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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Methods | PMC10504081 | |||
Patients and study design | spasticity, cognitive impairment, contracture, upper-extremity hemiparesis, ischemic stroke | SECONDARY, EVENT, ISCHEMIC STROKE | Eligible individuals suffered a first-time, unilateral, ischemic stroke in the middle cerebral artery territory that spared the diencephalon and basal ganglia 12–36 months before surgery. Individuals with persistent moderate-to-severe upper-extremity hemiparesis as defined by an FM-UE score of ≤42 and sufficient upper-... | PMC10504081 |
Rehabilitation | The rehabilitation protocol was focused on highly repetitive, challenging and salient upper-extremity task practice administered by a physical therapist or assistant | PMC10504081 | ||
Deep brain stimulation | PMC10504081 | |||
Surgical implantation and programming | movement disorders | MOVEMENT DISORDERS | Participants underwent stereotactic implantation of a single DBS lead in the area of the cerebellar DN contralateral to the lesioned cerebral hemisphere using a frame-based technique similar to that used in DBS for movement disorders (Supplementary Fig. Between the rehab-only and the DBS + rehab phases, participants un... | PMC10504081 |
DBS + rehab phase | At the end of programming, participants had their devices activated for a period of 4 to 8 months with continued rehabilitation. With a single exception, all had their device programmed for 30-Hz stimulation, consistent with our preclinical work | PMC10504081 | ||
Outcome measures | upper-extremity impairment | ADVERSE EVENTS, SECONDARY | The primary end point was safety as measured by the incidence of serious adverse events during study participation. Among the secondary measures, the first motor outcome metric for characterization of the effects of the investigative treatment on upper-extremity impairment was the FM-UE, as it was the measure that dete... | PMC10504081 |
Adverse events—primary outcome | death, illness or injury, birth defect, illness or injury or permanent impairment, congenital abnormality | FETAL DISTRESS, ADVERSE EVENTS, ADVERSE EVENT, DISEASE, EVENT, FETAL DEATH, ADVERSE EVENT, EVENTS | Adverse events, including serious safety events, device-related events and unanticipated events were actively monitored in scheduled and unscheduled visits by the research team. The definitions for adverse events and serious adverse events followed the US Food and Drug Administration guidelines where adverse events wer... | PMC10504081 |
Efficacy assessment—unblinded | Anxiety, spasticity, anxiety, depression, Depression | SECONDARY | All efficacy assessments were performed, unblinded and in person, as secondary measures for this phase 1 trial. Data were collected monthly from the presurgical baseline through 4 months after the DBS + rehab phase (Fig. Several other secondary measures were collected as part of this initial phase I exploration, includ... | PMC10504081 |
Brain imaging | BRAIN | Brain imaging included T1-weighted volumetric MRI of the head (Magnetom Prisma; Siemens Healthineers) performed before implantation of the DBS lead. FDG PET/CT studies were performed (Biograph TruePoint; Siemens Healthineers), adding physical therapy to the routine clinical protocol for cerebral metabolic imaging. Afte... | PMC10504081 | |
Statistical analysis | pre-DBS + | SECONDARY | Change scores for each secondary outcome measure were calculated individually across five separate time periods: pre-surgery versus post-surgery (month 1 minus consent), pre-rehab-only versus post-rehab-only (month 3 minus month 1), pre-DBS + rehab versus post-DBS + rehab (month 8–12 minus month 4), pre-rehab carryover... | PMC10504081 |
Reporting summary | Further information on research design is available in the | PMC10504081 | ||
Online content | Any methods, additional references, Nature Portfolio reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available at 10.1038/s41591-023-02507-0. | PMC10504081 | ||
Supplementary information |
Supplementary Figs. 1–3, Tables 1–4, study protocols 1–2 with summary of changes, DMC charter, summary of screen failures, detailed inclusion/exclusion criteria and surgical procedure details.Reporting Summary | PMC10504081 | ||
