title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
|---|---|---|---|---|
Publisher's note | All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or ... | PMC9875301 | ||
References | PMC9875301 | |||
Abstract | PMC10107656 | |||
Introduction | HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLAEMIA | Lomitapide is a microsomal triglyceride transfer protein inhibitor for patients with homozygous familial hypercholesterolaemia. Due to its mechanism of action, potential hepatic effects of lomitapide are of clinical interest. This study aimed to determine the long‐term hepatic safety of lomitapide. | PMC10107656 | |
Methods | HEPATIC FIBROSIS, LIVER FIBROSIS | Data were aggregated from the pivotal phase 3 and extension phase clinical trial with lomitapide (median 5.1 years; serum total bilirubin, transaminases, cytokeratin‐18 [CK‐18] and enhanced liver fibrosis [ELF] score, fat‐soluble vitamins and essential fatty acids), 8‐year data from the Lomitapide Observational Worldwi... | PMC10107656 | |
Results | hepatic stiffness, fibrosis | FIBROSIS, HY'S LAW CASE | In the phase 3 trial and the LOWER registry, any asymptomatic excursions in liver transaminase levels were not associated with elevations in bilirubin, and no Hy's law cases were detected in up to 8 years follow‐up. There were no clinically relevant increases among hepatic biomarkers CK‐18, CK‐18 fragments or ELF score... | PMC10107656 |
Conclusions | These data indicate that the hepatic safety of lomitapide remains favourable with no clinically significant elevations in hepatic biomarkers and hepatic stiffness remained normal for more than 9 years follow‐up. | PMC10107656 | ||
Phase 3 trial | NCT00730236; extension phase: NCT00943306; LOWER: NCT02135705.
Italian Working Group on Lomitapide; for MEDLINE indexing: Angelo Baldassare Cefalù, Alessia Di Costanzo, Simone Bini, Antonina Giammanco, Maurizio Averna, Gabriella Iannuzzo, Giuliana Fortunato, Marco Gentile, Maria Donata Di Taranto, Arturo Pujia, Tiziana... | PMC10107656 | ||
Abbreviations | fatty liver | FATTY LIVER, LIVER FIBROSIS | alanine aminotransferaseaspartate aminotransferasebody mass indexconfidence intervalcytokeratin‐18docosahexaenoic aciddrug‐induced liver injurydiscriminative scoreeicosapentaenoic acidenhanced liver fibrosis scorefull analysis setfibrosis‐4hyaluronic acidhigh‐density lipoprotein cholesterolhomozygous familial hyperchol... | PMC10107656 |
Key points | hepatocellular damage, fibrosis | HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLAEMIA, HEPATOCELLULAR DAMAGE, FIBROSIS | Lomitapide is an effective treatment for patients with homozygous familial hypercholesterolaemia which acts independently of the LDL receptor. As an inhibitor of the microsomal triglyceride transfer protein, lomitapide has been associated with a mild‐to‐moderate accumulation of hepatic fat. However, this did not transl... | PMC10107656 |
INTRODUCTION | DILI, liver abnormalities, hepatotoxicity, liver damage, cirrhosis, cholestasis, steatohepatitis, drug‐induced liver injury | HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLAEMIA, HOFH, CIRRHOSIS, LIVER DAMAGE, LIVER FIBROSIS, CHOLESTASIS, HEPATIC STEATOSIS, HEPATIC STEATOSIS, STEATOHEPATITIS | Lomitapide is a microsomal triglyceride transfer protein (MTP) inhibitor indicated as an adjunctive therapy for low‐density lipoprotein cholesterol (LDL‐C) lowering in patients with homozygous familial hypercholesterolaemia (HoFH). Lomitapide reduces LDL‐C by a mean of 50.0%–76.6%Idiosyncratic hepatotoxicity is an unpr... | PMC10107656 |
PATIENTS AND METHODS | The data described in this paper are derived from three different sources (Table | PMC10107656 | ||
Phase 3 clinical trial and long‐term extension study of lomitapide in patients with | NAFLD, beta‐carotene, fibrosis | LIVER FIBROSIS, COLD, FIBROSIS, CHRONIC LIVER DISEASE | The details of phase 3 clinical trial and its long‐term extension have been published before.Data from the clinical trial programme were used to evaluate mean liver transaminase levels and instances of Hy's law. For biomarker analysis, stored serum samples from the phase 3 trial were analysed by Pacific Biomarkers Inc ... | PMC10107656 |
