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2.
Transl Vis Sci Technol ; 12(5): 16, 2023 05 01.
Article in English | MEDLINE | ID: mdl-37184498

ABSTRACT

Purpose: Although a comprehensive knowledge of antibiotic/corticosteroid combinations is essential for the appropriate treatment of eye infections, the impact of their co-administration has not been well studied to date. A systematic pharmacodynamic/pharmacokinetic study to determine the effects of cotreatment with various antibiotics and corticosteroids was conducted. Methods: Four bacterial strains, seven antibiotics, and four corticosteroids were used in the analyses. Drug interactions were evaluated by considering antibacterial effects with a checkerboard assay and intracellular concentrations in human corneal epithelial cells. Results: The drug combinations that showed the most stable effects against Pseudomonas aeruginosa was levofloxacin-prednisolone. Stable combinations against the three types of Gram-positive bacteria were neomycin-prednisolone, ofloxacin-dexamethasone, ofloxacin-prednisolone, and polymyxin-dexamethasone. The cellular concentrations were changed for the gatifloxacin-fluorometholone, moxifloxacin-fluorometholone, tobramycin-dexamethasone, and tobramycin-prednisolone combinations. Conclusions: Loteprednol and fluorometholone reduced the antibacterial effects of all of the tested antibiotics in this study. Dexamethasone and prednisolone showed various effects in this regard, depending on the co-administered antibiotic. Prior knowledge of specific antibiotic/corticosteroid interactions provides valuable information to clinical practitioners by combining data on the antibacterial and intracellular uptake effects of their co-administration. Translational Relevance: When using antibiotics and corticosteroids, drug combinations can be selected by referring to the results of this study.


Subject(s)
Adrenal Cortex Hormones , Anti-Bacterial Agents , Bacteria , Corneal Diseases , Drug Interactions , Eye Infections, Bacterial , Humans , Adrenal Cortex Hormones/pharmacokinetics , Adrenal Cortex Hormones/pharmacology , Adrenal Cortex Hormones/therapeutic use , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteria/drug effects , Eye Infections, Bacterial/drug therapy , Eye Infections, Bacterial/microbiology , Epithelium, Corneal/metabolism , Cell Line , Drug Therapy, Combination/adverse effects , Drug Therapy, Combination/standards , Corneal Diseases/drug therapy , Corneal Diseases/microbiology
3.
Med J Aust ; 216(1): 43-52, 2022 Jan 17.
Article in English | MEDLINE | ID: mdl-34628650

ABSTRACT

INTRODUCTION: The absence of high quality evidence for basic clinical dilemmas in immune thrombocytopenic purpura (ITP) underlines the need for contemporary guidelines relevant to the local treatment context. ITP is diagnosed by exclusions, with a hallmark laboratory finding of isolated thrombocytopenia. MAIN RECOMMENDATIONS: Bleeding, family and medication histories and a review of historical investigations are required to gauge the bleeding risk and possible hereditary syndromes. Beyond the platelet count, the decision to treat is affected by individual bleeding risk, disease stage, side effects of treatment, concomitant medications, and patient preference. Treatment is aimed at achieving a platelet count > 20 × 109 /L, and avoidance of severe bleeding. Steroids are the standard first line treatment, with either 6-week courses of tapering prednisone or repeated courses of high dose dexamethasone providing equivalent efficacy. Intravenous immunoglobulin can be used periprocedurally or as first line therapy in combination with steroids. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: There is no consensus on choice of second line treatments. Options with the most robust evidence include splenectomy, rituximab and thrombopoietin receptor agonists. Other therapies include azathioprine, mycophenolate mofetil, dapsone and vinca alkaloids. Given that up to one-third of patients achieve a satisfactory haemostatic response, splenectomy should be delayed for at least 12 months if possible. In life-threatening bleeding, we recommend platelet transfusions to achieve haemostasis, along with intravenous immunoglobulin and high dose steroids.


