Double-blind Randomized Control Trial Research Articles

Clinical Effectiveness and Safety of Midazolam Compared With Lorazepam for Control of Seizures in Adults

What Is the Issue? The emergency treatment of prolonged seizures or status epilepticus is required to be rapid and efficient to prevent permanent brain damage or death. Benzodiazepines, such as midazolam, lorazepam, diazepam, and clonazepam, are established as first-line treatment medications for acute treatments of seizures. Various administration routes of delivery for these drugs have become available, but the comparative clinical effectiveness and safety among administration routes are still unclear. Decision-makers are interested in whether the current use of intramuscular (IM) midazolam for treatment of seizures by paramedics in a prehospital environment can be switched to IV lorazepam as normally used by nurses and physicians in clinic settings. What Did We Do? We identified and summarized the literature on the evidence of the clinical effectiveness and safety of midazolam compared to lorazepam in adults to control seizures. We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2019. One reviewer screened citations for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings. What Did We Find? We identified 1 systematic review (SR) that included 4 randomized controlled trials (RCTs), only 1 was relevant to this review. This double-blind RCT determined the efficacy of IM midazolam as noninferior to IV lorazepam for treatment of seizures by paramedics in a mixed population of adults (89%) and children (11%). The authors of the SR conducted a subanalysis of a dataset of participant-level data and showed that IM midazolam was as effective and safe as IV lorazepam in adult patients for prehospital seizure cessation. The findings of the adult population were similar to those of the whole randomized population of both adults and children. What Does This Mean? With the shorter time required to administration of midazolam by the IM route compared to administration of lorazepam by the IV route, and the comparable efficacy and safety between the 2 active treatments, the use of IM midazolam may be a better option in the prehospital environment when IV access in patients with seizures is not readily established. Switching of IM midazolam to IV lorazepam for treatment of seizures by paramedics may not be practical.

Meta-analysis of RCTs on the safety of non-fixation of mesh in TAPP inguinal hernia repair: an updated meta-analysis

ObjectiveThis meta-analysis aims to compare the clinical efficacy of mesh non-fixation and fixation in laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair, systematically evaluating the application value of the mesh non-fixation technique in clinical settings.MethodsA computerized search of PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases was conducted to identify randomized controlled trials (RCTs) comparing mesh non-fixation and fixation in TAPP inguinal hernia repair. Meta-analysis was performed using RevMan 5.3 software, and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence grading system was employed for outcome quality assessment. Publication bias analysis was performed using Begg’s test. A trial sequential analysis (TSA) was performed using TSA 0.9.5.10 Beta software.ResultsA total of nine RCTs involving 1,879 inguinal hernia patients were included. Meta-analysis results demonstrated that, compared to the fixation group, the non-fixation group exhibited significantly lower seroma occurrence rate [RR = 0.43, 95% CI (0.20, 0.89), P = 0.02, heterogeneity P = 0.28, I²=22%], Visual Analog Scale (VAS) pain score at 6 months postoperatively [MD=-0.21, 95% CI (-0.29, -0.12), P < 0.00001, heterogeneity P = 0.34, I²=0%], and cost [MD=-3.23 thousand yuan, 95% CI (-4.26, -2.19), P < 0.00001, heterogeneity P = 0.0003, I²=92%]. There were no statistically significant differences in overall complication rate [RR = 0.88, 95% CI (0.62, 1.23), P = 0.45, heterogeneity P = 0.11, I²=44%], overall infection event rate [RR = 0.96, 95% CI (0.36, 2.56), P = 0.93, heterogeneity P = 0.62, I²=0%] and recurrence rate [RR = 0.75, 95% CI (0.28, 1.99), P = 0.56, heterogeneity P = 0.44, I²=0%] between the two groups. The results of the TSA indicated that the observed lower seroma occurrence rate in the non-fixation group compared to the fixation group requires further validation through the inclusion of additional RCTs.ConclusionMesh non-fixation in TAPP inguinal hernia repair is deemed safe and does not elevate the risk of hernia recurrence. However, given certain limitations in this study, future comprehensive and reliable validation will require further multicenter, high-quality, large-sample double-blind RCTs.

Interventions for Adjunctive Care in Patients With Inflammatory Bowel Disease and Permanent Ileostomy: A Systematic Review.

