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2.
Cornea ; 40(11): 1502-1504, 2021 Nov 01.
Статья в английский | MEDLINE | ID: covidwho-2063050

Реферат

ABSTRACT: The coronavirus disease 2019 global pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several ophthalmic manifestations have been reported to be associated with SARS-CoV-2 infection, including conjunctivitis, acute sixth nerve palsy, and multiple cranial neuropathies. We present a unique case of unilateral phlyctenular keratoconjunctivitis in a 5-year-old boy in the setting of SARS-CoV-2 infection.


Тема - темы
COVID-19/diagnosis , Conjunctivitis, Viral/diagnosis , Eye Infections, Viral/diagnosis , Keratoconjunctivitis/diagnosis , SARS-CoV-2/pathogenicity , Administration, Oral , Anti-Bacterial Agents/administration & dosage , Ascorbic Acid/administration & dosage , Azithromycin/administration & dosage , COVID-19/drug therapy , COVID-19/virology , COVID-19 Nucleic Acid Testing , Child, Preschool , Conjunctivitis, Viral/drug therapy , Conjunctivitis, Viral/virology , Drug Therapy, Combination , Eye Infections, Viral/drug therapy , Eye Infections, Viral/virology , Fluorometholone/therapeutic use , Glucocorticoids/therapeutic use , Humans , Keratoconjunctivitis/drug therapy , Keratoconjunctivitis/virology , Male , Ophthalmic Solutions , Slit Lamp Microscopy , Tomography, Optical Coherence , Visual Acuity/physiology
3.
J Cardiovasc Pharmacol Ther ; 27: 10742484221128124, 2022.
Статья в английский | MEDLINE | ID: covidwho-2053690

Реферат

BACKGROUND: Because of logistic challenges associated with the COVID-19 pandemic, direct oral anticoagulants (DOAC) were favored over warfarin in patients presenting postoperative atrial fibrillation (AF) after cardiac surgery in our institution. Considering the limited evidence supporting the use of DOAC in this context, we sought to evaluate the safety and efficacy of this practice change. METHODS: A retrospective study was performed with patients from the Quebec City metropolitan area who were hospitalized at the Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval following cardiac surgery and who required oral anticoagulant (OAC) for postoperative AF. The primary objective was to compare the pre- and peri-COVID-19 period for OAC prescribing patterns and the incidence of thrombotic and bleeding events at 3 months post-surgery. The secondary objective was to compare DOAC to warfarin in terms of thrombotic events and bleeding events. RESULTS: A total of 233 patients were included, 142 from the pre-COVID-19 and 91 from the peri-COVID-19 period, respectively. Both groups had equivalent proportions of preoperative AF (48%) and new-onset postoperative AF (52%). The proportion of patients treated with a DOAC increased from 13% pre-COVID-19 to 82% peri-COVID-19. This change in practice was not associated with a significant difference in the incidence of thrombotic or bleeding events 3 months postoperatively. However, compared to DOAC, warfarin was associated with a higher incidence of major bleeding. Only 1 thrombotic event was reported with warfarin, and none were reported with DOAC. CONCLUSION: This study suggests that DOAC are an effective and safe alternative to warfarin to treat postoperative AF after cardiac surgery and that this practice can be safely maintained.


Тема - темы
Atrial Fibrillation , COVID-19 , Cardiac Surgical Procedures , Stroke , Administration, Oral , Anticoagulants/adverse effects , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Cardiac Surgical Procedures/adverse effects , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Humans , Pandemics , Retrospective Studies , Stroke/epidemiology , Warfarin/adverse effects
4.
Antimicrob Agents Chemother ; 66(10): e0063222, 2022 10 18.
Статья в английский | MEDLINE | ID: covidwho-2019711

Реферат

Ensitrelvir is a novel selective inhibitor of the 3C-like protease of SARS-CoV-2, which is essential for viral replication. This phase 1 study of ensitrelvir assessed its safety, tolerability, and pharmacokinetics of single (part 1, n = 50) and multiple (part 2, n = 33) ascending oral doses. Effect of food on the pharmacokinetics of ensitrelvir, differences in pharmacokinetics of ensitrelvir between Japanese and white participants, and effect of ensitrelvir on the pharmacokinetics of midazolam (a cytochrome P450 3A [CYP3A] substrate) were also assessed. In part 1, Japanese participants were randomized to placebo or ensitrelvir at doses of 20, 70, 250, 500, 1,000, or 2,000 mg. In part 2, Japanese and white participants were randomized to placebo or once-daily ensitrelvir at loading/maintenance dose 375/125 mg or 750/250 mg for 5 days. Most treatment-related adverse events observed were mild in severity and were resolved without treatment. Plasma exposures showed almost dose proportionality, and geometric mean half-life of ensitrelvir following the single dose was 42.2 to 48.1 h. Food intake reduced Cmax and delayed Tmax of ensitrelvir but did not impact the area under the curve (AUC), suggesting suitability for administration without food restriction. Compared with Japanese participants, plasma exposures were slightly lower for white participants. Ensitrelvir affected the pharmacokinetics of CYP3A substrates because of increase in AUC of midazolam coadministered with ensitrelvir 750/250 mg on day 6. In conclusion, ensitrelvir was well-tolerated and demonstrated favorable pharmacokinetics, including a long half-life, supporting once-daily oral dosing. These results validate further assessments of ensitrelvir in participants with SARS-CoV-2 infection.