Lomitapide Observational Worldwide Evaluation Registry ( | LOWER is a global, prospective, observational registry assessing long‐term safety and effectiveness of lomitapide in clinical practice. | PMC10107656 | ||
Italian patient cohort sub‐analysis from the Pan European Observational Study conducted by the Italian and European Working Group on Lomitapide in | hepatic steatosis | LIVER, PATHOLOGY, LIVER FIBROSIS, HEPATIC STEATOSIS | The Pan European Observational Study has been published previously.Investigators were asked to retrieve all available hepatic ultrasound and elastography performed on the dates closest to the baseline and last follow‐up visit. The degree of hepatic steatosis was classified as mild, moderate or severe according to the c... | PMC10107656 |
RESULTS | PMC10107656 | |||
Transaminases and Hy's law analysis | ±, Twenty‐nine | HOFH | Twenty‐nine HoFH patients in the pivotal phase 3 trial (follow‐up ≤1.5 years) were monitored for elevations in transaminases and any possible elevations in bilirubin (Figure Mean aminotransferase and bilirubin levels from the pivotal phase 3 trial in HoFH. Values represent means ± standard deviation. ULN for bilirubin ... | PMC10107656 |
Biomarkers of hepatic safety | NAFLD, NASH, fibrosis, steatohepatitis | INFLAMMATION, FIBROSIS, STEATOHEPATITIS | During treatment with lomitapide in the pivotal phase 3 and extension trials, circulating levels of CK‐18 and CK‐18 fragments were measured as biomarkers of hepatic inflammation and indicators of non‐alcoholic steatohepatitis (NASH). Mean levels of CK‐18 and CK‐18 fragments exhibited statistically significant mean incr... | PMC10107656 |
hepatic stiffness | In the present study, FIB‐4 scores were calculable in 25 patients belonging to the Italian cohort with baseline and follow‐up data on platelet levels and transaminases, ALT and AST. FIB‐4 results showed no significant increase in mean FIB‐4 scores from baseline for up to 110.4 months (>9 years; exposure range 1.4–110.4... | PMC10107656 | ||
Hepatic Imaging | ±, hepatic stiffness, hepatic steatosis, fibrosis | FIBROSIS, EVENT, HEPATIC STEATOSIS, HOFH | The baseline characteristics of 34 HoFH patients from the Italian cohort are reported in Table Baseline characteristics of a real‐world cohort of HoFH patients from ItalyAbbreviations: BMI, body mass index; HDL‐C, high‐density lipoprotein cholesterol; IQR, interquartile range; LDL‐C, low‐density lipoprotein cholesterol... | PMC10107656 |
Fat‐soluble vitamins and essential fatty acids | beta‐carotene | In the phase 3 trial, levels of fat‐soluble vitamins remained relatively stable through week 78 of phase 3 study. Mean vitamin E levels (which were supplemented with 400 IU vitamin E daily) decreased by −1.2 mg/dl from baseline to weeks 26 and 78, but values did not fall below the normal range (Table The fat‐soluble vi... | PMC10107656 | |
Apheresis schedules | In the phase 3 study, 18 (62.1%) patients were on LA at baseline. At week 26, three (16.7%) had stopped LA and three (16.7%) had reduced their apheresis frequency. In the Italian cohort, median LDL‐C levels decreased by 58% from 276.5 mg/dl (IQR 196.0–386.2) to 131.0 mg/dl (66.6–228.5) at last visit ( | PMC10107656 | ||
DISCUSSION | NAFLD, hepatic alterations, hepatic inflammation, cirrhosis, fibrosis, liver disease, hepatic stiffness, NASH, hepatic steatosis, liver inflammation, metabolic syndrome, steatohepatitis | HOFH, GENETIC CONDITION, CVD, LIVER, CIRRHOSIS, LIVER DAMAGE, LIVER FIBROSIS, FIBROSIS, EVENT, LIVER DISEASE, METABOLIC SYNDROME, HEPATIC STEATOSIS, EVENTS, HEPATIC FIBROSIS, STEATOHEPATITIS | In the present study, we examined the long‐term hepatic safety of lomitapide based on a range of data available from various sources, which enabled the evaluation of follow‐up for more than 9 years. The data show that lomitapide results in some hepatic alterations, but that overall, there were no clinically meaningful ... | PMC10107656 |
