title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
|---|---|---|---|---|
Discussion | anhedonia, TSD, depressive symptoms, MDD, depression | TSD | This was the first study to investigate the safety and pharmacokinetics of the CNS penetrant and selective P2X7 receptor antagonist JNJ-54175446 in MDD, and to explore its potential effects on mood-related phenomena such as reward propensity and changes in peripheral cytokine production following TSD. Although healthy ... | PMC10363543 |
Supplementary information | The online version contains supplementary material available at 10.1038/s41398-023-02557-5. | PMC10363543 | ||
Acknowledgements | MB acknowledges support from the NIHR Oxford cognitive health Biomedical Research Centre and Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. | PMC10363543 | ||
Author contributions | The author contributions to the paper are as follows: study conception and design: KR, PdeB, PvdA, JMAvG, GEJ; data collection: KR, JMAvG, GEJ; analysis and interpretation of results and draft paper preparation: KR, PdB, PvdA, JMAvG, MC, LvN, WCD, AB, MB, GEJ. All authors reviewed the results and approved the final ver... | PMC10363543 | ||
Competing interests | The current study was funded by Janssen Research and Development. KR MD, Dr GJ and Prof Dr JvG declare no competing interests. Dr PdB, Dr PvdA, Dr HB, Dr MC, Dr AB, Dr LvN and Prof Dr WD are employees of Janssen and own Johnson and Johnson equity. Dr MB is employed by the University of Oxford and has acted as a consult... | PMC10363543 | ||
References | PMC10363543 | |||
Trial objective | stroke | STROKE | To verify whether conventional rehabilitation combined with specific virtual reality is more effective than conventional therapy alone in restoring hand motor function and muscle tone after stroke. | PMC10071242 |
Trial design | This prospective single-blind randomized controlled trial compared conventional rehabilitation based on physiotherapy and occupational therapy (control group) with the combination of conventional rehabilitation and specific virtual reality technology (experimental group). Participants were allocated to these groups in ... | PMC10071242 | ||
Participants | Forty-six patients (43 of whom completed the intervention period and follow-up evaluation) were recruited from the Neurology and Rehabilitation units of the Hospital General Universitario of Talavera de la Reina, Spain. | PMC10071242 | ||
Intervention | Each participant completed 15 treatment sessions lasting 150 min/session; the sessions took place five consecutive days/week over the course of three weeks. The experimental group received conventional upper-limb strength and motor training (100 min/session) combined with specific virtual reality technology devices (50... | PMC10071242 | ||
Results | As measured by the Ashworth Scale, a decrease in wrist muscle tone was observed in both groups (control and experimental), with a notably larger decrease in the experimental group (baseline mean/postintervention mean: 1.22/0.39; difference between baseline and follow-up: 0.78; 95% confidence interval: 0.38–1.18; effect... | PMC10071242 | ||
Keywords | PMC10071242 | |||
Introduction | Stroke, stroke, hand motor function, upper-limb deficits, poststroke | STROKE, PATHOLOGY, CEREBROVASCULAR ACCIDENT, STROKE | Stroke is a leading cause of long-lasting disability. As many as 41.5 million new cases occur yearly in Europe, and 3.7 million survivors experience long-lasting impairments, whereas less than 15% of patients achieve full poststroke recovery [It is estimated that 80% of stroke patients have upper-limb deficits and have... | PMC10071242 |
Methods | PMC10071242 | |||
Study design, randomization, and blinding | This was a prospective single-blind randomized controlled trial comparing conventional rehabilitation (CG) with the combination of conventional rehabilitation and an SVR system (EG); all reporting of this trial is in accordance with the Consolidated Standards of Reporting Trials (CONSORT) statement [The study was appro... | PMC10071242 | ||