Subject(s)
Platelet Transfusion/standards , Practice Guidelines as Topic , Purpura, Thrombocytopenic, Idiopathic/therapy , Splenectomy/standards , Adult , Australia , Consensus , Drug Therapy, Combination/standards , Glucocorticoids/therapeutic use , Humans , Immunoglobulins, Intravenous/therapeutic use , New Zealand , Patient Preference , Platelet Count , Purpura, Thrombocytopenic, Idiopathic/blood , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Rituximab/therapeutic use
4.
Medicine (Baltimore) ; 100(37): e27279, 2021 Sep 17.
Article in English | MEDLINE | ID: mdl-34664886

ABSTRACT

ABSTRACT: The role of thoracic stereotactic body radiation therapy (SBRT) in addition to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant polymetastatic non-small-cell lung cancer (NSCLC) has not been well established. This retrospective study aimed to evaluate the efficacy and safety of EGFR-TKIs with thoracic SBRT for the treatment of this patient group.Polymetastatic NSCLC was defined as having >5 metastatic lesions. Patients with polymetastatic NSCLC harboring positive EGFR mutations after initial TKI therapy for at least 8 weeks were eligible for SBRT between August 2016and August 2019. Eligible patients were treated with thoracic SBRT, and TKIs were administered for the duration of SBRT and continued after SBRT until they were considered ineffective. The control group was treated with TKI monotherapy. Propensity score matching (ratio of 1:4) was used to account for differences in baseline characteristics. Progression-free survival (PFS), overall survival, and treatment safety were evaluated.In total, 136 patients were included in the study population. Among them, 120 patients received TKIs alone, and 16 patients received TKIs with thoracic SBRT. The baseline characteristics did not significantly differ between the two cohorts after propensity score matching. The median PFS was 17.8 months in the thoracic SBRT group and 10.8 months in the control group (P = .033). In the multivariate analysis, a Cox regression model showed that thoracic SBRT was an independent statistically significant positive predictor of improved survival, with a hazard ratio of 0.54 (P = .046). We recorded no severe toxic effects or grade 4 to 5 toxicities.Real-world data demonstrate that thoracic SBRT significantly extends PFS in EGFR-mutant polymetastatic NSCLC patients with tolerable toxicity. Given these results, randomized studies are warranted.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/therapy , Protein-Tyrosine Kinases/antagonists & inhibitors , Radiosurgery/standards , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/epidemiology , China/epidemiology , Drug Therapy, Combination/methods , Drug Therapy, Combination/standards , Drug Therapy, Combination/statistics & numerical data , Epidermal Growth Factor/administration & dosage , Epidermal Growth Factor/therapeutic use , ErbB Receptors/administration & dosage , ErbB Receptors/therapeutic use , Female , Humans , Male , Middle Aged , Progression-Free Survival , Propensity Score , Protein-Tyrosine Kinases/therapeutic use , Radiosurgery/methods , Radiosurgery/statistics & numerical data , Retrospective Studies
5.
Iran J Med Sci ; 46(5): 383-394, 2021 09.
Article in English | MEDLINE | ID: mdl-34539013

ABSTRACT

Background: Osteoarthritis (OA) is a degenerative joint disease that causes a variety of adverse health effects. Considering the need to identify additional effective therapeutic options for OA therapy, we investigated the effect of co-injection of apigenin and synovial membrane-derived mesenchymal stem cells (SMMSCs) on OA in male rats' knee joints. Methods: The study was performed in 2019 at the Department of Pharmacology, Shiraz University of Medical Sciences, Shiraz, Iran. Anterior cruciate ligament transection (ACLT) was used to induce OA. For three weeks, male Sprague-Dawley rats (eight groups, n=6 each) were treated once-weekly with intra-articular injections of apigenin alone or in combination with SMMSC (three million cells), phosphate-buffered saline, or hyaluronic acid. After three months, the interleukin 1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were measured in the cartilage homogenate. The expression of extracellular matrix (ECM) components including collagen 2a1, aggrecan, IL-1ß, TNF-α, inducible nitric oxide synthase (iNOS), transcription factor SOX-9, and matrix metalloproteinases 3 and 13 were assessed using real-time polymerase chain reaction (RT-PCR) analysis. Radiological evaluation and histopathological assessment were used to evaluate the knees. Results: Levels of TNF-α (P=0.009), MDA (P>0.001), and IL-1ß (P<0.001) decreased and the level of SOD increased (P=0.004) in the apigenin 0.3 µM with SMMSCs group. RT-PCR analysis indicated that IL-1ß in the apigenin 0.3 µM with SMMSCs group reduced significantly (P<0.001). This group also exhibited increased expression levels of SOX-9, collagen 2a1, and aggrecan (P<0.001). Conclusion: Apigenin may have supplementary beneficial effects on cell therapy in a rat model of OA due to its possible effect on the reduction of oxidative stress, suppression of inflammation, and promotion of production of ECM components.


