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The integration of positron emission tomography/computed tomography (PET/CT) has revolutionized the landscape of Alzheimer's disease (AD) research and therapeutic interventions. By combining structural and functional imaging, PET/CT provides a comprehensive understanding of disease pathology and response to treatment assessment. PET/CT, particularly with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG), facilitates the visualization of glucose metabolism in the brain, enabling early diagnosis, staging, and monitoring of neurodegenerative disease progression. The advent of amyloid and tau PET imaging has further propelled the field forward, offering invaluable tools for tracking pathological hallmarks, assessing treatment response, and predicting clinical outcomes. While some therapeutic interventions targeting amyloid plaque load showed promising results with the reduction of cerebral amyloid accumulation over time, others failed to demonstrate a significant impact of anti-amyloid agents for reducing the amyloid plaques burden in AD brains. Tau PET imaging has conversely fueled the advent of disease-modifying therapeutic strategies in AD by supporting the assessment of neurofibrillary tangles of tau pathology deposition over time. Looking ahead, PET imaging holds immense promise for studying additional targets such as neuroinflammation, cholinergic deficit, and synaptic dysfunction. Advances in radiotracer development, dedicated brain PET/CT scanners, and Artificial Intelligence-powered software are poised to enhance the quality, sensitivity, and diagnostic power of molecular neuroimaging. Consequently, PET/CT remains at the forefront of AD research, offering unparalleled opportunities for unravelling the complexities of the disease and advancing therapeutic interventions, although it is not yet enough alone to allow patients' recruitment in therapeutic clinical trials. [ABSTRACT FROM AUTHOR]

This paper studies legal disparities between men and women in a patriarchal framework. Throughout history, women have confronted discrimination in matters of inheritance, property ownership, and various other legal rights. We examine the consequences of legal discrimination for women's differential engagement and success within legal conflicts, using data from Ottoman courts in the early nineteenth century. The results show that women were parties to approximately 30 per cent of cases, with a modest gender gap of around eight to ten percentage points in terms of plaintiff win rates. The gap varied across courts and types of cases, consistent with gender disparities in legal knowledge and trial stakes in patriarchal societies. Notably, when litigating against male defendants, the disparity was more pronounced in provincial courts (Konya and Kütahya), as opposed to courts in the capital city (Galata and Üsküdar). Similarly, while the gender gap was greater in property and probate cases than those involving personal crimes and commercial exchange, the gap was reversed in family matters. The analysis suggests that a significant portion of the gender gap in litigation success can be attributed to disparities in evidence presentation (witness testimonies, written documents and legal opinions). [ABSTRACT FROM AUTHOR]

Franz Kafka’s novel The Trial (1915) is open to many interpretations. One aspect, however, which has not been taken sufficiently into account, is its relation to the antisemitic trials of his times, where Jews were accused of treason or ‘ritual murder’: the trials of Tisza (Hungary, 1882), Dreyfus (France, 1894–9), Hilsner (Czechoslovakia, 1899–1900), and Beiliss (Russia, 1912–13). Kafka knew about them and made comments in his correspondence or diaries. This ‘Jewish moment’ is essential for the understanding of the novel. However, Joseph K. has no religious or ethnic identity: Kafka discovers in the Jewish experience the quintessential human experience of Injustice. [ABSTRACT FROM AUTHOR]

In November 1881, the eminent physiologist and physician David Ferrier was prosecuted under the Cruelty to Animals Act 1876. The prosecution was raised by the Victoria Street Society, formerly known as the Society for the Protection of Animals Liable to Vivisection, through its activist founder, Frances Power Cobbe. This article examines the legislative context prior to Ferrier's trial, the personalities involved in the prosecution, and its course and outcome. The resultant impact, both personal, on Cobbe and Ferrier, and professional, on experimental neurophysiology, is discussed, in particular the foundation of the Association for the Advancement of Medicine by Research (AAMR) and the provision of legal support for medical practitioners subject to litigation. [ABSTRACT FROM AUTHOR]

Objectives Design Methods Results Conclusions Higher education students experience elevated levels of suicidal ideation, but often face barriers in accessing support. The Mental Imagery for Suicidality in Students Trial (MISST; ISRCTN13621293; NCT05296538) tested the feasibility and acceptability of a six‐session imagery‐based approach called Broad‐Minded Affective Coping (BMAC). This qualitative evaluation explored the experiences of MISST participants and staff.A qualitative study using one‐to‐one qualitative interviews with participants and staff recruited from MISST. Reflexive thematic analysis was used to explore trial participant and staff experiences to inform a future definitive trial.Student participants (n = 16), research assistants (n = 4) and the trial therapist (n = 1) were interviewed and transcripts analysed using reflexive thematic analysis.Four key themes were identified. The first theme highlights the value and challenges for students in talking about suicide. The ways in which communication and rapport can be built to facilitate this conversation are explored in theme 2. Theme 3 explains how working with the BMAC therapist increased participants’ awareness of their current mood, drew their attention to positive moments in their lives and helped them to actively recall these moments to interrupt negative cycles of rumination and suicidal ideation. The extent to which the BMAC is ‘fit for purpose’ is outlined in theme 4, generating specific recommendations for future intervention development.The BMAC offers a positive, time‐limited, structured intervention that is well suited to meet the needs of higher education students experiencing suicidal ideation. Further research is needed to test the effectiveness on mental health and suicide‐related outcomes. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusion Using a double‐dummy pilot randomized controlled trial design, we aimed to determine the feasibility and acceptability of comparing remote electrical neuromodulation (REN) to typical care intravenous pharmacologic interventions for the treatment of children and adolescents visiting the emergency department (ED) with migraine, and to compare parallel‐group versus crossover trial designs.There are limited data to guide the management of migraine in the ED. Children and adolescents are interested in neuromodulation, and specifically REN, for treatment in this setting, but there are no existing data on this approach.We employed a double‐dummy, double‐blind, pilot randomized controlled trial that tested two designs in two phases: a parallel‐group design and a crossover design (ClinicalTrials.gov identifier: NCT05102591). The intervention arms consisted of: (i) active REN stimulation with matched normal saline placebo intravenously, and (ii) matched sham REN stimulation, intravenous metoclopramide (0.15 mg/kg, maximum 10 mg), and intravenous ketorolac (0.5 mg/kg, maximum 30 mg). Youth aged 8.0–<18.0 years visiting a Canadian tertiary care pediatric ED with migraine attacks as per criteria B–E of the International Classification of Headache Disorders third edition were eligible. Primary outcomes were focused on trial feasibility and acceptability, and preliminary efficacy and safety data were also collected.A total of 34% (22/65) of those who screened eligible were enrolled. Three participants (14%) withdrew prior to receiving any study interventions. In all, 10 participants were allocated to typical care, and nine to REN. All treated participants (19/19) completed all assessments. Recruitment was higher during the parallel‐group phase: 1.1 participants/month versus 0.6 participants/month, and 36% (17/47) versus 28% (five of 18) of screened eligible were enrolled in the parallel‐group and crossover phases, respectively. Participants reported positive impressions of REN use in the ED, e.g., higher mean (standard deviation [SD]) levels of interest in using REN only at 3.7 (1.0) versus 2.8 (1.0) in using intravenous interventions only for a future ED visit. Participants and clinical staff reported overall positive impressions regarding the study protocol. Employing an 11‐point pain numerical rating scale, the mean (SD) reduction in pain severity score was 2.1 (1.3) and 2.9 (2.9) from baseline to 1 h, and 2.4 (1.6) and 4.0 (3.5) from baseline to 2 h for REN and intravenous interventions, respectively. One participant in the typical care group and none in the REN group experienced adverse events.We demonstrated the feasibility and acceptability of our trial protocol and of using REN to treat youth presenting to the ED with migraine. The parallel‐group design generated a higher recruitment rate than the crossover design. Our preliminary efficacy and safety data suggest that REN could be non‐inferior to typical care, but we were not powered for these outcomes. Further research on REN's use in the ED setting is warranted. [ABSTRACT FROM AUTHOR]

