Trial Group Research Articles

Assessing effectiveness of WhatsApp messaging program in oral hygiene care for orthodontic patients: A randomised controlled trial.

To evaluate the difference in the oral hygiene status of participants with fixed appliances between a 'weekly WhatsApp application oral hygiene message reminders' trial group and a 'verbal instructions' control group over a follow-up duration of 12 weeks. Prospective, single-blind, randomised controlled trial with an allocation ratio of 1:1 over a 12-week follow-up. Government Orthodontic Unit, Raub Dental Clinic, Raub, Pahang, Ministry of Health, Malaysia. A total of 40 patients aged 13-25 years undergoing orthodontic treatment with fixed appliances. The 40 patients were recruited and randomly allocated to a control (n = 20) or trial group (n = 20). Participants in the trial group received weekly oral hygiene reminders via the WhatsApp application for 12 weeks, while the control group did not receive any reminders. The primary outcome was oral hygiene, which was measured by the single-blinded examiner using the Orthodontic Plaque Index (OPI) at three orthodontic check-ups: baseline (T0); 6-week follow-up (T1); and 12-week follow-up (T2). The mean age was 17 years, and 80% were female patients. At the end of the 12-week follow-up, improvements in OPI scores were observed, regardless of the intervention. At T2, the median OPI score for the trial group (n = 20) was 0 (interquartile range [IQR = 0) while that for the control group (n = 20) was 2 (IQR = 0). A Mann-Whitney U test revealed a statistically significant difference (P <0.05), with effect size r = 0.87 between the control and trial groups, whereby the latter witnessed marked improvement in OPI throughout the visits. No harms or adverse effects occurred in this trial. The short-term findings demonstrated that participants receiving regular reminders of oral hygiene via WhatsApp messaging had a significant improvement in oral hygiene compared to the control group.

What do carers of people with high-grade glioma perceive could improve their preparedness to care, and what additional support do they require?

Concerning levels of stress, strain, and poorer mental health are observed in family carers of patients diagnosed with high-grade glioma (HGG). Understanding the reported unmet needs of these carers will enable future interventions to address such needs to improve their preparedness for care and well-being. In this secondary analysis, we aimed to explore: (i) what carers of people with HGG perceive could improve their preparedness to care; and (ii) what needs carers reported they required additional support with. Responses from 188 carers of patients with HGG participating in a randomized controlled trial of the Care-IS intervention were analyzed to identify reported unmet needs. Of this larger sample, 92 participants answered a qualitative question seeking to identify perceived unmet needs in carer preparedness over 12 months. These responses comprised the data for the current secondary analysis. Content analysis was used to analyze the qualitative data and observe trends across participant responses. Five overarching themes were identified: carer needs, providing emotional and practical care, coping with uncertainty, coping with the consequences of illness progression, and processing and supporting end-of-life care. Notably, the content analysis identified differences in response numbers between groups in the Care-IS trial, particularly with the control group having more needs regarding illness progression and end-of-life care. Future interventions aimed at improving the well-being and preparedness of carers of people with HGG should consider providing better support centered on carer needs, their changed circumstances, living with uncertainty, and care transition.

Assessing the effectiveness of membrane sweeping combined with cervical massage for term pre-induction cervical ripening: A single experimental study

Massage of the cervical region entails applying light pressure to the cervix to trigger the uterine contractions. Membrane sweeping, often called cervical sweeping or membrane stripping, releases hormones that may start labor by removing the amniotic sac from the uterine wall. Although membrane sweeping is helpful in several clinical trials, no studies have examined how effective cervical massage is when combined with membrane sweeping.This research compared the effectiveness of membrane sweeping and cervical massage as cervical ripening techniques in post-dated pregnancies before labor induction in specialized clinics. A total of 150 low-risk singleton pregnancies with a Modified Bishop Score (MBS) of fewer than five at 38 weeks of gestation were included. The experimental group received membrane sweeping with cervical massage, and the control group, which just received membrane sweeping, was randomly allocated to the participants. 48 hours after the intervention, changes in the MBS were used to gauge cervical favorability. Neonatal morbidity, membrane rupture, intrapartum and postpartum infections, and other complications were assessed.The mean ages and MBS of the primigravidae in the two research groups at induction were similar. After the intervention, the trial group's mean MBS was significantly higher than the control groups. Because of this, primigravidae observed a substantial change in the MBS after the operation. The experimental group's adverse effects and neonatal morbidity were comparable, except cardiotocographic abnormalities were observed more often in the control group.In some cases, when membrane sweeping cannot be conducted because of a closed cervical os, cervical massage combined with membrane sweeping appears successful and secure. A significant choice for obstetric care, this technique may aid cervical softening in post-dated pregnancies.