Subject(s)
Apigenin/pharmacology , Drug Therapy, Combination/standards , Mesenchymal Stem Cells , Osteoarthritis, Knee/drug therapy , Analysis of Variance , Animals , Apigenin/therapeutic use , Disease Models, Animal , Drug Therapy, Combination/methods , Drug Therapy, Combination/statistics & numerical data , Enzyme-Linked Immunosorbent Assay , Iran , Male , Rats , Rats, Sprague-Dawley , Synovial Membrane/physiology
6.
Diagn Microbiol Infect Dis ; 101(3): 115504, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34375862

ABSTRACT

The objective of this single-center, retrospective cohort study was to identify whether combination therapy is associated with a lower rate of adverse outcomes for the treatment of Gram negative non-HACEK IE. The primary endpoint was a composite of 60-day all-cause mortality, readmission, or recurrence of bacteremia. Of the 60 patients included, 56.7% met the primary composite outcome, with 20% overall mortality at 60 days. There was no difference in the primary composite outcome of 60-day readmission, infection recurrence or mortality between groups, with 62% of patients in the monotherapy group and 50% of patients in the combination therapy group experiencing the composite outcome (P = 0.36). Despite the high mortality and complicated nature of non-HACEK Gram negative IE, this study showed no difference in 60-day bacteremia recurrence, readmission or mortality among patients treated with combination therapy or monotherapy, suggesting that monotherapy may lead to similar clinical outcomes.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Drug Therapy, Combination/standards , Endocarditis, Bacterial/drug therapy , Gram-Negative Bacterial Infections/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Drug Therapy, Combination/methods , Female , Gram-Negative Bacteria/drug effects , Gram-Negative Bacterial Infections/microbiology , Gram-Negative Bacterial Infections/mortality , Humans , Male , Middle Aged , Retrospective Studies , Tertiary Care Centers/statistics & numerical data , Treatment Outcome , Young Adult
7.
Medicine (Baltimore) ; 100(33): e27004, 2021 Aug 20.
Article in English | MEDLINE | ID: mdl-34414990

ABSTRACT

BACKGROUND: Given the lack of evidence for survival benefit in patients with metastatic renal cell carcinoma from the addition of radiation therapy to tyrosine kinase inhibitor therapy, this Bayesian network meta-analysis aimed to evaluate survival outcomes in patients receiving radiation therapy plus tyrosine kinase inhibitor therapy. METHODS: The preferred reporting items for systematic reviews and meta-analyses reporting guidelines were followed to conduct this study. The electronic databases of PubMed, Cochrane Library, EMBASE, and Web of Science were searched from the inception to August 2021. All phase III clinical trials that reported the outcomes of tyrosine kinase inhibitor with radiation therapy compared with those of tyrosine kinase inhibitor or radiation therapy alone for patients with metastatic renal cell carcinoma were considered eligible for inclusion in this meta-analysis. Overall survival as the primary outcome of interest, and adverse events as secondary outcome of interest were recorded for meta-analysis. RESULTS: A Bayesian network meta-analysis is an appropriate statistical method to compare all treatment options by statistically simulating the estimated results of a comprehensive trial, and to compare treatments by common and associated comparators. In addition, Bayesian network meta-analysis can produce ranking probabilities of treatments, which may contribute to clinicians' clinical decision-making.


Subject(s)
Clinical Protocols , Drug Therapy, Combination/standards , Pyrazoles/standards , Pyrimidines/standards , Radiotherapy/standards , Bayes Theorem , Carcinoma, Renal Cell/therapy , Humans , Network Meta-Analysis , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Radiotherapy/methods , Systematic Reviews as Topic
8.
Medicine (Baltimore) ; 100(31): e26787, 2021 Aug 06.
Article in English | MEDLINE | ID: mdl-34397829