Background: Improving the uptake of relevant and reliable research is an important priority in long-term care to achieve sustainable and high-quality services for the increasingly older population. Aim: The purpose was to assess the effectiveness of a tailored, adaptive and a multifaceted KT capacity program, relative to usual practice, on the implementation of National Early Warning Score 2 (NEWS2). Methods: This study was carried out as a pragmatic cluster-randomized controlled trial. The capacity program consisted of an educational part to address implementation capacity gaps and a facilitation-upon-implementation part to address a relevant knowledge gap in nursing homes. A collective decision was made to address the challenge of early detection of clinical deterioration among nursing home residents, by implementing the (NEWS2) as clinical innovation. Public nursing homes in a Norwegian municipality (n = 21) with a total of 1 466 beds were eligible for inclusion. The study-period spanned over a 22-month period, including a 12-month follow-up. Data was extracted from the Electronic Patient Journal system and analyzed using multilevel growth model analysis. Results: The intervention had a large effect on the use of NEWS2 among care staff in intervention nursing homes, compared to the control group (standardized mean difference, d = 2.42). During the final month of the implementation period, residents in the intervention group was assessed with NEWS2 1.44 times (95% CI: 1.23, 1.64) per month, which is almost four times more often than in the control group (mean = 0.38, 95% CI: 0.19, 0.57). During the follow-up period, the effect of the intervention was not only sustained in the intervention group but there was a substantial increase in the use of NEWS2 in both the intervention (mean = 1.75, 95% CI: 1.55, 1.96) and control groups (mean = 1.45, 95% CI: 1.27, 1.65). Conclusions: This tailored implementation strategy had a large effect on the use of NEWS2 among care staff, demonstrating that integrated knowledge translation strategies can be a promising strategy to achieve evidence-based care in the nursing home sector. Trial registration: ISRCTN12437773. Registered 19/3 2020, retrospectively. [ABSTRACT FROM AUTHOR]

This article traces the informal institutionalization of the Norwegian Haugian revival during the first decades of the nineteenth century. The revival was the first nationwide popular movement in Norway and flourished in the footsteps of its protagonist Hans Nielsen Hauge (1771–1824). Lay preaching in religious assemblies was a core activity among the Haugians from the inception of the revival. As part of the institutionalization process, beliefs and practices related to lay ministry were both established and adapted. Although the institutionalization involved a significant break with previous teaching and practice, the Haugians themselves saw the adaptation of beliefs and practices mainly as a story of continuity, maintaining that the revival essentially remained the same. I argue that acknowledging both the changes in beliefs and practices, on the one hand, and the Haugians' claim to remaining the same, on the other hand, are key to understanding the development of the revival. [ABSTRACT FROM AUTHOR]

The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a multifactorial Bayesian adaptive platform trial that aims to improve the way that S. aureus bloodstream infection, a globally common and severe infectious disease, is treated. In a world first, the SNAP trial will simultaneously investigate the effects of multiple intervention modalities within multiple groups of participants with different forms of S. aureus bloodstream infection. Here, we formalise the trial structure, modelling approach, and decision rules that will be used for the SNAP trial. By summarising the statistical principles governing the design, our hope is that the SNAP trial will serve as an adaptable template that can be used to improve comparative effectiveness research efficiency in other disease areas.Trial registration NCT05137119 . Registered on 30 November 2021.

Abstract Background Improving the uptake of relevant and reliable research is an important priority in long-term care to achieve sustainable and high-quality services for the increasingly older population. Aim The purpose was to assess the effectiveness of a tailored, adaptive and a multifaceted KT capacity program, relative to usual practice, on the implementation of National Early Warning Score 2 (NEWS2). Methods This study was carried out as a pragmatic cluster-randomized controlled trial. The capacity program consisted of an educational part to address implementation capacity gaps and a facilitation-upon-implementation part to address a relevant knowledge gap in nursing homes. A collective decision was made to address the challenge of early detection of clinical deterioration among nursing home residents, by implementing the (NEWS2) as clinical innovation. Public nursing homes in a Norwegian municipality (n = 21) with a total of 1 466 beds were eligible for inclusion. The study-period spanned over a 22-month period, including a 12-month follow-up. Data was extracted from the Electronic Patient Journal system and analyzed using multilevel growth model analysis. Results The intervention had a large effect on the use of NEWS2 among care staff in intervention nursing homes, compared to the control group (standardized mean difference, d = 2.42). During the final month of the implementation period, residents in the intervention group was assessed with NEWS2 1.44 times (95% CI: 1.23, 1.64) per month, which is almost four times more often than in the control group (mean = 0.38, 95% CI: 0.19, 0.57). During the follow-up period, the effect of the intervention was not only sustained in the intervention group but there was a substantial increase in the use of NEWS2 in both the intervention (mean = 1.75, 95% CI: 1.55, 1.96) and control groups (mean = 1.45, 95% CI: 1.27, 1.65). Conclusions This tailored implementation strategy had a large effect on the use of NEWS2 among care staff, demonstrating that integrated knowledge translation strategies can be a promising strategy to achieve evidence-based care in the nursing home sector. Trial registration ISRCTN12437773 . Registered 19/3 2020, retrospectively.

