title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
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Provisions for post-trial care {30} | Participants who achieve two successive negative liquid media cultures, the first of which is at or before week 08, with no positives to follow by the week 16 visit, will not receive further standard of care TB-treatment (continuation phase) according to national guidelines to complete 6 months of treatment. Their plan... | PMC10243693 | ||
Outcomes {12} | anaemia, TB, leukopenia, neuropathy, toxicities | ANAEMIA, LEUKOPENIA, NEUROPATHY, THROMBOCYTOPENIA, RECURRENT DISEASE, EVENT, SECONDARY | The primary safety outcome is the occurrence of oxazolidinone class toxicities defined as peripheral or optical neuropathy, incident leukopenia, anaemia or thrombocytopenia, or AEs in line with tyramine pressor response, all of grade 2 or higher, possibly, probably or definitely related to DZD. Participants will be eva... | PMC10243693 |
Participant timeline {13} | EVENTS, JENSEN | The timeline of the study (see Fig. Schedule of events. WK, week of treatment; MGIT, liquid media (BD mycobacterium growth indicator tube); LJ, Loewenstein - Jensen solid media; MBLA, molecular bacterial load assay; PK, pharmacokinetics; X, refers to all visits mentioned above; ZN, Ziehl-Neelsen stain; PG, pharmacogeno... | PMC10243693 | |
Sample size {14} | Fifteen participants per arm with a total of 75 participants and a wide range of DZD doses (from 0mg to 800 mg BID) has been determined as an adequate sample size for population PK modelling, and for exposure-response modelling to detect a clinically meaningful dose-dependent relationship.Furthermore, the planned sampl... | PMC10243693 | ||
Recruitment {15} | TB | RECRUITMENT, RECRUITMENT | Sites will place recruitment teams in government health clinics where TB diagnostics are offered. Participants who test positive will be informed about the trial and invited for screening.Recruitment can be improved by individual and community awareness of the study and/or TB in general, through public announcements th... | PMC10243693 |
Assignment of interventions: allocation | PMC10243693 | |||
Sequence generation {16a} | The study will be a randomized, open-label trial. Randomization will be implemented after all screening results are available for participants who have given informed consent and who have been found eligible for participation.Participants will be allocated using the Internet-Based Randomization service system: RANDOMIZ... | PMC10243693 | ||
Concealment mechanism {16b} | The allocation sequence is generated by a web-based randomization system set up by the sponsor, with the investigator entering patient details. A minimization algorithm with a random element generates the treatment allocation; the random element prevents the investigator from knowing the allocation before the randomiza... | PMC10243693 | ||
Implementation {16c} | The web-based randomization system has been set up by the sponsor statistician on the Internet-Based Randomization service system: RANDOMIZE.NET. Participants will be enrolled by the allocated study staff (investigator). After all screening results are available and eligibility is proven, the investigator will request ... | PMC10243693 | ||
Assignment of interventions: blinding | PMC10243693 | |||
Who will be blinded {17a} | RECURRENT DISEASE | The personnel assessing participants’ outcomes, like the microbiology laboratory staff or the sponsor medical expert discussing the possibility of recurrent disease, will remain blinded to treatment assignment throughout the whole study in order to ensure unbiased assessment of efficacy endpoints, in attribution of AE ... | PMC10243693 | |
Procedure for unblinding if needed {17b} | EVENT | In the unlikely event that unblinding is necessary in the interest of participants’ safety and well-being throughout the study for sponsor, sponsor medical expert and other blinded staff, this will be requested from the unblinded statisticians and documented. | PMC10243693 | |
Data collection and management | PMC10243693 | |||
Plans for assessment and collection of outcomes {18a} | TTD | For this study, a data management group created a predefined data base. On a weekly basis, the sponsor receives data reports for review, including listings of blood results for the safety management of the participants. These listings help to identify and to act upon weaknesses in data capture but also quality. Further... | PMC10243693 | |
Plans to promote participant retention and complete follow-up {18b} | The process of promoting retention will begin at consent by building a trusting relationship between the participant and the clinical team, as participants are more likely to adhere to study schedules if they know from the outset what they are agreeing to. The study team will collect participants’ demographic informati... | PMC10243693 | ||
Data management {19} | ICH | Electronic case report forms (eCRF) will be created for each participant and all study data collected will be entered into the eCRF. Some data may still be captured entirely or partially on paper source documents and will manually be entered into the eCRF. Accuracy and completeness of the data will be checked by monito... | PMC10243693 | |