FUNDING INFORMATION | The phase 3 trial, extension phase study and the LOWER registry were funded by Amryt Pharmaceuticals DAC. The Italian study was funded as an investigator‐initiated study grant from Amryt Pharma. | PMC10107656 | ||
CONFLICT OF INTEREST | SOB | DL has received consultancy fees and/or honoraria from Amryt, Sanofi and Aegerion. LD has received consultancy fees and/or honoraria from Amgen, Akcea, Amryt, Pfizer, SOBI, Aurora Biopharma and Sanofi. SOB is an employee of Amryt Pharmaceuticals DAC. MA has received consultancy fees and/or honoraria from Akcea/Ionis, A... | PMC10107656 | |
ETHICS APPROVAL | The studies described were performed in accordance with the Helsinki Declaration of 1964, and its later amendments. All studies received institutional review board approval. All patients provided informed consent for study participation and publication of related data. | PMC10107656 | ||
REGISTRATION | MAY | Phase 3 trial: NCT00730236 reg. 8 August 2008; extension: NCT00943306 reg. 22 July 2009; LOWER: NCT02135705 reg. 12 May 2014. | PMC10107656 | |
Supporting information |
Data S1
Click here for additional data file. | PMC10107656 | ||
ACKNOWLEDGEMENTS | The authors thank Dr Nigel C Eastmond of Eastmond Medicomm Ltd for medical writing and editorial assistance with the collation of data and the preparation of this manuscript. Medical writing and editorial support was funded by Amryt Pharmaceuticals DAC. The authors thank the LOWER steering committee for provision of th... | PMC10107656 | ||
REFERENCES | PMC10107656 | |||
Background | postoperative pain | Thoracoscopic surgical techniques continue to advance, yet the intensity of postoperative pain remains significant, impeding swift patient recovery. This study aimed to evaluate the differences in postoperative pain and recuperation between patients receiving intrathecal morphine paired with low-dose bupivacaine and th... | PMC10691143 | |
Methods | NRS, pain | GROUP B, COMPLICATIONS | This randomized controlled trial enrolled 100 patients, who were allocated into three groups: Group M (5 μg/kg morphine intrathecal injection), Group B (5 μg/kg morphine combined with bupivacaine 3 mg intrathecal injection) and Group C (intrathecal sham injection). The primary outcome was the assessment of pain relief ... | PMC10691143 |
Results | Postoperative NRS scores for both rest and exercise at 6, 12, 24, and 48 h were significantly lower in groups M and B than in group C ( | PMC10691143 | ||
Conclusion | pain | Intrathecal administration of morphine combined with bupivacaine has been shown to effectively ameliorate acute pain in patients undergoing thoracoscopic surgery. | PMC10691143 | |
Trial registration | The trial was registered on ClinicalTrials.gov: ChiCTR2200058544, registered 10/04/2022. | PMC10691143 | ||
Keywords | PMC10691143 | |||
Background | pain, lung tumors, trauma | LUNG TUMORS, COMPLICATIONS, POSTOPERATIVE COMPLICATIONS | Video-assisted thoracoscopic surgery (VATS) has emerged as the principal surgical intervention for lung tumors [The evolution of surgical techniques and the integration of robotics have substantially reduced the extent of surgical trauma, supplanting traditional open surgery with less invasive methods. A solitary intra... | PMC10691143 |
Methods | PMC10691143 | |||
Ethics and registration | This study was approved by the Medical Ethics Committee in Affiliated Hospital of Yangzhou University, Jiangsu, China (Protocol/serial number: 2022-YKL3-08–002) on 8 March 2022. All study subjects gave informed consent for all treatments and investigations. All procedures in the study involving human participants were ... | PMC10691143 | ||
Patients inclusion and exclusion criteria | Subjects to be enrolled in the study were selected prior to an elective VATS procedure. | PMC10691143 | ||
Subject inclusion criteria |
An elective thoracoscopic lobectomy scheduled,The surgical procedure to be performed under general anaesthesia,Age from 18 to 64 years,Body Mass Index (BMI) from18 to 30 kg/mASA physical status classification system class I-II. | PMC10691143 | ||