Тема - темы
Antiviral Agents , COVID-19 , Indazoles , Triazines , Adult , Humans , Administration, Oral , Antiviral Agents/pharmacokinetics , Antiviral Agents/therapeutic use , Area Under Curve , COVID-19/drug therapy , Cytochrome P-450 CYP3A , Dose-Response Relationship, Drug , Double-Blind Method , Enzyme Inhibitors , Healthy Volunteers , Midazolam/therapeutic use , Peptide Hydrolases , Protease Inhibitors , SARS-CoV-2 , Indazoles/pharmacokinetics , Indazoles/therapeutic use , Triazines/pharmacokinetics , Triazines/therapeutic use , Triazoles/pharmacokinetics , Triazoles/therapeutic use
5.
Nature ; 609(7927): 582-589, 2022 09.
Статья в английский | MEDLINE | ID: covidwho-2016756

Реферат

Increased levels of proteases, such as trypsin, in the distal intestine have been implicated in intestinal pathological conditions1-3. However, the players and mechanisms that underlie protease regulation in the intestinal lumen have remained unclear. Here we show that Paraprevotella strains isolated from the faecal microbiome of healthy human donors are potent trypsin-degrading commensals. Mechanistically, Paraprevotella recruit trypsin to the bacterial surface through type IX secretion system-dependent polysaccharide-anchoring proteins to promote trypsin autolysis. Paraprevotella colonization protects IgA from trypsin degradation and enhances the effectiveness of oral vaccines against Citrobacter rodentium. Moreover, Paraprevotella colonization inhibits lethal infection with murine hepatitis virus-2, a mouse coronavirus that is dependent on trypsin and trypsin-like proteases for entry into host cells4,5. Consistently, carriage of putative genes involved in trypsin degradation in the gut microbiome was associated with reduced severity of diarrhoea in patients with SARS-CoV-2 infection. Thus, trypsin-degrading commensal colonization may contribute to the maintenance of intestinal homeostasis and protection from pathogen infection.


Тема - темы
Gastrointestinal Microbiome , Intestine, Large , Symbiosis , Trypsin , Administration, Oral , Animals , Bacterial Secretion Systems , Bacterial Vaccines/administration & dosage , Bacterial Vaccines/immunology , Bacteroidetes/isolation & purification , Bacteroidetes/metabolism , COVID-19/complications , Citrobacter rodentium/immunology , Diarrhea/complications , Feces/microbiology , Gastrointestinal Microbiome/genetics , Humans , Immunoglobulin A/metabolism , Intestine, Large/metabolism , Intestine, Large/microbiology , Mice , Murine hepatitis virus/metabolism , Murine hepatitis virus/pathogenicity , Proteolysis , SARS-CoV-2/pathogenicity , Trypsin/metabolism , Virus Internalization
6.
Am J Otolaryngol ; 43(6): 103610, 2022.
Статья в английский | MEDLINE | ID: covidwho-2007384

Реферат

OBJECTIVES: To investigate the clinical characteristics of infantile subglottic hemangioma (SGH), and to observe the safety and efficacy of propranolol in the treatment of SGH. METHODS: The data of 21 children diagnosed with SGH and treated with propranolol in our hospital from March 2013 to January 2021 were retrospectively analyzed and followed up. RESULTS: Among the 21 cases, there were 7 males and 14 females. SGH was found 11 left-sided, 9 right-sided and 1 bilateral-sided. The clinical manifestations included stridor (13/21), respiratory distress (6/21), barking cough (5/21), feeding difficulty (4/21), three concave sign (4/21), cyanosis (2/21) and hoarseness (1/21). 8 patients had multiple cutaneous hemangiomas. The age of presentation ranged from 1 to 8 months, with a median of 1.1 months. 18 cases (85.7 %) had a history of misdiagnosis, 14 bronchitis/pneumonia, 5 laryngomalacia, 2 laryngeal obstruction and 1 asthma. The median ages at diagnosis were 3 months, with a range of 1.2-28 months. The treatment duration ranged from 6 to 25.6 months, with an average of (14.3 ± 4.9) months. Age at termination of treatment ranged from 9 to 38 months, with a median of 18.6 months, and only 2 cases were beyond 2 years old at that time. No adverse side effects from propranolol therapy occurred and all 21 cases were cured. CONCLUSIONS: We advocate a strong index of suspicion for SGH presenting with respiratory symptoms under 2 years old who has poor effect or repeated condition after routine treatment. Laryngoscopy combined with contrast-enhanced CT can confirm the diagnosis of SGH. Oral propranolol is safe and effective, and that early diagnosis and intervention of propranolol without further delay are crucial to the successful management. We advocate continue propranolol treatment beyond 18 months of age, furthermore, 2 years old may be the best time for therapy termination.