Inhibition of CD40L with Frexalimab in Multiple Sclerosis

BackgroundThe CD40–CD40L costimulatory pathway regulates adaptive and innate immune responses and has been implicated in the pathogenesis of multiple sclerosis. Frexalimab is a second-generation anti-CD40L monoclonal antibody being evaluated for the treatment of multiple sclerosis.MethodsIn this phase 2, double-blind, randomized trial, we assigned, in a 4:4:1:1 ratio, participants with relapsing multiple sclerosis to receive 1200 mg of frexalimab administered intravenously every 4 weeks (with an 1800-mg loading dose), 300 mg of frexalimab administered subcutaneously every 2 weeks (with a 600-mg loading dose), or the matching placebos for each active treatment. The primary end point was the number of new gadolinium-enhancing T1-weighted lesions seen on magnetic resonance imaging at week 12 relative to week 8. Secondary end points included the number of new or enlarging T2-weighted lesions at week 12 relative to week 8, the total number of gadolinium-enhancing T1-weighted lesions at week 12, and safety. After 12 weeks, all the participants could receive open-label frexalimab.ResultsOf 166 participants screened, 129 were assigned to a trial group; 125 participants (97%) completed the 12-week double-blind period. The mean age of the participants was 36.6 years, 66% were women, and 30% had gadolinium-enhancing lesions at baseline. At week 12, the adjusted mean number of new gadolinium-enhancing T1-weighted lesions was 0.2 (95% confidence interval [CI], 0.1 to 0.4) in the group that received 1200 mg of frexalimab intravenously and 0.3 (95% CI, 0.1 to 0.6) in the group that received 300 mg of frexalimab subcutaneously, as compared with 1.4 (95% CI, 0.6 to 3.0) in the pooled placebo group. The rate ratios as compared with placebo were 0.11 (95% CI, 0.03 to 0.38) in the 1200-mg group and 0.21 (95% CI, 0.08 to 0.56) in the 300-mg group. Results for the secondary imaging end points were generally in the same direction as those for the primary analysis. The most common adverse events were coronavirus disease 2019 and headaches.ConclusionsIn a phase 2 trial involving participants with multiple sclerosis, inhibition of CD40L with frexalimab had an effect that generally favored a greater reduction in the number of new gadolinium-enhancing T1-weighted lesions at week 12 as compared with placebo. Larger and longer trials are needed to determine the long-term efficacy and safety of frexalimab in persons with multiple sclerosis. (Funded by Sanofi; ClinicalTrials.gov number, NCT04879628.)

Modeling the association of bivariate interval-censored data under the additive hazards model

. Bivariate interval-censored failure time data occurs in many fields such as medical followup studies. In this article, we propose an estimation procedure for the association between two related interval-censored survival times when they follow a copula model jointly and the additive hazards model marginally. A simulation study was conducted for assessing the finite sample performance of the presented method and suggests that it works well in practical situations. The proposed method is applied to the AIDS Clinical Trial Group (ACTG) 181 data that motivated this research.