Extended data | PMC10504081 | |||
Extended data | is available for this paper at 10.1038/s41591-023-02507-0. | PMC10504081 | ||
Supplementary information | The online version contains supplementary material available at 10.1038/s41591-023-02507-0. | PMC10504081 | ||
Acknowledgements | BRAIN | We thank all study participants who devoted time to our research and trusted us with their health in a clinical trial that involved an experimental neurological intervention. We thank all research personnel who dedicated time and effort to the success of the clinical trial including physical and occupational therapists... | PMC10504081 | |
Author contributions | All authors contributed extensively to the work presented in this paper. The rationale for stimulating the cerebellothalamocortical pathway to promote motor recovery was provided previously by A.G.M. and K.B.B. A.G.M. and K.B.B. supervised the project, while A.W. and M.S. helped conduct the trial. A.G.M. and S.N. perfo... | PMC10504081 | ||
Peer review | PMC10504081 | |||
Data availability | Raw data related to safety and feasibility, the primary endpoints of the study, can be shared upon request and review by Cleveland Clinic and the study sponsors. Secondary endpoint data and PET imaging data, analyzed or raw, may also be shared. Depending on the data that are requested, we will need to consult with the ... | PMC10504081 | ||
Competing interests | SECONDARY | A.G.M. serves as Chief Medical Officer and Chair of the Scientific Advisory Board for Enspire DBS Therapy and is paid with stock options. As the inventor, A.G.M. will receive portions of commercialization and/or Cleveland Clinic Foundation stock revenue and payments through Cleveland Clinic Foundation with fees deducte... | PMC10504081 | |
References | PMC10504081 | |||
Background | pancreatic cancer | METASTASIS, PANCREATIC CANCER | Lymph node metastasis (LNM) is a critical prognostic factor in resectable pancreatic cancer (PC) patients, determining treatment strategies. This study aimed to develop a clinical model to adequately and accurately predict the risk of LNM in PC patients. | PMC10465378 |
Methods | 13,200 resectable PC patients were enrolled from the SEER (Surveillance, Epidemiology, and End Results) database, and randomly divided into a training group and an internal validation group at a ratio of 7:3. An independent group ( | PMC10465378 | ||
Result | A total of six risk predictors (including age at diagnosis, race, primary site, grade, histology, and T-stage) were identified and included in the nomogram. The areas under the curves (AUCs) [95% confidential interval (CI)] were 0.711 (95%CI: 0.700–0.722), 0.700 (95%CI: 0.683–0.717), and 0.845 (95%CI: 0.749–0.942) in t... | PMC10465378 | ||
Conclusion | pancreatic cancer | PANCREATIC CANCER | We constructed a nomogram model for predicting LNM in pancreatic cancer patients, which may help oncologists and surgeons to choose more individualized clinical treatment strategies and make better clinical decisions.
| PMC10465378 |
Keywords | PMC10465378 | |||
Introduction | malignancy | GASTROINTESTINAL CANCERS, LYMPH NODE METASTASIS | PC is the most aggressive and lethal malignancy in gastrointestinal cancers. The overall 5-year survival rate is less than 10%, with few significant improvements for years (Ansari et al. The nomogram model has been widely used in the prediction of lymph node metastasis. However, there is a lack of nomograms for predict... | PMC10465378 |
Materials and methods | PMC10465378 | |||
Data collection | death, pancreatic cancer | PANCREATIC CANCER | In our study, patients diagnosed with pancreatic cancer from 2000 to 2019 were collected from the SEER database. The exclusion criteria were as follows: diagnosed confirmation with clinical diagnosis only, radiography without microscopic confirm, direct visualization without microscopic confirmation or unknown; more th... | PMC10465378 |
Statistical analysis | NRI | REGRESSION | The median (IQR), frequency (proportions), Mann–Whitney U tests, independent t-tests, Pearson’s chi-square test, Fisher’s exact test, and univariate and multivariate binary logistic regression analysis were calculated by SPSS (SPSS Inc., Chicago, USA). Nomograms, ROC curves, calibration plots, the nutrition risk index ... | PMC10465378 |
