On inflammatory hypothesis of depression: what is the role of IL-6 in the middle of the chaos?

Many patients with major depressive disorder (MDD) are reported to have higher levels of multiple inflammatory cytokines including interleukin 6 (IL-6). Recent studies both pre-clinical and clinical have advocated for the functional role of IL-6 in development of MDD and suggested a great potential for targeting this cytokine to open new avenues in pharmacotherapy of depression. The purpose of the present narrative review was to provide an integrated account of how IL-6 may contribute to development of depression. All peer-reviewed journal articles published before July 2020 for each area discussed were searched by WOS, PubMed, MEDLINE, Scopus, Google Scholar, for original research, review articles, and book chapters. Publications between 1980 and July 2020 were included. Alterations in IL-6 levels, both within the periphery and the brain, most probably contribute to depression symptomatology in numerous ways. As IL-6 acts on multiple differing target tissues throughout the body, dysregulation of this particular cytokine can precipitate a multitude of events relevant to depression and blocking its effects can prevent further escalation of inflammatory responses, and potentially pave the way for opening new avenues in diagnosis, treatment, and prevention of this debilitating disorder.

Evaluation of Adherence to Antiemetic Treatment Guidelines in Patients With Chemotherapy-Induced Nausea and Vomiting in Teaching Hospitals in Tehran.

The present study evaluated adherence to antiemetic guidelines for prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in four tertiary university teaching hospitals in Tehran. This prospective observational study enrolled 382 adult patients on chemotherapy at oncology centers affiliated to medical universities located in Tehran. Patients were followed up during their chemotherapy cycles. Risk factors related to CINV were evaluated, and information on antiemetic prescribing patterns was gathered using direct interview and patient medical records. Guideline adherence was found to be low; however, 81.3% of the patients experienced chemotherapy without CINV. Low frequency of adherence to the guidelines in prescription patterns does not mean that prescription patterns were very different. Indeed, some drugs were added to base guideline recommendation regiments, since in high and moderate emetogenic chemotherapy categories, some novel antiemetics recommended by international guidelines are not yet included in Iranian pharmacopeia. It was shown that two drug classes were added as a common practice, namely, H1/H2 antagonists and dopamine receptor antagonist (metoclopramide). Statistically significant differences were found between antiemetic prescribing patterns of physicians and chemotherapy regimen category (aspect of emetogenic potential) (p < 0.001). The most commonly prescribed regimen in the minimal-emetic-risk category and the low-emetic-risk category was reported to be the combination of corticosteroids, 5HT3, and H1/H2 antagonists, 33% and 66.1% respectively. Moreover, corticosteroids +5HT3 and H1/H2 antagonists + NK1 antagonist were found to be the most frequently prescribed regimen in the moderate-emetic-risk category (39.7%) and high-emetic-risk category (41.8%). Antiemetic prescribing patterns were not completely compatible with the guidelines in moderate and high emetogenic chemotherapy categories. Differences were detected in two states of over- and undertreatment. The present study confirmed low level of adherence of antiemetic prescribing patterns with international guidelines. However, it could not be proved that high levels of adherence with the guidelines result in reduction of CINV incidence. Complete success in CINV control cannot be achieved only by adherence to the established guidelines as novel antiemetics recommended by the guidelines have not been included in the Iranian pharmacopeia as yet. The authors do recommend implementation of strategies for increasing guideline-compliant prescriptions with the aim of improving patients' outcomes. We also suggest that policymakers in healthcare system point more critically to overprescribing as an issue of concern.

Therapeutic Effects of Tamsulosin in Nightmare Disorder: A Randomized, Double Blind, Placebo-Controlled, Cross-Over, Pilot Study.