ABSTRACT

BACKGROUND: Lopinavir, ritonavir, atazanavir, and saquinavir had been reportedly used or suggested for coronavirus disease 2019 (COVID-19) treatment. They may cause electrocardiography changes. We aim to evaluate risk of PR prolongation, QRS widening, and QT prolongation from lopinavir, ritonavir, atazanavir, and saquinavir. METHODS: In accordance with preferred reporting items for systematic reviews and meta-analyses guidelines, our search was conducted in PubMed Central, PubMed, EBSCOhost, and ProQuest from inception to June 25, 2020. Titles and abstracts were reviewed for relevance. Cochrane Risk of Bias Tool 2.0 and Downs and Black criteria was used to evaluate quality of studies. RESULTS: We retrieved 9 articles. Most randomized controlled trials have low risk of biases while all quasi-experimental studies have a positive rating. Four studies reporting PR prolongation however only 2 studies with PR interval >200 ms. One of which, reported its association after treatment with ritonavir-boosted saquinavir treatment while another, during treatment with ritonavir-boosted atazanavir. No study reported QRS widening >120 ms with treatment. Four studies reporting QT prolongation, with only one study reaching QT interval >450 ms after ritonavir-boosted saquinavir treatment on healthy patients. There is only one study on COVID-19 patients reporting QT prolongation in 1 out of 95 patients after ritonavir-boosted lopinavir treatment. CONCLUSION: Limited evidence suggests that lopinavir, ritonavir, atazanavir, and saquinavir could cause PR prolongation, QRS widening, and QT prolongation. Further trials with closer monitoring and assessment of electrocardiography are needed to ascertain usage safety of antivirals in COVID-19 era.


Subject(s)
Atazanavir Sulfate/adverse effects , Long QT Syndrome/etiology , Lopinavir/adverse effects , Ritonavir/adverse effects , Saquinavir/adverse effects , Adult , Atazanavir Sulfate/therapeutic use , Cytochrome P-450 CYP3A Inhibitors/adverse effects , Drug Therapy, Combination/methods , Drug Therapy, Combination/standards , Electrocardiography/methods , Humans , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Saquinavir/therapeutic use
9.
Medicine (Baltimore) ; 100(29): e26587, 2021 Jul 23.
Article in English | MEDLINE | ID: mdl-34398013

ABSTRACT

ABSTRACT: Poor availability and a lack of affordability of bypassing agents (recombinant activated factor VII and activated prothrombin complex concentrate) in west China prompted us to investigate an alternative cost-effective combination therapy. We aimed to explore the feasibility of therapeutic plasma exchange (TPE)-based combination therapy in the treatment of acquired hemophilia A (AHA).We retrospectively investigated the clinical features of AHA in 6 patients who were treated with a combination of TPE, corticosteroids, and rituximab in our department for 9 years between January, 2011 and December, 2019.We examined 1 male and 5 female patients. The median age at diagnosis of AHA was 51 years (18-66 years). In all patients, FVIII activity levels were low (median: 1.5%; 1-3%), FVIII inhibitor titers were high (median: 24.5 BU/mL; 13.2-48.6 BU/mL), and activated partial thromboplastin time was markedly prolonged (median: 99.4 s; 60.9-110.1 s). They underwent 2 to 8 cycles of plasma exchange and were given varying combinations of dexamethasone, methylprednisolone, prednisone, and rituximab. After TPE bleeding gradually stopped, and activated partial thromboplastin time decreased. After 3 months of treatment, FVIII inhibitors completely disappeared.TPE when combined with corticosteroids and rituximab, as adjunctive immunosuppressive agents, may be an effective and reliable treatment for AHA. When there is no alternative, intensive first-line treatment including TPE may be lifesaving.


Subject(s)
Hemophilia A/therapy , Plasma Exchange/standards , Adult , China , Drug Therapy, Combination/standards , Drug Therapy, Combination/statistics & numerical data , Feasibility Studies , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Plasma Exchange/methods , Plasma Exchange/statistics & numerical data , Retrospective Studies
10.
J Drugs Dermatol ; 20(3): 244-250, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33683089

