Impact of Post Manufacturing Handling of Protein-Based Biologic Drugs on Product Quality and User Centricity.

This article evaluates the current gaps around the impact of post-manufacturing processes on the product qualities of protein-based biologics, with a focus on user centricity. It includes the evaluation of the regulatory guidance available, describes a collection of scientific literature and case studies to showcase the impact of post-manufacturing stresses on product and dosing solution quality. It also outlines the complexity of clinical handling and the need for communication, and alignment between drug providers, healthcare professionals, users, and patients.

Examination of the Protein Drug Supply Chain in a Swedish University Hospital: Focus on Handling Risks and Mitigation Measures.

Protein drugs, such as monoclonal antibodies, have proved successful in treating cancer and immune system diseases. The structural complexity of these molecules requires careful handling to ensure integrity and stability of the drug. In this study, a failure mode and effects analysis was performed based on a Gemba Walk method in a Swedish University Hospital.

Probable tirofiban-induced thrombotic microangiopathy after stent thrombosis: a case report.

Background: Glycoprotein (GP) IIb-IIIa inhibitors are antithrombotic drugs used in selected patients during and after percutaneous coronary interventions (PCIs), usually as a bail-out in the setting of no-reflow or thrombotic complications. A notorious life-threatening adverse effect of this drug class is immune-mediated drug-induced thrombocytopenia (DITP). Thrombotic microangiopathy (TMA) induced by GP IIb-IIIa inhibitors has never been reported.

A secondary qualitative analysis of stakeholder views about participant recruitment, retention, and adherence in decentralised clinical trials (DCTs).

Background: Decentralised clinical trials (DCTs) are clinical trials where all or most trial activities occur in or near participants' homes instead of hospitals or research sites. While more convenient for participants, DCTs may offer limited opportunities to build trust with investigators and trial teams. This qualitative analysis explored DCT stakeholder views to inform strategies for maximising participant recruitment, retention, and adherence.

Sex-Related Differences in Long-Term Outcomes After Early-Onset Myocardial Infarction.

Importance: There is growing awareness of sex-related differences in cardiovascular risk profiles, but less is known about whether these extend to pre-menopausal females experiencing an early-onset myocardial infarction (MI), who may benefit from the protective effects of estrogen exposure.

Methods: A nationwide study involving 125 Italian Coronary Care Units recruited 2,000 patients between 1998 and 2002 hospitalized for a type I myocardial infarction before the age of 45 years (male, = 1,778 (88.9%).

Managing antibody stability: Effects of stressors on Ipilimumab from the commercial formulation to diluted solutions.

The stability of the monoclonal antibody Ipilimumab, the active ingredient of Yervoy®, used for the treatment of different types of cancer, has been investigated. Shaking/temperature, light exposure and dilution, protein drug renowned stressors, were applied on a 30-45-day series of experiments to observe the physicochemical and biological behavior of the molecule. Ipilimumab demonstrated stability under shaking and heat up to 45 days, without any unfolding during the induced combined stressors.

Long-term outcomes of early-onset myocardial infarction with non-obstructive coronary artery disease (MINOCA).

Background: Acute myocardial infarction with non-obstructive coronary artery disease (MINOCA) is frequent in patients experiencing an early-onset MI, but data concerning its long-term prognosis are limited and conflicting.

Methods: The Italian Genetic Study on Early-onset MI enrolled 2000 patients experiencing a first MI before the age of 45 years, and had a median follow-up of 19.9 years.

A systematic review of methods used to conduct decentralised clinical trials.

Aims: To evaluate, using quantitative and qualitative approaches, published data on the design and conduct of decentralised clinical trials (DCTs).

Methods: We searched MEDLINE, EMBASE, CENTRAL, PsycINFO, ProQuest Dissertations and Theses, ClinicalTrials.gov, OpenGrey and Google Scholar for publications reporting, discussing, or evaluating decentralised clinical research methods.

Learning from remote decentralised clinical trial experiences: A qualitative analysis of interviews with trial personnel, patient representatives and other stakeholders.

Aims: The aim of the study was to identify actionable learning points from stakeholders in remote decentralised clinical trials (RDCTs) to inform their future design and conduct.

Methods: Semistructured interviews were carried out with a purposive sample of stakeholders, including senior managers, trial managers, technology experts, principal investigators, clinical investigators, research scientists, research nurses, vendors, patient representatives and project assistants. The interview data were coded using a thematic approach, identifying similarities, differences and clustering to generate descriptive themes.

Application of Healthcare 'Big Data' in CNS Drug Research: The Example of the Neurological and mental health Global Epidemiology Network (NeuroGEN).

Neurological and psychiatric (mental health) disorders have a large impact on health burden globally. Cognitive disorders (including dementia) and stroke are leading causes of disability. Mental health disorders, including depression, contribute up to one-third of total years lived with disability.

Postmortem tissue distribution of morphine and its metabolites in a series of heroin-related deaths.

The abuse of heroin (diamorphine) and heroin-related deaths are increasing around the world. The interpretation of the toxicological results from suspected heroin-related deaths is notoriously difficult, especially in cases where there may be limited samples. To help forensic practitioners with heroin interpretation, we determined the concentration of morphine (M), morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) in blood (femoral and cardiac), brain (thalamus), liver (deep right lobe), bone marrow (sternum), skeletal muscle (psoas), and vitreous humor in 44 heroin-related deaths.

