Guidance by physicians and pharmacists during antidepressant therapy:Patients' needs and suggestions for improvement

Background: Guidance of patients treated with antidepressants is paramount for successful therapy. The aim was to assess patients' needs and suggestions for improvement of guidance by physicians and pharmacists during second generation antidepressant (SGA) therapy. Methods: Five focus group discussions were held with a total of 34 patients using an SGA. The discussions were conducted flexibly and responsively using a semi-structured topic list. All focus group discussions were video-recorded and transcripts were analyzed using ATLAS.ti for coding, thematic and open analysis. Results: Participants stated they were in need of better guidance. They suggested improving content of information during decisional moments, patient-health care professional communication and communication between health care professionals, and finally, organization of guidance. Barriers to achieving improved guidance were cited. Conclusions: Content, communication and organization of guidance are pivotal for achieving optimal guidance. Participants mentioned their current experienced guidance had limitations and brought up solutions for improvement. A next step would be to discuss the suggested solutions with health care professionals to assess their views and to discuss the possibility for implementation. After implementation, future studies could be aimed at determination of its impact on patients' treatment efficacy, quality of life, treatment satisfaction and healthcare costs

POSEIDON Trial Phase 1b Results: Safety, Efficacy and Circulating Tumor DNA Response of the Beta Isoform-Sparing PI3K Inhibitor Taselisib (GDC-0032) Combined with Tamoxifen in Hormone Receptor Positive Metastatic Breast Cancer Patients.

PURPOSE: The strategy of combining endocrine therapy with PI3K-mTOR inhibition has shown promise in estrogen receptor (ER)-positive breast cancer, but new agents and combinations with a better therapeutic index are urgently needed. Taselisib is a potent, selective, beta-isoform-sparing PI3 kinase inhibitor. PATIENTS AND METHODS: 30 patients with ER-positive, metastatic breast cancer who had failed prior endocrine therapy were treated with escalating doses of taselisib (2 or 4 mg in an intermittent or continuous schedule) combined with tamoxifen 20 mg once daily in this phase 1b study using a "rolling six" design. RESULTS: Taselisib combined with tamoxifen was generally well tolerated, with treatment-emergent adverse events as expected for this class of drugs, including diarrhea (13 patients, 43%), mucositis (10 patients, 33%), and hyperglycemia (8 patients, 27%). No dose-limiting toxicities were observed. Objective responses were seen in 6 of 25 patients with RECIST-measurable disease (ORR 24%). Median time to disease progression was 3.7 months. Twelve of 30 patients (40%) had disease control for 6 months or more. Circulating tumor (ct)DNA studies using next-generation tagged amplicon sequencing identified early indications of treatment response and mechanistically relevant correlates of clinical drug resistance (e.g., mutations in KRAS, ERBB2) in some patients. CONCLUSIONS: Taselisib can be safely combined with tamoxifen at the recommended phase 2 dose of 4 mg given once daily on a continuous schedule. Preliminary evidence of antitumor activity was seen in both PIK3CA mutant and wild-type cancers. The randomized phase 2 part of POSEIDON (testing tamoxifen plus taselisib or placebo) is currently recruiting

Population pharmacokinetics of factor IX in hemophilia B patients undergoing surgery

Essentials Factor IX (FIX) dosing using body weight frequently results in under and overdosing during surgery. We aimed to establish a population pharmacokinetic (PK) model describing the perioperative FIX levels. Population PK parameter values for clearance and V1 were 284 mL h−170 kg−1 and 5450 mL70 kg−1. Perioperative PK parameters differ from those during non-surgical prophylactic treatment. Summary: Background Hemophilia B is a bleeding disorder characterized by a deficiency of coagulation factor IX (FIX). In the perioperative sett

Instructions for monitoring clinical parameters in the Summary of Product Characteristics (SmPC) for psychotropic drugs: Overview and applicability for clinical practice

background The Summary of Product Characteristics (SmPC) for psychotropic drugs includes instructions for clinical and biomarker monitoring intended to optimise effectiveness and minimise harm. aim To evaluate which monitoring instructions are given in the SmPC and to assess the applicability in clinical practice. method The reasons and requirements for monitoring in Smpcs for psychotropic drugs were assessed and somatic parameters were distinguished from non-somatic parameters, thereby the applicability was assessed. results An average of 3.3 instructions per drug label was found. Monitoring was primarily for safety reasons (78%). Requirement was predominantly mandatory (71%). Somatic parameters were most often mentioned (80%). Only 34% of the instructions were determined applicable. conclusion Monitoring instructions for psychotropic drugs are aimed at improving safe use. However, most instructions on monitoring do not provide sufficient information to be applicable in clinical practice

