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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Patient characteristics | We enrolled patients with a current episode of AF lasting 7 days or less and randomized them to receive an intravenous infusion of 3 or 5 mg kg | PMC10803288 | ||
Efficacy endpoints | The primary endpoint of cardioversion within 90 min occurred in 42% (5 of 12) and 55% (12 of 22) of patients receiving AP30663 at 3 mg kg | PMC10803288 | ||
Safety endpoints | ADVERSE EVENTS, ADVERSE EVENT, EVENTS | Adverse events were reported in 50% (13 of 26) of patients for the AP30663 5 mg kgAdverse events in the safety analysis setAll data are based on investigator-reported adverse events. Data reported are the number of patients (%) and number of events (A mean decrease in heart rate was seen for all groups. This occurred e... | PMC10803288 | |
Change in QTcF from baseline in the safety analysis set. | NONSUSTAINED VENTRICULAR TACHYCARDIA | Plot showing the least squares mean and 90% CIs based on a linear mixed-effects model at the indicated time points. AP30663 3 mg kgWith Holter monitoring, the most important ventricular finding was episodes of nonsustained ventricular tachycardia seen in both the active and placebo groups with the longest episodes bein... | PMC10803288 | |
Pharmacokinetic endpoint | The plasma concentration over time is shown in Extended Data Fig. | PMC10803288 | ||
Discussion | In this phase 2 clinical trial, AP30663, a new KAmong currently existing drugs for pharmacological AF cardioversion, vernakalant and flecainide are the most efficaciousThe clinical efficacy of AP30663 aligns with the effects observed in animal models, where AP30663 showed a pronounced effect on the atrial effective ref... | PMC10803288 | ||
Methods | PMC10803288 | |||
Trial design | arrhythmias, coronavirus disease 2019 | ARRHYTHMIAS, CORONAVIRUS DISEASE 2019 | We conducted a phase 2 randomized, double-blind, placebo-controlled, parallel-group trial with an adaptive design with the potential to test doses between 2 and 6 mg kgThe maximum number of individuals that could be enrolled based on the adaptive design was 108. Patients wore 12-lead Holter monitors to assess both effi... | PMC10803288 |
Trial population | heart failure, ischemic heart disease | TORSADE DE POINTES, HEART FAILURE, ISCHEMIC HEART DISEASE, HEART | Male and female patients aged 18–80 years with a body weight of 50–110 kg and a current episode of symptomatic AF lasting between 3 h and 7 days were deemed eligible. Patients were required to be treated with anticoagulation according to current guidelines. Patients were allowed to have stable ischemic heart disease an... | PMC10803288 |
Inclusion criteria | The inclusion criteria were: provision of written informed consent; clinical indication for cardioversion of AF; current episode of symptomatic AF lasting between 3 h and 7 days inclusive at randomization; adequate anticoagulation according to international or national guidelines; body weight 50–110 kg inclusive (with ... | PMC10803288 | ||
Exclusion criteria | renal dysfunction | The exclusion criteria were: significant clinical illness or surgical procedure within 4 weeks before the screening visit; present renal dysfunction (estimated glomerular filtration rate less than 30 ml minThe trial was conducted at ten sites in Hungary and Denmark. | PMC10803288 | |
Trial intervention | The trial ended up testing 3 mg kgIf patients did not cardiovert within the 90 min after the start of the infusion, they were to undergo an electrical (direct current) cardioversion. | PMC10803288 | ||
Trial endpoints | ADVERSE EVENTS, SECONDARY, RECURRENCE | The primary endpoint was the proportion of patients converting from AF to sinus rhythm within 90 min from the start of the infusion and who subsequently had no AF recurrence within 1 min of conversion. Key secondary efficacy endpoints included time to conversion from AF, the proportion of patients with relapse of AF wi... | PMC10803288 | |
Statistical analyses | To ensure an efficient adaptive trial design, Bayesian statistics were used. In part 1 of the trial, a dose of 3 mg kgECG parameters were analyzed based on a linear mixed-effects model; a least squares mean with 90% CIs was reported for these.The safety analysis set was prespecified to be used for all safety analyses a... | PMC10803288 | ||
Reporting summary | Further information on research design is available in the | PMC10803288 | ||
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/s41591-023-02679-9. | PMC10803288 | ||
Supplementary information |
Supplementary Notes 1–3. Supplementary Note Reporting Summary | PMC10803288 | ||
Extended data | PMC10803288 | |||
AP30663 chemical structure. | AP30663 chemical name: (3
| PMC10803288 | ||
Changes in heart rate in the safety analysis set. | The plots show least squares mean and 90% CI based on a linear mixed-effects model. AP30663 3 mg/kg n = 15 patients, AP30663 5 mg/kg n = 22 patients, Placebo n = 26 patients.