Abstract Background Morphine relieves dyspnea in various clinical circumstances. Whether or not this applies to patients admitted to intensive care units (ICUs) for acute respiratory failure (ARF) is unknown. We evaluated the efficacy and safety of low-dose morphine on dyspnea in patients admitted to the ICU for ARF. Methods In this single-center, double-blind, phase 2, randomized, controlled trial, we assigned non-intubated adults admitted to the ICU for ARF with severe dyspnea, defined by a visual analog scale for dyspnea (dyspnea-VAS) from zero (no dyspnea) to 100 mm (worst imaginable dyspnea) ≥40 mm, to receive a low dose of Morphine Hydrochloride (intravenous titration followed by subcutaneous relay) or Placebo. All patients received standard therapy, including etiological treatment and non-invasive respiratory support. Results Twenty-two patients were randomized, 11 in each group. The average dyspnea (median [interquartile range]) over 24 hours did not significantly differ between the two groups (40 [25 – 43] mm in the Morphine group vs. 40 [36 – 49] mm in the Placebo group, p=0.411). Dyspnea-VAS was lower in the Morphine group than in the Placebo group at the end of intravenous titration (30 [11 – 30] vs. 35 [30 – 44], p=0.044) and four hours later (18 [10 – 29] vs. 50 [30 – 60], p=0.043). The cumulative probability of intubation was higher in the Morphine group than in the Placebo group (p=0.046) Conclusion In this phase 2 pilot trial, morphine did not improve 24-hour average dyspnea in adult patients with ARF, even though it had a statistically significant immediate effect. Of concern, Morphine use was associated with a higher intubation rate. Trial registration The protocol was declared on the ClinicalTrial.gov database (no. NCT04358133) and was published in September 2022.

The Roman legal system has its origin in the era of the foundation of Rome and was applied until the death of the emperor Iustinianus, from the 8th century BC to the 6th century AD. Compared to other ancient peoples, creators of law, the Romans were the only ones who generated a special category of „professionals” managing to lay the foundations of the unique ancient model of law elaborated in a „scientific” way. Also, to the Romans, two essential elements that have become constant in positive law stand out: the principle of individual property and the distinction between Ius Publicum and Ius Privatum. What can be emphasized with certainty is the special aptitude and talent that prevails throughout the entire history of Rome in the elaboration and knowledge of law, a fact that is also highlighted by the creation of a true archetype of the Roman citizen, at first the pontiff-jurist, and, later, only jurist-magistrate. The great success of Roman law, however, was the standardization of its rules through the Corpus Iuris Civilis, which brought together all the legal norms of Roman origin in a written document.

This study focuses on the analysis of the Qizilbash inspection that took place during the time of Yavuz Sultan Selim. The legal processes of the suspects Seydî Sevindik and İshak, who were accused of being Qizilbash, have been examined. The examination of two court records through a case analysis contains important data in understanding how the Qizilbash inspection, which occurred as a result of the Ottoman Empire’s struggle with the Safavid State in the early 16th century, was carried out administratively and legally. In addition, the relevant case records highlight that those accused of being Qizilbash, and against whom surveillance and intelligence decisions were made, were prosecuted after certain legal stages. Therefore, by analyzing the information contained in the records, the identification, monitoring, intelligence, trials of Qizilbashes, and the penalties imposed, as well as the methods of punishment, have been discussed. As a result, it has been concluded that at least some of those who were investigated on the grounds of being Qizilbash were prosecuted within the norms of the legal system and under certain conditions.

The paper focuses on the lectures given by Piero Calamandrei in 1952 at the University of Mexico, which were collected in the famous volume Processo e democrazia published by Cedam in 1954. The volume, translated in China in 2005, has aroused lively interest among Chinese scholars. The Author expresses his appreciation for the scholarly tradition stemming from Calamandrei and, in particular, he emphasises the profile of judiciary’s autonomy and independence, which distinguishes liberal and democratic systems from authoritarian ones. Lastly, the Author dwells on the relationship between judges and lawyers, which should take place in a climate of active and mutual trust.

The works of Piero Calamandrei, professor of procedural law, had a wide circulation and extraordinary influence in Latin America, and, generally, in the Spanish speaking world, thanks to the translations and editions by Santiago Sentís Melendo. However, this cannot be claimed for the ‘other’ Calamandrei, the constituent and professor of constitutional law, who has only recently and partially gained access to that cultural sphere.

AbstractUp to 50% of diffuse large B-cell lymphoma (DLBCL) patients are ineligible for participation in clinical trials. Ineligible patients have inferior outcomes, but less is known about the impact of commonly used organ-function-based inclusion criteria on drug efficacy estimates. Data on DLBCL patients treated with CHOP+/-rituximab were retrieved from the Danish Lymphoma Registry. Trial inclusion criteria were extracted from four international DLBCL trials (REMoDL-B, GOYA, POLARIX, and HOVON-84). Differences in overall survival (OS) and 5-year restricted mean survival differences (5 y-RMSDs) between trial eligible and ineligible patients were computed. The effectiveness of adding rituximab to CHOP was quantified by the 5 y-RMSD between CHOP and R-CHOP-treated patients and the impact of individual trial criteria on estimated effectiveness was quantified by Shapley-values. In total, 4,083 R-CHOP-treated and 890 CHOP-treated DLBCL patients were included. Across the trials, 18.6-29.3% of the included R-CHOP-treated patients were deemed ineligible for trial based on organ function and performance status alone. Ineligible patients had significantly worse survival, with adjusted absolute differences in 5-year OS of 9-15%. The impact of individual criteria on the estimated effectiveness of adding rituximab to CHOP was small (Shapley-value range, −2.74-0.31). Using a smaller set of criteria derived from a data-driven approach, the number of eligible patients increased by 16-38% and the 5 y-RMSD increased by 0.7-3.1 months. In conclusion, OS among trial ineligible DLBCL patients is inferior as expected, but relaxing trial criteria would have increased the number of trial participants without making major changes in estimated efficacy for a hypothetical CHOP versus R-CHOP trial. This does not necessarily imply that trial findings based on selected patients are unreliable, as the estimated effectiveness of adding rituximab to CHOP was only slightly affected by omitting selected inclusion criteria. [ABSTRACT FROM AUTHOR]