Confidentiality {27} | In the trial database and forms, participants will only be identified by a participant identification number, consisting of six figures, which represent the respective site and the enrollment number of the participant. The corresponding participant identification log will be kept in a securely locked separate trial sit... | PMC10243693 | ||
Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33} | Genetic blood samples, stored for future testing, will be labelled using anonymous codes. Results of any genetic tests will not be disclosed to anybody not involved with the study. | PMC10243693 | ||
Statistical methods | PMC10243693 | |||
Statistical methods for primary and secondary outcomes {20a} | TTP | TTP | To establish an exposure-response model for DZD, the change in liquid culture MGIT time to positivity (TTP) will be modelled and linked to derived PK metrics. The model for TTP will be based on a previously develop and published model, linking a latent variable describing the decline in bacterial load to a model of pro... | PMC10243693 |
Interim analyses {21b} | The data management and safety board (DSMB) will act as an advisory capacity to the Trial Steering Committee (TSC), to safeguard the interest of trial participants and to review the results of the interim analyses. It will also provide the TSC with recommendations on the continuation, premature closure of the trial or ... | PMC10243693 | ||
Methods for additional analyses (e.g. subgroup analyses) {20b} | death, TTP | REGRESSION, TTP | Descriptive summary statistics, such a mean/median of the time to culture conversion will be tabulated. Proportion of participants achieving culture conversion at each time point during treatment will be summarized.A Cox regression model will be used to compare each arm with different DZD doses to the background regime... | PMC10243693 |
Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c} | SECONDARY | The primary analysis population is the intent-to-treat (ITT) analysis population. The ITT analysis population will consist of all randomized patients in the groups to which they were randomly assigned, and who have taken at least one dose of study treatment.A secondary analysis will be of the adequate adherence (AA) an... | PMC10243693 | |
Plans to give access to the full protocol, participant level-data and statistical code {31c} | TB | The PanACEA consortium intends to make the protocol and dataset available, e.g. via the TB PACTS TB trials database. | PMC10243693 | |
Oversight and monitoring | PMC10243693 | |||
Composition of the coordinating centre and trial steering committee {5d} | TSC | The TSC will be composed of at least 3 voting members, including a representative of the sponsor, the coordinator of the PanACEA consortium and an independent clinician.The role of the TSC is to provide overall supervision of the trial and ensure that the trial is conducted in accordance with Good Clinical Practice and... | PMC10243693 | |
Composition of the data monitoring committee, its role and reporting structure {21a} | TB | The DSMB will consist of five members: a clinician with experience in treatment for drug-sensitive and MDR-TB, an epidemiologist, a pharmacologist, a statistician and a TB laboratory science expert. The DSMB will be installed to safeguard the interest of trial participants and include an element of expert advice that i... | PMC10243693 | |
Adverse event reporting and harms {22} | ADVERSE EVENT | All participants will be instructed during informed consent to report at any time any occurrence of AEs to the investigator. In addition, AEs will be solicited at every scheduled visit. The severity of AEs will be classified following the U.S. National Institutes of Health Common Terminology for Adverse Events 5.0 (CTC... | PMC10243693 | |
Frequency and plans for auditing trial conduct {23} | The sponsor has created an audit plan that includes three audits performed by qualified auditors of partner institutions in the PanACEA consortium that take on trial-related responsibilities, and of subcontractors. | PMC10243693 | ||
Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25} | Protocol amendments, after being fully approved by applicable ethics committees and regulatory agencies, will be transmitted to investigators and a protocol amendment training will be performed and documented. | PMC10243693 | ||
Dissemination plans {31a} | TB | Trial outcomes will be important for TB participants and their treating healthcare providers. The results of this trial will be disseminated via scientific publications through high-impact, international, peer-reviewed journals and through scientific conferences; open access schemes will be used. | PMC10243693 | |
Discussion | hypoxemia, infection | INFECTION | The occurrence of COVID-19 during trial preparation affected IMP production, and COVID-19 in trial participants may generate false safety signals if attributed to the trial drugs. Therefore, we included guidance on COVID-19 testing based on symptoms or hypoxemia into the trial-specific manuals and discussed preventive ... | PMC10243693 |
Trial status | RECRUITMENT | At the time of writing this publication, the protocol version 2.1 was used in South Africa and protocol version 2.0 in Tanzania. Recruitment started at the end of October 2021 and is expected to end in Q3 2022.