| PMC10803288 | ||
Extended data | is available for this paper at 10.1038/s41591-023-02679-9. | PMC10803288 | ||
Supplementary information | The online version contains supplementary material available at 10.1038/s41591-023-02679-9. | PMC10803288 | ||
Acknowledgements | We thank the patients who participated in the trial and the site investigators and staff. Grant funding for the present study was received from Wellcome Trust (Translational Award, 200450/Z/16/Z) and Innovation Fund Denmark (8064-00074B). | PMC10803288 | ||
Author contributions | N.E., M.G., U.S.S., J.G.D. and B.H.B. designed the trial. B.V. and A.G.H. amended the trial design based on input from J.T., among others. P.D., S.H.H. and D.L.B. served on the data monitoring committee. A.G.H. and B.V. monitored the trial for the sponsor while in the conduct phase. A.G.H. performed the supplementary s... | PMC10803288 | ||
Peer review | PMC10803288 | |||
Data availability | Data originating from the trial are considered commercially sensitive; as such, they are not publicly available. To the extent that current legislation allows it, the authors will provide access to individual deidentified participant-level data that underlie the data presented in this article to researchers who provide... | PMC10803288 | ||
Competing interests | Nordisk, MyoKardia | HEART, HEART DISEASE, EDWARDS | A.G.H., B.V., U.S.S., J.G.D., M.G. and B.H.B. are employees of Acesion Pharma and hold shares or warrants in the company. N.E. is a consultant to Acesion Pharma. P.D. received consulting fees and honoraria from Acesion Pharma. D.L.B. has served on the Advisory Boards of Angiowave, Bayer, Boehringer Ingelheim, Cardax, C... | PMC10803288 |
References | PMC10803288 | |||
Background | PATHOLOGY | This study focused on the impact of therapeutic alliance on therapy dropout in a naturalistic sample of patients with borderline pathology receiving dialectical behavior therapy (DBT) in a residential setting. We assumed that low therapeutic alliance shortly after admission would be associated with elevated dropout. | PMC10439653 | |
Methods | DSM-5 borderline personality disorder | REGRESSION, PATHOLOGY | 44 participants with borderline pathology (≥ 3 DSM-5 borderline personality disorder criteria) in a residential DBT program completed a quality assurance questionnaire set assessing demographic information, pretreatment psychopathology and therapeutic alliance during the first seven days of their residential stay. Pred... | PMC10439653 |
Results | The dropout rate was 34.1% ( | PMC10439653 | ||
Conclusions | PATHOLOGY | This study supports the importance of therapy process variables, here the therapeutic alliance at the beginning of treatment, as predictors of therapy dropout in borderline pathology. If this finding is replicated, it shows the potential importance of monitoring the therapeutic relationship throughout the therapeutic p... | PMC10439653 | |
Keywords | Open Access funding enabled and organized by Projekt DEAL. | PMC10439653 | ||
Methods | PMC10439653 | |||
Recruitment | BPD | DISORDER | We approached all patients from age 18 to 65 that were discharged from our residential personality disorder unit between January 2019 and December 2021, and who fulfilled three or more criteria for BPD (Borderline Personality characteristics; BPC) as defined by DSM-5 ( | PMC10439653 |
Procedure | Within the first week of their residential stay, all participants who met the inclusion criteria were informed about the objectives and conditions of the study. They gave their written informed consent to participate in the study and to publish the results. The ethical standards were in line with the Declaration of Hel... | PMC10439653 | ||
Measures | PMC10439653 | |||
Clinical measures | Depression, Trauma, depressive symptoms | Borderline symptom severity was assessed using the Borderline Symptom List [BSL; The Beck Depression Inventory – Second Edition (BDI-II) was used to assess current depressive symptoms [The Childhood Trauma Questionnaire [CTQ; The Posttraumatic Diagnostic Scale [PDS; To assess the severity of general psychopathology, we... | PMC10439653 | |
Working alliance | The patient-rated therapeutic alliance was assessed via the short (12-item) version of the Working Alliance Inventory [WAI-SR; 24]. It consists of three subscales with four items each rated using a 5-point response scale: (1) agreement on the tasks of treatment, (2) agreement on the goals of treatment and (3) developme... | PMC10439653 | ||
Treatment | personality disorder | The residential treatment in our personality disorder unit is certified by the German DBT Board of Certification (DDBT). As common in DBT settings, patients were seen in outpatient counseling sessions before starting DBT (DBT briefing). The briefing, which lasts one hour, includes examination of the patient, assessment... | PMC10439653 | |