ABSTRACT

BACKGROUND: The prevalence and clinical presentation of acne vulgaris in Latin America are comparable to that in Europe and the United States. This review aims at insight into the role of Over the Counter (OTC) products in acne treatment and maintenance in Latin America. METHODS: A panel of dermatologists from Latin America employed an online procedure to answer questions on this topic: What is used, by whom, when, how, and why? Before the meeting, a survey was completed by dermatologists from Latin America on OTC products for acne recommended by the panel in their clinical practice. The survey information and a literature review on Latin American acne guidelines and clinical studies were used to address this topic. RESULTS: The survey responders' choices on OTC products for monotherapy comprised alpha-hydroxy acid and beta-hydroxy acid-containing serum, ceramides-containing foaming cleanser, a soap-free exfoliating cleanser, adapalene, and benzoyl peroxide-containing products. The clinicians recommended OTC cleansing products mainly for younger patients at a starter level and for women with adult acne. The use of these OTC products is similar to practice described in therapeutic acne guidelines and algorithms for Latin American countries, Spain and Portugal, Europe, and the United States. CONCLUSIONS: Advisors agreed that OTC products and skincare recommendations, in addition to the use of prescription medications, are a crucial part of successful acne therapy. Participants noted that the use of quality OTC products could improve acne symptomatology and severity. J Drugs Dermatol. 2021;20(3):244-250. doi:10.36849/JDD.5779 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL fTEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.


Subject(s)
Acne Vulgaris/therapy , Dermatologic Agents/therapeutic use , Dermatology/statistics & numerical data , Nonprescription Drugs/therapeutic use , Practice Patterns, Physicians'/statistics & numerical data , Acne Vulgaris/epidemiology , Administration, Cutaneous , Cosmetics/administration & dosage , Dermatology/standards , Drug Therapy, Combination/methods , Drug Therapy, Combination/standards , Drug Therapy, Combination/statistics & numerical data , Humans , Latin America/epidemiology , Nonprescription Drugs/standards , Practice Guidelines as Topic , Practice Patterns, Physicians'/standards , Prescription Drugs/therapeutic use , Prevalence , Skin Care/methods , Skin Care/statistics & numerical data , Treatment Outcome
12.
Eur J Clin Microbiol Infect Dis ; 40(2): 255-260, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32880024

ABSTRACT

To examine antimicrobial management of brain abscess and prioritize future trials. Self-administered, Internet-based survey of practices for treatment of community-acquired bacterial brain abscess among infectious diseases (ID) specialists in France, Sweden, Australia, and Denmark during November 2019. Respondents were also asked to rank future randomized controlled trials (RCTs) from 1 (high priority) to 6 (low priority). 310 ID specialists (45% female) from France (35%), Sweden (29%), Australia (25%), and Denmark (11%) participated in the survey, primarily from university hospitals (69%) with an on-site neurosurgical department (61%). Preferred empiric intravenous (IV) antimicrobials were cefotaxime (154/273, 56%) or ceftriaxone (68/273, 25%) combined with metronidazole for a median of 4 weeks (IQR 4-6), 4 weeks (IQR 2-4), and 6 weeks (IQR 4-6) for aspirated, excised, and conservatively treated patients, respectively. Early transition to oral antimicrobials (i.e., < 4 weeks of IV antimicrobials) was used by 134/269 (50%), whereas consolidation therapy with oral antimicrobials after a standard IV regimen (i.e., 4-8 weeks) was used by 123/264 (47%). Median prioritization scores for future RCTs were as follows: 1 (IQR 1-2) for an early transition to oral antimicrobials and duration of therapy, 3 (IQR 2-4) for comparisons of antimicrobial regimens, use of adjunctive dexamethasone, and neurosurgical aspiration versus excision, and 4 (IQR 3-5) for intracavitary antimicrobial instillation and drainage, and for prophylactic anti-epileptic therapy. Willingness to include patients into RCTs reflected prioritization scores. Duration of intravenous antimicrobial treatment and use of oral antimicrobials varies substantially among ID specialists. RCTs are needed to define optimal treatment of brain abscess.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Bacterial Infections/drug therapy , Brain Abscess/drug therapy , Community-Acquired Infections/drug therapy , Drug Therapy, Combination/standards , Adult , Aged , Australia , Denmark , Female , France , Humans , Male , Middle Aged , Physicians , Randomized Controlled Trials as Topic , Surveys and Questionnaires , Sweden
13.
J Am Acad Dermatol ; 84(3): 747-760, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32682025

ABSTRACT

BACKGROUND: Prurigo nodularis (PN) is a chronic disease characterized by intensely pruritic, raised, nodular lesions. Because there are currently no United States Food and Drug Administration-approved therapies specifically for PN, management is highly variable, and no consensus exists on treatment regimens. OBJECTIVE: To provide practical guidance to help United States dermatologists diagnose and effectively treat patients with PN. METHODS: We participated in a roundtable discussion to develop consensus recommendations on diagnosis and treatment of PN from a United States perspective. RESULTS: The core findings in PN are the presence of firm, nodular lesions; pruritus lasting at least 6 weeks; and a history or signs, or both, of repeated scratching, picking, or rubbing. The diagnostic workup involves a complete review of systems, considering potential systemic diseases, and assessment of disease severity, including disease burden and pruritus intensity. Treatment should be selected based on a patient's clinical presentation, comorbidities, and response to prior treatments and should address both neural and immunologic components of pruritus. LIMITATIONS: Data on PN are from anecdotal or small clinical trials, and all treatments are currently used off-label. CONCLUSION: An effective treatment approach for patients with PN should be based on clinical judgment and tailored to the individual needs of the patient.