The evidence for the management of patients with Crohn's disease (CD) and permanent ileostomy (PI) is limited. We aimed to summarize the interventional studies related to the provision of adjunctive ostomy care in this population. MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to January 5, 2024. Eligible studies were non-randomized or randomized controlled trials (RCTs), or comparative cohort studies predominantly recruiting participants with CD and/or ulcerative colitis (UC) with PI assessing interventions for the management of high stoma output, disease recurrence, peristomal skin care, pouching systems, behavioral interventions, mental health support, and diet. Out of 3217 records, 6 were eligible and all were RCTs (n = 95). Out of these, 5 adopted a crossover design, and 1 study was a double-blind parallel-group RCT. All except 1 were published more than 20 years ago (1976-2003). Two studies exclusively included patients with UC, one included CD, and the remaining included both UC and CD. Four studies assessed pharmacological interventions (loperamide, 5-aminosalysilate [5-ASA], azodisal sodium, and budesonide), one assessed oral supplement with different osmolarities, and one assessed dietary intervention (unrefined vs refined carbohydrate). A decrease in ileostomy output was the primary outcome of interest in 4 studies. None of the studies assessed interventions for peristomal skin care, quality of life, stoma pouching systems, behavioral interventions, mental health, or CD recurrence. This study highlights that the evidence base to inform care for patients with IBD and PI is almost non-existent. There is an urgent need for focused research in this area to inform evidence-based treatment decisions.

Comparable bleeding and inflammation outcomes between heparin-coated and uncoated minimal invasive extracorporeal circuits in isolated coronary artery bypass surgery - A double-blinded randomized control trial.

Minimally invasive extracorporeal circulation has been shown to be non-inferior or even superior to conventional cardiopulmonary bypass circuits in isolated coronary artery bypass grafting, but there is little evidence whether the addition of a heparin-coated circuit can further reduce the inflammatory response and amount of bleeding in these patients. A single-center randomized control trial enrolled 49 adult patients scheduled to undergo isolated coronary artery bypass grafting with minimally invasive extracorporeal circulation (MiECC) between January 2015 and December 2018. Patients were randomized 1:1 to either the heparin-coated circuit group, or the uncoated (control) circuit group. The primary outcome was chest tube output 18h after weaning from MiECC, and secondary outcomes included inflammatory (TNF-α, IL-6, IL-8, IL-10) and complement (C3a, C4d, C5a, sC5b-9) biomarkers, platelet count and function (D2D, TAT, SDC1, PF4), number of transfused blood products, and 30-day survival. Patients were randomized to undergo myocardial revascularization using heparin-coated circuits (n = 25), and to the uncoated MiECC circuit (n = 24), with comparable baseline demographics. No significant difference was observed in chest tube output and for all secondary outcomes. IL-6 and IL-8 were increased from baseline at 18h after weaning (effect size 0.29 and 0.05, respectively) and sC5b-9 was lower (effect size 0.11) in the heparin-coated than in the uncoated MiECC, although not significantly different. Compared with an uncoated MiECC circuit, heparin-coated MiECC circuit was not associated with a reduction in postoperative bleeding, transfusion, inflammation, complement activation, and platelet biomarkers, following isolated coronary artery bypass grafting.

The Effect of Ginkgo Biloba Extract on Oxidative Stress, Anti-Inflammatory and Antiapoptotic in Vitiligo Treated with Topical Desoxymethasone

Vitiligo is a progressive and multifactorial condition of skin, mucosa, and hair depigmentation. Loss of functional melanocytes leads to the appearance of white macules on the skin, often affecting the lips and genitalia. The impact extends to psychological stress, decreased quality of life, and risk of psychiatric morbidity. Various therapeutic strategies have been designed to inhibit the immune response in vitiligo to reduce melanocyte damage while increasing melanocyte repopulation. There is no standardized method of evaluating treatment outcomes in vitiligo patients. Herbal medicines several studies have shown that GB also has many benefits for health and healing skin diseases, one of which is used in treating vitiligo. Therefore, this study aimed to evaluate the potential of Ginkgo biloba extract as a therapeutic supplement in enhancing the positive effects of desoxymethasone on vitiligo. Using a double-blind randomized control trial clinical trial research design, 26 subjects were divided into treatment and control groups. The control group received standard vitiligo therapy with topical desoxymethasone and placebo, while the treatment group received topical desoxymethasone plus Ginkgo biloba extract. Melanin index, VASI score, MDA, TNF-α, CD8 expression, and caspase 3 were measured before and after treatment. The results showed that the administration of Ginkgo biloba extract had a significant effect in reducing MDA, TNF-α, CD8 expression, and caspase 3 levels, and improving melanin index and erythema in vitiligo patients who received topical desoxymethasone therapy. These findings demonstrate the positive potential of Ginkgo biloba extract as an adjunct to vitiligo therapy, resulting in favorable clinical and molecular impacts in patients undergoing combination treatments.