Participants | end-stage cancer, Stroke, cognitive impairment, trembling, stroke, function loss, upper-limb motor impairment, psychiatric, dysmetria, hemineglect | STROKE, PATHOLOGY, STROKE | The study included 46 patients (43 of whom completed the intervention period and follow-up evaluation), with a mean age of 63.1 years (SD: 12.8). Nineteen percent (n = 8) were women. The participants were recruited from the Neurology and Rehabilitation units of the Hospital General Universitario of Talavera de la Reina... | PMC10071242 |
Outcomes | In our study, we used the basic set of assessment measures recommended for clinical practice and research to assess the physical function and activity level of the upper limb; these measures are included in the current standardized protocols of evidence-based practice [The primary outcome was hand motor function. For q... | PMC10071242 | ||
Fugl-Meyer assessment-upper extremity (FMA-UE) | stroke | STROKE | The FMA is considered a valid, fully suitable instrument to evaluate the motor function of the upper limb after stroke, given its excellent psychometric properties and its appropriate scale. The upper-limb subscale of this instrument, the FMA-UE, is of great value for predicting the degree of independence that can be a... | PMC10071242 |
Action research arm test (ARAT) | The ARAT assesses the ability to manipulate small and large objects, with a variety of qualitative items that allow a numerical quantification of each of the subtests: grasp, grip, pinch and gross movement [ | PMC10071242 | ||
Ashworth Scale | The Ashworth Scale measures resistance to passive movement on a scale of 0 to 4; it has a Kendall’s W of 0.765 (p = 0.000) for the elbow, and its reliability is 0.4 to 0.75 for 95% of the assessments [ | PMC10071242 | ||
Data analysis | poststroke | REGRESSION, LITTLE | The sample size was calculated using the program Epidat 4.2. At the time when the study was designed, the methodologist and statistician calculated the size of the sample using an estimated effectiveness ratio of 90% in the experimental group and 50% in the control group, a power level of 80%, and confidence level of 9... | PMC10071242 |
Results | PMC10071242 | |||
Discussion | spasticity, stroke, hand motor function, poststroke, subacute stroke | STROKE, DISEASE | The main purpose of this clinical trial was to test whether conventional rehabilitation combined with SVR technology is more effective than an intervention based exclusively on occupational therapy and physiotherapy for improving hand motor function in adults with subacute stroke.Previous studies [In this study of pati... | PMC10071242 |
Limitations of the study | poststroke | The results of the present study cannot be extrapolated to other poststroke phases or to rehabilitation programs with fewer weekly sessions.The design of our study does not include a long-term follow-up to clarify the evolution of the intervention groups (CG vs. EG) or the differences found. In addition, this study was... | PMC10071242 | |
Conclusions | stroke, spasticity | STROKE | The outcomes of the study suggest that conventional rehabilitation combined with an SVR-based method can be more effective than conventional therapy alone in improving hand motor function and voluntary movement and normalizing muscle tone in subacute stroke patients. With combined treatment, hand and wrist functionalit... | PMC10071242 |
Acknowledgements | The authors would like to thank the participants and the staff of the Hospital General Universitario (Talavera de la Reina, Spain) for their collaboration in this study. | PMC10071242 | ||
Author contributions | MRH: conceptualization, methodology, software, validation, formal analysis, investigation, and writing—original draft preparation. BPL: conceptualization, validation, and writing—original draft preparation. JJCA: conceptualization, methodology, software, validation, formal analysis, and writing—original draft preparati... | PMC10071242 | ||
Funding | The study was sponsored by the University of Castilla-La Mancha (grant #2020-GRIN-29192). This funding contributed to the purchase of the SVR technology used for this study. | PMC10071242 | ||
Availability of data and materials | Not applicable. | PMC10071242 | ||
Declarations | PMC10071242 | |||