Construction, validation, and clinical usefulness of the nomogram | REGRESSION | Univariate and multivariate logistic regression analyses were utilized to find the independent factors in predicting LNM and the minimum Akaike’s information criterion (AIC) was performed to choose the optimal model parameters and construct a nomogram for evaluating the risk of LNM. The predictors include age at diagno... | PMC10465378 | |
Results | PMC10465378 | |||
Patient characteristics | pancreatic cancer | PANCREATIC CANCER | A total of 13,200 resectable pancreatic cancer patients were enrolled in our research between 2000 and 2019 according to the screening flowchart from the SEER database and randomly divided into a training group (Clinicopathological characteristics in resectable pancreatic cancerNote: OthersOthers | PMC10465378 |
Univariate and multivariate logistic regression results | REGRESSION, LYMPH NODE METASTASIS | The clinicopathological factors associated with LNM were revealed by the univariate and multivariate logistic regression analysis. Univariate logistic regression analysis showed that age at diagnosis, race, primary site, grade, histology, and T-stage were significant factors for LNM in PC patients (Table Risk variables... | PMC10465378 | |
Construction and validation of the nomogram based on predictors of lymph nodes metastasis | pancreatic cancer, NRI | PANCREATIC CANCER, LYMPH NODE METASTASIS | The minimum Akaike’s information criterion (AIC) was used to select the optimal model parameters and construct a nomogram for assessing the risk of LNM (Arunajadai The nomogram for the risk of lymph node metastasis in resectable pancreatic cancer patientsROC of the nomogram for the training cohort (The calibration plot... | PMC10465378 |
Discussion | cancers, tumor, cancer death, adenocarcinoma, pancreatic head cancer | CANCERS, TUMOR, ADENOCARCINOMA, LYMPH NODE METASTASIS, LIVER METASTASIS, PANCREATIC NEUROENDOCRINE NEOPLASM | PC is one of the most lethal of all cancers with high mortality, which is the seventh leading cause of cancer death worldwide (Sung et al. In our study, a total of six clinicopathological factors were considered as risk factors associated with LNM in PC patients, including age at diagnosis, grade, histology, T-stage, p... | PMC10465378 |
Conclusion | In summary, the nomogram for predicting the preoperative LNM in PC patients was developed based on the SEER database, which shows good performance and clinical application.
| PMC10465378 | ||
Acknowledgements | All the researchers and staff of the SEER program should be highly appreciated. | PMC10465378 | ||
Author contributions | HC, XX, XK, and QZ designed this research and revised the manuscript. HC and JX collected the data. Statistical analysis was conducted by HC and XX. Figures and tables were generated by HC, XX, and JX. HC wrote the original manuscript. XX, XK, and QZ supervised this study. All authors contributed to this article and ap... | PMC10465378 | ||
Funding | The article received support from the fund from the Joint Project of Henan Province and Ministry (LHGJ20200516, and LHGJ20200500). | PMC10465378 | ||
Data availability | The data of this study are available for all authors. | PMC10465378 | ||
Declarations | PMC10465378 | |||
Conflict of interest | All authors declare no conflict of interest. | PMC10465378 | ||
Ethical approval | Data from our hospital have been approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical University. While, data from the SEER database were in no need of informed consent and medical ethics review. | PMC10465378 | ||
References | PMC10465378 | |||
Methods | subarachnoid block | It is a Prospective Randomized Double-Blind Study. It includes 68 patients undergoing urological procedures under subarachnoid block. Group LD: Patients will receive 3.5 ml of Isobaric Levobupivacaine 0.5% + Dexmedetomidine 10 µg (0.1ml) Group RD: will receive 3.5ml of Isobaric Ropivacaine 0.5% + Dexmedetomidine 10 µg ... | PMC9987288 | |
Results | Time taken for onset of sensory and motor block is significantly more in ropivacaine while duration of block is more in levobupivacaine. | PMC9987288 | ||
