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Journal of Foot and Ankle Research Jun 2024Running retraining is commonly used in the management of medial tibial stress syndrome (MTSS) but evidence for its effectiveness is lacking. The primary aim of this... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Running retraining is commonly used in the management of medial tibial stress syndrome (MTSS) but evidence for its effectiveness is lacking. The primary aim of this study is to determine if the addition of running retraining to best standard care is beneficial in the management of runners with MTSS.
METHODS
This study is an assessor-blinded and participant-blinded, parallel-group, randomised controlled trial. The trial will recruit 64 participants aged between 18 and 45 years, with a clinical diagnosis of MTSS that has affected their running participation for at least four weeks. Participants will be randomised to receive best standard care (control) or running retraining and best standard care (intervention group) over an 8-week period. Best standard care will consist of load management advice, symptom management advice, footwear advice and a strengthening program. Running retraining will consist of a cue to reduce running step length. Outcomes will be measured at weeks 1, 2, 4 and 8. The primary outcome measure will be the University of Wisconsin Running Injury and Recovery Index at week 4. Secondary outcome measures include: (i) Exercise Induced Leg Pain Questionnaire-British Version, (ii) global rating of change scale, (iii) worst pain experienced during a run, (iv) weekly run volume, (v) reactive strength index score, (vi) single leg hop test, (vii) soleus single leg maximum voluntary isometric contraction, (viii) gastrocnemius single leg maximum voluntary isometric contraction, (ix) single leg plantar flexor endurance test, (x) running step length, and (xi) running step rate. Data will be analysed using the intention-to-treat principle.
DISCUSSION
This randomised controlled trial will evaluate if reducing running step length provides additional benefit to best standard care in the management of runners with MTSS over an 8-week period.
TRIAL REGISTRATION
Australian New Zealand Clinical Trials Registry: ACTRN12624000230550.
Topics: Humans; Running; Medial Tibial Stress Syndrome; Adult; Male; Young Adult; Female; Adolescent; Middle Aged; Exercise Therapy; Treatment Outcome; Standard of Care
PubMed: 38873909
DOI: 10.1002/jfa2.12029 -
Neurorehabilitation and Neural Repair Jun 2024Actual and imagined cued gait trainings have not been compared in people with multiple sclerosis (MS).
BACKGROUND
Actual and imagined cued gait trainings have not been compared in people with multiple sclerosis (MS).
OBJECTIVE
To analyze the effects of cued motor imagery (CMI), cued gait training (CGT), and combined CMI and cued gait training (CMI-CGT) on motor, cognitive, and emotional functioning, and health-related quality of life in people with MS.
METHODS
In this double-blind randomized parallel-group multicenter trial, people with MS were randomized (1:1:1) to CMI, CMI-CGT, or CGT for 30 minutes, 4×/week for 4 weeks. Patients practiced at home, using recorded instructions, and supported by ≥6 phone calls. Data were collected at weeks 0, 4, and 13. Co-primary outcomes were walking speed and distance, analyzed by intention-to-treat. Secondary outcomes were global cognitive impairment, anxiety, depression, suicidality, fatigue, HRQoL, motor imagery ability, music-induced motivation, pleasure and arousal, self-efficacy, and cognitive function. Adverse events and falls were continuously monitored.
RESULTS
Of 1559 screened patients, 132 were randomized: 44 to CMI, 44 to CMI-CGT, and 44 to CGT. None of the interventions demonstrated superiority in influencing walking speed or distance, with negligible effects on walking speed (η = 0.019) and distance (η = 0.005) observed in the between-group comparison. Improvements in walking speed and walking distance over time corresponded to large effects for CMI, CMI-CGT, and CGT (η = 0.348 and η = 0.454 respectively). No severe study-related adverse events were reported.
CONCLUSIONS
CMI-GT did not lead to improved walking speed and distance compared with CMI and CGT alone in people with MS. Lack of a true control group represents a study limitation.
TRIAL REGISTRATION
German Clinical Trials Register, DRKS00023978.