Subject(s)
Consensus , Dermatologic Agents/therapeutic use , Practice Guidelines as Topic , Prurigo/diagnosis , Chronic Disease/drug therapy , Dermatology/standards , Diagnosis, Differential , Drug Therapy, Combination/methods , Drug Therapy, Combination/standards , Humans , Off-Label Use , Prurigo/drug therapy , Prurigo/etiology , Treatment Outcome , United States
15.
Isr Med Assoc J ; 11(22): 665-672, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33249784

ABSTRACT

BACKGROUND: The coronavirus disease-2019 (COVID-19) and its management in patients with epilepsy can be complex. Prescribers should consider potential effects of investigational anti-COVID-19 drugs on seizures, immunomodulation by anti-seizure medications (ASMs), changes in ASM pharmacokinetics, and the potential for drug-drug interactions (DDIs). The goal of the Board of the Israeli League Against Epilepsy (the Israeli Chapter of the International League Against Epilepsy, ILAE) was to summarize the main principles of the pharmacological treatment of COVID-19 in patients with epilepsy. This guide was based on current literature, drug labels, and drug interaction resources. We summarized the available data related to the potential implications of anti-COVID-19 co-medication in patients treated with ASMs. Our recommendations refer to drug selection, dosing, and patient monitoring. Given the limited availability of data, some recommendations are based on general pharmacokinetic or pharmacodynamic principles and might apply to additional future drug combinations as novel treatments emerge. They do not replace evidence-based guidelines, should those become available. Awareness to drug characteristics that increase the risk of interactions can help adjust anti-COVID-19 and ASM treatment for patients with epilepsy.


Subject(s)
Anticonvulsants , Antiviral Agents , COVID-19 Drug Treatment , Drug Interactions , Drug Therapy, Combination , Epilepsy , Medication Therapy Management , Anticonvulsants/classification , Anticonvulsants/pharmacology , Antiviral Agents/classification , Antiviral Agents/pharmacology , Comorbidity , Drug Monitoring/methods , Drug Therapy, Combination/adverse effects , Drug Therapy, Combination/methods , Drug Therapy, Combination/standards , Drug-Related Side Effects and Adverse Reactions/etiology , Drug-Related Side Effects and Adverse Reactions/prevention & control , Epilepsy/diagnosis , Epilepsy/drug therapy , Epilepsy/epidemiology , Humans , Israel/epidemiology , Medication Therapy Management/standards , Medication Therapy Management/trends , Patient Selection , Practice Guidelines as Topic , Risk Adjustment/methods , Risk Adjustment/trends , SARS-CoV-2
16.
Drugs ; 80(17): 1799-1809, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33025535