Evidence on management of behavioral symptoms in motor neuron disease (MND) is lacking. The MiNDToolkit, an online psychoeducational platform, supports carers dealing with behavioral symptoms (BehSymp). The study objectives were to ascertain recruitment and retention rates, carer and healthcare professional (HCP) use of the platform, and completion of online assessments, to inform a full-scale trial. Design: Randomized, parallel, multi-center, feasibility trial. England and Wales, across diverse MND services; recruitment from July/21 to November/22; last participant follow-up in March/23. Carers of people with motor neuron disease (PwMND) with BehSymp, recruited through MND services. After confirming eligibility, participants completed screening and baseline assessments online via the MiNDToolkit platform and were randomized centrally in a 1:1 ratio to MiNDToolkit or control. MiNDToolkit offered tailored modules to carers for the 3-month study period. Carers in the intervention group could receive additional support from MiNDToolkit trained HCPs. The control group was offered access to the intervention at the end of the study. Data were collected on platform usage and psychosocial variables. One hundred and fifty-one carers from 11 sites were invited to join the study (letter, face-to-face); 30 were screened; 29 were randomized. Fifteen people were allocated to the control arm; 14 to intervention. Carers were mostly female; median age for was 62.5 (IQR: 58, 68; intervention) and 57 (IQR: 56, 70; controls). Study retention was high (24/29 = 82.76%); carers engaged with the platform on average 14 times (median (IQR):14.0 (10.0, 18.5)) during the study period. The MiNDToolkit study was feasible and well accepted by carers and trained HCPs. A definitive trial is warranted. [ABSTRACT FROM AUTHOR]

Aims: To explore the effectiveness of continuous home wound care on patients with diabetic foot ulcers (DFUs). Design: A non‐randomized parallel controlled non‐inferiority trial. Methods: Patients with Wagner grade I–III DFUs hospitalized in two distant campuses of the same hospital were included. All patients received infection treatment and wound bed preparation during hospitalization; after discharge, patients in one of the campuses received routine outpatient wound care, and those treated in the other received continuous home wound care. The per‐protocol analysis was performed to compare ulcer healing indicators, knowledge, health belief, self‐management behaviour and medical expenses of the two groups. Results: Between October 2021 and December 2022, 116 patients were enrolled in the study; 107 completed. The home care was not inferior in terms of ulcer healing rate and demonstrated significant enhancements in the understanding of warning signs, health belief and self‐management behaviour. Additionally, the home care saved 220.38 yuan (24.32 UK pounds) in direct medical expenses for each additional one square centimetre of ulcer healing. Conclusion: The continuous home wound care enhanced self‐management behaviour of the patients and saved their medical expenses while not compromising ulcer healing. Impact: This is to date the first study to conduct continuous home wound care practice for patients with DFUs and confirmed its safety and non‐inferiority in ulcer healing, and supported its superiority in improving self‐management behaviour and saving medical expenses. Reporting Method: We have adhered to the transparent reporting of evaluations with nonrandomized designs statements and the corresponding checklist was followed. Patient or Public Contribution: The patients and their primary caregivers were involved in intervention design, we received input from them about the factors that facilitate and hinder patient self‐management behaviours to develop intervention strategies. [ABSTRACT FROM AUTHOR]

Context Metabolic measures are frequently used to predict type 1 diabetes (T1D) and to understand effects of disease-modifying therapies. Objective Compare metabolic endpoints for their ability to detect preventive treatment effects and predict T1D. Methods Six-month changes in metabolic endpoints were assessed for (1) detecting treatment effects by comparing placebo and treatment arms from the randomized controlled teplizumab prevention trial, a multicenter clinical trial investigating 14-day intravenous teplizumab infusion and (2) predicting T1D in the TrialNet Pathway to Prevention natural history study. For each metabolic measure, t-Values from t tests for detecting a treatment effect were compared with chi-square values from proportional hazards regression for predicting T1D. Participants in the teplizumab prevention trial and participants in the Pathway to Prevention study selected with the same inclusion criteria used for the teplizumab trial were studied. Results Six-month changes in glucose-based endpoints predicted diabetes better than C-peptide–based endpoints, yet the latter were better at detecting a teplizumab effect. Combined measures of glucose and C-peptide were more balanced than measures of glucose alone or C-peptide alone for predicting diabetes and detecting a teplizumab effect. Conclusion The capacity of a metabolic endpoint to detect a treatment effect does not necessarily correspond to its accuracy for predicting T1D. However, combined glucose and C-peptide endpoints appear to be effective for both predicting diabetes and detecting a response to immunotherapy. These findings suggest that combined glucose and C-peptide endpoints should be incorporated into the design of future T1D prevention trials. [ABSTRACT FROM AUTHOR]

Background: Morphine relieves dyspnea in various clinical circumstances. Whether or not this applies to patients admitted to intensive care units (ICUs) for acute respiratory failure (ARF) is unknown. We evaluated the efficacy and safety of low-dose morphine on dyspnea in patients admitted to the ICU for ARF. Methods: In this single-center, double-blind, phase 2, randomized, controlled trial, we assigned non-intubated adults admitted to the ICU for ARF with severe dyspnea, defined by a visual analog scale for dyspnea (dyspnea-VAS) from zero (no dyspnea) to 100 mm (worst imaginable dyspnea) ≥40 mm, to receive a low dose of Morphine Hydrochloride (intravenous titration followed by subcutaneous relay) or Placebo. All patients received standard therapy, including etiological treatment and non-invasive respiratory support. Results: Twenty-two patients were randomized, 11 in each group. The average dyspnea (median [interquartile range]) over 24 hours did not significantly differ between the two groups (40 [25 – 43] mm in the Morphine group vs. 40 [36 – 49] mm in the Placebo group, p=0.411). Dyspnea-VAS was lower in the Morphine group than in the Placebo group at the end of intravenous titration (30 [11 – 30] vs. 35 [30 – 44], p=0.044) and four hours later (18 [10 – 29] vs. 50 [30 – 60], p=0.043). The cumulative probability of intubation was higher in the Morphine group than in the Placebo group (p=0.046) Conclusion: In this phase 2 pilot trial, morphine did not improve 24-hour average dyspnea in adult patients with ARF, even though it had a statistically significant immediate effect. Of concern, Morphine use was associated with a higher intubation rate. Trial registration: The protocol was declared on the ClinicalTrial.gov database (no. NCT04358133) and was published in September 2022. [ABSTRACT FROM AUTHOR]