Subject exclusion criteria | Psychiatric, opioid abuse, Allergies | CARDIAC DISEASES, HEPATIC INSUFFICIENCY, RENAL FAILURE, DISEASE, MORPHINE ALLERGY, ADVERSE REACTION, COAGULOPATHY, CHRONIC PAIN, ALLERGIES |
Allergies to the local anesthetics, morphine, or drugs used in the study,Cardiac diseases, hepatic insufficiency, and renal failure,Subject’s refusal to participate in the study,Inability to understand what the study is about,Previous cardiothoracic surgery,Any contraindication to intrathecal injection (morphine aller... | PMC10691143 |
Procedures | postoperative nausea and vomiting, NRS | GROUP B, STERILE, STERILE, CAVITY, INFILTRATED | After patients were admission, oxygen was administered and ECG, HR, NBP and SPOThe enrolled patients were randomized by random number method into three groups: Group M (5 μg/kg morphine intrathecal injection), Group B (5 μg/kg morphine combined with bupivacaine 3 mg intrathecal injection) and Group C (intrathecal sham ... | PMC10691143 |
Measurement | nausea/vomiting, itching, drowsiness, irritable, Pruritus, nausea and vomiting, vomiting, pain, over-sedation, cough, pruritus, Nausea, NRS, urinary retention | PRURITUS, ADVERSE EVENTS | Patients’ baseline data, surgery and anaesthesia were collected. Mean blood presssure and heart rate at eight time points were recorded: After patient admission (T0), 10 min after intrathecal block (T1), 1 min after double-lumen tracheal intubation (T2), 1 min before surgical cut (T3), 1 min after surgical cut (T4), 5 ... | PMC10691143 |
Statistical analysis | blood loss, pruritus, pain | BLOOD LOSS, DISEASE | Variables were summarized as mean ± SD for normally distributed continuous variables (including demographic profile of the patients, duration of surgery, fluid intake and output, hemodynamic changes, Intra-operative remifentanil use, propofol use, first feeding time, first time out of bed, QoR-15 score), and intergroup... | PMC10691143 |
Sample size considerations | pain | 48 h post-operative coughing on the NRS scores was defined as a clinically meaningful effect. Assuming a standard deviation of 2 for each of the three pain score outcomes on the basis of a preliminary study. The pretest result was an NRS score of 1.3 for group M, 1.2 for group B and 3.3 for group C at 48 h postoperativ... | PMC10691143 | |
Discussion | chronic pain, pain | CHRONIC PAIN | This prospective, interventional, single-blind, randomized study reveals that the combination of intrathecal morphine and bupivacaine offers effective analgesia for patients undergoing VATS. Compared to conventional general anesthesia, this anesthesia approach delivered superior pain control during the first 48 h post-... | PMC10691143 |
Acknowledgements | Assistance with the study: the authors gratefully thank the Departments of Anaesthesiology and cardiothoracic surgery. Affiliated Hospital of Yangzhou University in Yangzhou, Jiangsu for allowing and supporting this study. | PMC10691143 | ||
Authors’ contributions | Miao GUO, Suhong TANG and Dawei YANG helped to design and conduct the study. Yixin WANG and Fengxia LIU analysed the data and approved the final manuscript. Miao GUO, Lin WANG and Jianyou ZHANG wrote and handed in the final manuscript. The authors read and approved the final manuscript. | PMC10691143 | ||
Funding | Project of Yangzhou Municipal Science and Technology Bureau (YZ2022109). | PMC10691143 | ||
Availability of data and materials | The datasets analyzed during the current study are available from the corresponding author upon reasonable request. | PMC10691143 | ||
Declarations | PMC10691143 | |||
Ethics approval and consent to participate | The study was approved by the Medical Ethics Committee at the Affiliated Hospital of Yangzhou University (Protocol/serial number: 2022-YKL3-08–002). All study subjects gave informed consent for all treatments and investigations. All procedures in the study involving human participants were performed in accordance with ... | PMC10691143 | ||