Instructions for monitoring clinical parameters in the Summary of Product Characteristics (SmPC) for psychotropic drugs: Overview and applicability for clinical practice

background The Summary of Product Characteristics (SmPC) for psychotropic drugs includes instructions for clinical and biomarker monitoring intended to optimise effectiveness and minimise harm. aim To evaluate which monitoring instructions are given in the SmPC and to assess the applicability in clinical practice. method The reasons and requirements for monitoring in Smpcs for psychotropic drugs were assessed and somatic parameters were distinguished from non-somatic parameters, thereby the applicability was assessed. results An average of 3.3 instructions per drug label was found. Monitoring was primarily for safety reasons (78%). Requirement was predominantly mandatory (71%). Somatic parameters were most often mentioned (80%). Only 34% of the instructions were determined applicable. conclusion Monitoring instructions for psychotropic drugs are aimed at improving safe use. However, most instructions on monitoring do not provide sufficient information to be applicable in clinical practice

Instructies voor monitoren van klinische parameters in de registratieteksten van psychofarmaca: Overzicht en toepasbaarheid voor de klinische praktijk

background The Summary of Product Characteristics (SmPC) for psychotropic drugs includes instructions for clinical and biomarker monitoring intended to optimise effectiveness and minimise harm. aim To evaluate which monitoring instructions are given in the SmPC and to assess the applicability in clinical practice. method The reasons and requirements for monitoring in Smpcs for psychotropic drugs were assessed and somatic parameters were distinguished from non-somatic parameters, thereby the applicability was assessed. results An average of 3.3 instructions per drug label was found. Monitoring was primarily for safety reasons (78%). Requirement was predominantly mandatory (71%). Somatic parameters were most often mentioned (80%). Only 34% of the instructions were determined applicable. conclusion Monitoring instructions for psychotropic drugs are aimed at improving safe use. However, most instructions on monitoring do not provide sufficient information to be applicable in clinical practice

Instructies voor monitoren van klinische parameters in de registratieteksten van psychofarmaca: Overzicht en toepasbaarheid voor de klinische praktijk

background The Summary of Product Characteristics (SmPC) for psychotropic drugs includes instructions for clinical and biomarker monitoring intended to optimise effectiveness and minimise harm. aim To evaluate which monitoring instructions are given in the SmPC and to assess the applicability in clinical practice. method The reasons and requirements for monitoring in Smpcs for psychotropic drugs were assessed and somatic parameters were distinguished from non-somatic parameters, thereby the applicability was assessed. results An average of 3.3 instructions per drug label was found. Monitoring was primarily for safety reasons (78%). Requirement was predominantly mandatory (71%). Somatic parameters were most often mentioned (80%). Only 34% of the instructions were determined applicable. conclusion Monitoring instructions for psychotropic drugs are aimed at improving safe use. However, most instructions on monitoring do not provide sufficient information to be applicable in clinical practice

POSEIDON trial phase 1B results : Safety, efficacy and circulating tumor DNA response of the beta isoform-sparing PI3K inhibitor taselisib (GDC-0032) combined with tamoxifen in hormone receptor positive metastatic breast cancer patients

Purpose: The strategy of combining endocrine therapy with PI3K-mTOR inhibition has shown promise in estrogen receptor (ER)–positive breast cancer, but new agents and combinations with a better therapeutic index are urgently needed. Taselisib is a potent, selective, beta-isoform–sparing PI3 kinase inhibitor. Patients and Methods: 30 patients with ER-positive, metastatic breast cancer who had failed prior endocrine therapy were treated with escalating doses of taselisib (2 or 4 mg in an intermittent or continuous schedule) combined with tamoxifen 20 mg once daily in this phase 1b study using a "rolling six" design. Results: Taselisib combined with tamoxifen was generally well tolerated, with treatment-emergent adverse events as expected for this class of drugs, including diarrhea (13 patients, 43%), mucositis (10 patients, 33%), and hyperglycemia (8 patients, 27%). No dose-limiting toxicities were observed. Objective responses were seen in 6 of 25 patients with RECIST-measurable disease (ORR 24%). Median time to disease progression was 3.7 months. Twelve of 30 patients (40%) had disease control for 6 months or more. Circulating tumor (ct)DNA studies using next-generation tagged amplicon sequencing identified early indications of treatment response and mechanistically relevant correlates of clinical drug resistance (e.g., mutations in KRAS, ERBB2) in some patients. Conclusions: Taselisib can be safely combined with tamoxifen at the recommended phase 2 dose of 4 mg given once daily on a continuous schedule. Preliminary evidence of antitumor activity was seen in both PIK3CA mutant and wild-type cancers. The randomized phase 2 part of POSEIDON (testing tamoxifen plus taselisib or placebo) is currently recruiting