An Oral Interleukin-23–Receptor Antagonist Peptide for Plaque Psoriasis

BackgroundThe use of monoclonal antibodies has changed the treatment of several immune-mediated inflammatory diseases, including psoriasis. However, these large proteins must be administered by injection. JNJ-77242113 is a novel, orally administered interleukin-23–receptor antagonist peptide that selectively blocks interleukin-23 signaling and downstream cytokine production.MethodsIn this phase 2 dose-finding trial, we randomly assigned patients with moderate-to-severe plaque psoriasis to receive JNJ-77242113 at a dose of 25 mg once daily, 25 mg twice daily, 50 mg once daily, 100 mg once daily, or 100 mg twice daily or placebo for 16 weeks. The primary end point was a reduction from baseline of at least 75% in the Psoriasis Area and Severity Index (PASI) score (PASI 75 response; PASI scores range from 0 to 72, with higher scores indicating greater extent or severity of psoriasis) at week 16.ResultsA total of 255 patients underwent randomization. The mean PASI score at baseline was 19.1. The mean duration of psoriasis was 18.2 years, and 78% of the patients across all the trial groups had previously received systemic treatments. At week 16, the percentages of patients with a PASI 75 response were higher among those in the JNJ-77242113 groups (37%, 51%, 58%, 65%, and 79% in the 25-mg once-daily, 25-mg twice-daily, 50-mg once-daily, 100-mg once-daily, and 100-mg twice-daily groups, respectively) than among those in the placebo group (9%), a finding that showed a significant dose–response relationship (P<0.001). The most common adverse events included coronavirus disease 2019 (in 12% of the patients in the placebo group and in 11% of those across the JNJ-77242113 dose groups) and nasopharyngitis (in 5% and 7%, respectively). The percentages of patients who had at least one adverse event were similar in the combined JNJ-77242113 dose group (52%) and the placebo group (51%). There was no evidence of a dose-related increase in adverse events across the JNJ-77242113 dose groups.ConclusionsAfter 16 weeks of once- or twice-daily oral administration, treatment with the interleukin-23–receptor antagonist peptide JNJ-77242113 showed greater efficacy than placebo in patients with moderate-to-severe plaque psoriasis. (Funded by Janssen Research and Development; FRONTIER 1 ClinicalTrials.gov number, NCT05223868.)

A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis

BackgroundNonalcoholic steatohepatitis (NASH) is a progressive liver disease with no approved treatment. Resmetirom is an oral, liver-directed, thyroid hormone receptor beta–selective agonist in development for the treatment of NASH with liver fibrosis.MethodsWe are conducting an ongoing phase 3 trial involving adults with biopsy-confirmed NASH and a fibrosis stage of F1B, F2, or F3 (stages range from F0 [no fibrosis] to F4 [cirrhosis]). Patients were randomly assigned in a 1:1:1 ratio to receive once-daily resmetirom at a dose of 80 mg or 100 mg or placebo. The two primary end points at week 52 were NASH resolution (including a reduction in the nonalcoholic fatty liver disease [NAFLD] activity score by ≥2 points; scores range from 0 to 8, with higher scores indicating more severe disease) with no worsening of fibrosis, and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score.ResultsOverall, 966 patients formed the primary analysis population (322 in the 80-mg resmetirom group, 323 in the 100-mg resmetirom group, and 321 in the placebo group). NASH resolution with no worsening of fibrosis was achieved in 25.9% of the patients in the 80-mg resmetirom group and 29.9% of those in the 100-mg resmetirom group, as compared with 9.7% of those in the placebo group (P<0.001 for both comparisons with placebo). Fibrosis improvement by at least one stage with no worsening of the NAFLD activity score was achieved in 24.2% of the patients in the 80-mg resmetirom group and 25.9% of those in the 100-mg resmetirom group, as compared with 14.2% of those in the placebo group (P<0.001 for both comparisons with placebo). The change in low-density lipoprotein cholesterol levels from baseline to week 24 was −13.6% in the 80-mg resmetirom group and −16.3% in the 100-mg resmetirom group, as compared with 0.1% in the placebo group (P<0.001 for both comparisons with placebo). Diarrhea and nausea were more frequent with resmetirom than with placebo. The incidence of serious adverse events was similar across trial groups: 10.9% in the 80-mg resmetirom group, 12.7% in the 100-mg resmetirom group, and 11.5% in the placebo group.ConclusionsBoth the 80-mg dose and the 100-mg dose of resmetirom were superior to placebo with respect to NASH resolution and improvement in liver fibrosis by at least one stage. (Funded by Madrigal Pharmaceuticals; MAESTRO-NASH ClinicalTrials.gov number, NCT03900429.)

Post-disclosure distress among racial and ethnic groups in a preclinical AD trial.