PubMed: 38873806
DOI: 10.1177/15459683241260724 -
Euro Surveillance : Bulletin Europeen... Jun 2024BackgroundDenmark possesses an exceptional historical data collection on tuberculosis (TB) from 1876 to the present, providing a unique opportunity to assess TB...
BackgroundDenmark possesses an exceptional historical data collection on tuberculosis (TB) from 1876 to the present, providing a unique opportunity to assess TB epidemiology over 147 years in Denmark.AimOur aim was to describe the TB disease burden in Denmark in relation to historical events, living conditions and health interventions during the past 147 years.MethodsWe performed a nationwide register-based ecological study including all persons with TB in Denmark from 1876 through 2022, correlating the TB incidence to social, economic and health indicators.ResultsIn Denmark, the overall TB incidence and mortality declined markedly over the past 147 years, only marginally influenced by specific TB interventions such as sanatoria, Bacillus Calmette-Guèrin (BCG) vaccination, mass screenings and antibiotics. Parallel to this decline, the country experienced improved living conditions, as illustrated by decreased infant mortality and increased life expectancy and wealth. In 1978, Denmark became a low-incidence country for TB with risk groups predominantly affected, and with a continuous change in demographics towards fewer Danish-born cases and relatively more migrant cases.ConclusionsThe decline over time in TB incidence and mortality in Denmark preceded specific TB interventions and can, first of all, be attributed to improved living conditions. TB has now become a rare disease in Denmark, predominantly occurring in particular risk groups. Future elimination of TB will require a combination of specific health interventions in these risk groups combined with a continued focus on improving socioeconomic status and living conditions.
Topics: Humans; Denmark; Incidence; Tuberculosis; Female; Male; Registries; History, 20th Century; History, 19th Century; History, 21st Century; Adult; Middle Aged; Infant; Socioeconomic Factors; Mass Screening; Aged; Life Expectancy; Adolescent; BCG Vaccine; Risk Factors; Child, Preschool; Young Adult; Child; Population Surveillance
PubMed: 38873798
DOI: 10.2807/1560-7917.ES.2024.29.24.2300652 -
Frontiers in Immunology 2024The five-year survival rates for pancreatic ductal adenocarcinoma (PDAC) have scarcely improved over the last half-century. It is inherently resistant to FDA-approved... (Review)
Review
The five-year survival rates for pancreatic ductal adenocarcinoma (PDAC) have scarcely improved over the last half-century. It is inherently resistant to FDA-approved immunotherapies, which have transformed the outlook for patients with other advanced solid tumours. Accumulating evidence relates this resistance to its hallmark immunosuppressive milieu, which instils progressive dysfunction among tumour-infiltrating effector T cells. This milieu is established at the inception of neoplasia by immunosuppressive cellular populations, including regulatory T cells (T), which accumulate in parallel with the progression to malignant PDAC. Thus, the therapeutic manipulation of T has captured significant scientific and commercial attention, bolstered by the discovery that an abundance of tumour-infiltrating T correlates with a poor prognosis in PDAC patients. Herein, we propose a mechanism for the resistance of PDAC to anti-PD-1 and CTLA-4 immunotherapies and re-assess the rationale for pursuing T-targeted therapies in light of recent studies that profiled the immune landscape of patient-derived tumour samples. We evaluate strategies that are emerging to limit T-mediated immunosuppression for the treatment of PDAC, and signpost early-stage trials that provide preliminary evidence of clinical activity. In this context, we find a compelling argument for investment in the ongoing development of T-targeted immunotherapies for PDAC.
Topics: Humans; Carcinoma, Pancreatic Ductal; T-Lymphocytes, Regulatory; Pancreatic Neoplasms; Immunotherapy; Animals; Lymphocytes, Tumor-Infiltrating; Tumor Microenvironment; Immune Checkpoint Inhibitors
PubMed: 38873607
DOI: 10.3389/fimmu.2024.1406250 -
Frontiers in Pharmacology 2024Dilated cardiomyopathy (DCM) is a fatal myocardial condition with ventricular structural changes and functional deficits, leading to systolic dysfunction and heart...