Nightmare disorder is associated with functional impairment, distress, and low quality of life; however, studies on pharmacotherapy of this debilitating disorder yielded mixed results. Prazosin, a non-selective α1 blocker is reported to be effective in treatment of post-traumatic stress disorder-related nightmares. We aimed at investigating therapeutic effects of tamsulosin which has higher affinity for blocking α1A and α1D adrenoceptors in treatment of nightmare disorder. A randomized, double blind, cross-over, placebo-controlled pilot study was conducted. Patients were randomly assigned to receive Tamsulosin 0.4 mg once daily or placebo for period of four weeks. Following a 2-week wash-out period, they were crossed over to the other group and received drug or placebo for duration of 4 additional weeks. Nightmare frequency and intensity measurements were carried out using Disturbing Dreams and Nightmares Severity Index (DDNSI). Blood pressure measurements were also performed. According to per protocol analysis, mean DDNSI scores decreased following administration of tamsulosin and a statistical trend towards significance was reported (p=0.065, d=0.236). Results of intention to treat analysis showed significant difference in DDNSI scores after drug use (p=0.030, d=0.651). Additionally, DDNSI scores dropped significantly following placebo use. However, intention to treat analysis showed no statistically significant difference pre and post placebo period (0.064, d=0.040). Tamsulosin may be effective in treatment of nightmare disorder. However, further larger clinical trials are recommended to clarify the effectiveness of tamsulosin and α1 subtypes in pharmacotherapy of nightmares.

Structure and Function of a Provincial Renal Pharmacy Program: Applying the Chronic Care Model to Address Equitable Access to Medication and Pharmacy Services.

Purpose: We described the rationale, structure, design, and components of a provincial pharmacy services network for patients with kidney disease as a model for enabling equitable access and universal care to pharmacy services and medications across a wide range of clinical conditions, and geographic expanse in British Columbia (BC). Sources of Information: These include minutes from 53 Pharmacy Services and Formulary (PS&F) Committee meetings held from 1999 to November 2022, documentation available on the British Columbia Renal (BCR) website, direct observation and participation in committee meetings, as well as interviews with key individuals involved in different aspects of the program. Methods: We reviewed documents and data describing the evolution, rationale, and functioning of the BCR provincial pharmacy services system and used a variety of sources as mentioned above. In addition, a qualitative thematic synthesis of reports of chronic care models (CCMs) was conducted to map the program components into the chronic disease management models. Key Findings: The components of the provincial pharmacy program (PPP) include (1) a PS&F committee, with interdisciplinary and geographical representation; (2) a community of dispensing pharmacies with standardized protocols and information; (3) a dedicated medication and pharmacy services budget, and regular evaluation of budget, outcomes, and performance; (4) provincial contracts for specific medications; (5) communication and education; and (6) information management system. Program components are described in the context of chronic disease management models. The PPP includes dedicated formularies for people with kidney disease at different points in the disease trajectory, including those on and off dialysis. Equitable access to medications is supported across the province. All medications and counseling services are provided to all patients registered in the program, through a robust distributed model, including community- and hospital-based pharmacies. Provincial contracts managed centrally ensure best economic value, and centralized education and accountability structures ensure sustainability. Limitations: Limitations of the current report include lack of formal evaluation of the program on patient outcomes, but this is relative as the intention of this article is to describe the program which has existed for over 20 years and is fully functional. Formal evaluation of a complex system would include by costs, cost avoidance, provider, and patients' satisfaction. We are developing a formal plan for this reason. Implications: The PPP is embedded in the provincial infrastructure of BCR and enables the provision of essential medications and pharmacy services for patients with kidney disease throughout the spectrum. The leveraging of local and provincial resources, knowledge, and expertise to implement a comprehensive PPP, ensures transparency and accountability and may serve as a model for other jurisdictions.