Ethics approval and consent to participate | The Research and Medical Ethics Committee of the Integrated Area of Talavera de la Reina approved this study (protocol code: 12/2018). All participants received verbal and written information about the study and gave their written informed consent. | PMC10071242 | ||
Consent for publication | Not applicable. | PMC10071242 | ||
Competing interests | Meditouch | The authors declare no potential conflicts of interest with respect to the research, authorship, or publication of this article. The Meditouch | PMC10071242 | |
References | PMC10071242 | |||
Background | Studies have shown that supplementation with recombinant human GH (rh-GH) during ovarian stimulation (OS) may improve the ovarian response and clinical outcomes of IVF. However, it remains unclear whether GH is associated with the ploidy status of embryos, and therefore, is unable to explain the underlying reason for t... | PMC10585718 | ||
Methods | ANEUPLOIDY | This was a single center retrospective cohort study. The data of all women aged 38–46 years who underwent their first preimplantation genetic testing for aneuploidy (PGT-A) cycle between January 2021 and June 2022 were reviewed. Patients in the GH group received 4 IU/day subcutaneous GH supplementation from the beginni... | PMC10585718 | |
Results | The baseline and cycle characteristics between the two groups were similar. The proportion of cycles which obtained euploid blastocysts was significantly higher in the GH group than that in the control group (41.43% vs. 27.21%, P = 0.00). The GH group had a significantly higher euploid blastocyst rate per cohort (32.47... | PMC10585718 | ||
Conclusions | GH supplementation during OS is associated with a significantly increased probability of obtaining euploid blastocysts in women aged 38–40 years, but this benefit is not significant in women aged 41–46 years. Our results explained the underlying reason for the effect of GH on IVF outcomes in existing studies, and might... | PMC10585718 | ||
Trial registration | NCT05574894, | PMC10585718 | ||
Keywords | PMC10585718 | |||
Background | congenital disabilities | PREGNANCY LOSS | With the postponement of women’s marriage and childbearing in recent decades, the number of women with advanced maternal age (AMA) seeking in vitro fertilization (IVF) has increased significantly. However, owing to the reduction of euploid embryos in women with AMA, they experience a higher prevalence of IVF failure, p... | PMC10585718 |
Methods | PMC10585718 | |||
Study design and population | This cohort study retrospectively collected the data of all women aged 38–46 years who underwent their first OS cycle scheduled for PGT-A in Shanghai JiAi Genetics and IVF Institute from January 2021 to June 2022 in the institutional electronic database. Each participant was required to have a body mass index (BMI) in ... | PMC10585718 | ||
IVF-ET procedures and PGT-A | ovarian hyperstimulation | OVARIAN HYPERSTIMULATION | OS, oocyte retrieval, fertilization, blastocyst culture, endometrial preparation, embryo transfer, and luteal phase support were performed according to standard protocols in our IVF center, as previously described in detail [Briefly, a flexible antagonist protocol for controlled ovarian hyperstimulation was used for ea... | PMC10585718 |
Study outcomes | heartbeat and breath | The primary goal of a scheduled PGT-A cycle is to obtain euploid blastocysts for transfer. Therefore, the primary outcome was the proportion of cycles which obtained euploid blastocysts, calculated as the number of cycles with ≥ 1 euploid blastocyst divided by the total number of OS cycles in a cohort. Secondary outcom... | PMC10585718 | |
Statistical analysis | ANEUPLOIDY | PSM was used to identify the patients with or without GH supplement who were most similar in baseline and stimulation characteristics and to adjust for confounders related to aneuploidy. The variables in the PSM included indications for PGT-A, age, BMI, number of previous OS cycles, basal estradiol (E2), FSH, AMH, and ... | PMC10585718 | |
Results | PMC10585718 | |||
Baseline and cycle characteristics of patients in the GH and control groups before and after PSM | RPL | RECURRENT PREGNANCY LOSS, PREGNANCY LOSS | A total of 692 women with AMA undergoing PGT-A were included in this study, including 143 in the GH group and 549 in the control group (Fig.