Trialists need a thorough understanding of whether reactions to Alzheimer's disease (AD) biomarker information differ among racial and ethnic groups in preclinical AD trials. We used data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease Study to analyze cognitively unimpaired participants' responses on the Impact of Event Scale (IES) 24 to 72hours after amyloid disclosure. We fit a linear regression model to test whether mean IES scores differed among participants from specific racial and ethnic groups. We considered potential effect modification by amyloid status. Reactions to disclosure did not significantly differ among participant groups based on self-reported race and ethnicity. Although the results were not significant when stratified by amyloid status, all racial and ethnic groups except for participants self-reporting Hispanic/Latino ethnicity were observed to have higher mean IES in the elevated amyloid group. These results support continued use of current disclosure methods in preclinical AD trials.

Modified dietary fat intake for treatment of gallstone disease in people of any age.

The prevalence of gallstones varies between less than 1% and 64% in different populations and is thought to be increasing in response to changes in nutritional intake and increasing obesity. Some people with gallstones have no symptoms but approximately 2% to 4% develop them each year, predominantly including severe abdominal pain. People who experience symptoms have a greater risk of developing complications. The main treatment for symptomatic gallstones is cholecystectomy. Traditionally, a low-fat diet has also been advised to manage gallstone symptoms, but there is uncertainty over the evidence to support this. To evaluate the benefits and harms of modified dietary fat intake in the treatment of gallstone disease in people of any age. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE ALL Ovid, Embase Ovid, and three other databases to 17 February 2023 to identify randomised clinical trials in people with gallstones. We also searched online trial registries and pharmaceutical company sources, for ongoing or unpublished trials to March 2023. We included randomised clinical trials (irrespective of language, blinding, or status) in people with gallstones diagnosed using ultrasonography or conclusive imaging methods. We excluded participants diagnosed with another condition that may compromise dietary fat tolerance. We excluded trials where data from participants with gallstones were not reported separately from data from participants who did not have gallstones. We included trials that investigated other interventions (e.g. trials of drugs or other dietary (non-fat) components) providing that the trial groups had received the same proportion of drug or other dietary (non-fat) components in the intervention. We intended to undertake meta-analysis and present the findings according to Cochrane recommendations. However, as we identified only five trials, with data unsuitable and insufficient for analyses, we described the data narratively. We included five trials but only one randomised clinical trial (69 adults), published in 1986, reported outcomes of interest to the review. The trial had four dietary intervention groups, three of which were relevant to this review. We assessed the trial at high risk of bias. The dietary fat modifications included a modified cholesterol intake and medium-chain triglyceride supplementation. The control treatment was a standard diet. The trial did not report on any of the primary outcomes in this review (i.e. all-cause mortality, serious adverse events, and health-related quality of life). The trial reported on gallstone dissolution, one of our secondary outcomes. We were unable to apply the GRADE approach to determine certainty of evidence because the included trial did not provide data that could be used to generate an estimate of the effect on this or any other outcome. The trial expressed its finding as "no significant effect of a low-cholesterol diet in the presence of ursodeoxycholic acid on gallstone dissolution." There were no serious adverse events reported. The included trial reported that they received no funding that could bias the trial results through conflicts of interest. We found no ongoing trials. The evidence about the effects of modifying dietary fat on gallstone disease versus standard diet is scant. We lack results from high-quality randomised clinical trials which investigate the effects of modification of dietary fat and other nutrient intakes with adequate follow-up. There is a need for well-designed trials that should include important clinical outcomes such as mortality, quality of life, impact on dissolution of gallstones, hospital admissions, surgical intervention, and adverse events.

Effect of Heart-Healthy Dietary Patterns on Blood Pressure: A Systematic Review and Meta-analysis

Abstract OBJECTIVE To systematically evaluate the antihypertensive effect of dietary patterns of blood pressure management. METHODS The researchers searched the following databases: PubMed, Embase, the Cochrane Library, Web of Science, Scopus, China Knowledge Network, China Biomedical Literature Service, Wanfang Database, and Wipu.com by computer. Search for randomized controlled trials (RCTs) on the effects of Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH), and Chinese Heart-Healthy (CHH) diet on blood pressure in English and Chinese. RCTs, which were published from the time of the study until 02/2023. The investigators assessed and screened the literature before conducting a systematic evaluation and meta-analysis using Stata 15 software. RESULTS This study included 27 publications containing 7,409 study subjects, including 3,677 in the trial group and 3,732 in the control group. Dietary models for blood pressure management were effective in reducing systolic blood pressure [weighted mean difference (WMD) = −3.94, 95% confidence interval (CI): (−5.10, −2.77), P &amp;lt; 0.001] and diastolic blood pressure [WMD = −2.32, 95% CI: (−3.01, −1.63), P &amp;lt; 0.001]. CONCLUSIONS Dietary models for blood pressure management have a clear positive impact on blood pressure management in patients, and more high-quality studies with standardized design and long intervention period are needed in the future to provide strong evidence for healthy diet-based blood pressure management.