| PMC10243693 | |
Acknowledgements | TB, Alphonce | BRUCE, FRANCIS, DAWSON | The authors would like to acknowledge the members of the data safety monitoring board (Prof. Robert Horsburgh Jr., Prof Andrew Nunn, Prof. Gary Maartens, Prof. Jae-Joon Yim, Dr Ndeky Maria Oriyo),We are grateful to Prof. Kelly Dooley, Vanderbilt University, for invaluable support during study design and conduct, Prof. ... | PMC10243693 |
Authors’ contributions {31b} | MH, RA | The study design was conceptualized by NH, ES, MH, and LG. Funding and study drug is made available by YLC and LG. The study protocol was written by SS, NH, AD, AJM, ES, LtB, RA, YLC, LG, and MH. The study is set up and conducted by AD, SS, LH, AJM, LtB, RA, MB, TMcH, LMW, LTM, NN, MS, AL, RSW, MS, FAM, BM, LG, YLC, an... | PMC10243693 | |
Funding {4} | TB, Infection | INFECTION | Open Access funding enabled and organized by Projekt DEAL. The study is funded by LegoChem Biosciences, Inc, and conducted under the umbrella of PanACEA, the PanAfrican Consortium for the Evaluation of anti-TB Antibiotics, which receives funding through the European and Developing Countries Clinical Trials Partnership ... | PMC10243693 |
Availability of data and materials {29} | All parties conducting the trial will have access to the final trial dataset. | PMC10243693 | ||
Declarations | PMC10243693 | |||
Ethics approval and consent to participate {24} | This study protocol was approved by the Ethic committee of the Ludwig-Maximilians-University of Munich, Germany and by applicable ethics committees of the trial sites. These include:South African Health Products and Regulatory Authority, Arcadia, South AfricaHuman Research Ethics committee, University of the Witwatersr... | PMC10243693 | ||
Consent for publication {32} | “Informed consent forms” of the study may be provided by the corresponding author upon reasonable request. | PMC10243693 | ||
Competing interests {28} | All authors except LG and YLC report receiving research funding from LegoChem Biosciences to their institutions. LG receives compensation as a consultant. YLC is an employee of LegoChem Biosciences. Further, the authors would like to report receiving delamanid (Deltyba®) free of charge, from Otsuka Novel Products GmbH. | PMC10243693 | ||
References | PMC10243693 | |||
Introduction | Across the literature, training interventions that have attempted to reduce hamstring strain injury (HSI) incidence, have aimed to mitigate the influence of the modifiable risk factors of HSI (i.e., eccentric hamstring strength and bicep femoris long head (BFCurrently, the NHE has been a key focus of training research ... | PMC9980768 | ||
Materials and methods | An intervention study design was employed for the present study ( | PMC9980768 | ||
Schematic diagram of pre-testing, seven-week intervention and post-testing. | PMC9980768 | |||
Participants | 38 collegiate athletes who participated in regular team sports (football, futsal, rugby union, rugby league, ice hockey, American football, basketball, netball). All participants reported competing across a range of competitive levels from university (collegiate) to semi-professional level sports participation. Partici... | PMC9980768 | ||
Lower limb resistance training programe, including sets x reps and estimated one repetition maximum percentages, performed by the control and intervention groups across the seven-week training intervention. | In conjunction to the control resistance training programme, the intervention groups were prescribed either additional sprint or NHE training at the start or end of each training session ( | PMC9980768 | ||
Additional training performed by the NHE or sprint intervention groups across the seven-week training intervention, including sets x reps. | The study aimed to control for any other resistance training performed by the participants, advising that outside the prescribed programme no further lower-limb resistance training could be performed. Only an individual’s sport-specific and upper body resistance training was permitted. | PMC9980768 | ||
Data collection | PMC9980768 | |||
Bicep femoris long head muscle architecture | All testing commenced with resting US imaging of the BFTo collect the ultrasound images, a layer of conductive gel was placed across the linear array probe; the probe was then placed on the skin over the scanning site and aligned longitudinally to the BF and perpendicular to the skin. During collection of the ultrasoun... | PMC9980768 | ||
Countermovement jump | Following muscle architecture assessment, participants performed a standardised dynamic warm-up consisting of body weight squats, forward and reverse lunges, submaximal squat jumps and CMJs. Three maximal effort CMJs, with a one-minute rest between trials was assessed using a Kistler force platform, sampling at 1000 Hz... | PMC9980768 | ||