Flowchart detailing the distribution of the two study groups. GH = growth hormone; OS = ovarian stimulation; PGT-A = preimplantation genetic screening; PS = propensity score; SET... | PMC10585718 |
PGT-A results between the GH and control groups | REGRESSION | There was no significant difference in the biopsy cycle rates between the two groups (Table
PGT-A cycle outcome of women in the GH and control groups after PSMNo. of OS cycles obtaining no blastocysts,n (%)32(22.86)68(25.00)a. Pearson’s chi-square test was used to compare the between group difference of the number of ... | PMC10585718 | |
Clinical outcomes after embryo transfer | By the end of the study, 47 patients in the GH group and 67 patients in the control group had undergone embryo transfer cycles, all of which were single euploid blastocyst transfers. Implantation, clinical pregnancy, ongoing pregnancy and live birth outcomes were similar between the GH and control groups (Table
Clinic... | PMC10585718 | ||
Discussion | ANEUPLOIDY | In this retrospective cohort study with PSM, GH supplementation was associated with higher proportion of cycles with euploid blastocysts, euploidy blastocyst rate per cohort, and mean euploid blastocyst rate per cycle in women with AMA. Moreover, GH supplementation was an independent factor in improving the acquisition... | PMC10585718 | |
Conclusions | In conclusion, GH supplementation during OS is associated with a significantly increased probability of obtaining euploid blastocysts in women aged 38–40 years, but this benefit is not significant in patients aged 41–46 years. Our results might be helpful for AMA patients undergoing PGT-A cycles to obtain a better outc... | PMC10585718 | ||
Acknowledgements | The authors thank Professor Jiangfeng Ye Ph.D. for her help with the statistical analysis of the data. | PMC10585718 | ||
Authors’ contributions | XS and LL contributed to the conception and design of the study. YS, MX, YX, and CL acquired and analyzed the data. JF, MX, and CL completed the PGT. YS and MX drafted the article. All authors contributed to manuscript revision, read, and approved the submitted version. | PMC10585718 | ||
Funding | This study is supported by the Special Project for Clinical Research in the Health Industry of the Shanghai Municipal Health Commission (20224Y0218, 20204Y0071). The funding source had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to ... | PMC10585718 | ||
Data Availability | The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Upon publication, we will share the individual participant data and study protocols that support the findings of this article, provided that they have been deidentified, with no specific end date f... | PMC10585718 | ||
Declarations | PMC10585718 | |||
Competing interests | The authors declare no competing interests. | PMC10585718 | ||
Ethics approval and consent to participate | The study protocol was approved by the Research Ethics Committee of the Shanghai JiAi Genetics and IVF Institute (Approval Number: JIAI E2022-14, Study ID: JIAI E2022-022, NCT05574894, | PMC10585718 | ||
Consent for publication | Not applicable. | PMC10585718 | ||
References | PMC10585718 | |||
Background: | Parkinson’s disease, PD | Coinvestigators listed in the Supplementary Material.Apomorphine sublingual film (SL-APO) and subcutaneous apomorphine (SC-APO) have been used for the treatment of OFF episodes in Parkinson’s disease (PD). No study has prospectively compared efficacy and safety of these formulations. | PMC10741320 | |
Objective: | PD | To compare SL-APO with SC-APO for treatment of OFF episodes in PD. | PMC10741320 | |
Methods: | PD | An open-label, randomized, crossover study assessed SL-APO versus SC-APO in patients with PD and OFF episodes ( | PMC10741320 | |
Results: | Propensity score matching applied on 159 patients (STN-DBS | PMC10741320 | ||
Conclusions: | depression | We report Class IIb evidence of beneficial effects of STN-DBS on quality of sleep at 36-month follow-up, which were associated with QoL improvement independent of depression and dopaminergic medication. Our study highlights the importance of sleep for assessments of DBS outcomes. | PMC10741320 | |