Dialectical behavior therapy | BPD | DBT is a cognitive-behavioral treatment program that was developed to treat suicidal patients with BPD [ | PMC10439653 | |
Therapeutic alliance in DBT | The therapeutic alliance in DBT is enforced by three dialectical principles. The patient-therapist relationship is seen as a “real” relationship, patient and therapist are equally affected by behavioral principles. Beyond that, DBT comprehends this relationship as a dynamic interaction that needs conflicts and conflict... | PMC10439653 | ||
Standard inpatient care | Standard Inpatient Care (SIC) included all non-specific therapeutic elements. Over an eight- to ten-week period, participants received 30-minute supportive conversations with the primary nurse twice a week, art or music therapy twice a week, and weekly body therapy. In addition, all patients received morning rounds, mo... | PMC10439653 | ||
Definition of dropout | dysfunctional behavior, therapy-disrupting behaviors, Dysfunctional behaviors, non-suicidal self-injuries, maladaptive behavior, dysfunctional behaviors, BPD | To assess treatment discontinuation, we recorded whether the participant was discharged from our unit before week eight or before the final discharge date set at week six. The reasons for discontinuation were documented (by the patient or by the ward). In all cases, contingency management was the reason for discharge o... | PMC10439653 | |
Data analyses | The initial analyses included group comparisons with Mann-Whitney-U-tests and χ² statistics as well as exploratory correlation analyses. These statistics were obtained using SPSS 25 [ | PMC10439653 | ||
Results | PMC10439653 | |||
Discussion | BPD, PTSD, substance abuse | PATHOLOGY | The purpose of this study was to investigate whether early patient-rated therapeutic alliance is related to dropout in a residential DBT treatment. It is a follow-up to a previous study which showed that a change of therapist between DBT-briefing and -treatment increased the dropout rate of DBT [Our results support the... | PMC10439653 |
Acknowledgements | We acknowledge support for the publication costs by the Open Access Publication Fund of Bielefeld University and the Deutsche Forschungsgemeinschaft (DFG). | PMC10439653 | ||
Authors’ contributions | TB | CS recruited patients, conducted therapies, organized and supervised the assessments, performed the statistical analysis and drafted the manuscript. MB participated in the study design and supervised therapies. MD participated in the study design and manuscript preparation. TB participated in the study design and manus... | PMC10439653 | |
Funding | Open Access funding enabled and organized by Projekt DEAL. | PMC10439653 | ||
Data availability | The dataset supporting the conclusions of this article is shared upon request directed to Carolin Steuwe (carolin.steuwe@evkb.de). | PMC10439653 | ||
Declarations | PMC10439653 | |||
Competing interests | The authors declare no competing interests. | PMC10439653 | ||
Ethics approval and consent to participate | 48147 | DER | All participants gave their written informed consent to study participation and ethical standards were in accordance with the declaration of Helsinki. The requirement for ethical approval was waived by the Ethics Committee Münster (Ethikkommission der Ärztekammer Westfalen-Lippe und der Westfälischen Wilhelms-Universit... | PMC10439653 |
Consent for publication | of clinical data and information was obtained. | PMC10439653 | ||
Abbreviations | Depression, Trauma | Beck Depression Inventory 2nd EditionBorderline Personality CharacteristicsBorderline Personality DisorderChildhood Trauma QuestionnaireDialectical Behavior TherapyDBT Board of CertificationDissociative Experiences ScaleDiagnostic and Statistical Manual of Mental DisordersGlobal Severity Index (SCL-90-R)Posttraumatic S... | PMC10439653 | |
References | PMC10439653 | |||
Objective | This study aims to investigate the topical steroid regimen after small incision lenticule extraction (SMILE) for its effect on very early restoration of visual quality. | PMC10520117 | ||
Methods | A total of 180 patients (360 eyes) who underwent SMILE were enrolled. These patients were randomly assigned to three groups, with 60 patients in each group. The only difference among these three groups was the administration of 0.1% fluorometholone (FML) eye drops within two hours after SMILE: no FML in group A, 0.1% F... | PMC10520117 | ||
Results | The CDVA, MTF cut-off and SR values were significantly higher in group C, when compared to the other two groups, at 2 and 4 h after SMILE ( | PMC10520117 | ||
Conclusion | The administration of 0.1% FML eye drops every half hour within two hours after SMILE accelerates the restoration of visual and optical quality, and reduces the incidence of subjective symptoms during the very early phase after surgery. | PMC10520117 | ||