Examination of the Virulence of Actinobacillus pleuropneumoniae Serovar 16 in Pigs.

Different virulence variants of A. pleuropneumoniae are involved in the etiology of porcine pleuropneumonia. The purpose of the present trial was examination of the virulence of the Actinobacillus pleuropneumoniae A-85/14 strain, the type strain of serovar 16, in an animal challenge experiment. Thirty 12-week-old piglets seronegative for A. pleuropneumoniae were allocated into three trial groups each of 10 animals, and they were infected intranasally with 106, 107, or 108 colony forming units (cfu) of the strain, respectively. Clinical signs were recorded twice a day, and the animals were euthanized 6 days after the infection. Typical clinical signs and postmortem lesions of porcine pleuropneumonia were seen in the animals of each trial group; however, they were generally mild, and no significant differences could be seen between the three groups. Even 106 colony forming units of A. pleuropneumoniae A-85/14 strain could induce clinical signs and lesions. Based on these results, the type strain of serovar 16 of A. pleuropneumoniae must be regarded as a typical pathogenic strain of the species.

Sacubitril/valsartan improves the prognosis of acute myocardial infarction: a meta-analysis.

To systematically evaluate the effect of sacubitril/valsartan (SV) on the prognosis of patients with acute myocardial infarction (AMI), and to provide evidence for expanding the clinical application of SV. PubMed, EMbase, Web of Science, and Cochrane Library were searched from inception to October 2023 for randomized controlled trials (RCTs) of SV in patients with AMI. The article was screened and evaluated by the Cochrane 5.1.0 bias risk assessment tool. RevMan5.3 was used for meta-analysis of the outcome indicators. Ten RCTs involving 7230 patients were included. The results showed that SV increased left ventricular eject fraction ( MD = 2.86, 95% CI [1.81-3.90], P < 0.00001) and reduced readmission rate ( RR = 0.46, 95% CI [0.32-0.68], P < 0.0001), decreased N-terminal pro-brain natriuretic peptide ( MD = -477.46, 95% CI [-914.96 to -39.96], P = 0.03), and reduced major adverse cardiovascular and cerebrovascular event (MACCE) ( RR = 0.48, 95% CI [0.27-0.85], P = 0.01). There was no significant difference in the rate of adverse reaction (AR) between the trial group and the control group ( RR = 0.88, 95% CI [0.60-1.30], P = 0.52). SV can effectively improve the prognosis of AMI, prevent complications, and there is no significant difference in safety compared with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker.

Sequential hybrid ablation vs. surgical CryoMaze alone for treatment of atrial fibrillation: results of multicentre randomized controlled trial.

Data on the hybrid atrial fibrillation (AF) treatment are lacking in patients with structural heart disease undergoing concomitant CryoMaze procedures. The aim was to assess whether the timely pre-emptive catheter ablation would achieve higher freedom from AF or atrial tachycardia (AT) and be associated with better clinical outcomes than surgical ablation alone. The trial investigated patients with non-paroxysmal AF undergoing coronary artery bypass grafting and/or valve repair/replacement with mandatory concomitant CryoMaze procedure who were randomly assigned to undergo either radiofrequency catheter ablation [Hybrid Group (HG)] or no further treatment (Surgery Group). The primary efficacy endpoint was the first recurrence of AF/AT without class I or III antiarrhythmic drugs as assessed by implantable cardiac monitors. The primary clinical endpoint was a composite of hospitalization for arrhythmia recurrence, worsening of heart failure, cardioembolic event, or major bleeding. We analysed 113 and 116 patients in the Hybrid and Surgery Groups, respectively, with a median follow-up of 715 (IQR: 528-1072) days. The primary efficacy endpoint was significantly reduced in the HG [41.1% vs. 67.4%, hazard ratio (HR) = 0.38, 95% confidence interval (CI): 0.26-0.57, P < 0.001] as well as the primary clinical endpoint (19.9% vs. 40.1%, HR = 0.51, 95% CI: 0.29-0.86, P = 0.012). The trial groups did not differ in all-cause mortality (10.6% vs. 8.6%, HR = 1.17, 95%CI: 0.51-2.71, P = 0.71). The major complications of catheter ablation were infrequent (1.9%). Pre-emptively performed catheter ablation after the CryoMaze procedure was safe and associated with higher freedom from AF/AT and improved clinical outcomes.