In this paper, we introduce an analytic approach for assessing effects of multilevel interventions on disparity in health outcomes and health-related decision outcomes (i.e., a treatment decision made by a healthcare provider). We outline common challenges that are encountered in interventional health disparity research, including issues of effect scale and interpretation, choice of covariates for adjustment and its impact on effect magnitude, and the methodological challenges involved with studying decision-based outcomes. To address these challenges, we introduce total effects of interventions on disparity for the entire sample and the treated sample, and corresponding direct effects that are relevant for decision-based outcomes. We provide weighting and g-computation estimators in the presence of study attrition and sketch a simulation-based procedure for sample size determinations based on precision (e.g., confidence interval width). We validate our proposed methods through a brief simulation study and apply our approach to evaluate the RICH LIFE intervention, a multilevel healthcare intervention designed to reduce racial and ethnic disparities in hypertension control. [ABSTRACT FROM AUTHOR]

We investigated the effects of daily ultraviolet A1 (UV-A1, 340–400 nm) exposures on mood states (#R19055, approval on 21 October 2020). Based on our earlier findings of the influence of diurnal preference on mood, we investigated further whether diurnal preference plays a role in the influence of UV-A1 on mood states. Forty-one healthy participants aged 19–55 years were randomized to receive either UV-A1 (n = 21) or control (n = 20) exposures (violet light, 390–440 nm). The irradiations were administered on three consecutive mornings on the skin of the buttocks and middle back. Diurnal preference was assessed with the modified 6-item Morningness-Eveningness Questionnaire (mMEQ). Changes in mood were assessed with Total Mood Disturbance (TMD) score of the 40-item Profile of Mood States (POMS) before the first irradiation, immediately after each irradiation and one week after the last irradiation. Mood improved among those subjected to UV-A1 exposures compared with the controls (p = 0.031). Individuals with more pronounced morningness had mood improvement (p = 0.011), whereas those with more pronounced eveningness did not (p = 0.41). At follow-up of one week after the last irradiation the mood improvement had disappeared. [ABSTRACT FROM AUTHOR]

Copyright of Araucaria is the property of Araucaria-Revista Iberoamericana de Filosofia, Politica y Humanidades and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The issue of the role of the European Court of Human Rights in the formation of the procedures of criminal prosecution in Moldova is critically important for understanding the efficiency of the national justice system and determining strategies for its further improvement. The influence of the ECHR on criminal procedures directly influences the guarantee of human rights and the fairness of legal proceedings. The article aims to analyse the influence of the decisions of the ECHR on criminal justice in Moldova. Statistical methods of percentage ratios were used to evaluate crime dynamics, and characteristics of Moldova's legal system were formed based on the comparative analysis. The results found that complying with the European Convention on Human Rights will reduce crimes and increase trust in the legal system. The stable dynamics of crime reduction for 7% annually is observed based on statistical analysis. Recommendations of the ECHR and directions for improving criminal justice in Moldova were formed. The study results indicate the high efficiency of the changes made in national judicial practice. The perspective area is a study of the long-term influence of the decisions of the ECHR on the formation of legal norms and procedures in the criminal justice of Moldova. Special attention should be given to analysing the methods of integrating European standards into the Moldovan legal system with consideration of local peculiarities and needs. [ABSTRACT FROM AUTHOR]

Aims The aim is to describe the rationale, design, delivery, and baseline characteristics of the Stroke prevention and rhythm control Treatment: Evaluation of an Educational programme of the European society of cardiology in a cluster-Randomized trial in patients with Atrial Fibrillation (STEEER-AF) trial. Methods and results STEEER-AF is a pragmatic trial designed to objectively and robustly determine whether guidelines are adhered to in routine practice and evaluate a targeted educational programme for healthcare professionals. Seventy centres were randomized in six countries (France, Germany, Italy, Poland, Spain, and UK; 2022–23). The STEEER-AF centres recruited 1732 patients with a diagnosis of atrial fibrillation (AF), with a mean age of 68.9 years (SD 11.7), CHA2DS2-VASc score of 3.2 (SD 1.8), and 647 (37%) women. Eight hundred and forty-three patients (49%) were in AF at enrolment and 760 (44%) in sinus rhythm. Oral anticoagulant therapy was prescribed in 1543 patients (89%), with the majority receiving direct oral anticoagulants (1378; 89%). Previous cardioversion, antiarrhythmic drug therapy, or ablation was recorded in 836 patients (48.3%). Five hundred fifty-one patients (31.8%) were currently receiving an antiarrhythmic drug, and 446 (25.8%) were scheduled to receive a future cardioversion or ablation. The educational programme engaged 195 healthcare professionals across centres randomized to the intervention group, consisting of bespoke interactive online learning and reinforcement activities, supported by national expert trainers. Conclusion The STEEER-AF trial was successfully deployed across six European countries to investigate guideline adherence in real-world practice and evaluate if a structured educational programme for healthcare professionals can improve patient-level care. Clinical Trial Registration Clinicaltrials.gov , NCT04396418. [ABSTRACT FROM AUTHOR]