Antibacterial Efficacy of Benzalkonium Chloride Gel with Tongue Brush on S. Mutans and L. Acidophilus and Tongue Coating – A Randomized Controlled Trial

Introduction: The tongue microbiota, like other parts of the oral cavity, plays a significant role in the development of dental caries. S. mutans and L. acidophilus species, are associated with the initiation and progression of dental caries.  Aim: To assess the efficacy of benzalkonium Chloride gel along with tongue cleaning aids in the reduction of tongue coating and bacterial count on dorsal surface of the tongue.  Materials and Methods: A double blinded randomized control trial was conducted among 17-25 years old college students. A total of 60 participants were randomly divided into 4 groups according to their use of tongue cleaning aids as follows: Group A, Tongue Brush Alone; Group B, Tongue Brush with Chlorhexidine Mouthwash (Clohex ADS); Group C, Tongue Brush with Chlorhexidine Gel (Hexigel); and Group D, Tongue Brush with Benzalkonium Chloride Gel. The Winkel tongue coating index (WTCI) was used to measure the tongue coating at baseline and at 14th day and the participant’s tongue coatings on dorsal surface were sampled using swab method, and the number of S. mutans and L. acidophilus colonies were counted before and after intervention.  Results: Both the Hexigel group and Benzalkonium chloride gel group reduced both the bacterial load and tongue coating at 14th Day compared to the baseline data.  Conclusion: This study suggests that usage of Tongue brush along with Benzalkonium Chloride gel decreased the tongue coating and the number of bacteria on the dorsal tongue surface.

Use of Tear Substitutes to enhance the Image Quality of the Optic Nerve and Retina by Optical Coherence Tomography

&amp;lt;i&amp;gt;Background &amp; Objectives&amp;lt;/i&amp;gt;: Dry eye disease (DED) has become very prevalent, with the increased usage of internet and video terminals. The present study was carried out to compare the efficacy of tear substitutes in enhancing the signal strength of measurements of optic nerve head, retinal nerve fiber layer and macula by Optical coherence tomography (OCT), and resultant change in image quality. Thus proving the role of artificial tear substitutes in increasing the diagnostic accuracy of Optical coherence tomography (OCT) measurements. &amp;lt;i&amp;gt;Methods&amp;lt;/i&amp;gt;: A double blinded randomized control trial was performed on one hundred and fifty patients needing optical coherence tomography. They were randomly allocated into three groups to receive any one of the three tear substitutes Group 1 –Sodium hyaluronate (Molecular Weight M Wt 799.6g/mol) Group 2 – Poly ethylene glycol (Molecular Weight M Wt 400g/mol), Group -3 Hydroxy Propyl Methyl cellulose (Molecular Weight M Wt 1261.4 g/mol); Measurement of signal strength for optic nerve head, retinal nerve fiber thickness RNFL and sub foveal thickness SFT was done before and after instillation of tear substitutes. Data was analyzed using the Statistical Package for Social Sciences SPSS 22 version software. P value &amp;lt;0.05 was considered statistically significant. &amp;lt;i&amp;gt;Results&amp;lt;/i&amp;gt;: The groups were comparable with respect to mean age and gender distribution. The mean signal strength (SS) of Optic Nerve Head (ONH) evaluation improved in all the groups in both eyes. The increase was the highest in Group II in both eyes. The increase in retinal nerve fiber layer thickness [RNFL] was seen in both eyes in all the groups. Improvement in macular evaluation sub foveal thickness (SFT) was seen in Group II of both eyes and group III in the Left eye. &amp;lt;i&amp;gt;Interpretation and Conclusion&amp;lt;/i&amp;gt;: All tear substitutes improved the quality of the image but the improvement varied with regard to the parameters measured, thus proving artificial tear application is an essential for Optical coherence tomography OCT measurements in persons prone to dry eye This reduces the scope for error due to bad images and thereby the possibility of misdiagnosis of ophthalmic disease.