Eccentric hamstring strength | The assessment of eccentric knee flexor strength was performed using the Nordbord device (Vald Performance, Newstead, Australia), which has been used in the literature previously [ | PMC9980768 | ||
Lower limb maximal strength | For the isometric mid-thigh pull (IMTP), the procedures and guidelines previously described were used [ | PMC9980768 | ||
Sprinting | Prior to completing the sprint assessment, two 20 m practice sprints at 50- and 75% of perceived maximum intensity, which also served as a brief familiarisation period. Three maximum effort trials of the 20 m sprint were performed, with brief rest periods of two minutes prescribed between trials. Instructions were prov... | PMC9980768 | ||
Data analysis | PMC9980768 | |||
Bicep femoris architectural digitization | All sonograms were analysed off-line with Image J version 1.52 software (National Institute of Health, Bethesda, MD, USA). Images were first calibrated to the known field of view (10-cm), then for each image a fascicle of interest was identified. Finally, muscle thickness, pennation angle, observed FL and distance betw... | PMC9980768 | ||
Force-time analysis | Raw force-time data for the CMJ, IMTP and NHE was analysed in Microsoft Excel (Excel 2016, Microsoft, Washington, USA). For the CMJ, velocity of centre of mass at take-off was determined as a measure of performance (take-off velocity) [For the IMTP, peak absolute and relative net force was determined as the maximum for... | PMC9980768 | ||
Reliability and measurement error | A subsample performed two PRE-testing sessions (n = 24), to determine the between-session reliability and measurement of each variable of interest. All data was first tested using the Shapiro-Wilk test to check if it satisfied parametric assumptions. A two-way random-effects model intraclass correlation coefficient (IC... | PMC9980768 | ||
Pre to post intervention changes | Data obtained at pre was taken forward to perform comparisons at post training, as parametric assumptions were met for all measures using the Shapiro-Wilk test, between- pre and post in the modifiable risk factors (BFAll statistical analyses performed using SPSS software (version 25; SPSS Inc. Chicago, IL, USA) with th... | PMC9980768 | ||
Results | PMC9980768 | |||
Reliability and measurement error | Between session reliability and measurement error for all variables of interest are presented in | PMC9980768 | ||
Pre- to Post-intervention changes | At pre-testing, there were trivial non-significant differences observed between all groups for bicep femoris fascicle length and eccentric hamstring strength measures (Hedge’s | PMC9980768 | ||
Body mass | Trivial increases (g <0.34) in body mass were observed across all groups from PRE to POST ( | PMC9980768 | ||
Pairwise comparisons of body mass for all training groups. | PMC9980768 | |||
Bicep femoris fascicle length | A non-significant time×training interaction was observed for absolute and relative BF | PMC9980768 | ||
Gardner-Altman estimation plots identifying Pre- and Post-intervention individual changes for absolute bicep femoris fascicle length and Hedge’s | PMC9980768 | |||
Gardner-Altman estimation plots identifying Pre- and Post-intervention individual changes for relative bicep femoris fascicle length and Hedge’s | PMC9980768 | |||
Pairwise comparisons of Bicep femoris fascicle length for all training groups. | PMC9980768 | |||
Eccentric hamstring strength | Peak and relative peak force demonstrated a significant time×training interaction ( | PMC9980768 | ||
Gardner-Altman estimation plots identifying Pre- and Post-intervention individual changes for peak eccentric hamstring force and Hedge’s | PMC9980768 | |||
Gardner-Altman estimation plots identifying Pre- and Post-intervention individual changes for relative peak eccentric hamstring force and Hedge’s | PMC9980768 | |||
Pairwise comparisons of eccentric hamstring measures for all training groups. | PMC9980768 | |||
Countermovement jump | A non-significant time×training interaction was observed for take-off velocity and jump momentum (p = 0.834 & 0.518, respectively). Pairwise comparisons, revealed small increases ( | PMC9980768 | ||
Gardner-Altman estimation plots identifying Pre- and Post-intervention individual changes for take-off velocity and Hedge’s | PMC9980768 | |||
Gardner-Altman estimation plots identifying Pre- and Post-intervention individual changes for jump momentum and Hedge’s g effect size with the 95% CI indicated by the ends of the vertical error bar. | PMC9980768 | |||
Pairwise comparisons of countermovement jump measures for all training groups. | All other CMJ variables; countermovement time, displacement, and peak braking force, showed non-significant time×training interaction, with trivial differences from PRE to POST for all training groups. | PMC9980768 | ||
Isometric mid-thigh pull | For peak absolute and relative net force attained from the IMTP assessment, a significant time×training interaction was observed ( | PMC9980768 | ||