Results: | MOVEMENT DISORDER | No difference was observed between SL-APO and SC-APO for change from predose to 90 minutes postdose in Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part III score at week 4 (primary endpoint), assessed by a blinded rater (–13.6 vs. –13.8, respectively; | PMC10741320 | |
Conclusions: | Patients reported overall preference for and greater satisfaction with SL-APO over SC-APO. | PMC10741320 | ||
INTRODUCTION | Parkinson’s disease, PD | Oral carbidopa/levodopa (CD/LD) is the cornerstone of Parkinson’s disease (PD) treatment [Apomorphine, a D1-family and D2-family agonist with an affinity similar to dopamine, is used for the treatment of OFF episodes in patients with PD [SC-APO is a reliable, effective treatment option for managing OFF episodes; howeve... | PMC10741320 | |
METHODS | PMC10741320 | |||
Study design and participants | PD, ; mouth, idiopathic PD | DISORDER, SECONDARY PARKINSONISM | This multicenter, open-label, randomized, crossover study assessed SL-APO compared with SC-APO in patients with PD and OFF episodes and was conducted in Europe (EudraCT: 2016-003456-7). Herein we provide a brief review of methods, with full methodology available in the Supplementary Methods. Eligible patients were ≥18 ... | PMC10741320 |
Procedures | PD | The study consisted of open-label dose-optimization and open-label treatment phases (Study design. SL-APO (Dose optimization of SC-APO (Initially, use of the antiemetic domperidone was optional if clinically warranted and was not to be used prophylactically. After a protocol amendment, domperidone use remained optional... | PMC10741320 | |
Evaluations | BLIND | The primary efficacy endpoint was change from predose to 90 min postdose in MDS-UPDRS Part III score after 4 weeks of dosing in each crossover period, assessed in clinic by a rater blinded to treatment assignment. The blind was maintained by ensuring that the rater did not witness in-clinic dosing, that visible injecti... | PMC10741320 | |
Statistical analysis | SECONDARY | The primary objective of the study was to demonstrate superiority of SL-APO over SC-APO in improving motor function assessed as change from predose to 90 min postdose in MDS-UPDRS Part III score for SL-APO compared with SC-APO after 4 weeks of dosing in each crossover period (primary endpoint). The sample size calculat... | PMC10741320 | |
RESULTS | PMC10741320 | |||
Efficacy | Movement Disorder, Parkinson’s Disease Rating Scale, SE | MOVEMENT DISORDER, SECONDARY | The primary endpoint of change from predose to 90 min postdose in MDS-UPDRS Part III score at week 4 was comparable for SL-APO and SC-APO (least squares [LS] mean [standard error], –13.6 [1.5] vs. –13.8 [1.5]; Change from predose in MDS-UPDRS Part III score at week 4 over time (treatment phase mITT population). Data re... | PMC10741320 |
PK | The t | PMC10741320 | ||
DISCUSSION | nausea, lip swelling, stomatitis, nausea and vomiting, vomiting, PD | MOUTH ULCERATION, STOMATITIS, INJECTION SITE HEMATOMA, SECONDARY, INJECTION SITE REACTION, BLIND, EVENTS, INJECTION SITE ERYTHEMA | This open-label, randomized, crossover study was designed to meet regulatory requirements as a registrational study in the European Union. The purpose was to compare efficacy, safety, tolerability, and patient preference for SL-APO and SC-APO, with the 90-min primary endpoint chosen based on prior PK studies [Prior stu... | PMC10741320 |
Supplementary Material | PMC10741320 | |||
Supplementary Material | Click here for additional data file. | PMC10741320 | ||
ACKNOWLEDGMENTS | The study was supported by funding from Sumitomo Pharma America, Inc. (Marlborough, MA, USA). The authors would like to thank all coinvestigators, including Dr. Valentina Leta, for their contributions to the study. Medical writing and editorial assistance were provided by Maureen Wallace-Nadolski, PhD, and Jessica Deck... | PMC10741320 | ||
SUPPLEMENTARY MATERIAL | The supplementary material is available in the electronic version of this article: | PMC10741320 | ||
FUNDING | The study was supported by funding from Sumitomo Pharma America, Inc. (Marlborough, MA). | PMC10741320 | ||
CONFLICTS OF INTEREST | Parkinson’s, Zambon | FOX | FS is an Editorial Board member of this journal, but was not involved in the peer-review process nor had access to any information regarding its peer review and has received grants and/or research support from Zambon and honoraria or consultation fees from Bial, Biogen, Britania Pharmaceuticals, Chiesi, Cynapsus Therap... | PMC10741320 |