Dilated cardiomyopathy (DCM) is a fatal myocardial condition with ventricular structural changes and functional deficits, leading to systolic dysfunction and heart failure (HF). DCM is a frequent complication in oncologic patients receiving Doxorubicin (Dox). Dox is a highly cardiotoxic drug, whereas its damaging spectrum affects most of the organs by multiple pathogenic cascades. Experimentally reproduced DCM/HF through Dox administrations has shed light on the pathogenic drivers of cardiotoxicity. Growth hormone (GH) releasing peptide 6 (GHRP-6) is a GH secretagogue with expanding and promising cardioprotective pharmacological properties. Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats. Myocardial changes were sequentially evaluated by transthoracic echocardiography. Autopsy was conducted at the end of the administration period when ventricular dilation was established. Semiquantitative histopathologic study included heart and other internal organs samples. Myocardial tissue fragments were also addressed for electron microscopy study, and characterization of the transcriptional expression ratio between Bcl-2 and Bax. Serum samples were destined for REDOX system balance assessment. GHRP-6 administration in parallel to Dox prevented myocardial fibers consumption and ventricular dilation, accounting for an effective preservation of the LV systolic function. GHRP-6 also attenuated extracardiac toxicity preserving epithelial organs integrity, inhibiting interstitial fibrosis, and ultimately reducing morbidity and mortality. Mechanistically, GHRP-6 proved to sustain cellular antioxidant defense, upregulate prosurvival gene Bcl-2, and preserve cardiomyocyte mitochondrial integrity. These evidences contribute to pave potential avenues for the clinical use of GHRP-6 in Dox-treated subjects.
PubMed: 38873418
DOI: 10.3389/fphar.2024.1402138 -
Frontiers in Oncology 2024Indications for HSCT are increasing worldwide, paralleled by a growing demand for donors of therapeutic cells.
INTRODUCTION
Indications for HSCT are increasing worldwide, paralleled by a growing demand for donors of therapeutic cells.
METHODS
Herein, we report our real-world experience of adult HPC donor assessment during a 5-year study period (2018-2023): we have retrospectively revised data of 455 potential related stem cell donors, consecutively evaluated at our center. Donor medical history was assessed by a questionnaire and an interview with a trained physician experienced in donation procedures to evaluate donor fitness and medical history. Pre-existing health disorders were fully investigated. Behavioral risk factors for communicable infectious diseases were also routinely explored.
RESULTS AND DISCUSSION
Overall, 351 donors were finally assessed as eligible for HPC donation, and 233 underwent stem cell collection, 158 through apheresis from mobilized peripheral blood, and 75 through bone marrow harvest. Among them, 27 donors were selected despite the presence of pre-existing health conditions, which would be potential exclusion criteria for unrelated donors: 16 suffered from well-controlled cardiovascular diseases (CVD) and 11 from allergic diathesis. Most of the selected donors with pre-existing disorders were candidates for apheresis HPC collection (21, 77.8%), while only six (22.2%) underwent BM harvest. We then analyzed the data relative to the corresponding 233 allogeneic HSCT to explore if the presence of pre-existing diseases in the donors could show any association with transplant characteristics. Transplants from CVD and allergy donors showed no significant disparities in comparison with those from healthy donors. A significant difference emerged regarding the disease severity, with a higher proportion of patients with high/very high disease risk index (DRI) among those receiving grafts from CVD donors (68.7% in transplants from CVD donors versus 36.0% in transplants from healthy donors, p=0.005). Multivariate analysis confirmed that high/very high DRI patients had an increased probability of receiving donations from CVD donors (OR, 4.89; 95%CI, 1.15-20.86; p=0.031). Among donors with well-controlled pre-existing conditions, no adverse events were recorded during stem cell collection or at follow-up. Our results suggest that in patients at high risk for relapse requiring a prompt allogeneic transplant, a familiar donor might be accepted for HPC apheresis donation on less strict criteria than unrelated donors, without risk for both donor and patient.
PubMed: 38873255
DOI: 10.3389/fonc.2024.1389068 -
Chemical Science Jun 2024The construction and application of metal-organic cages with accessible internal cavities have witnessed rapid development, however, the precise synthesis of complex...