Conclusions | Addition of Dexmedetomidine to Isobaric Levobupivacaine significantly prolongs the duration of analgesia and anaesthesia compared to Ropivacaine and maintains stable hemodynamics. Ropivacaine is a suitable drug for day care whilst levobupivacaine is an excellent agent for longer surgeries. Dexmedetomidine is an effecti... | PMC9987288 | ||
Results | REGRESSION, REGRESSION | There is a significant difference in Onset of Sensory Block {T10} between study group. {P value < 0.001}. There is a significant difference in Time for onset of motor block between study group. {P value 0.016}. The mean time for complete block {in minutes} was 8.03 ± 2.53 in Group LD and it was 9.18 ± 1.8 in Group RD. ... | PMC9987288 | |
Acknowledgements | Sensory Block | REGRESSION | Immeasurable appreciation and deepest gratitude are extended to all our colleagues whose help and support contributed in making this study possible. We thank our families for their unwavering support of our academic and professional endeavors. Above all, we are forever thankful to Father Almighty for providing us with ... | PMC9987288 |
Design | Cluster randomized control trial. | PMC10389722 | ||
Setting | The intervention was conducted in the primary care setting in the province of BC between December 2010 and February 2012. | PMC10389722 | ||
Participants | We randomized 4 833 FPs by geographic location into an Early intervention arm (n = 2 417) and a Delayed control arm (n = 2 416). | PMC10389722 | ||
Intervention | The Education for Quality Improvement in Patient Care (EQIP) program mailed to each FP in BC, a ‘portrait’ of their individual prescribing of antibiotics to women with UAC, plus therapeutic recommendations and a chart of trends in antibiotic resistance. | PMC10389722 | ||
Main outcome measures | Antibiotic prescribing preference to treat UAC. | PMC10389722 | ||
Results | SAID | Implementing exclusion criteria before and after a data system change in the Ministry of Health caused the arms to be unequal in size–intervention arm (1 026 FPs, 17 637 UAC cases); control arm (1 352 FPs, 25 566 UAC cases)–but they were well balanced by age, sex and prior rates of prescribing antibiotics for UAC. In t... | PMC10389722 | |
Data Availability | A minimal dataset underlying the primary result has been made available as a | PMC10389722 | ||
Introduction | infections | INFECTIONS | Indicators show that infections caused by antimicrobial resistant organisms continue to increase in Canada [In 2010, as part of a collaboration between the British Columbia (BC) Ministry of Health and the BC Medical Association, an initiative known as Education for Quality Improvement of Patient care (EQIP) mailed fami... | PMC10389722 |
Methods | PMC10389722 | |||
Study design and setting | The intervention was conducted in the primary care setting in the province of BC between December 2010 and February 2012. FPs were identified through the College of Physicians and Surgeons of British Columbia registrant directory containing public information on individuals currently registered and licensed with the Co... | PMC10389722 | ||
Randomization | BLIND | Active FPs during 2009 in the province were eligible to receive the UAC portrait intervention. Physicians were included in the study if they met all of the following criteria: did not opt out of the program via their registration package; had evidence of medical practice in the form of Medical Services Plan billings in... | PMC10389722 | |
Personalized portrait intervention | infection | INFECTION, DISEASE | An interdisciplinary team with expertise in antimicrobial resistance, infection disease, primary care, pharmacoepidemiology, and public health developed an educational portrait aimed to improve the quality of antimicrobial prescribing for UAC in primary care. The EQIP UAC portrait (The EQIP portrait was a two-page pers... | PMC10389722 |
Databases | DISEASE | Prescription records were obtained from a linked administrative database at the BC Ministry of Health. The database contains records of all prescriptions dispensed at community pharmacies with the exception of patients who were federally insured at the time (e.g., Veterans, Royal Canadian Mounted Police, and First Nati... | PMC10389722 | |