Copyright of Sakarya University Journal of Law Faculty (SHD) is the property of Sakarya University Journal of Law Faculty (SHD) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Patients from socioeconomically disadvantaged backgrounds are underserved in randomised controlled trials, yet they experience a much greater burden of disease compared with patients from socioeconomically advantaged areas. It is crucial to make trials more inclusive to ensure that treatments and interventions are safe and effective in real-world contexts. Improving how information about trials is verbally communicated is an unexplored strategy to make trials more inclusive. This study examined how trials are communicated verbally, comparing consultations involving patients from the most and least socioeconomically disadvantaged areas. Methods: Secondary qualitative analysis of 55 trial consultation transcripts from 41 patients, sampled from 3 qualitative studies embedded in their respective UK multi-site, cancer-related randomised controlled trials. Patients living in the most and least socioeconomically disadvantaged areas, defined using English Indices of Multiple Deprivation decile scores, were purposively sampled. Analysis was largely thematic and drew on the constant comparison method. Results: Recruiters communicated clinical uncertainty in a similar way for patients living in different socioeconomic areas. Consultations with disadvantaged patients were, on average, half the duration of those with advantaged patients, and tended to involve recruiters providing less in-depth explanations of trial concepts, used phrasing that softened trial arm risks, and described trial processes (e.g. randomisation) using informal or metaphorical phrasing. Disadvantaged and advantaged patients differed in the concerns they expressed; disadvantaged patients voiced fewer concerns and asked fewer questions but were also less likely to be invited to do so by recruiters. Conclusion: Interactions about trials unfolded in different ways between patients living in different socioeconomic areas, likely due to both patient- and recruiter-related factors. We present considerations for recruiters when discussing trials with patients from socioeconomically disadvantaged backgrounds, aimed at enhancing trial communication. Future research should examine disadvantaged patients' and recruiters' experiences of verbal trial communication to inform guidance that addresses the needs and preferences of underserved groups. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the effects of vitamin D and/or calcium supplementation on sleep quality in individuals with prediabetes. Methods: A 24-week randomized controlled trial (RCT) was conducted in a 212 Chinese population with prediabetes. Participants were randomly assigned to four groups: vitamin D + calcium group (1600 IU/day + 500 mg/day, n = 53), vitamin D group (1600 IU/day, n = 54), calcium group (500 mg/day, n = 51), and control group (placebo, n = 54). The Pittsburgh Sleep Quality Index (PSQI) was used as the primary outcome to assess sleep quality. Questionnaires and fasting blood samples were collected at baseline and post-intervention for demographic assessment and correlation index analysis. Results: After a 24-week intervention, a significant difference was observed in serum 25(OH)D concentration among the four groups (P < 0.05), and the total PSQI score in vitamin D + calcium group was lower compared to the preintervention levels. Subgroup analyses revealed improved sleep quality with calcium supplementation (P < 0.05) for specific groups, including women, individuals with a low baseline 25(OH)D level (< 30 ng/mL), and individuals in menopause. Moreover, correlation analysis revealed a negative correlation between the extent of change in sleep efficiency scores before and after the calcium intervention and the degree of change in insulin efficiency scores (r = − 0.264, P = 0.007), as well as the magnitude of change in islet beta cell function (r = − 0.304, P = 0.002). Conclusions: The combined intervention of vitamin D and calcium, as well as calcium interventions alone, exhibits substantial potential for improving sleep quality in individuals with prediabetes. Clinical trial registration: The trial was registered in August 2019 as ChiCTR190002487. [ABSTRACT FROM AUTHOR]

Proximal humeral fractures (PHFs) are a common injury among the older population. An ideal therapeutic protocol has yet to be developed, and numerous clinical trials are being conducted to find the best therapeutic approach. The purpose of this study is to evaluate the current body of knowledge available via interventional clinical trials.In December 2022, interventional clinical trials relating to PHFs on Clinicaltrials.gov were screened. Trial characteristics included duration, status, intervention, phase, outcomes, location, and study design. Publications associated with each trial were searched on PubMed/Medline using the ClinicalTrials.gov registry number.The final dataset comprised 64 trials. The most common trial status was completed (36%). The majority did not have a Food and Drug Administration-defined phase (67%), was randomized (81%), involved a single facility (72%), used a parallel assignment intervention model (80%), and used an open-label approach (45%). Eleven trials were associated with a publication, and the publication rate was 17%. Average enrollment was 86 participants, and mean trial duration was 51.4 months. Europe/UK/Russia/Turkey participated in the most trials (70%). Most of the trials were initiated after 2010 (87.5%). Procedure-related interventions (55%) were most common. Disability/function was the most common primary outcome assessed (61%). The low publication rate and the multitude of trials conducted after 2010 highlight the urgency and need for trial results to be published to establish an ideal therapeutic protocol. Since the majority of the trials involved a single institution and an open-label approach, reinforcing blinding and establishing multi-centered trials can improve the validity of the clinical trial results. [ABSTRACT FROM AUTHOR]

Objective: Salicylic acid (SA) has been used for treatment of acne of different severity levels. However, there are few researches about the safety and efficacy for treatment of mild to moderate acne, and the improvement of the skin condition by using 2% supramolecular salicylic acid (SSA) compared to Davuwen Adapaline gel. Methods: A multicenter, randomized, assessor‐blind and parallel‐controlled study was conducted. A total of 500 patients (trial group: 249, control group: 251) with mild to moderate (grade I–II) facial acne vulgaris were recruited in this study over a 16‐week trial period. Patients in the trial group were treated with Broda 2% SSA hydrogel, while control group treated with Davuwen Adapaline gel once a day. The number of inflammatory papules, comedones, and pustules were counted and the rate of lesion reduction was calculated pre‐ and post‐treatment. Then, the skin physiological indicators, including L*a*b*, TEWL, skin sebum and hydration were measured. Statistical analysis was conducted using SAS 9.4. Significance was set at p = 0.05. Results: At the end of 12 weeks' therapy, the regression and markedly improvement rate of the trail group and the control group were 51.01% and 43.10% respectively, and there was no significant difference in the improvement rate between two groups (p = 0.0831). Although, there was no difference in adverse events rate between two groups, the adverse events rate of the trail group was 0.40%, a little lower than the control group (0.80%). Moreover, there was a significant difference in the numbers of pores at T1 between two groups. Conclusion: Both 2% SSA and Adapaline gel were equally effective in the treatment of mild to moderate acne vulgaris. 2% SSA is worth the clinical promotion and application in mild to moderate acne vulgaris. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Culture & Haci Bektas Veli Research Quarterly is the property of Turkish Cultur & Haci Bektas Veli Research Quarterly and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Antalya Bilim University Law Review is the property of Antalya International University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Research in law and literature often uses the term "narrative" as a shorthand for various kinds of motivated legal reasoning, indicating that facts, doctrines, and the relations among them have been chosen and arranged for a particular purpose. Alternatively, speaking of "narrative" may be a way of conveying that one is concerned with interpretation, and may be a signal that the discussion will focus on images, symbols, representations, or ideologies, even if their narrative features play little or no role in the analysis. This article shows how research on narrative might help to clarify aspects of trial strategy and legal doctrine. The first section considers omniscient narration as a way of understanding the effects of various defense strategies, in a criminal trial. The second section considers the role of omniscient narration in the development of the "fellow- servant" rule in the nineteenth century. The law of evidence provides an especially fruitful area for such investigations, but questions of narrative form and technique can help to clarify many other aspects of forensic argumentation and analysis, in both procedural and substantive contexts. [ABSTRACT FROM AUTHOR]