Consent for publication | Not applicable. | PMC10691143 | ||
Competing interests | The authors declare that they have no competing interests. | PMC10691143 | ||
References | PMC10691143 | |||
Background | CHRONIC DISEASES | Effective emotional regulation is recognized as essential to a good mental health of people with chronic diseases, and Mind–body and Art Therapies (MBATs) could have a positive effect on emotional regulation skills in this population. Thus, we aimed to evaluate the effect of MBATs on emotional regulation as measured by... | PMC10536705 | |
Methods | chronic somatic illnesses, body-focused, chronic somatic illness | DISORDER, DISEASE | A convergent mixed approach nested in a pragmatic superiority two arms parallel randomized controlled trial was conducted. French speaking adults with one or more chronic somatic illnesses and not suffering from a chronic psychiatric disorder unrelated to one of their chronic somatic illness were included. At inclusion... | PMC10536705 |
Results | A total of 150 patients was randomized (75 per groups) at the end of the study. At T1, 133 patients filled out the final questionnaire (67 in G1 vs 66 in G2) and 112 interviews were analysed (54 in G1 vs 58 in G2). All 150 patients were analysed (intention to treat) using a multiple imputation approach. The mean DERS s... | PMC10536705 | ||
Conclusions | chronic disease | CHRONIC DISEASE | This study only partially supports benefits on MBAT on emotional regulation skills enhancement in patients with chronic disease receiving MBATs, as measured by the DERS scale. | PMC10536705 |
Trial registration | The protocol was registered on Clinical Trials (NCT02911207). | PMC10536705 | ||
Supplementary Information | The online version contains supplementary material available at 10.1186/s12906-023-04173-8. | PMC10536705 | ||
Keywords | PMC10536705 | |||
Introduction | chronically ill, anxiety, depressive symptoms | CHRONICALLY ILL | According to the World Health Organization, for the first time, a large part of the world's population can expect to live into their sixties and beyond [A large panel of methods are used in TPE [Art therapy experiences have showed a decrease in anxiety symptoms [Regarding mind–body therapies, meditation and Pilates hav... | PMC10536705 |
Methods | We used a concurrent triangulation mixed methods design based on a 1:1 allocation ratio within a pragmatic randomized clinical trial with two parallel groups, one benefiting from the intervention immediately (G1) and the other starting the intervention six months later (G2). The degree of pragmatism in our trial is pre... | PMC10536705 | ||
Population | chronic somatic illnesses, chronic somatic illness | DISORDER, RECRUITMENT | The included patients were adults with one or more chronic somatic illnesses, who had given their consent, who spoke French, who were able to carry out a creative and physical activity and who had no chronic psychiatric disorder unrelated to a chronic somatic illness, and had been offered participation in MBATs propose... | PMC10536705 |
Randomization procedure | DISEASE | The study used a randomized controlled wait-list design. All participants attended an initial evaluation of 1 h at inclusion (T0), which consisted of a non-directive interview focused on the patient’s experience of the disease, followed by an initial emotional regulation assessment (T0). After the initial evaluation, e... | PMC10536705 | |
Intervention | MBATS proposed by the FCS in usual care setting, as described in Table Type of activities tested | PMC10536705 | ||
Quantitative emotional regulation assessment | The Difficulties in Emotion Regulation Scale (DERS), developed by Gratz & Roemer in 2004, is the Gold Standard to assess emotional regulation [Participants had to indicate how often each item applied to themselves, with responses ranging from 1 to 5, where 1 is almost never and 5 is almost always. The scale yields a to... | PMC10536705 | ||
