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Daridorexant as a novel pharmacotherapeutic approach in insomnia: a systematic review and meta-analysis

Dutta S, Singhal S, Shah R, Charan J, Dhingra S, Haque M

Expert Opin Drug Saf, 2023;22(12):1237-1251.
PMID: 37526060 DOI: 10.1080/14740338.2023.2243217

BACKGROUND: Insomnia is a multi-factorial disorder with conventional treatment options that are not satisfactory for many patients. This metaanalysis analyzed the safety and efficacy of daridorexant.
METHODS: An electronic database search for RCTs was conducted on Medline via PubMed, Cochrane, and Clinicaltrials.gov using the terms 'Daridorexant,' 'RCT,' 'Insomnia' trials evaluating the efficacy and/or safety of daridorexant for insomnia were included. The data were synthesized using Cochrane review manager version 5.4.1. Cochrane risk of bias 2.0 tool and GRADEpro-GDT were used to assess the methodological and evidence quality, respectively.
RESULTS: Of 109 searched studies, four trials were included. The risk of treatment-emergent adverse events with 25 mg daridorexant [risk ratio (RR) = 1.12 (0.88, 1.43), p = 0.36; I2 = 0%] and 50 mg daridorexant [RR = 1.25 (0.88, 1.79), p = 0.22; I2 = 28%] and serious adverse events with 25 mg [RR = 0.86 (0.23, 3.19), p = 0.82, I2 = 56%] and 50 mg [RR = 1.32 (0.29, 6.08), p = 0.72, I2 = 52%] was comparable to placebo [Moderate quality evidence]. Risk of nasopharyngitis was also comparable to placebo. The efficacy parameters like wake after sleep onset, latency to persistent sleep, and subjective total sleep time showed significant improvement with daridorexant. The risk of bias is low for three studies and some concern for one.
CONCLUSION: Daridorexant is a safer and efficacious agent for induction and maintenance of sleep for chronic insomnia.
PROSPERO: The registration number is CRD42022335233.
CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifiers are NCT03575104, NCT03545191, NCT03679884, and NCT02839200).
Application of Ti3 C2 MXene Quantum Dots for Immunomodulation and Regenerative Medicine

Rafieerad A, Yan W, Sequiera GL, Sareen N, Abu-El-Rub E, Moudgil M, et al.

Adv Healthc Mater, 2019 08;8(16):e1900569.
PMID: 31265217 DOI: 10.1002/adhm.201900569

Inflammation is tightly linked to tissue injury. In regenerative medicine, immune activation plays a key role in rejection of transplanted stem cells and reduces the efficacy of stem cell therapies. Next-generation smart biomaterials are reported to possess multiple biologic properties for tissue repair. Here, the first use of 0D titanium carbide (Ti3 C2 ) MXene quantum dots (MQDs) for immunomodulation is presented with the goal of enhancing material-based tissue repair after injury. MQDs possess intrinsic immunomodulatory properties and selectively reduce activation of human CD4+ IFN-γ+ T-lymphocytes (control 87.1 ± 2.0%, MQDs 68.3 ± 5.4%) while promoting expansion of immunosuppressive CD4+ CD25+ FoxP3+ regulatory T-cells (control 5.5 ± 0.7%, MQDs 8.5 ± 0.8%) in a stimulated lymphocyte population. Furthermore, MQDs are biocompatible with bone marrow-derived mesenchymal stem cells and induced pluripotent stem cell-derived fibroblasts. Finally, Ti3 C2 MQDs are incorporated into a chitosan-based hydrogel to create a 3D platform with enhanced physicochemical properties for stem cell delivery and tissue repair. This composite hydrogel demonstrates increased conductivity while maintaining injectability and thermosensitivity. These findings suggest that this new class of biomaterials may help bridge the translational gap in material and stem cell-based therapies for tissue repair and treatment of inflammatory and degenerative diseases.
Fulltext Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA)

Sartelli M, Weber DG, Ruppé E, Bassetti M, Wright BJ, Ansaloni L, et al.

