Drugs in Context

De novo metastatic breast cancer (dnMBC) accounts for ~6-10% of all breast cancers and for ~30% of MBC with increasing incidence over time. Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+ /HER2- ) tumours are the most frequent subtype with a similar incidence to that observed amongst recurrent MBC (rMBC). Higher frequency of PI3KCA and ARID2 mutations and a lower frequency of ESR1 mutations and of genes involved in DNA damage, as compared with rMBC, have been reported in HR+ /HER2- dnMBC; however, these are not correlating with prognosis, whilst tumour mutational burden is inversely correlated with outcome...

Cancer pain requires careful comprehensive patient evaluation and an appropriate and personalized clinical approach by a trained multidisciplinary team. The proper assessment of breakthrough cancer pain (BTcP) is part of an all-inclusive multidimensional evaluation of the patient. The aim of this narrative review is to explore the relationship between high-rate BTcP, which strongly impacts health- related quality of life and tumour characteristics, in the face of novel approaches that should provide guidance for future clinical practice...

Psoriatic arthritis is a chronic systemic inflammatory disease that presents with a variable clinical course and is typically associated with joint inflammation, together with cutaneous psoriasis. In recent decades, knowledge of the pathogenesis of psoriatic arthritis has advanced considerably and has allowed for development of new highly effective therapies, transforming the treatment landscape. Upadacitinib is a Janus kinase inhibitor (JAK) that is orally reversible with high selectivity for JAK1 and its signal transduction molecules...

BACKGROUND: Prucalopride is a selective serotonin type 4 (5-HT4 ) receptor agonist indicated for treatment of chronic idiopathic constipation (CIC) in adults (2 mg orally, daily). 5-HT4 receptors are present in the central nervous system; therefore, non-clinical and clinical assessments were performed to evaluate the tissue distribution and abuse potential of prucalopride. METHODS: In vitro receptor-ligand binding studies were performed to assess the affinity of prucalopride (≤1 mM) for peptide receptors, ion channels, monoamine neurotransmitters and 5-HT receptors...

BACKGROUND: Antibiotics are prescribed to nearly one-half of patients with viral respiratory tract infections (RTI) in outpatient settings. This use is ineffective and may cause undue harm and excess cost from unnecessary antibiotic exposure. We implemented a multifaceted intervention to address inappropriate antibiotic prescribing for viral RTI. Here, we discuss the impact over 4 years, before and during the SARS-CoV-2 pandemic. METHODS: This observational study describes the implementation and initial impact of a multimodal stewardship intervention on inappropriate antibiotic prescribing for viral RTIs in outpatient care settings at a single centre...

Antimicrobial stewardship programmes in the outpatient setting have recently become an area of focus in an effort to improve antimicrobial prescribing. The Centers for Disease Control and Prevention and The Joint Commission have recently addressed this concern and provided a framework for the implementation of an outpatient stewardship programme. This manuscript offers detailed guidance on how to design and implement an outpatient antimicrobial stewardship programme and reviews the literature on current strategies...

Novel diagnostic stewardship in infectious disease consists of interventions that modify ordering, processing, and reporting of diagnostic tests to provide the right test for the right patient, prompting the right action. The interventions work upstream and synergistically with traditional antimicrobial stewardship efforts. As diagnostic stewardship continues to gain public attention, it is critical that antimicrobial stewardship programmes not only learn how to effectively leverage diagnostic testing to improve antimicrobial use but also ensure that they are stakeholders and leaders in developing new diagnostic stewardship interventions within their institutions...

BACKGROUND: Proton-pump inhibitors, along with a prokinetic agent, are widely used to provide symptomatic relief amongst patients with acid peptic disease (APD). This article evaluates the effectiveness and safety of the omeprazole-domperidone combination amongst patients with type 2 diabetes mellitus for the management of APD. METHODS: PRIDE-2 (PRoton-pump Inhibitor in patients with type 2 DiabEtes mellitus) is a retrospective study reviewing electronic medical records of patients with type 2 diabetes mellitus and APD who were receiving the omeprazole-domperidone combination and visiting multiple Indian healthcare settings between March 2018 and April 2021...

The SARS-CoV-2 pandemic is the most globally impacting health issue our world has faced over the last century. As of January 7, 2022, around 300 million cases have been reported worldwide, with over 5 million deaths. The SARS-CoV-2 infection causes a hyperactive host immune response leading to an excessive inflammatory reaction with the release of many cytokines - cytokine storm - commonly noticed in acute respiratory distress syndrome, sepsis and fulminant multiorgan failure. Since the beginning of the pandemic, the scientific medical community has worked on therapeutic procedures that interfere with the exaggerated immune response...

Schizophrenia is a common debilitating disorder characterized by significant impairments in how reality is perceived, combined with behavioural changes. In this review, we describe the lurasidone development programme for adult and paediatric patients. Both the pharmacokinetic and pharmacodynamic characteristics of lurasidone are revisited. In addition, pivotal clinical studies conducted on both adults and children are summarized. Several clinical cases, which demonstrate the role of lurasidone in real-world practice, are also presented...