A double blinded randomized prospective trial of comparison between control and study group, nefopam versus tramadol on shivering scores after spinal anesthesia in patients undergoing Transurethral resection of prostate

IntroductionShivering is a common and distressing complication that can occur after subarachnoid block (SAB) in patients, particularly those undergoing transurethral resection of the prostate (TURP) due to the use of irrigating fluid and older age group. This study aims to compare the effectiveness of nefopam and tramadol in reducing intraoperative shivering compared to a control group, in Indian patients. MethodologyThis study is a double-blinded randomized control trial with a total of 99 patients undergoing elective TURP under SAB were enrolled. The patients were randomly divided into three groups (GT, GN, and GC): GT received tramadol (0.5 mg kg-1) and GN received nefopam (0.15 mg kg-1). Both tramadol and nefopam were premixed into 100 ml of normal saline (NS) and GC received 100 ml NS, given over 15 min just before SAB. The induction protocol was the same for all groups, and shivering score, hemodynamic parameters, and body temperature (BT) were recorded. ResultsThe overall incidence of shivering was 29.67 % (27/91), with the lowest incidence being in GN (16.67 %, 5/30), followed by GT (22.58 %, 7/31) and GC (50 %, 15/30). Both nefopam and tramadol resulted in a significant (p < 0.05) decrease in the incidence of shivering compared to control. Among the hemodynamic parameters and BT, no significant difference was seen between GT, GN, and GC (p > 0.05). ConclusionBoth nefopam and tramadol were effective in reducing the incidence but the severity was controlled better with nefopam during TURP under SAB.

Impact of Nutrition Supplementation on linear growth among 12–18 months children of Belagavi city: A randomized control trial

BackgroundAdequate nutrition is one of the most important factors influencing growth & immunity. Bovine colostrum (BC) is the first milk produced after birth of a calf and is a rich natural source of macronutrients, micronutrients, immunoglobulins, growth factors and peptides with anti-microbial activity. ObjectiveThe current study was conducted to test the hypothesis whether BC supplementation would lead to an increase in linear growth of children of age 12–18 months. The secondary objectives were 1) To measure biomedical parameters among 12–18 months children in the 2 groups, i.e., BC and control group. 2) To assess the acceptability and tolerability of BC among children. Materials & methodsA double blinded randomized control trial was conducted among children in the age group of 12–18 months. A total of 78 participants were included and were randomly divided into experiment and control groups. Anthropometric measurements and biochemical parameters were measured before and after intervention. The acceptability and tolerability of BC was assessed through a questionnaire filled by the mothers of study participant. ResultsThere was a significant difference observed in Body mass index (BMI), Chest circumference and Mid upper arm circumference in the BC group but there was not any significant difference found in biochemical parameters. Mothers of study participant reported high acceptability and no side effects of the intervention. ConclusionSupplementation of BC in children's diet lead to improved anthropometric outcomes in children of Belagavi city and was acceptable by them.

A Systematic Review and Meta-Analysis of Randomized Trials to Evaluate the Impact of Exercise on Heart Rate Variability Post-Bariatric Surgery.

Bariatric surgery is an approach used to treat patients with obesity in a small minority of eligible patients. Non-pharmacological therapies are important to maintain decent health status post-bariatric surgery. We performed a systematic review with meta-analysis to evaluate the effects of exercise on heart rate variability (HRV) in patients submitted to bariatric surgery. The searches were made via MEDLINE/PubMed (via the National Library of Medicine), EMBASE, Web of Science, and Scopus databases. We included non-blind, single-, or double-blind randomized control trials in patients older than 18 years of age submitted to bariatric surgery. The intervention group should be submitted to an exercise training protocol, including aerobic, strength, and other exercise modality after bariatric surgery. We documented 245 studies, and after screening and eligibility phases, only 4 were included. We observed no significant change for the SDNN: subtotal = 19.74 (CI: -4.98, 44.45), p = 0.12, I2 = 85% (very low quality of evidence); pNN50: subtotal = 13.09 (CI: -9.17, 35.35), p = 0.25, I2 = 93% (very low quality of evidence); RMSSD: subtotal = 8.44 (CI: -3.61, 25.50), p = 0.17, I2 = 95% (very low quality of evidence); SD1: subtotal = 9.36 (CI: -4.48, 23.21), p = 0.19, I2 = 96% (very low quality of evidence). We could not detect significant effects of exercise on resting HRV after bariatric surgery. The low certainty of the results via the evidence level analysis suggest further studies might be beneficial.