ALLiance for sEcondary PREvention after an acute coronary syndrome. The ALLEPRE trial: A multicenter fully nurse-coordinated intensive intervention program.

The main objective of cardiovascular disease prevention is to reduce morbidity and mortality by promoting a healthy lifestyle, reducing risk factors, and improving adherence to medications. Secondary prevention after an acute coronary syndrome has proved to be effective in reducing new cardiovascular events, but its limited use in everyday clinical practice suggests that there is considerable room for improvement. The short-term results of evidence-based studies of nurse-coordinated secondary prevention programs have been positive, but there is a lack of long-term outcome data.

Pharmacogenomic Approach to Selecting Antiplatelet Therapy in Patients With Acute Coronary Syndromes: The PHARMCLO Trial.

Background: Although clopidogrel is still frequently used in patients with acute coronary syndromes (ACS), its efficacy is hampered by interpatient response variability caused by genetic polymorphisms associated with clopidogrel's metabolism.

Objectives: The goal of this study was to evaluate whether selecting antiplatelet therapy (clopidogrel, prasugrel, or ticagrelor) on the basis of a patient's genetic and clinical characteristics leads to better clinical outcomes compared with the standard of care, which bases the selection on clinical characteristics alone.

Methods: Patients hospitalized for ACS were randomly assigned to standard of care or the pharmacogenomic arm, which included the genotyping of ABCB1, CYP2C19*2, and CYP2C19*17 using an ST Q3 system that provides data within 70 min at each patient's bedside.

[ST-segment elevation myocardial infarction in a patient with thrombophilia taking new oral anticoagulants].

We report the case of a 65--year-old woman admitted for inferior ST-segment elevation myocardial infarction complicated by complete atrioventricular block. The patient was under treatment with a novel oral anticoagulant (NOAC, rivaroxaban) because of a history of recurrent idiopathic pulmonary embolism. Emergency angiography showed complete acute thrombotic occlusion of the right coronary artery.

Multi-dimensional nursing form: a novel means of approaching nurse-led secondary cardiology prevention.

Background And Aim: Secondary prevention after an acute coronary syndrome (ACS) has proved to be effective in patients with coronary heart disease, and is strongly recommended by the international guidelines. However, there is a lack of widespread secondary preventive programmes in real-world clinical practice, even though it has been shown that these can be successfully conducted by nurses.

Method And Results: We have designed a multicentre randomised trial involving patients with ACS in which nurses will fully coordinate secondary prevention in the intervention arm using a multidimensional nursing form after attending ad hoc teaching sessions.

Postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in rabbits over 24 h.

The interpretation of postmortem drug levels is complicated by changes in drug blood levels in the postmortem period, a phenomena known as postmortem drug redistribution. We investigated the postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in a rabbit model. Heroin (1 mg/kg) was injected into anesthetised rabbit; after 1 h, an auricular vein blood sample was taken and the rabbit was euthanised.

Nefopam Hydrochloride: A Fatal Overdose.

Nefopam is a non-opiate analgesic commonly used for the treatment of moderate to severe pain. A case of a 37-year-old male who was found dead in the morning is presented. An autopsy was performed and femoral venous blood, heart blood, urine, and vitreous humor were submitted for toxicological analysis.

Preparation and analytical characterization of 1-(1-phenylcyclohexyl)piperidine (PCP) and 1-(1-phenylcyclohexyl)pyrrolidine (PCPy) analogues.

Classic examples of psychoactive arylcycloalkylamines include ketamine and 1-(1-phenylcyclohexyl)piperidine (PCP) and many others serve as important structural templates for neuropharmacological research. The recent emergence of PCP analogues that can be obtained from internet retailers requires the implementation of appropriate monitoring strategies for harm reduction purposes. Access to analytical data plays a key part when encountering these substances, especially if reference material is not available.

From the street to the laboratory: analytical profiles of methoxetamine, 3-methoxyeticyclidine and 3-methoxyphencyclidine and their determination in three biological matrices.

Three psychoactive arylcyclohexylamines, advertised as "research chemicals," were obtained from an online retailer and characterized by gas chromatography ion trap electron and chemical ionization mass spectrometry, nuclear magnetic resonance spectroscopy and diode array detection. The three phencyclidines were identified as 2-(ethylamino)-2-(3-methoxyphenyl)cyclohexanone (methoxetamine), N-ethyl-1-(3-methoxyphenyl)cyclohexanamine and 1-[1-(3-methoxyphenyl)cyclohexyl]piperidine. A qualitative/quantitative method of analysis was developed and validated using liquid chromatography (HPLC) electrospray tandem mass spectrometry and ultraviolet (UV) detection for the determination of these compounds in blood, urine and vitreous humor.

Phenazepam: the drug that came in from the cold.

In the past few years there has been concern in Western Europe and in the US about the rise in abuse of phenazepam, a benzodiazepine that was originally developed in the USSR in the mid- to late 1970s.(1-4) Although phenazepam is one of the most widely prescribed benzodiazepines in Russia and other commonwealth of independent state (CIS) countries, it has not been licensed elsewhere in the world. Due to very limited licensed geographical distribution, there is very little peer-reviewed literature that is not written in Russian.