Prescribing endpoints | Women with visits indicating UAC were identified from MSP billing records in which the first 3 digits of the ICD-9 diagnosis code in the record indicated | PMC10389722 | ||
Statistical analysis | REGRESSIONS | We measured the percentages of women coded with UAC who received any antibiotic during the 12-month post-intervention window (Dec 3, 2010 to Dec 3, 2011) in the Early and Delayed arm, as well as the FPs’ preferences for each type of antibiotic. We compared the preferences both by calculating differences with 95% confid... | PMC10389722 | |
Results | PMC10389722 | |||
Physician demographics | The target population was 4,832 family physicians from British Columbia. 2,416 physicians did not meet the eligibility criteria, and 39 physicians opted out of the program ( | PMC10389722 | ||
Study physician flow diagram. | PMC10389722 | |||
Physician characteristics. | PMC10389722 | |||
Primary and secondary outcomes | Tables | PMC10389722 | ||
Prescribing outcomes, 12 months pre and post intervention. | PMC10389722 | |||
Prescribing outcomes, 3 months pre and post intervention. | REGRESSION | Logistic regression models, accounting for clustering of patients by physician, showed the preference odds for a nitrofurantoin prescription following a UAC diagnosis increased by 57% in the 12 months after the intervention (relative risk (RR) = 1.57, 95% confidence interval (CI): 1.43–1.71). The increase in nitrofuran... | PMC10389722 | |
Physician feedback | There were 295 physicians who completed and returned a reflective activity form ( | PMC10389722 | ||
Physician reflective survey results. | cystitis | CYSTITIS | With regards to all the information in the portrait, 222 (75%) agreed their prescribing data accurately reflected their first-line prescribing for cystitis. 153 (52%) reported being surprised by the rates of | PMC10389722 |
Discussion | cystitis | CYSTITIS | Our study described the impact of a personalized prescribing portrait intervention on antibiotic use for UAC in the primary care setting of BC. The prescribing impact from the UAC portrait was greater than previous portraits implemented by the EQIP initiative [FPs were asked to complete a reflective survey where they w... | PMC10389722 |
Conclusion | ACUTE CYSTITIS | Our analysis showed the educational intervention was effective at increasing use of nitrofurantoin and decreasing use of ciprofloxacin and TMP-SMX for treatment of uncomplicated acute cystitis. This intervention demonstrated that high quality educational interventions with clearly stated recommendations for action, sup... | PMC10389722 | |
Supporting information | PMC10389722 | |||
CONSORT 2010 checklist of information to include when reporting a randomised trial*. | (DOC)Click here for additional data file. | PMC10389722 | ||
Uncomplicated acute cystitis sample portrait. | (PDF)Click here for additional data file. | PMC10389722 | ||
Cystitis complicating factors, case definitions. | (PDF)Click here for additional data file. | PMC10389722 | ||
Continuing Medical Education credit reflective exercise. | (PDF)Click here for additional data file. | PMC10389722 | ||
References | PMC10389722 | |||
Subject terms | Toxicities, SD, TRAEs, DLBCL | SOLID TUMOUR, PROLIFERATION, ADVERSE EVENTS, DISEASE, SOLID TUMORS, SECONDARY, DIFFUSE LARGE B-CELL LYMPHOMA | Bromodomain and extraterminal proteins (BET) play key roles in regulation of gene expression, and may play a role in cancer-cell proliferation, survival, and oncogenic progression. CC-90010-ST-001 (NCT03220347) is an open-label phase I study of trotabresib, an oral BET inhibitor, in heavily pretreated patients with adv... | PMC10011554 |
Introduction | DLBCL | SOLID TUMORS | Bromodomain and extraterminal proteins (BET) are epigenetic readers that bind to acetylated lysine residues on histones in chromatinTrotabresib (CC-90010; BMS-986378) is an orally administered, potent, reversible inhibitor of BET family members. CC-90010-ST-001 is a phase I, multicenter, open-label study to assess the ... | PMC10011554 |
Results | PMC10011554 | |||
Patients and treatment | aggressive tumors, DLBCL | SOLID TUMORS | Patients were enrolled at 11 study sites in France, Italy, Japan, and Spain. Patient enrollment in part A took place between July 31, 2017 and November 12, 2018, with a total of 69 patients enrolled and treated, of whom 67 had advanced or unresectable solid tumors and two had R/R DLBCL. Patient enrollment in part B beg... | PMC10011554 |