One of the most relevant and differentiating aspects provided by the 2021 European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure is the retraction of the historical stepped and vertical pharmacological treatment scheme for heart failure with reduced ejection fraction (HFrEF). Subsequently, it was replaced by an updated algorithm that places four therapeutic families in the same initial horizontal step with an equally high degree of recommendation (class I)...

Tachycardia-induced cardiomyopathy is an entity characterized by reversible dysfunction of the left ventricle, which can be induced by different types of arrhythmia such as atrial fibrillation, atrial flutter, incessant supraventricular tachycardia and ventricular arrhythmia (more frequent causes). Correct identification of the causative arrhythmia and normalization of the heart rate (e.g through medical treatment, electrical cardioversion, ablation) can lead to recovery of left ventricular function. Tachycardia-induced cardiomyopathy should be suspected in patients with tachycardia and left ventricular dysfunction (heart failure setting), especially when there is no history of previous heart disease...

Point-of-care ultrasound (POCUS) plays a strategic role in the diagnostic and therapeutic evaluation of critically ill patients and, especially, in those who are haemodynamically unstable. In this context, POCUS allows a more precise identification of the cause, its differential diagnosis, the eventual coexistence with another entity and, finally, guiding of the therapeutic approach. It implies a portable use of ultrasound in acute settings covering different specified protocols, such as echocardiography, vascular, lung or abdominal ultrasound...

BACKGROUND: Due to changing face of dermatophytosis in India, many dermatologists practice different dosing patterns of itraconazole (ITZ). Recently, a new form of ITZ, super-bioavailable ITZ (SBITZ), has been commercialized to overcome the pharmacokinetic challenges of conventional ITZ (CITZ). Serum and sebum concentration of ITZ plays an important role in the management of dermatophytosis. Hence, the current study compares the rate and extent of serum and sebum concentration of SBITZ and CITZ at different dosing to determine their efficacy and safety in patients with dermatophytosis...

The role of sodium-glucose cotransporter 2 inhibitors (SLTG2i), developed initially as glucose-lowering agents, has represented a novelty in patients with heart failure (HF) and reduced ejection fraction (HFrEF) since dapagliflozin (DAPA-HF study) and empagliflozin (EMPEROR-Reduced study) were able to reduce morbidity and mortality in this setting regardless of the presence or absence of diabetes. In previous large clinical trials (EMPA-REG OUTCOME study, CANVAS, DECLARE-TIMI 58), SGLT2i have been shown to attenuate HF progression expressed by reducing the risk of HF hospitalizations in patients with type 2 diabetes mellitus mostly without HF at baseline...

The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway is dysregulated in patients with heart failure (HF) resulting in myocardial and vascular dysfunction that contributes to its progression. Vericiguat is a novel direct sGC stimulator that targets in at least two ways the NO-sGC-cGMP pathway with the subsequent restoration of cGMP activity. The VICTORIA trial assessed the effects of vericiguat ( versus placebo) in 5050 patients with chronic HF (NYHA class II-IV), left ventricular ejection fraction (LVEF) <45%, elevated natriuretic peptide levels and a recent HF decompensation (hospitalized or outpatient intravenous diuretics)...

Circulatory support with extracorporeal membrane oxygenation (ECMO) is being increasingly used in several critical situations but evidence of its impact on outcomes is inconsistent. Understanding of the specific indications and appropriate timing of implantation of this technology might lead to improved results. Indeed, the line between success and futility may be sometimes very thin when facing a patient in critical condition. New techniques with lighter, simpler and effective devices are being developed. Hence, ECMO has become an accessible technology that is being increasingly used outside of the operating room by heart failure specialists, critical care cardiologists and intensivists...

The assessment and treatment of breakthrough cancer pain (BTcP) remain a major challenge in medicine due to its high impact on several aspects of health-related quality of life. BTcP should be carefully monitored in all cancer care settings by a multidisciplinary team to provide an appropriate and personalized clinical approach. The aim of this paper is to provide healthcare professionals involved in cancer pain management with a review of the relevant literature on the relationship between background cancer pain and BTcP which, by definition, occurs despite adequately controlled background cancer pain...

BACKGROUND: Hyperfunctional platelets play important roles in thromboembolism in patients with β-thalassaemia/ haemoglobin E (β-thal/HbE). Our previous study revealed ex vivo inhibitory effects of deferiprone on normal platelets. Herein, we aimed to investigate the in vivo effects on platelets in patients with β-thal/HbE. METHODS: A prospective, self-controlled clinical study on 30 patients with β-thal/HbE who had received therapeutic deferiprone (20...

Propranolol is a β-adrenergic antagonist used in the management of hypertension, cardiac arrhythmia, and angina pectoris. There is some evidence that propranolol may benefit individuals with behavioural and psychological symptoms of dementia (BPSD). A total of three case series, one randomized controlled trial and one case report were identified (from a literature search of three major databases: PubMed, Ovid, and Cochrane collaboration) that assessed the use of propranolol for the management of BPSD...