ABSTRACT

Erdosteine is a drug approved for the treatment of acute and chronic pulmonary diseases, originally developed as a mucolytic agent. It belongs to the thiol-based family of drugs that are known to also possess potentially important antioxidant and anti-inflammatory properties, and exhibit antibacterial activity against a variety of medically important bacterial species. Erdosteine is a prodrug that is metabolized to the ring-opening compound metabolite M1 (MET 1), which has mucolytic properties. Experimental studies have documented that erdosteine prevents or reduces lung tissue damage induced by oxidative stress and, in particular, that Met 1 also regulates reactive oxygen species production. The RESTORE study, which has been the only trial that investigated the effects of a thiol-based drug in chronic obstructive pulmonary disease (COPD) frequent exacerbators, documented that erdosteine significantly reduces the risk of acute exacerbations of COPD (AECOPDs), shortens their course, and also decreases the risk of hospitalization from COPD. The preventive action of erdosteine on AECOPDs was not affected by the presence or absence of inhaled corticosteroids (ICSs) or blood eosinophil count. These findings clearly contrast with the Global Initiative for Chronic Obstructive Lung Disease strategy's approach to use erdosteine only in those COPD patients not treated simultaneously with an ICS. Furthermore, they support the possibility of using erdosteine in a step-down approach that in COPD is characterized by the withdrawal of the ICS.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Antioxidants/pharmacology , Expectorants/pharmacology , Pulmonary Disease, Chronic Obstructive/drug therapy , Thioglycolates/pharmacology , Thiophenes/pharmacology , Administration, Inhalation , Antioxidants/therapeutic use , Drug Therapy, Combination/methods , Drug Therapy, Combination/standards , Expectorants/therapeutic use , Humans , Lung/drug effects , Lung/pathology , Oxidative Stress/drug effects , Practice Guidelines as Topic , Pulmonary Disease, Chronic Obstructive/pathology , Symptom Flare Up , Thioglycolates/therapeutic use , Thiophenes/therapeutic use , Treatment Outcome
17.
J Drugs Dermatol ; 19(10): 935-940, 2020 Oct 01.
Article in English | MEDLINE | ID: mdl-33026777

ABSTRACT

BACKGROUND: Atopic dermatitis (AD) is a common skin condition characterized by disturbed barrier function, skin inflammation, and cutaneous dysbiosis. Clinically, it manifests as chronic-recurrent xerosis, pruritus, and erythematous lesions. Its pathophysiology is complex, making the selection of appropriate treatment options a task. AIM: To share insights gained from a literature review and discussions with experts in dermatology on key factors related to the prevention, treatment, and management of AD in relation to the skin microbiome. METHODS: Results from an expert panel were summarized and discussed to provide updated recommendations for the treatment and maintenance of AD. RESULTS: Evidence supports a strategy for managing inflammatory skin diseases with a selenium-rich post-biotic thermal water and biomass containing moisturizer. The moisturizer helps to restore homeostasis of the skin, re-populate a diverse microbiome, encourage the growth of commensal bacteria, and improve barrier function and symptoms of AD. CONCLUSIONS: Normalization of skin microbiome diversity using a topical moisturizer containing post-biotic aqua and biomass may offer a valuable option for the treatment and maintenance of inflammatory skin diseases. Clinicians should discuss the benefits of this treatment in the context of a full AD management program that covers prevention, active treatment, and maintenance. J Drugs Dermatol. 2020;19(10):935-940. doi:10.36849/JDD.2020.5393.


Subject(s)
Dermatitis, Atopic/therapy , Dermatologic Agents/administration & dosage , Hydrotherapy/methods , Microbiota/immunology , Skin/microbiology , Administration, Cutaneous , Adult , Child, Preschool , Combined Modality Therapy/methods , Combined Modality Therapy/standards , Dermatitis, Atopic/complications , Dermatitis, Atopic/immunology , Dermatitis, Atopic/microbiology , Dermatology/methods , Dermatology/standards , Drug Therapy, Combination/methods , Drug Therapy, Combination/standards , Humans , Infant , Practice Guidelines as Topic , Prebiotics/administration & dosage , Probiotics/administration & dosage , Severity of Illness Index , Skin/drug effects , Skin/immunology , Symbiosis/immunology , Treatment Outcome , Water Loss, Insensible/drug effects , Water Loss, Insensible/immunology
18.
PLoS Biol ; 18(9): e3000856, 2020 09.
Article in English | MEDLINE | ID: mdl-32941420