Safety | Safety and tolerability were the primary endpoints of the study. Safety results for part A at the most recent follow-up were consistent with the preliminary analysis reported previously | PMC10011554 | ||
Treatment-related adverse events reported in ≥10% of patients in the overall study population, or in ≥2 patients at grade ≥3 severity. | pneumonia, TRAEs, leukopenia, syncope, lymphopenia, inappropriate antidiuretic hormone secretion, presyncope, any-grade, hypokalemia | PNEUMONIA, FEBRILE NEUTROPENIA, ESSENTIAL HYPERTENSION, LEUKOPENIA, DIABETES MELLITUS, LYMPHOPENIA, ABDOMINAL INFECTION, SKIN HEMORRHAGE, HYPERAMYLASEMIA, INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION | Grade 3 essential hypertension, hypokalemia, lipase increased, liver function test abnormal, presyncope, skin hemorrhage, and grade 4 blood creatinine phosphokinase increased, diabetes mellitus, and inappropriate antidiuretic hormone secretion were reported in one patient each in the overall part A population. Grade 3 ... | PMC10011554 |
Efficacy | DLBCL | SECONDARY | Preliminary efficacy was a secondary endpoint of the study. Response rates in part A were unchanged from those previously reportedOf the 23 patients with R/R DLBCL treated in part B, 15 (65.2%) were evaluable for response (Fig. | PMC10011554 |
Summary of antitumoral activity. | Source data are provided as a source data file. | PMC10011554 | ||
Pharmacodynamics | BLOOD | The pharmacodynamic effects of trotabresib in peripheral blood were assessed as an exploratory endpoint. Blood C-C motif chemokine receptor 1 ( | PMC10011554 | |
Discussion | tumor, high-grade astrocytoma, DLBCL, malignancies, glioblastoma, tumors | TUMOR, THROMBOCYTOPENIA, MINOR, SOLID TUMORS, DISEASE, BRAIN TUMOR, ADVANCED CANCER, MALIGNANCIES, GLIOBLASTOMA, TUMORS, DIFFUSE ASTROCYTOMA | Effective new treatments for patients with advanced malignancies are urgently needed, particularly for those patients who have tumor types with limited treatment options or whose tumors are refractory to currently available therapies. BET inhibitors have a mechanism of action that differs from existing marketed drugs, ... | PMC10011554 |
Methods | PMC10011554 | |||
Study design | The CC-90010-ST-001 trial comprises three parts (Fig. | PMC10011554 | ||
Patient selection | follicular lymphoma, DLBCL, endometrial carcinoma, bidimensionally measurable disease, midline carcinoma, transformed lymphoma, NHL | DISEASE PROGRESSION, SALIVARY GLAND CARCINOMA, FOLLICULAR LYMPHOMA, DISEASE, SOLID TUMORS, BCC, ENDOMETRIAL CARCINOMA, NHL | Patients were enrolled from July 31, 2017 to January 11, 2021. The study included patients aged ≥18 years with an ECOG PS of 0 or 1. Part A included patients with histologically or cytologically confirmed advanced or unresectable solid tumors or R/R advanced NHL that had progressed on standard anticancer therapy or for... | PMC10011554 |
Endpoints | Tumors, Cancer | TUMORS, ADVERSE EVENT, SECONDARY, CANCER | The primary endpoints of the study were the safety and tolerability of trotabresib, as well as the MTD and/or RP2D of trotabresib. Safety was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03Secondary objectives were the preliminary efficacy of trotabresib in terms of cli... | PMC10011554 |
Pharmacokinetic and pharmacodynamic assays | Serial blood samples for PK and pharmacodynamic analyses were collected for each dosing schedule after the first and last doses in cycle 1. Additional blood samples for assessment of the food effect on trotabresib PK in part C were collected during cycle 2. The food effect–evaluable population comprised all patients wi... | PMC10011554 | ||
Statistical analyses | toxicity, PD | REGRESSION | Bayesian logistic regression model based on dose-limiting toxicity was used to provide initial guidance for dose recommendations in the dose-escalation phase. The final decision was reached by considering the totality of safety, PK, and PD data. For binary efficacy endpoints, two-sided 95% Clopper–Pearson exact confide... | PMC10011554 |
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