The relationship between blinding integrity and medication efficacy in randomised-controlled trials in patients with anxiety disorders: A systematic review and meta-analysis.

Blinding is thought to minimise expectancy effects and biases in double-blind randomised-controlled trials (RCTs). However, whether blinding integrity should be assessed and reported remains debated. Furthermore, it is unknown whether blinding failure influences the outcome of RCTs in anxiety disorders. We carried out a systematic review to understand whether blinding integrity is assessed and reported in anxiolytic RCTs. A secondary aim was to explore whether blinding integrity is associated with treatment efficacy. Our protocol was pre-registered (PROSPERO CRD42022328750). We searched electronic databases for placebo-controlled, randomised trials of medication in adults with generalised and social anxiety disorders, and in panic disorder, from 1980. We extracted data regarding blinding integrity and treatment efficacy. Risk of bias was assessed with the Cochrane risk of bias tool. Where possible, we subsequently calculated Bang's Blinding Index, and assessed the association between blinding integrity and treatment effect size. Of the 247 RCTs that met inclusion criteria, we were able to obtain assessments of blinding integrity from nine (3.64%). Overall, blinding failed in five of these trials (55.56%), but blinding was intact in 80% of placebo arms. We found a significant association between reduced blinding integrity among assessors and increased treatment effect size (betas < -1.30, p's < 0.001), but this analysis involved only four studies of which two were outlying studies. In patients, we saw a non-significant trend where reduced blinding integrity in the placebo groups was associated with increased treatment efficacy, which was not present in active medication arms. [Correction added on 19 August 2024, after first online publication: Results of the RCTs and its assessment of blinding integrity have been updated.] CONCLUSION: Consistent with work in other psychiatric disorders, blinding integrity is rarely reported in anxiolytic RCTs. Where it is reported, blinding appears to often fail. We found signals that suggest unblinding of clinician assessors (driven by two studies with complete unblinding), and of patients in placebo arms, might be associated with larger treatment effect sizes. We recommend that data regarding blinding integrity, along with the reasons patients and assessors offer for their beliefs regarding group allocation, are systematically collected in RCTs of anxiolytic treatment.

The Effectiveness of Combined Prebiotic and Postbiotic Moisturiser as an Adjuvant Therapy in Improving Maskne

Personal protective equipment (PPE) has become the new social norm as part of COVID-19 protection since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, but it has had an impact on the skin barrier, particularly the face. Maskne refers to acne eruptions around the facemask area. The combination of friction, repeated pressure, sweat, or stress on the skin from wearing the mask results in acne or exacerbates pre-existing acne. This study aimed to analyse the effectiveness of a combined prebiotic and postbiotic moisturiser (CPPM) as an adjuvant therapy for improving maskne. This was a double-blind randomised control trial with systematic random sampling of 1:1 to receive either CPPM or placebo moisturisers. From December 2022 to May 2023, patients diagnosed with maskne at the Dermatology Clinic, Hospital Al-Sultan Abdullah, Universiti Teknologi MARA (UiTM), Bandar Puncak Alam, Selangor, Malaysia were studied. Subjects were assessed at baseline, week 2 and 4 after the application of moisturisers, using modified global acne grading system (mGAGS) and Cardiff Acne Disability Index (CADI) score. A total of 150 patients completed the study. Using the mGAGS score, compared to baseline, the mean score reduction was statistically significant at week 4 [5.33 (±4.06) vs 1.13 (±4.33); p&lt; 0.001] in the CPPM arm compared to the placebo arm. In terms of CADI score, compared to baseline, there was also a significant reduction in mean score at week 4 [2.23 (±2.53) vs 0.55 (±2.59); p&lt; 0.001] in the CPPM arm compared to the placebo arm. This study found that using CPPM as an adjuvant moisturiser improved maskne significantly.