DATA AVAILABILITY | Access to de-identified participant data will be provided after a research proposal is submitted online ( | PMC10741320 | ||
REFERENCES | PMC10741320 | |||
Background | toxicity | DRUG INTERACTIONS | Combinations of drugs are becoming increasingly common in oncology treatment. In some cases, patients can benefit from the interaction between two drugs, although there is usually a higher risk of developing toxicity. Due to drug–drug interactions, multidrug combinations often exhibit different toxicity profiles than t... | PMC9979534 |
Method | To improve the performance of BOINcomb in the above extreme scenarios, we widen the range of variation of the boundaries by setting the self-shrinking dose escalation and de-escalation boundaries. We refer to the new design as adaptive shrinking Bayesian optimal interval design for combination drug (asBOINcomb). We con... | PMC9979534 | ||
Results | Our simulation results show that asBOINcomb is more accurate and stable than BOINcomb, especially in some extreme scenarios. Specifically, in all ten scenarios, the percentage of correct selection is higher than the BOINcomb design within 30 to 60 patients. | PMC9979534 | ||
Conclusion | The proposed asBOINcomb design is transparent and simple to implement and can reduce the trial sample size while maintaining accuracy compared with the BOINcomb design. | PMC9979534 | ||
Keywords | PMC9979534 | |||
Introduction | toxicity, cancer | CANCER, DISEASES | Drug combination therapy provides an important method for the treatment of difficult diseases such as cancer. The purpose of drug combination therapy is to induce synergistic therapeutic effects, increase the combined dose intensity, and achieve better therapeutic effects without cross-toxicity. The purpose of a drug c... | PMC9979534 |
Methods | PMC9979534 | |||
BOIN design | toxicity | The BOIN (Bayesian optimal interval) design is a Bayesian model-assisted phase I dose-finding design proposed by Liu and Yuan Y (2015). The design is simple and flexible and performs comparably to model-based designs [if if otherwise, i.e., The trial continues until the prespecified sample size is exhausted or the tria... | PMC9979534 | |
BOINcomb design | The two-dimensional BOIN design for drug combination trials is based on an extension of the one-dimensional design. The details are as follows. Assume that The rules of BOINcomb are as follows:Treat the first cohort of subjects with the lowest dose combination (1, 1).Assuming that the current cohort is treated with dos... | PMC9979534 | ||
Simulation studies | PMC9979534 | |||
Simulation studies | DLTs | After determining the optimal bounding range (∆According to Fig. PCS comparison of BOINcomb and asBOINcomb designs for simulation studies with multiple sample sizesAccording to Fig. Comparison of PNMTDC of BOINcomb and asBOINcomb designs for simulation studies with multiple sample sizesAccording to Fig. Comparison of D... | PMC9979534 | |
Trial example | toxicity, TNBC, Toxicity, thyroid cancer | TRIPLE-NEGATIVE BREAST CANCER, SOLID TUMOR, T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA, REGRESSION, TUMOR GROWTH, THYROID CANCER | To further evaluate the proposed strategy, we applied the proposed design to a clinical trial of PF03084014 combined with doxorubicin for the treatment of advanced triple-negative breast cancer (TNBC). PF-03084014 is a reversible, noncompetitive, and selective secretase inhibitor that blocks the NOTCH signaling pathway... | PMC9979534 |
Discussion | From statistical and clinical viewpoints, the proposed combination designs are simple and easy to understand. But there are some practical or ethical issues that have not been considered in actual trials. The above design aims to find individual MTDC in the drug combination trial and is not suitable for finding MTDC pr... | PMC9979534 | ||
Conclusion | We improve the two-dimensional Bayesian optimal interval design by proposing adaptively-shrinking dose escalation/de-escalation boundaries, which converge with increasing sample size. In addition, we introduce the parameter | PMC9979534 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.