World J Emerg Surg, 2016;11:33.
PMID: 27429642 DOI: 10.1186/s13017-016-0089-y

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.
Antimicrobial Susceptibility Patterns of an Emerging Multidrug Resistant Nosocomial Pathogen: Acinetobacter baumannii

Tewari R, Chopra D, Wazahat R, Dhingra S, Dudeja M

Malays J Med Sci, 2018 May;25(3):129-134.
PMID: 30899194 DOI: 10.21315/mjms2018.25.3.13

Multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) bacterium, a nosocomial pathogen associated with a high mortality rate and limited therapeutic options have emerged as a serious problem throughout the world. The present study aimed to assess the current levels of antibiotic susceptibility among the isolates of Acinetobacter species. The sensitivity patterns were analysed from various clinical specimens obtained from both in-patients and outpatients of a teaching hospital. Isolation was performed on 5% sheep blood agar and MacConkey agar. Urine samples were inoculated into CLED agar. Antibiotic susceptibility was performed by the disc diffusion method. A total of 16,452 samples were collected. The total number of samples positive for Acinetobacter species was 67 (0.4%). The highest number of isolates 26 (38.8%) were obtained from urine. Majority 80.3% of the isolates exhibited resistance to three or more classes of antibiotics. All isolates were susceptible to colistin (100%). The susceptibility rate of A. baumannii isolates was 80% for tigecycline and 53.3% for carbapenem. Combination therapies including colistin and tigecycline seem to be the rational treatment for MDR A. baumannii until new alternatives come forward.
An evidence-based review of neuronal cholesterol role in dementia and statins as a pharmacotherapy in reducing risk of dementia

Dutta S, Rahman S, Ahmad R, Kumar T, Dutta G, Banerjee S, et al.

Expert Rev Neurother, 2021 12;21(12):1455-1472.
PMID: 34756134 DOI: 10.1080/14737175.2021.2003705

INTRODUCTION: Dementia is a progressive neurodegenerative disorder impairing memory and cognition. Alzheimer's Disease, followed by vascular dementia - the most typical form. Risk factors for vascular dementia include diabetes, cardiovascular disease, hyperlipidemia. Lipids' levels are significantly associated with vascular changes in the brain.
AREAS COVERED: The present article reviews the cholesterol metabolism in the brain, which includes: the synthesis, transport, storage, and elimination process. Additionally, it reviews the role of cholesterol in the pathogenesis of dementia and statin as a therapeutic intervention in dementia. In addition to the above, it further reviews evidence in support of as well as against statin therapy in dementia, recent updates of statin pharmacology, and demerits of use of statin pharmacotherapy.
EXPERT OPINION: Amyloid-β peptides and intraneuronal neurofibrillary tangles are markers of Alzheimer's disease. Evidence shows cholesterol modulates the functioning of enzymes associated with Amyloid-β peptide processing and synthesis. Lowering cholesterol using statin may help prevent or delay the progression of dementia. This paper reviews the role of statin in dementia and recommends extensive future studies, including genetic research, to obtain a precise medication approach for patients with dementia.
Fulltext Acute abdomen in the immunocompromised patient: WSES, SIS-E, WSIS, AAST, and GAIS guidelines

Coccolini F, Improta M, Sartelli M, Rasa K, Sawyer R, Coimbra R, et al.

World J Emerg Surg, 2021 08 09;16(1):40.
PMID: 34372902 DOI: 10.1186/s13017-021-00380-1

Immunocompromised patients are a heterogeneous and diffuse category frequently presenting to the emergency department with acute surgical diseases. Diagnosis and treatment in immunocompromised patients are often complex and must be multidisciplinary. Misdiagnosis of an acute surgical disease may be followed by increased morbidity and mortality. Delayed diagnosis and treatment of surgical disease occur; these patients may seek medical assistance late because their symptoms are often ambiguous. Also, they develop unique surgical problems that do not affect the general population. Management of this population must be multidisciplinary.This paper presents the World Society of Emergency Surgery (WSES), Surgical Infection Society Europe (SIS-E), World Surgical Infection Society (WSIS), American Association for the Surgery of Trauma (AAST), and Global Alliance for Infection in Surgery (GAIS) joined guidelines about the management of acute abdomen in immunocompromised patients.