The construction and application of metal-organic cages with accessible internal cavities have witnessed rapid development, however, the precise synthesis of complex metal-organic capsules with multiple cavities and achievement of multi-guest encapsulation, and further in-depth comprehension of host-multi-guest recognition remain a great challenge. Just like building LEGO blocks, herein, we have constructed a series of high-order layered metal-organic architectures of generation ( = 1/2/3/4 is also the number of cavities) by multi-component coordination-driven self-assembly using porphyrin-containing tetrapodal ligands (like plates), multiple parallel-podal ligands (like clamps) and metal ions (like nodes). Importantly, these high-order assembled structures possessed different numbers of rigid and separate cavities formed by overlapped porphyrin planes with specific gaps. The host-guest experiments and convincing characterization proved that these capsules G2-G4 could serve as host structures to achieve multi-guest recognition and unprecedentedly encapsulate up to four C molecules. More interestingly, these capsules revealed negative cooperation behavior in the process of multi-guest recognition, which provides a new platform to further study complicated host-multi-guest interaction in the field of supramolecular chemistry.
PubMed: 38873050
DOI: 10.1039/d4sc01204f -
Chronic Diseases and Translational... Jun 2024Exercise and medication have similar benefits in reducing blood pressure (BP); however, hypertension management initiatives primarily focus on medicines. This is due to...
Effectiveness of m-health technology-enabled physical activity program on physical activity adoption and adherence in people with hypertension in India: A randomized controlled trial protocol.
BACKGROUND
Exercise and medication have similar benefits in reducing blood pressure (BP); however, hypertension management initiatives primarily focus on medicines. This is due to scarce research on the effectiveness of implementation strategies for optimal exercise adoption and adherence. Smartphones were found to be effective in delivering hypertension care and increase exercise adherence. Despite this, only a small number of research projects in India have used smartphones as a strategy for managing hypertension.
METHODS
We hypothesized that smartphone application-based care would lead to higher exercise adherence among adults (30-79 years) with hypertension compared to those who receive usual care. It will be a multicentric, randomized controlled, parallel-design, superiority clinical trial. The outcome assessor and data analyst will be blinded to group allocation. Participants in the intervention group will receive mobile application-based care for 6 weeks. Participants in the usual care group will receive a standard intervention. Both groups will receive the same number of follow-ups.
RESULTS
The primary outcome is the difference in the proportion of people adherent to the recommended level of physical activity evaluated using an exercise adherence rating scale in the intervention group and the control group. Exercise adoption will be measured as the percentage of eligible participants in each study setting willing to initiate the exercise program. The secondary outcome includes differences in systolic and diastolic BP and self-management (evaluated using the Hypertension Self-Care Profile). The trial outcome will be accompanied by a process evaluation.
CONCLUSIONS
This research will inform about the comparative effectiveness of conventional and m-health interventions for exercise adoption and adherence in people with hypertension in resource-constrained settings.
PubMed: 38872762
DOI: 10.1002/cdt3.101 -
Frontiers in Aging Neuroscience 2024The lack of cognitive awareness, anosognosia, is a clinical deficit in Alzheimer's disease (AD) dementia. However, an increased awareness of cognitive function,...
INTRODUCTION
The lack of cognitive awareness, anosognosia, is a clinical deficit in Alzheimer's disease (AD) dementia. However, an increased awareness of cognitive function, hypernosognosia, may serve as a marker in the preclinical stage. Subjective cognitive decline (SCD) might correspond to the initial symptom in the dynamic trajectory of awareness, but SCD might be absent along with low awareness of actual cognitive performance in the preclinical stage. We hypothesized that distinct meta-cognitive profiles, both hypernosognosia and anosognosia, might be identified in preclinical-AD. This research evaluated the association between cerebrospinal fluid (CSF) AD biomarkers and the awareness of episodic memory, further exploring dyadic (participant-partner) SCD reports, in the preclinical Alzheimer's continuum.