Manipulating Environmental Clutter Reveals Dynamic Active Sensing Strategies in Big Brown Bats

Vocalizing animals confront acoustically challenging conditions in which background noise (clutter) can mask or shift attention away from biologically relevant signals. Echolocating big brown bats (Eptesicus fuscus) are excellent comparative models for studying how animals differentiate between multiple sound sources in complex acoustic scenes. We trained four big brown bats to fly down an asymmetrical corridor producing distinct clutter echoes from the two sides. While in flight, they were presented with playbacks of exemplars of an echolocation call, a social communication call, or waterfall noise, from one or both sides of this corridor; a silence condition served as a control. We predicted that bats would perceive the playbacks, as indexed by modifications of their vocalizations and shifts in their head aim. Bats completed flights at a high rate of success in all conditions. Although bats produced calls in similar sized sonar sound groups in playback and silent trials, they emitted more echolocation calls and shortened the time intervals between calls in response to playbacks. These comparisons suggest the playbacks increased the perceptual difficulty of the task to some extent. Bats aimed their heads towards the left side of the corridor where clutter echoes were acoustically stronger but also sparser. Changes in head aim in response to playbacks were small. Our data suggest that big brown bats flying through clutter detect differences in the information content of surrounding acoustic scenes and alter their echolocation behavior accordingly.

Abstract WMP94: Quantifying the Enhanced Clinical Benefit of Endovascular Thrombectomy Performed With Contemporary Workflows and Devices

Background: To date, the magnitude of the benefit of endovascular thrombectomy (EVT) over medical management in acute ischemic stroke has been quantified by the data of the five breakthrough RCTs of 2015. But contemporary EVT care has faster EVT workflow speeds and achieves higher rates of reperfusion. Updated quantitative estimates of the benefit of EVT vs medical management are needed. Methods: Contemporary FDA-monitored (TIGER/ARISE II) and pivotal (HERMES) EVT trial group differences were quantified for workflow speed (door-to-reperfusion time) and reperfusion rates (eTICI distribution). The projected effect of the faster workflow speed in further improving disability (mRS) outcomes were calculated using established HERMES treatment time-benefit models and the projected effect of higher reperfusion rates using established HERMES eTICI tier-specific outcomes. Results: Contemporary EVT trial groups, compared with pivotal trial EVT groups, had door-to-reperfusion 57 minutes faster (146m vs 89m), successful reperfusion 22.6% more often (71.0% vs 93.6%), and excellent reperfusion 45.1% more often (29.4% vs 74.5%). Figure 1 shows the resulting projected improvements in mRS distributions. For functional independence (mRS 0-2), outcome rates for MM vs pivotal EVT vs contemporary EVT were 25.2% vs 44.6% vs 74.5%. The number needed to treat (NNT) for 1 more patient to achieve functional independence improved from 5.2 to 2.5. For nondisabled outcome (mRS 0-1), outcome rates were 10.1% vs 27.4% vs 46.0%. The NNT for 1 more patient to achieve nondisabled outcome improved from 5.8 to 2.8. Over the entire mRS range, the NNT for 1 more patient to have less disability by at least one mRS level improved from 2.6 to 1.6. Conclusion: Formal modeling indicates that contemporary EVT confers substantially enhanced benefits over medical management. Among every 100 patients treated with EVT, 63 will have a less disabled long-term outcome including 36 more becoming disability-free.