ABSTRACT

Antibiotic combination therapies are important for the efficient treatment of many types of infections, including those caused by antibiotic-resistant pathogens. Combination treatment strategies are typically used under the assumption that synergies are conserved across species and strains, even though recent results show that the combined treatment effect is determined by specific drug-strain interactions that can vary extensively and unpredictably, both between and within bacterial species. To address this problem, we present a new method in which antibiotic synergy is rapidly quantified on a case-by-case basis, allowing for improved combination therapy. The novel CombiANT methodology consists of a 3D-printed agar plate insert that produces defined diffusion landscapes of 3 antibiotics, permitting synergy quantification between all 3 antibiotic pairs with a single test. Automated image analysis yields fractional inhibitory concentration indices (FICis) with high accuracy and precision. A technical validation with 3 major pathogens, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, showed equivalent performance to checkerboard methodology, with the advantage of strongly reduced assay complexity and costs for CombiANT. A synergy screening of 10 antibiotic combinations for 12 E. coli urinary tract infection (UTI) clinical isolates illustrates the need for refined combination treatment strategies. For example, combinations of trimethoprim (TMP) + nitrofurantoin (NIT) and TMP + mecillinam (MEC) showed synergy, but only for certain individual isolates, whereas MEC + NIT combinations showed antagonistic interactions across all tested strains. These data suggest that the CombiANT methodology could allow personalized clinical synergy testing and large-scale screening. We anticipate that CombiANT will greatly facilitate clinical and basic research of antibiotic synergy.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Drug Resistance, Multiple, Bacterial/drug effects , Drug Synergism , Microbial Sensitivity Tests/methods , Algorithms , Amdinocillin/administration & dosage , Amdinocillin/pharmacology , Anti-Bacterial Agents/pharmacology , Drug Therapy, Combination/methods , Drug Therapy, Combination/standards , Escherichia coli/isolation & purification , Escherichia coli Infections/drug therapy , Escherichia coli Infections/microbiology , Humans , Microbial Sensitivity Tests/instrumentation , Nitrofurantoin/administration & dosage , Nitrofurantoin/pharmacology , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/isolation & purification , Reproducibility of Results , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcus aureus/isolation & purification , Trimethoprim/administration & dosage , Trimethoprim/pharmacology , Urinary Tract Infections/drug therapy , Urinary Tract Infections/microbiology
19.
Mech Ageing Dev ; 192: 111354, 2020 12.
Article in English | MEDLINE | ID: mdl-32946885

ABSTRACT

Multimorbidity (MM) is a widespread problem and it poses unsolved issues like the healthcare professionals' training. A training curriculum has been proposed, but it has not been sufficiently explored in a clinical context. The eMULTIPAP course is part of the MULTIPAP complex intervention, applied through a pragmatic controlled, cluster randomized clinical trial to general practitioners (GP) and his/her patients with MM with 12 months follow-up. The eMULTIPAP course is based on problem-based learning, constructivism and Ariadne principles. It has been assessed according to the Kirkpatrick model and has shown knowledge improvement and high applicability of learning with more motivation to consider MM in the clinical practice. It has also improved the Medication Appropriateness Index at 6-months and at 12- months. We conclude that the eMULTIPAP course generates significant changes in GP's learning, enhancing clinical practice in multimorbidity scenarios.


Subject(s)
Education, Medical, Continuing/methods , Multimorbidity , Physicians, Primary Care/education , Polypharmacology , Primary Health Care/standards , Problem-Based Learning/methods , Aged , Drug Therapy, Combination/methods , Drug Therapy, Combination/standards , Educational Measurement , Female , Humans , Inappropriate Prescribing/prevention & control , Male , Polypharmacy , Primary Health Care/methods , Quality Improvement , Staff Development/methods
20.
Medicine (Baltimore) ; 99(32): e21627, 2020 Aug 07.
Article in English | MEDLINE | ID: mdl-32769925

ABSTRACT

BACKGROUND: Acupoint application combined with western medicine has been used for treating allergic rhinitis widely. However, the efficacy and safety of acupoint application combined with western medicine for allergic rhinitis are unclear. This study aims to evaluate the efficacy and safety of acupoint application combined with western medicine for allergic rhinitis. METHODS: Randomized controlled trials of acupoint application combined with western medicine for allergic rhinitis will be searched in PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database from inception to July, 2020. And Baidu Scholar, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain more relevant studies comprehensively. Two researchers will perform data extraction and risk of bias assessment independently. Statistical analysis will be conducted in RevMan 5.3. RESULTS: This study will summarize the present evidence by exploring the efficacy and safety of acupoint application combined with western medicine for the treatment of allergic rhinitis. CONCLUSIONS: The findings of the study will provide helpful evidence for the efficacy and safety of acupoint application combined with western medicine in the treatment of allergic rhinitis, facilitating clinical practice and further scientific studies. ETHICS AND DISSEMINATION: The private information from individuals will not publish. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/NSGJH.


Subject(s)
Acupuncture Points , Clinical Protocols , Drug Therapy, Combination/standards , Patient Safety/standards , Rhinitis, Allergic/therapy , Acupuncture Therapy/methods , Drug Therapy, Combination/adverse effects , Humans , Meta-Analysis as Topic , Systematic Reviews as Topic , Treatment Outcome
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