Oral Hydroalcoholic Extract of Licorice for Management of Mild to Moderate Coronavirus Disease-19 Patients: A Double-Blind Randomized Clinical Trial

Background: Licorice is proposed as a treatment option for coronavirus disease-19 (COVID-19) by inhibiting the virus binding, penetration and replication; it also modulates various cellular signaling pathways. In this double-blind randomized-controlled trial, efficacy of Licorice hydroalcoholic extract oral formulation has been evaluated in patients with mild–moderate COVID-19in an outpatient clinic. Methods: A total of 40 mild to moderate outpatient Covid-19cases were randomly assigned into either Licorice or placebo groups (n=20 in each). Patients in Licorice group were given 700 mg capsules of hydroalcoholic extract of Licorice, trice a day for 2 weeks, while controls were given placebo capsules that were filled with Avicel (microcrystalline cellulose). Blood samples were collected from all participants before starting the medication and on days three, seven, and 14 for laboratory parameters including quantitative C-reactive protein (CRP), WBCs, lymphocytes, and neutrophils counts. The clinical symptoms were also recorded. Results: Our results showed that Licorice extract significantly decreased the frequency of cough on day seven (P=0.004) and the frequency of dyspnea on day three (P=0.02). No significant differences were found in the frequency of nausea, diarrhea, body pain, sore throat, runny nose, dizziness, lethargy, and loss of taste or smell between the two groups. Patients in Licorice group showed significantly higher oxygen saturations on days three, seven, and 14. Other laboratory parameters did not show any changes between the two groups. Conclusion: Licorice extract improved some clinical symptoms such as cough and dyspnea while only increased the oxygen saturation. Further studies with larger sample sizes at different stages of Covid-19are suggested.

Non-invasive brain stimulation for treatment-resistant schizophrenia: protocol of a systematic review and network meta-analysis

BackgroundNon-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia.MethodsWe will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel–Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach.DiscussionOur network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients.Systematic review registrationPROSPERO-ID CRD42023410645.

The Effect of Palmitoylethanolamide (PEA) on Skeletal Muscle Hypertrophy, Strength, and Power in Response to Resistance Training in Healthy Active Adults: A Double-Blind Randomized Control Trial

BackgroundPalmitoylethanolamide (PEA) has analgesic/anti-inflammatory properties that may be a suitable alternative to over-the-counter (OTC) non-steroidal analgesics/anti-inflammatories. While OTC pain medications can impair strength training adaptations, the mechanism of action of PEA is distinct from these and it may not negatively affect skeletal muscle adaptations to strength training.MethodsThe primary aim of this study was to investigate the effects of daily PEA supplementation (350 mg Levagen + equivalent to 300 mg PEA) combined with 8-weeks of resistance training on lean body mass with secondary aims addressing strength, power, sleep, and wellbeing compared to placebo (PLA) in young, healthy, active adults. In a randomized, controlled, double-blinded trial, 52 untrained, recreationally active participants aged 18–35 y were allocated to either the PEA or PLA groups. Participants consumed either 2 × 175 mg Levagen + PEA or identically matched maltodextrin capsules during an 8-week period of whole-body resistance training. This trial assessed the pre- to post- changes in total and regional lean body mass, muscular strength (1-RM bench, isometric mid-thigh pull), muscular power [countermovement jump (CMJ), bench throw], pain associated with exercise training, sleep, and wellbeing compared with the PEA or PLA condition.Results48 Participants were included in the final intention to treat (ITT) analysis and we also conducted per protocol (PP) analysis (n = 42). There were no significant between-group differences for total or regional lean muscle mass post-intervention. There was a significantly higher jump height (CMJ) at week 10 in the PEA group compared to the PLA (Adjusted mean difference [95% CI] p-value; ITT: − 2.94 cm [− 5.15, − 0.74] p = 0.010; PP: − 2.93 cm [− 5.31, − 0.55] p = 0.017). The PLA group had higher 1-RM bench press post-intervention compared with the PEA group (ITT: 2.24 kg [0.12, 4.37] p = 0.039; PP: 2.73 kg [0.40, 5.06] p = 0.023). No significant treatment effects were noted for any of the other outcomes.ConclusionPEA supplementation, when combined with 8 weeks of strength training, did not impair lean mass gains and it resulted in significantly higher dynamic lower-body power when compared with the PLA condition.Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR: ACTRN12621001726842p).