A randomized open labelled controlled clinical study to evaluate the role of Krutamalakadya Sutra in the management of Bhagandara with special reference to Fistula-In-Ano

Acharya Sushruta has included Bhagandara as one among the Ashtamahagadas. Fistula in ano is an ano-rectal condition with a worldwide prevalence of 8.6 cases per 100,000 population. Ksharasutra ligation is one of the popular modalities in treatment of Bhagandara. In present era, there are different types of Ksharasutra available. Most widely used Ksharasutra is Apamarga Ksharasutra which is having Chedana, Bhedana, Lekhana properties and anti-inflammatory effect on the fistula tract. But some of the problems are faced during preparation and also in the course of Ksharasutra therapy viz, collection and preservation of Snuhi (Euphorbia nerifolia) latex is very difficult and time taking process. The main complaints reported by the patients are pain and discomfort during the course of treatment with Ksharasutra for Bhagandara, which requires management with oral analgesics. Considering the above problems, a non irritant preparation such as Krutamalakadya Varti mentioned in Sushruta Samhita in the chapter of Bhagandara Chikitsa Adhyaya is modified in the form of Krutamalakadya Sutra which contains following ingredients such as Aragvadha, Haridra, Ahimsra, Madhu and Ghrita is taken for the study. Krutamalakadya Sutra is also having a good binding property, as well as Chedana, Bhedana, Lekhana, Vedanasthapana, Vrana Shodhana and Vrana Ropana properties. A total of 30 subjects were taken, Trial group treated with Krutamalakadya Sutra and control group treated with Apamarga Ksharasutra. The study shows that preparation of Krutamalakadya Sutra is much easier than Apamarga Ksharasutra and had high efficacy in subjective parameters like burning sensation compared to Apamarga Ksharasutra.

Evaluation of Black Soldier Fly Larvae Meal on Growth, Body Composition, Immune Responses, and Antioxidant Capacity of Redclaw Crayfish (Cherax quadricarinatus) Juveniles

This study investigated the effects of substituting fish meal (FM) with black soldier fly (Hermetia illucens) meal (BSM) on the growth performance, body composition, immune response, and antioxidant enzyme activity of juvenile redclaw crayfish (Cherax quadricarinatus). Four isonitrogenous (41%) and isolipidic (11%) diets (i.e., FM substitutes) were formulated from BSM prepared using larvae that were fed soybean meal (BSM-S), fishery byproducts (BSM-F), or pitaya (BSM-P). The experimental diets were fed twice daily to triplicate groups of juvenile redclaw crayfish (0.56 ± 0.04 g). After the feed trial, the FM and BSM-F groups exhibited significantly lower feed conversion ratios and significantly higher weight gain; specific growth rates; and concentrations of saturated fatty acids, highly unsaturated fatty acids, eicosapentaenoic acid, and docosahexaenoic acid in the muscle. Among the tested groups, the BSM-F group exhibited significantly enhanced immune responses and increased antioxidant enzyme activity (i.e., superoxide dismutase, phenoloxidase, and glutathione peroxidase); the BSM-P group exhibited a significantly higher feed intake and hepatopancreatic index; and the FM group exhibited a significantly higher muscle body index and apparent digestibility for the dry matter of crude protein. The findings indicate that the juvenile redclaw crayfish fed BSM-F achieved the highest weight gain among the groups.

Improving the inclusion of an under-served group in trials: development and implementation of the INCLUDE Impaired Capacity to Consent Framework

BackgroundFor the potential benefits of trials to reach all that they should, trials must be designed to ensure that those taking part reflect the population who will receive the intervention. However, adults with impaired capacity to consent are frequently excluded from trials — partly because researchers are unfamiliar with the legal and ethical frameworks and lack the necessary methodological expertise. Researchers identified a need for guidance on designing more inclusive trials. Building on the NIHR INCLUDE initiative, we developed the INCLUDE Impaired Capacity to Consent Framework to help researchers design inclusive trials.MethodsThe framework was developed over five phases: (1) establishing the scope and content of the framework and adapting the INCLUDE Ethnicity Framework for this population; (2) scoping the relevance of the framework to different populations and piloting in a range of trials; (3) consulting people living with impairing conditions and carers to explore their views about the framework and identify missing content areas; (4) refining the framework; and (5) the development of an implementation toolkit of resources to support researchers using the framework.ResultsThe framework has two parts: a set of four key questions to help researchers identify who should be included in their trial, and a series of worksheets covering intervention design, recruitment and consent processes, data collection and analysis, and public involvement and dissemination. It is supported by a summary of the ethical and legal frameworks and a website of resources on capacity and consent. Implementation resources include infographics and animations, a library of completed frameworks, and facilitated workshops for researchers.The framework and toolkit were launched at a webinar (November 2022), with polling demonstrating an increase in attendees’ awareness about research involving adults lacking capacity. A post-webinar survey found that stakeholders viewed the framework and toolkit as valuable tools to facilitate greater inclusion of this under-served population in trials. The framework is available online: https://www.capacityconsentresearch.com/include-impaired-capacity-to-consent-framework.html.ConclusionsThe INCLUDE Impaired Capacity to Consent Framework and implementation toolkit can support researchers to design more inclusive trials and other types of research studies. Further engagement, including with funders who are key to ensuring uptake, and evaluation is needed.