In principle, the legal system regulates the life of a community so that conflicts do not occur, although often these conflicts cannot be avoided, a principle of legal certainty is needed in resolving disputes through arbitration and how the execution of an arbitral award in Indonesia can be applied or implemented. The legal system has an important role to play in resolving these conflicts. The legal system in the judicial world has a major influence in the application of law, especially for judges in examining and deciding a case. Judges in deciding a case will definitely pay great attention to the legal system in their jurisdiction. In addition, the Panel of Judges uses the decisions of other judges who decide cases whose substance in principle has similarities to be used as a reference and consideration in deciding a case. [ABSTRACT FROM AUTHOR]

The birth of the new Criminal Code brought nuances of renewal in the world of justice in Indonesia. However, it also caused upheaval and differences of opinion regarding regulating several aspects of criminal law, including regulating Criminal Acts Against the Judicial Process (Contempt of Court). The regulation of Contempt of Court actions in the new Criminal Code raises pros and cons in society, including advocates who often intersect with the judicial world. The existence of several articles regulating multi-interpretive contempt of court actions is considered to threaten the existence of the Advocate's Right to Immunity in Court. This study aims to analyze the regulation of the Contempt of Court criminal acts regarding the right to immunity of advocates in Court. The research method used is normative legal research using an analytical descriptive approach. This study found that the articles of Contempt of Court in the new Criminal Code, which are multiinterpretive, can limit the space for advocates to express opinions and defend themselves before the court. If these articles are not interpreted properly and correctly, they can become a medium for criminalization by specific individuals against advocates in court. [ABSTRACT FROM AUTHOR]

Background There is strong evidence that those recruited into studies are not always representative of the population for whom the research is most relevant. Development of the study design and funding decisions are points in the research process where considerations about inclusion of under-served populations may usefully be made. Current practical guidance focuses on designing and modifying participant recruitment and retention approaches but an area that has not been addressed is recruitment site selection. Methods We present case studies of three NIHR funded trials to demonstrate how publicly available UK population datasets can be used to facilitate the identification of under-served communities for inclusion in trials. The trials have different designs, address different needs and demonstrate recruitment planning across Trauma centres, NHS Trusts and special educational settings. We describe our use of national freely available datasets, such as those provided by NHS Digital and the Office for National Statistics, to identify potential recruitment sites with consideration of health status, socio-economic status and ethnicity as well as clinical and risk factors to support inclusivity. For all three studies, we produced lists of potential recruitment sites in excess of the number anticipated as necessary to meet the recruitment targets. Discussion We reflect on the challenges to our approach and some potential future developments. The datasets used are all free to use but each has their limitations. Agreeing search parameters, acceptable proxies and identifying the appropriate datasets, then cross referencing between datasets takes considerable time and particular expertise. The case studies are trials, but the methods are generalisable for various other study types. Conclusion Through these exemplars, we aim to build on the NIHR INCLUDE project, by providing trialists with a much needed practical approach to embedding EDI into trial design at the grant application stage.

The paper examines the essence of the appellate court as a controlling judicial instance and clarifies the basic principle according to which the appellate court works and issues judicial acts. Based on this, a check was made to match the nature of the appellate court proceedings with the nature of the classification of his powers as proposed in art. 334 of the Bulgarian Criminal Procedure Code. At the end of the paper, a new classification of his powers, compatible with the nature of appellate judicial review, was developed.

Abstract Three forms of muscular dystrophy‐dystroglycanopathies are linked to the ribitol pathway. These include mutations in the isoprenoid synthase domain‐containing protein (ISPD), fukutin‐related protein (FKRP), and fukutin (FKTN) genes. The aforementioned enzymes are required for generation of the ribitol phosphate linkage in the O‐glycan of alpha‐dystroglycan. Mild cases of dystroglycanopathy present with slowly progressive muscle weakness, while in severe cases the eyes and brain are also involved. Previous research showed that ribose increased the intracellular concentrations of cytidine diphosphate‐ribitol (CDP‐ribitol) and had a therapeutic effect. Here, we report the safety and effects of oral ribose supplementation during 6 months in a patient with limb girdle muscular dystrophy type 2I (LGMD2I) due to a homozygous FKRP mutation. Ribose was well tolerated in doses of 9 g or 18 g/day. Supplementation with 18 g of ribose resulted in a decrease of creatine kinase levels of 70%. Moreover, metabolomics showed a significant increase in CDP‐ribitol levels with 18 g of ribose supplementation (p

Abstract Background The process of obtaining prior informed consent for experimental treatment does not fit well into the clinical reality of acute and intensive care. The therapeutic window of interventions is often short, which may reduce the validity of the consent and the rate of enrolled participants, to delay trial completion and reduce the external validity of the results. Deferred consent and ‘opt-out’ are alternative consent methods. The SafeBoosC-III trial was a randomised clinical trial investigating the benefits and harms of cerebral oximetry monitoring in extremely preterm infants during the first 3 days after birth, starting within the first 6 h after birth. Prior, deferred and opt-out consent were all allowed by protocol. This study aimed to evaluate the use of different consent methods in the SafeBoosC-III trial, Furthermore, we aimed to describe and analyse concerns or complaints that arose during the first 6 months of trial conduct. Methods All 70 principal investigators were invited to join this descriptive ancillary study. Each principal investigator received a questionnaire on the use of consent methods in their centre during the SafeBoosC-III trial, including the possibility to describe any concerns related to the consent methods used during the first 6 months of the trial, as raised by the parents or the clinical staff. Results Data from 61 centres were available. In 43 centres, only prior informed consent was used: in seven, only deferred consent. No centres used the opt-out method only, but five centres used prior and deferred, five used prior, deferred and opt-out (all possibilities) and one used both deferred and opt-out. Six centres applied to use the opt-out method by their local research ethics committee but were denied using it. One centre applied to use deferred consent but was denied. There were only 23 registered concerns during the execution of the trial. Conclusions Consent by opt-out was allowed by the protocol in this multinational trial but only a few investigators opted for it and some research ethics boards did not accept its use. It is likely to need promotion by the clinical research community to unfold its potential.