METHODS
We analyzed 314 cognitively unimpaired (CU) middle-aged individuals (mean age: 60, SD: 4) from the ALFA+ cohort study. Episodic memory was evaluated with the delayed recall from the Memory Binding Test (MBT). Awareness of episodic memory, meta-memory, was defined as the normalized discrepancy between objective and subjective performance. SCD was defined using self-report, and dyadic SCD profiles incorporated the study partner's report using parallel SCD-Questionnaires. The relationship between CSF Aβ42/40 and CSF p-tau181 with meta-memory was evaluated with multivariable regression models. The role of SCD and the dyadic contingency was explored with the corresponding stratified analysis.
RESULTS
CSF Aβ42/40 was non-linearly associated with meta-memory, showing an increased awareness up to Aβ-positivity and a decreased awareness beyond this threshold. In the non-SCD subset, the non-linear association between CSF Aβ42/40 and meta-memory persisted. In the SCD subset, higher Aβ-pathology was linearly associated with increased awareness. Individuals presenting only study partner's SCD, defined as unaware decliners, exhibited higher levels of CSF p-tau181 correlated with lower meta-memory performance.
DISCUSSION
These results suggested that distinct meta-cognitive profiles can be identified in preclinical-AD. While most individuals might experience an increased awareness associated with the entrance in the AD continuum, hypernosognosia, some might be already losing insight and stepping into the anosognosic trajectory. This research reinforced that an early anosognosic profile, although at increased risk of AD-related decline, might be currently overlooked considering actual diagnostic criteria, and therefore its medical attention delayed.
PubMed: 38872632
DOI: 10.3389/fnagi.2024.1394460 -
Trials Jun 2024The TRANSLATE (TRANSrectal biopsy versus Local Anaesthetic Transperineal biopsy Evaluation) trial assesses the clinical and cost-effectiveness of two biopsy procedures...
Statistical analysis plan for the TRANSLATE (TRANSrectal biopsy versus Local Anaesthetic Transperineal biopsy Evaluation of potentially clinically significant prostate cancer) multicentre randomised controlled trial.
BACKGROUND
The TRANSLATE (TRANSrectal biopsy versus Local Anaesthetic Transperineal biopsy Evaluation) trial assesses the clinical and cost-effectiveness of two biopsy procedures in terms of detection of clinically significant prostate cancer (PCa). This article describes the statistical analysis plan (SAP) for the TRANSLATE randomised controlled trial (RCT).
METHODS/DESIGN
TRANSLATE is a parallel, superiority, multicentre RCT. Biopsy-naïve men aged ≥ 18 years requiring a prostate biopsy for suspicion of possible PCa are randomised (computer-generated 1:1 allocation ratio) to one of two biopsy procedures: transrectal (TRUS) or local anaesthetic transperineal (LATP) biopsy. The primary outcome is the difference in detection rates of clinically significant PCa (defined as Gleason Grade Group ≥ 2, i.e. any Gleason pattern ≥ 4 disease) between the two biopsy procedures. Secondary outcome measures are th eProBE questionnaire (Perception Part and General Symptoms) and International Index of Erectile Function (IIEF, Domain A) scores, International Prostate Symptom Score (IPSS) values, EQ-5D-5L scores, resource use, infection rates, complications, and serious adverse events. We describe in detail the sample size calculation, statistical models used for the analysis, handling of missing data, and planned sensitivity and subgroup analyses. This SAP was pre-specified, written and submitted without prior knowledge of the trial results.
DISCUSSION
Publication of the TRANSLATE trial SAP aims to increase the transparency of the data analysis and reduce the risk of outcome reporting bias. Any deviations from the current SAP will be described and justified in the final study report and results publication.
TRIAL REGISTRATION
International Standard Randomised Controlled Trial Number ISRCTN98159689, registered on 28 January 2021 and registered on the ClinicalTrials.gov (NCT05179694) trials registry.
Topics: Humans; Male; Prostatic Neoplasms; Biopsy; Multicenter Studies as Topic; Anesthesia, Local; Data Interpretation, Statistical; Cost-Benefit Analysis; Neoplasm Grading; Perineum; Randomized Controlled Trials as Topic; Equivalence Trials as Topic; Prostate; Rectum; Predictive Value of Tests
PubMed: 38872174
DOI: 10.1186/s13063-024-08224-4