Effectiveness of methylene blue as a local anesthetic and analgesic in perianal operations: A prospective double-blind randomized control trial

BackgroundPerianal operations often result in significant postoperative pain, which negatively affects patient comfort and recovery. The search for effective pain relief options has led to the investigation of methylene blue, a biological stain with potential analgesic properties. AimsThis study aimed to evaluate the analgesic and anaesthetic effects of a mixture of methylene blue and lidocaine compared to plain lidocaine in the management of postoperative pain after perianal operations. MethodsA prospective, double-blinded, randomized controlled trial was conducted at a single center between 2015 and 2023. A total of 727 adult patients undergoing perianal surgical operations were randomly assigned to two groups: the experimental group received a solution of methylene blue and lidocaine, while the control group received plain lidocaine. Pain levels were assessed using the Visual Analog Scale (VAS), and follow-up visits and phone calls were conducted. The analysis included 727 participants who underwent operations for perianal abscess, fistula, fissure, and haemorrhoid. The participants were divided into the experimental group (N=329) and the control group (N=398). The data were analyzed using SPSS version 28, applying descriptive and inferential statistical methods. ResultsThe study included a total of 727 patients, with a mean age of 47 years (ranging from 18 to 90 years). Among the patients, 56.5% were males and 43.5% were females. The two groups showed significant differences in terms of postoperative analgesic use and pain-free days (p<0.001). Specifically, the methylene blue group had lower Visual Analog Scale (VAS) scores compared to the control group (p<0.05, p<0.001), respectively. No significant differences in immediate complications were observed between the two groups. ConclusionMethylene blue is an effective intervention for reducing postoperative pain after perianal operations, potentially decreasing the need for additional pain medication. The findings of this study suggest that methylene blue has a promising role in pain management without an increase in complications.

Efficacy and safety of topical capsaicin in the treatment of osteoarthritis pain: A systematic review and meta-analysis.

Osteoarthritis (OA) affects hundreds of millions of people worldwide. The objective was to critically appraise the efficacy and safety of topical capsaicin in reducing pain in OA. MEDLINE (PubMed) and Embase (Ebsco) were searched from inceptions until February 2023. The eligibility criteria included randomized controlled trials (RCTs), evaluating topical capsaicin in OA patients. Standard Cochrane methods were used to extract data and to appraise eligible studies. Eight double-blind RCTs involving 498 patients were included. Five trials (62.5%) were at an overall low risk of bias, and three (37.5%) were at a high risk of bias. Meta-analysis showed that, in various OA patients, compared with placebo, topical capsaicin (0.0125%-5%) may reduce pain severity measured with visual analog scale (standardized mean difference = -0.84, 95% confidence intervals [CIs] = -1.48 to -0.19, p = 0.01; eight studies). However, topical capsaicin may increase burning sensation at the application site (risk ratio = 5.56, 95% CI = 1.75-17.69, p = 0.004, numbers needed to harm = 3; five studies) when compared with placebo. Limitations include short study durations, small sample sizes, high heterogeneity, and overall low-to-very-low certainty of the evidence. Topical capsaicin may reduce OA pain at follow-ups of up to 3 months. Larger trials, potentially evaluating capsaicin in combination with phytopharmaceuticals having anti-inflammatory effects, with longer follow-ups might be needed to reduce the existing uncertainties. Topical capsaicin might be recommended for short-term management of pain in OA patients intolerant to nonsteroidal anti-inflammatory drugs.

Sacubitril/valsartan and cardiovascular biomarkers among patients with recent COVID-19 infection: The PARACOR-19 randomized clinical trial.

The PARACOR-19 randomized controlled trial (RCT) was designed to examine the effects of sacubitril/valsartan on markers of cardiac injury, inflammation, structure, and function among patients who have recovered from acute coronavirus disease 2019 (COVID-19) infection. PARACOR-19 was a single-centre, double-blind RCT of patients with cardiovascular risk factors and a history of COVID-19 infection 4-16 weeks prior to enrolment. Patients were randomized to sacubitril/valsartan (titrated to the maximum dose of 97/103 mg twice daily) versus matching placebo. Co-primary endpoints were change from baseline to 12 weeks in high-sensitivity cardiac troponin T (hs-cTnT) and soluble ST2 (sST2). Exploratory endpoints included change from baseline to 12 weeks in additional circulating biomarkers. Overall, 42 patients were randomized between August 2021 and March 2023 (n = 20 sacubitril/valsartan, n = 22 placebo). Median (25th-75th) time from COVID-19 diagnosis to enrolment was 67 (48-80) days. Median age was 67 (62-71) years, 48% were female, and 91% were White. Compared with placebo, sacubitril/valsartan did not have a significant effect on the co-primary endpoints of change from baseline in hs-TnT and sST2 (all p ≥ 0.29). In exploratory analyses, sacubitril/valsartan led to a 46% greater reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and 51% greater reduction in C-terminal telopeptide of collagen type I (CITP). Permanent drug discontinuation occurred in four patients in the sacubitril/valsartan group and three patients in the placebo group. There were no deaths and one patient was hospitalized in each group. In this pilot RCT of patients who recovered from acute COVID-19, sacubitril/valsartan did not lower hs-cTnT or sST2 compared with placebo. Exploratory analyses suggested potential benefits of sacubitril/valsartan on cardiac wall stress and collagen turnover as measured by NT-proBNP and CITP. Sacubitril/valsartan was well tolerated. ClinicalTrials.gov NCT04883528.