Proximal humeral fractures (PHFs) are a common injury among the older population. An ideal therapeutic protocol has yet to be developed, and numerous clinical trials are being conducted to find the best therapeutic approach. The purpose of this study is to evaluate the current body of knowledge available via interventional clinical trials.In December 2022, interventional clinical trials relating to PHFs on Clinicaltrials.gov were screened. Trial characteristics included duration, status, intervention, phase, outcomes, location, and study design. Publications associated with each trial were searched on PubMed/Medline using the ClinicalTrials.gov registry number.The final dataset comprised 64 trials. The most common trial status was completed (36%). The majority did not have a Food and Drug Administration-defined phase (67%), was randomized (81%), involved a single facility (72%), used a parallel assignment intervention model (80%), and used an open-label approach (45%). Eleven trials were associated with a publication, and the publication rate was 17%. Average enrollment was 86 participants, and mean trial duration was 51.4 months. Europe/UK/Russia/Turkey participated in the most trials (70%). Most of the trials were initiated after 2010 (87.5%). Procedure-related interventions (55%) were most common. Disability/function was the most common primary outcome assessed (61%). The low publication rate and the multitude of trials conducted after 2010 highlight the urgency and need for trial results to be published to establish an ideal therapeutic protocol. Since the majority of the trials involved a single institution and an open-label approach, reinforcing blinding and establishing multi-centered trials can improve the validity of the clinical trial results.

The study is devoted to ambiguous issues of using artificial intelligence (AI) in judicial process. The purpose of the study is to present foreign experience of using information technologies in court proceedings based on the example of the most controversial and debated ideas concerning resources of artificial intelligence in the system of evidence. Special attention is paid to successful mechanisms of using AI in foreign judicial practice at the stage of evidence assessment. The study presents several decisions of foreign courts, formed with the help of AI. The findings allow to express opinion about admissibility of evidence evaluated by AI. The study employs methods of general scientific cognition and special methods including comparative legal. The dialectical method allows to investigate genesis and progressive development of judicial process technologization. The methods of analysis and synthesis, induction and deduction contribute to highlighting disadvantages of predictive coding at the proving stage and advantages of electronic research of evidence, options for simultaneous disclosure of evidence using different methods on the example of specific court decisions. The comparative legal method helps to identify best practices of using artificial intelligence in the system of evidence in foreign countries. The study not only describes the tools of predicting justice in European judicial practice, but also examines the problems of Chinese "instrumental justice" that can arise in any country. Conclusion justifies predictive coding as a tool of predictive justice, provided that general rules for information disclosure are developed and specifics of machine learning for a particular case are considered. It is noted that artificial intelligence has not yet become the predominant method in any types of legal proceedings. This may be explained by insufficient confidence in it across legal communities and time needed to form a successful history of its use for solving legally significant tasks in various spheres of human life.

Abstract Background Women of reproductive age (WRA) in developing countries are often at risk of micronutrient deficiencies due to inadequate intakes and excessive losses. Objective The purpose of this trial is to assess the effectiveness of United Nations International Multiple Micronutrient Antenatal Preparation-Multiple Micronutrient Supplements (UNIMMAP-MMS) versus iron-folic acid (IFA) among WRA in reducing anemia. Methods Three parallel groups of WRA will participate in a community-based, individually randomized, double-blinded, placebo-controlled superiority trial. After consent, the sample of 375 mildly or moderately anemic women based on hemoglobin by Hemocue will be randomly assigned across two interventions and one control arm. Trial participants in intervention arms will receive UNIMMAP-MMS or IFA while those in the control arm will receive placebos twice a week for 17 weeks. The primary outcome will be a change in mean hemoglobin (Hb) concentrations. Outcome assessors and study participants will be blinded to the type of supplements and study arm. Discussion The World Health Organization (WHO) added UNIMMAP-MMS to its essential medicine lists in 2021 but recommended rigorous study. Several factors in addition to inadequate intakes of iron and folic acid contribute to the high prevalence of anemia among WRA in the Somali region. The findings of this study will provide evidence on the effect of UNIMMAP-MMS and IFA on Hb concentrations and anemia prevalence among anemic WRA. Trial registration ClinicalTrials.gov NCT05682261. Registered on January 12, 2023.

BACKGROUND: In January 2021, vericiguat, a soluble guanylate cyclase stimulator, was approved by the U.S. Food and Drug Administration (FDA) to reduce the risk of cardiovascular death and heart failure (HF) hospitalization among patients with a recent worsening HF event based on the VICTORIA (VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial. OBJECTIVES: This study sought to leverage a contemporary U.S. registry of patients hospitalized for heart failure (HF) to characterize patients who may be candidates for vericiguat based on FDA label and the VICTORIA trial eligibility criteria. METHODS: The authors studied patients hospitalized for HF with ejection fraction (EF)

Background: Non‐inferiority trials comparing different active drugs are often subject to treatment non‐adherence. Intention‐to‐treat (ITT) and per‐protocol (PP) analyses have been advocated in such studies but are not guaranteed to be unbiased in the presence of differential non‐adherence. Methods: The REMoxTB trial evaluated two 4‐month experimental regimens compared with a 6‐month control regimen for newly diagnosed drug‐susceptible TB. The primary endpoint was a composite unfavorable outcome of treatment failure or recurrence within 18 months post‐randomization. We conducted a simulation study based on REMoxTB to assess the performance of statistical methods for handling non‐adherence in non‐inferiority trials, including: ITT and PP analyses, adjustment for observed adherence, multiple imputation (MI) of outcomes, inverse‐probability‐of‐treatment weighting (IPTW), and a doubly‐robust (DR) estimator. Results: When non‐adherence differed between trial arms, ITT, and PP analyses often resulted in non‐trivial bias in the estimated treatment effect, which consequently under‐ or over‐inflated the type I error rate. Adjustment for observed adherence led to similar issues, whereas the MI, IPTW and DR approaches were able to correct bias under most non‐adherence scenarios; they could not always eliminate bias entirely in the presence of unobserved confounding. The IPTW and DR methods were generally unbiased and maintained desired type I error rates and statistical power. Conclusions: When non‐adherence differs between trial arms, ITT and PP analyses can produce biased estimates of efficacy, potentially leading to the acceptance of inferior treatments or efficacious regimens being missed. IPTW and the DR estimator are relatively straightforward methods to supplement ITT and PP approaches. [ABSTRACT FROM AUTHOR]