Keywords | PMC10520117 | |||
Introduction | myopia | MYOPIA | Small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) are presently the two popular techniques for myopia treatment [The postoperative treatment regimens for SMILE and FS-LASIK are usually similar, which include the administration of antibiotics and steroid eye dro... | PMC10520117 |
Patients and methods | PMC10520117 | |||
Ethics statement | The present prospective study was approved by the Ethics Committee of Fujian Medical University (Fuzhou, China) and was conducted in compliance with the principles of the Declaration of Helsinki. A written informed consent was obtained from all patients. | PMC10520117 | ||
Participants and treatment procedures | EYE | In the present study, 180 patients (360 eyes), who underwent SMILE at the Eye Center of Fujian Medical University between July and November 2019, were randomly divided into three groups using a random number table, with 60 patients (120 eyes) in each group. The protocol for the SMILE procedure was the same as the proto... | PMC10520117 | |
Examination and measurements | blurred vision, dryness | INTRAOCULAR PRESSURE | The corrected distance visual acuity (CDVA), mean spherical equivalent (MSE) and intraocular pressure (IOP) were measured before SMILE, at 2, 4 and 24 h, one week after SMILE, and at each follow-up visit thereafter. The CDVA was examined using a standard Landolt visual acuity chart, and the values were converted to the... | PMC10520117 |
Statistical analysis | SPSS 18.0 (SPSS Inc., Chicago, Illinois, USA) was used for the statistical analysis. The variables used for the present study comprised the parametric data, and these were tested as normal distribution. All measurements were repeated for three times, and the mean values were used for the analysis. Two-way ANOVA was use... | PMC10520117 | ||
Results | PMC10520117 | |||
Study participants | The demographics of the study participants are summarized in Table Demographic information of patients at pre-operation* | PMC10520117 | ||
CDVA, MTF, SR and OSI after SMILE | In groups A, B and C, in which different 0.1% FML regimens were administered, CDVA was examined at 2, 4 and 24 h and one week after SMILE. The number of eyes in each group, with a CDVA higher than 1.0 (logMAR, 0.00), is presented in Fig. The number of eyes in each group that had a visual acuity of higher than 1.0 (logM... | PMC10520117 | ||
Authors’ contributions | QL was involved in data curation, formal analysis, investigation, methodology, resources, software, supervision, validation, visualization, writing of the original draft and review and editing of the manuscript. ZS was involved in project administration and review and editing of the manuscript. XZ was involved in valid... | PMC10520117 | ||
Funding | The authors have not disclosed any funding. | PMC10520117 | ||
Data availability | The authors confirm that the data that support the findings of the study are available within the article. | PMC10520117 | ||
Declarations | PMC10520117 | |||
Conflicts of interest | The authors declare that they have no conflicts of interest related to the publication of this manuscript. | PMC10520117 | ||
Ethical approval | The prospective study was approved by the Ethics Committee of Fujian Medical University (Fuzhou, China). All procedures performed in studies that involved human participants were in accordance with the ethical standards of the institutional and/or national research committee, and the 1964 Helsinki Declaration and its l... | PMC10520117 | ||
Informed consent | Written informed consent was obtained from all participants included in the study. | PMC10520117 | ||
References | PMC10520117 | |||
Background | CIPN | CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY, ADVERSE EFFECT | Chemotherapy-induced peripheral neuropathy (CIPN) is a painful, dose-limiting adverse effect of commonly used chemotherapeutic agents. The purpose of this exploratory study was to evaluate the efficacy and safety of mirogabalin in patients with moderate to severe CIPN during chemotherapy and the effects of 12 weeks’ in... | PMC10640752 |
Methods | CIPN, NRS, pain | ADVERSE EVENTS | Patients experiencing moderate to severe CIPN while undergoing oxaliplatin- or taxane-containing chemotherapy for colorectal, gastric, non-small-cell lung, or breast cancer received mirogabalin at between 5 and 15 mg twice daily. The primary endpoint was change in numeric rating scale (NRS) score for pain from baseline... | PMC10640752 |
Results | NRS | Of 58 patients who consented to participation, 52 were eligible and constituted the full analysis set and safety analysis set. From baseline to week 12 (last observation carried forward [LOCF]), NRS score decreased by 30.9%: mean change (95% confidence interval [CI]), − 1.7 (− 2.4 to − 1.0) ( | PMC10640752 | |