Effects of short foot exercises with ultrasound bio-feedback on motor learning and foot alignment: A double blinded randomized control trial.

Short foot exercises (SFE) take a long time to master and require a feedback tool to improve motor learning. This study aimed to investigate the effect of bio-feedback of talonavicular joint movements in learning SFE with ultrasound (US) imaging. This study included thirty-one healthy volunteers and was designed as a double-blind randomized control trial. Subjects were randomly assigned to one of two groups: the control group, which performed SFE under verbal instruction, and the US bio-feedback (USBF) group, which performed SFE with real-time bio-feedback of the talonavicular joint alignment. All subjects underwent two sessions of 5 minutes each, and SFE was performed as a self-exercise, between sessions, for one week. The difference in foot length and navicular height were assessed at baseline, after Session1, before Session2, and one week after Session2. These differences were compared between the two groups using the Mann-Whitney U test. In terms of navicular height change, the USBF group (7.5 ± 4.3 mm) was significantly higher than the control group (4.2 ± 3.3 mm) one week after session 2 (p= 0.04, effect size = 0.86). SFE with USBF is an effective intervention for performing SFE.

Efficacy and safety of aripiprazole or bupropion augmentation and switching in patients with treatment-resistant depression or major depressive disorder: A systematic review and meta-analysis of randomized controlled trials.

To report the first and largest systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate the efficacy and safety of aripiprazole or bupropion augmentation and switching in patients with treatment-resistant depression (TRD) or major depressive disorder(MDD). We conducted a systematic literature retrieval via PubMed, Embase, Web of Science, and Cochrane until April 2023 for RCT, which evaluated the efficacy and safety of aripiprazole or bupropion augmentation and switching for patients with TRD or MDD. Outcomes measured were changes in the Montgomery-Asberg Depression Rating Scale (MADRS), response and remission rate, and serious adverse events. Five RCTs, including 4480 patients, were included for meta-analysis. Among them, two RCTs were rated as "high risk" in three aspects (allocation concealment, blinding of participants and personnel and blinding of outcome assessment) because of the non-blind method, and the quality evaluation of the remaining works of literature was "low risk". Augmentation treatment with Aripiprazole (A-ARI) was associated with a significant higher response rate compared with augmentation treatment with bupropion (A-BUP) (RR: 1.15; 95% CI: 1.05, 1.25; P = 0.0007; I2 = 23%). Besides, A-ARI had a significant higher remission rate compared with switching to bupropion (S-BUP) (RR: 1.22; 95% CI: 1.00, 1.49; P = 0.05; I2 = 59%) and A-BUP had a significant higher remission rate compared with S-BUP (RR: 1.20; 95% CI: 1.06, 1.36; P = 0.0004; I2 = 0%). In addition, there was no significant difference in remission rate(RR: 1.05; 95% CI: 0.94, 1.17; P = 0.42; I2 = 33%), improvement of MADRS(WMD: -2.07; 95% CI: -5.84, 1.70; P = 0.28; I2 = 70%) between A-ARI and A-BUP. No significant difference was observed in adverse events and serious adverse events among the three treatment strategies. A-ARI may be a better comprehensive antidepressant treatment strategy than A-BUP or S-BUP for patients with TRD or MDD. More large-scale, multi-center, double-blind RCTs are needed to further evaluated the efficacy and safety of aripiprazole or bupropion augmentation and switching treatment strategies.