Quantitative analysis | The characteristics of the study population were described using descriptive statistics. The analysis was performed with an intent-to-treat approach, i.e. on all patients randomized to the initial group regardless of their participation in activities. Missing data regarding the outcome were dealt with by implementing a... | PMC10536705 | ||
Qualitative analysis | DISEASE | Non-directive interviews were carried out at the inclusion to explore the participants' experiences regarding their disease, and after 6 months of MBATs to explore the participants' perceived changes associated to the intervention. The interviews were conducted by 4 investigators trained in TPE and 5 medical residents,... | PMC10536705 | |
Ethics and regulation | MAY | All the requirements of French Law were fully complied with. An ethics committee (Comité de Protection des Personnes – Tours – Région Centre-Ouest 1) endorsed the protocol on June 28, 2016. The protocol and the database were registered on May 12, 2016 by the French National Data Protection Committee (CNIL) according to... | PMC10536705 | |
Availability of data and materials | The dataset(s) supporting the conclusions of this article is(are) available upon request to the authors. | PMC10536705 | ||
Results | A total of 150 patients were included at T0 (75 in G1 and 75 in G2). The flowchart of the inclusion process is displayed in Fig. Flowchart of the studyAmong those patients, 78% (Patients’ characteristics (After 6 months (T1), 133 patients filled out the final questionnaire (67 and 66 patients for G1 and G2 respectively... | PMC10536705 | ||
Quantitative results | PMC10536705 | |||
Evolution of the DERS sub-scores | In the overall sample, none of the 6 DERS sub-scores were significantly improved by the intervention. In patients who followed 80% or more of their activity program, we observed a significant decrease in the impulse dimension in the intervention group compared to the control group (-2.6 vs -0.13, | PMC10536705 | ||
Effects on impulse | In the DERS, Impulse focuses on difficulties to control oneself in a negative emotional context. Half of the interviewees (51%, 57/112) described a better control of their impulsive behaviours (verbatim 1). | PMC10536705 | ||
Effects on awareness | In the DERS, awareness assesses the extent to which individuals are able to monitor one’s emotions. Half of the participants (51%, 57/112) reported an improvement in their ability to listen to their feelings, to better perceive and identify their emotions (verbatim 2). Furthermore, the majority of the participants (66%... | PMC10536705 | ||
Effects on clarity | Clarity assesses an individual’s ability to identify, distinguish and describe specific emotion. Nearly half of the participants (47% of the interviewees, 53/112) reported a better understanding of their emotions and how they impacted on their physical symptoms (verbatim 4). | PMC10536705 | ||
Effects on acceptance | CHRONIC ILLNESSES | Acceptance is focused on an individual’s ability to accept one's emotional response. Only 12% (14/112) of them spontaneously reported a better acceptance of their emotions after 6 months of intervention. However, the majority of the participants (69%, 77/112) described a better acceptance of their difficulties and chro... | PMC10536705 | |
Effects on strategy | EVENTS, DISEASE | Strategy assesses an individual’s ability to implement emotional regulation strategies in a negative emotional context. A large majority of participants (87%, 98/112) reported having implemented new emotional regulation strategies. We identified either cognitive (77%, 86/112) or behavioural strategies (74%, 83/112).Amo... | PMC10536705 | |
Discussion | chronically ill, ’ emotional skills, cancer | CHRONICALLY ILL, CANCER | Our study is the first to evaluate the effect of MBATs on emotional regulation in chronically ill patients by use of a randomized clinical trial design. Our main quantitative analysis was inconclusive as it did not show a favourable effect of MBATs on emotional regulation, compared to the control intervention, as measu... | PMC10536705 |