Conclusions | cancer, CIPN | CANCER | Intervention with mirogabalin during chemotherapy may be effective and safe for cancer patients with moderate to severe CIPN. It can contribute to completion of chemotherapy without worsening of CIPN. | PMC10640752 |
Trial registration | Japan Registry of Clinical Trials (jRCTs031210101, registered 20/5/2021). | PMC10640752 | ||
Supplementary Information | The online version contains supplementary material available at 10.1186/s12885-023-11560-4. | PMC10640752 | ||
Keywords | PMC10640752 | |||
Background | cancers, neuropathic pain, CIPN, pain, chronic CIPN, neurotoxic | CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY, CANCERS, ADVERSE EVENT, ONCOLOGY | Chemotherapy-induced peripheral neuropathy (CIPN) is a major adverse event affecting patients receiving treatment with neurotoxic chemotherapeutic agents including platinum, taxanes, and vinca alkaloids [Many clinical trials relating to pain treatment of CIPN have been reported. Most of these previous studies were cond... | PMC10640752 |
Methods | PMC10640752 | |||
Study design | CIPN, Same-type cancer | MAY | The present study was conducted as part of the MiroCIP study, carried out in Japan. MiroCIP study comprised two parts: a multicenter prospective ongoing registrational study that started in May 2021, and this exploratory, interventional, open-label, single-arm study carried out between May 2021 and September 2022 (Fig.... | PMC10640752 |
Trial registration | The MiroCIP study is registered in the Japan Registry of Clinical Trials under the identifier jRCTs031210101 (date of registration, 20/5/2021). | PMC10640752 | ||
Participating institutions | The present interventional part of MiroCIP study was carried out at 12 institutions across Japan (Supplementary Table | PMC10640752 | ||
Patients | allergy, CIPN, pain | ADVERSE EVENT, ALLERGY, COMPLICATIONS | Key eligibility criteria included age ≥ 20 years, a diagnosis of CIPN grade ≥ 2 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, and a pain numerical rating scale (NRS) score ≥ 4; patients had colorectal, gastric, non-small-cell lung, or breast cancer and were undergoing chemotherapy... | PMC10640752 |
Treatment | renal impairment | RENAL IMPAIRMENT | The treatment period was 12 weeks. Mirogabalin was administered orally at 5 mg twice daily during the first week of the titration period and was titrated up to 10–15 mg twice daily in the following weeks based on age, symptoms, and renal function. For patients with moderate renal impairment (i.e. creatinine clearance 3... | PMC10640752 |
Endpoints | sleep disturbance, CIPN, pain, NRS pain, Neurotoxicity, Cancer | ONCOLOGY, ADVERSE EVENTS, CANCER | The primary efficacy endpoint was the change in NRS pain score from baseline to week 12 [Secondary efficacy endpoints included changes from baseline to weeks 4 and 12 in NRS scores in the last 7 days for tingling (0 = “no tingling” to 10 = “worst tingling possible”) and sleep disturbance (0 = “no sleep disturbance” to ... | PMC10640752 |
Sample size | The target sample size was set at 55 patients for feasibility reasons, as this was an exploratory interventional study. In previous clinical trials on the efficacy of mirogabalin, the standard deviations (SDs) for the change in NRS score from baseline to 12 weeks were 1.5 [ | PMC10640752 | ||
Statistical analyses | Efficacy analyses were carried out using data for the full analysis set (FAS), defined as all eligible patients who had received at least one dose of the study drug and for whom baseline data were available. Supplementary analyses for efficacy endpoints were conducted using data for the per protocol set (PPS), defined ... | PMC10640752 | ||
Results | PMC10640752 | |||
Patients | chemotherapy-induced peripheral neuropathy | CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY | Fifty-eight patients were screened, 57 were enrolled, and 52 received at least one dose of study drug (FAS) (Fig. Patient disposition. The per protocol set (PPS) comprised 30 patients, after exclusion of 22 patients from the full analysis set (FAS) for violations of protocol (study drug not administered in compliance w... | PMC10640752 |
Changes in NRS score for pain | Pain | Results for the primary efficacy endpoint (Fig. Pain (including tingling) assessed by numeric rating scale score over 12 weeks of mirogabalin treatment: in the total (full analysis set) (The trend in reduction in NRS score from baseline was not clinically meaningful different irrespective to presence or absence of dose... | PMC10640752 | |
Changes in NRS scores for tingling and sleep disturbance | Supplementary Table | PMC10640752 |
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