In-feed Praziquantel treatment ofgrass carp (Ctenopharyngodon idella) infected with eye flukes.

Praziquantel (PZQ) isadrug effective against several parasitic diseases offish caused byPlatyhelminthes. The study assesses the efficacy ofselected in-feed PZQ doses ineliminating metacercariae Diplostomum pseudospathaceum ingrass carp. The fish were infected with D.pseudospathaceum inlaboratory conditions and subsequently treated with PZQ atdaily doses of30 (PZQ1), 50 (PZQ2), and 100 (PZQ3) mg/kgbwfor seven days. The treatment trial was followed bya23-day observation period during which the fish were parasitologically examined ondays0, 2, 8 and 23. Smaller fish were infected with asignificantly higher (P < 0.05) number ofmetacercariae than bigger fish among three weight groups asfollows: upto7 g > 7 to12 g > 12 g. The in-feed PZQ atdoses of30, 50 and 100mg/kgbwfor seven days was 47%, 84% and 88% effective against metacercariae D.pseudospathaceum, respectively. Asignificant decrease (P < 0.01) inmoving and anincrease (P < 0.01) intheimmotile metacercariae inthe eye's lens were recorded inall the trial groups oneach sampling day. Anincreasing proportion ofmotile metacercariae inthe post-treatment observation period was seen inPZQ2 and PZQ3, indicating adecreasing trend inthe actual efficacy inanenvironment with noreinfection possibility.

COLONTOWN Searching Safari: Education to remove barriers to pursue clinical trials for patients with metastatic colorectal cancer (mCRC).

82 Background: Clinical trials can expand otherwise limited treatment options for patients with metastatic cancer. Yet, the complexity of the trial landscape can prevent patients from pursuing trials. Even in mCRC patients motivated to participate in trials, 79% described trial search negatively, mainly ‘overwhelming.’ We hypothesized that “clinical trial-literacy” and familiarity with the tools/process of pursuing trials were critical precursors for patients to incorporate trials into their treatment plan. To test this, we, as managers of COLONTOWN, a large, online CRC patient/caregiver community, developed an interactive course. Methods: We reviewed many posts from the COLONTOWN clinical trial groups to identify gaps between the desire to participate in a trial and the knowledge/tools needed to do so. We then determined those most likely to benefit as mCRC MSS patients interested in, but not in urgent need of, trials. We developed a 4-week long course with 5 hours of live online sessions and 5 hours of homework. Participants built fluency in the language of clinical trials, learned about available tools, and identified and assessed trials in the context of their personal needs and disease dynamics. Unlike most other trial resources, the focus was on informed patient-centered decision-making, not on the science or mechanics of trials. The course was offered 3 times in 2022/23 with iterative improvements after each session. Participants (n=48) were assessed for their attitudes around trials before and after the course to measure impact. Results: We found that our repeatable, scalable course improves mCRC patient perceptions of and skills to pursue trials as evidenced by pre-course vs. post-course surveys. This included average response to “How prepared do you feel to find a clinical trial?” increasing from 2.1 to 3.8 on a 5-pt scale and positive sentiment about the process rising from 7% to 71% (table). Positive feedback on meeting course objectives and amount of coursework being ‘just right’ (96% and 92% of responses, respectively) support the material’s value for time invested. Conclusions: Through systematic skill building, self reflection, and practical tools, our guided course can build confidence and empower patients and caregivers to take the next step to pursue clinical trials. Patient education can indeed help overcome often-overlooked emotional and knowledge barriers to pursuing clinical trials present even in a motivated patient population. Next, we plan to create and assess the benefit of an additional on-demand e-learning course and to expand to other patient groups. [Table: see text]