Conclusion | chronically ill | CHRONICALLY ILL | The quantitative results of this study did not support the causal effect of MBATs on patients' emotional regulation. However, the qualitative part of our mixed methods study highlighted a wild range of potential benefits of these complementary therapies in the population of chronically ill patients regarding their abil... | PMC10536705 |
Acknowledgements | Pierre Caillault | The authors would like to thank the following contributors for their essential participation to this study: Mathilde Bourgueil, Catherine Greffier, Erwan Rabiller, Myrtille Richard, Cécile Ferriot, Clément Le Glatin, Claire Fesquet, Pierre Caillault, Marianne Bourdon, Lise Gross and everyone at the Fabrique Créative de... | PMC10536705 | |
Authors’ contributions | Conceptualization: ALR, EA, BL, LM. Data curation: ALR, EA, PC, GB, ML, BL, LM. Formal Analysis: ALR, ML, MD, EA, GB, PC, BL, LM. Funding acquisition: ALR, ML, EA, BL, LM. Investigation: ALR, ML, MD, GB, BL. Methodology: ALR, EA, BL, LM. Project administration: ALR, ML, BL, LM. Resources: ALR, ML, BL, LM. Software: EA,... | PMC10536705 | ||
Funding | This study was funded by the "Direction Générale de l'Offre de Soins" (PREPS 2015 / 15–0304 / EVAD).This study was supported by a grant from the French Ministry of Health (PREPS 2015 / 15-0304 / EVAD). | PMC10536705 | ||
Availability of data and materials | Data are available in supplementary materials (Additional file | PMC10536705 | ||
Declarations | PMC10536705 | |||
Ethics approval and consent to participate | Informed consent was obtained from all subjects and/or their legal guardian(s). All methods were carried out in accordance with relevant guidelines and regulations. The study was approved by the French ethics committee “Comité de Protection des Personnes TOURS—Région Centre—Ouest 1” (FDA IRB n°IORG0008143) on July 30, ... | PMC10536705 | ||
Consent for publication | Not Applicable. | PMC10536705 | ||
Competing interests | The authors declare no competing interests. | PMC10536705 | ||
References | PMC10536705 | |||
Key Points | PMC10167565 | |||
Question | Does pharmacogenetics-informed ( | PMC10167565 | ||
Findings | depressive disorder, depressive symptoms | ADVERSE EFFECTS | In this randomized clinical trial of 111 patients with major depressive disorder, dosing based on preemptive pharmacogenetic testing led to faster attainment of therapeutic plasma concentrations and potentially fewer and less severe adverse effects. No effect on depressive symptoms was found. | PMC10167565 |
Meaning | These findings indicate that pharmacogenetics-informed dosing of tricyclic antidepressants can be safely applied and contributes to personalized antidepressant treatment. | PMC10167565 | ||
Importance | ADVERSE EFFECTS | Evidence of the clinical benefit of pharmacogenetics-informed treatment (PIT) with antidepressants is still limited. Especially for tricyclic antidepressants (TCAs), pharmacogenetics may be of interest because therapeutic plasma concentrations are well defined, identification of optimal dosing can be time consuming, an... | PMC10167565 | |
Objective | MDD, unipolar major depressive disorder | To determine whether PIT results in faster attainment of therapeutic TCA plasma concentrations compared with usual treatment in patients with unipolar major depressive disorder (MDD). | PMC10167565 | |
Design, Setting, and Participants | Depression, unipolar nonpsychotic MDD, bipolar or psychotic disorder, comedications | DISORDER | This randomized clinical trial compared PIT with usual treatment among 111 patients at 4 centers in the Netherlands. Patients were treated with the TCAs nortriptyline, clomipramine, or imipramine, with clinical follow-up of 7 weeks. Patients were enrolled from June 1, 2018, to January 1, 2022. At inclusion, patients ha... | PMC10167565 |
Intervention | In the PIT group, the initial TCA dosage was based on | PMC10167565 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.