Gardner-Altman estimation plots identifying Pre- and Post-intervention individual changes for peak net force and Hedge’s | PMC9980768 | |||
Gardner-Altman estimation plots identifying Pre- and Post-intervention individual changes for peak net relative force and Hedge’s | PMC9980768 | |||
Pairwise comparisons of peak net IMTP force for all training groups. | * = significant increase | PMC9980768 | ||
Sprinting | Non-significant time×training interactions were observed for sprint and Nordic training groups for 0-10-, 0-20- and 10–20 m ( | PMC9980768 | ||
Gardner-Altman estimation plots identifying Pre- and Post-intervention individual changes for 0-10m sprint time and Hedge’s | PMC9980768 | |||
Gardner-Altman estimation plots identifying Pre- and Post-intervention individual changes for 0-20m sprint time and Hedge’s | PMC9980768 | |||
Gardner-Altman estimation plots identifying Pre- and Post-intervention individual changes for 10-20m sprint time and Hedge’s | PMC9980768 | |||
Pairwise comparisons of sprint measures between Nordic and sprint training groups. | RPE | No significant group×time interactions was observed for RPE ( | PMC9980768 | |
Mean (±95%CI) Rating of perceived exertion measured using a numeric scale (1–10) for the Nordic hamstring exercise, Sprint and control groups. | DOMS | The average DOMS reported ( | PMC9980768 | |
Mean (±95%CI) 24-hr post soreness measured using a numeric pain rating scale (1–10) for the Nordic hamstring exercise, Sprint, and control groups. | PMC9980768 | |||
Discussion | The results of the present study demonstrate that a multi-modal approach to hamstring training is highly effective in increasing both the modifiable risk factors of HSI (eccentric hamstring strength and BF | PMC9980768 | ||
Modifiable risk factors | The results of the present study identified meaningful increases (i.e., >SDD) for the modifiable risk factors (absolute and relative BFThe observed changes seen within the present study for BFConsistent with previous training interventions, absolute and relative eccentric hamstring strength was increased across all tra... | PMC9980768 | ||
Athletic performance | Meaningful increases in CMJ take-off velocity were observed for all training groups. The increase in take-off velocity, would also represent an increased jump height, although the smaller measurement error observed with take-off velocity means the increases observed are less likely to be an effect of random error. It s... | PMC9980768 | ||
Compliance | The present study was highly effective at increasing both modifiable risk factors of HSI (eccentric hamstring strength of BF | PMC9980768 | ||
Limitations | The present study is not without its limitations; firstly, although all participants reported participation in regular sport (predominantly team sport); competitive level, season, positional demands could have influenced the adaptations. This meant that individuals would have been exposed to a variety of external runni... | PMC9980768 | ||
Conclusions | The present study set out to determine the effect of a short-term training intervention with supplemental sprint or NHE, imbedded within an ecologically valid lower limb training programme, on the magnitude of adaptations to the modifiable risk factors of HSI, BF | PMC9980768 | ||
Supporting information | (XLSX)Click here for additional data file. | PMC9980768 | ||
Key Points | PMC10638655 | |||
Question | DISORDER | Does social contagion affect adoption of the practice of emergency department initiation of buprenorphine for opioid use disorder? | PMC10638655 | |
Findings | SECONDARY | In this secondary analysis of a multicenter, cluster-randomized trial of 5 health care systems and 1026 clinicians, including attending physicians, residents, and advanced practice practitioners, the number of interactions with another clinician initiating buprenorphine in the emergency department had a dose-dependent ... | PMC10638655 | |
Meaning | opioid use disorder | SECONDARY, INTERACTION | Interaction with other clinicians initiating buprenorphine was associated with increased likelihood of self-adoption, suggesting that there may be a role for social factors in practice uptake.This secondary analysis of a cluster randomized trial examines the factors, including social contagion, associated with the adop... | PMC10638655 |
Importance | EMERGENCY | Emergency department (ED) initiation of buprenorphine is safe and effective but underutilized in practice. Understanding the factors affecting adoption of this practice could inform more effective interventions. | PMC10638655 | |
Objective | opioid use disorder | To quantify the factors, including social contagion, associated with the adoption of the practice of ED initiation of buprenorphine for patients with opioid use disorder. | PMC10638655 |
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