. URL: http://www.controlled-trials.com; Unique identifier: ISRCTN04708680. URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2010-021258-20. [ABSTRACT FROM AUTHOR]

It is essential to identify intermediate marker endpoints of carcinogenesis for the evaluation of the effectiveness of cancer-chemopreventive agents. We have observed that levels of proteolytic activities (as detected by 4 different substrates) are increased 2-3-fold (P < 0.003) in oral buccal mucosa cells of smokers and patients with oral leukoplakia or erythroplakia as compared to a nonsmoking comparison group. In addition, proteolytic activity levels in the buccal cells were increased nearly 3-fold in patients with oral trauma (P < 0.01) or diabetes (P < 0.02), as well as pregnant women (P < 0.04). Excluding these subgroups of patients in epidemiological studies increase the differences in levels of proteolytic activities between both the nonsmoking comparison group and smokers and between the comparison group and patients with oral leukoplakia or erythroplakia. Evaluation of prerandomization levels of proteolytic activities of patients in cancer chemoprevention trials will increase the statistical power by allowing stratified randomization based on levels of proteolytic activities. The observed increases in levels of proteolytic activities in tissues at higher than normal risk of cancer development suggest that levels of proteolytic activities should be used as immediate marker endpoints in human cancer prevention trials using protease inhibitors as potential anticarcinogenic agents.