Contexte: Nous avons décrit la raison d'être, la structure, la conception et les composantes d'un réseau provincial de services en pharmacie pour les patients atteints d'insuffisance rénale comme un modèle permettant des soins universels et un accès équitable aux services pharmaceutiques et aux médicaments dans un large éventail de conditions cliniques et d'étendues géographiques en Colombie-Britannique (C.-B.). Sources: Les procès-verbaux de 53 réunions du Pharmacy Services and Formulary Committee tenues entre 1999 et novembre 2022, la documentation disponible sur le site BC Renal, l'observation directe et la participation aux réunions du comité, ainsi que les entretiens avec des personnes clés impliquées dans différents aspects du program. Méthodologie: Nous avons examiné les documents et les données décrivant l'évolution, la raison d'être et le fonctionnement du système provincial de services pharmaceutiques BC Renal et nous avons utilisé diverses sources, comme mentionné ci-dessus. Une synthèse thématique qualitative des rapports sur les modèles de soins chroniques (MSC) a également été réalisée afin d'intégrer les composantes du program aux modèles de gestion des maladies chroniques. Principaux résultats: Les composantes du program provincial de pharmacie (PPP) comprennent: 1) un comité des services pharmaceutiques et des listes de médicaments, avec une représentation interdisciplinaire et géographique; 2) une communauté de pharmacies d'officine disposant de protocoles et de renseignements normalisés; 3) un budget dédié aux médicaments et aux services pharmaceutiques, ainsi qu'une évaluation régulière du budget, des résultats et du rendement; 4) des contrats provinciaux pour certains médicaments particuliers; 5) des structures de communication et d'éducation; et 6) un système de gestion de l'information. Les composantes du program sont décrites dans le contexte des modèles de gestion des maladies chroniques. Le PPP comprend des formulaires dédiés pour les personnes atteintes d'insuffisance rénale à différents points de la trajectoire de la maladie, qui sont sous dialyze ou non. Un accès équitable aux médicaments est assuré dans toute la province. Tous les médicaments et les services de conseil sont fournis à tous les patients inscrits au program, par le biais d'un robuste modèle de distribution, comprenant des pharmacies communautaires et hospitalières. Des contrats provinciaux gérés de façon centralisée assurent la meilleure valeur économique, et les structures centralisées d'éducation et de responsabilisation assurent la durabilité. Limites: L'absence d'évaluation formelle du program sur les résultats des patients, bien que cela soit relatif puisque l'intention de cet article est de décrire un program pleinement fonctionnel qui existe depuis plus de 20 ans. L'évaluation formelle d'un système complexe porterait sur les coûts, les économies de coûts, la satisfaction des prestataires et des patients. Nous sommes en processus d'élaboration d'un plan formel. Résultats: Le PPP est intégré à l'infrastructure provinciale BC Renal et permet la fourniture de médicaments et de services pharmaceutiques essentiels aux patients atteints de l'ensemble du specter de l'insuffisance rénale. L'exploitation des ressources, des connaissances et de l'expertise locales et provinciales pour mettre en œuvre un PPP complet garantit la transparence et la responsabilisation, et peut servir de modèle à d'autres administrations.

Clinical effects of topical antifungal therapy in chronic rhinosinusitis: a randomized, double-blind, placebo-controlled trial of intranasal fluconazole.

Several studies have been in favor of fungi as a possible pathogenesis of chronic rhinosinusitis (CRS); however, to date, there is no scientific consensus about the use of antifungal agents in disease management. The aim of the present study was to investigate the efficacy of intranasal fluconazole in improving disease symptoms and objective outcomes of patients with CRS. A randomized, double-blind, placebo-controlled study was conducted on 54 patients who were diagnosed with CRS and had not been responsive to routine medical treatments. They were randomly assigned to receive either fluconazole nasal drop 0.2 % or placebo in addition to the standard regimen for a duration of 8 weeks. Patients' outcomes were evaluated according to Sino-Nasal Outcome Test 20 (SNOT-20), endoscopic scores, and Computed Tomography (CT) scores. No statistically significant difference was found in SNOT-20 (p = 0.201), endoscopic (p = 0.283), and CT scores (p = 0.212) of the patients at baseline and after 8-week course of treatment between drug and placebo group. Similar to many studies, the use of topical antifungal treatment for patients with CRS was not shown to be significantly effective. However, further studies are needed to obtain high levels of consistent evidence in order to arrive at a decision whether antifungal therapy is effective in management of CRS or not.