Тема - темы
Hemangioma , Laryngeal Neoplasms , Male , Female , Child , Humans , Infant , Child, Preschool , Propranolol/therapeutic use , Retrospective Studies , Laryngeal Neoplasms/diagnosis , Laryngeal Neoplasms/drug therapy , Hemangioma/diagnosis , Hemangioma/drug therapy , Laryngoscopy , Treatment Outcome , Administration, Oral
7.
Expert Rev Clin Pharmacol ; 15(9): 1095-1105, 2022 Sep.
Статья в английский | MEDLINE | ID: covidwho-2004912

Реферат

INTRODUCTION: The optimal anticoagulation strategy for venous thromboembolism (VTE) prevention among COVID-19 patients, hospitalized or in the community setting, is still challenging and largely based on real-world evidence. AREAS COVERED: We analyzed real-world data regarding the safety and effectiveness of anticoagulant treatment, both parenteral and oral, for VTE prevention or atrial fibrillation (AF)/VTE treatment among COVID-19 patients. EXPERT OPINION: The efficacy of low-molecular-weight heparin (LMWH) doses for VTE prevention correlates with COVID-19 disease status. LMWH prophylactic dose may be useful in COVID-19 patients at the early stage of the disease. LMWH intermediate or therapeutic dose is recommended in COVID-19 patients with an advanced stage of the disease. COVID-19 patients on VKA therapy for atrial fibrillation (AF) and VTE should switch to NOACs in the community setting or LMWH in the hospital setting. No definitive data on de-novo starting of NOACs or VKA therapy for VTE prevention in COVID-19 outpatients are available. In patients at high risk discharged after hospitalization due to COVID-19, thromboprophylaxis with NOACs may be considered.


Тема - темы
Atrial Fibrillation , COVID-19 , Venous Thromboembolism , Administration, Oral , Anticoagulants/adverse effects , Atrial Fibrillation/drug therapy , COVID-19/drug therapy , Heparin, Low-Molecular-Weight/adverse effects , Humans , Venous Thromboembolism/chemically induced , Venous Thromboembolism/drug therapy , Venous Thromboembolism/prevention & control
8.
Vaccine ; 40(47): 6873-6879, 2022 Nov 08.
Статья в английский | MEDLINE | ID: covidwho-1996604

Реферат

BACKGROUND: Since 1971, Cameroon has been facing an ever-growing series of cholera epidemics; despite all the efforts made by the government to address this substantial public health problem. In 2020, in addition to the COVID-19 pandemic, Cameroon recorded a high cholera case fatality rate of 5.3% following epidemics noted in the South, Littoral, and South-West regions which is far higher than the 1% World Health Organization acceptable rate. METHODOLOGY/PRINCIPAL FINDINGS: The Ministry of Public Health organized a reactive vaccination campaign against cholera to address the high mortality rate in the affected health districts. The first round was in August 2020 and the second in March 2021. We conducted a cross-sectional study and reviewed this vaccination campaign's challenges, best practices, and lessons. The vaccination coverage for the two doses of the oral cholera vaccine was 80.4%, with a refusal rate as high as 67%. People 20 years and above recorded the lowest vaccination coverage. The main challenge was misinformation about the cholera vaccine. The best practice was thorough population sensitization through community actors. CONCLUSION: Proper communication will always brave the odds of hesitancy and favor mass population vaccination to thwart hesitancy and consolidate herd immunity.


Тема - темы
COVID-19 , Cholera Vaccines , Cholera , Humans , Cholera/epidemiology , Cholera/prevention & control , COVID-19/epidemiology , COVID-19/prevention & control , Cross-Sectional Studies , Cameroon/epidemiology , Pandemics/prevention & control , Mass Vaccination , Vaccination , Administration, Oral
9.
Dermatol Ther ; 35(8): e15605, 2022 Aug.
Статья в английский | MEDLINE | ID: covidwho-1985775
10.
Am J Cardiol ; 181: 38-44, 2022 10 15.
Статья в английский | MEDLINE | ID: covidwho-1982506

Реферат

Atrial fibrillation/flutter (AF) and COVID-19 are associated with an elevated risk of arterial and venous thrombosis. Whether preadmission oral anticoagulation (OAC) for AF reduces the incidence of in-hospital death or thrombotic events among patients with COVID-19 is unknown. We identified 630 patients with pre-existing AF and a hospitalization diagnosis of COVID-19 and stratified them according to preadmission OAC use. Multivariable logistic regression was employed to relate preadmission OAC to composite in-hospital mortality or thrombotic events. Unadjusted composite in-hospital mortality or thrombotic complications occurred less often in those on than not on preadmission OAC (27.1% vs 46.8%, p <0.001). After adjustment, the incidence of composite in-hospital all-cause mortality or thrombotic complications remained lower with preadmission OAC (odds ratio 0.37, confidence interval 0.25 to 0.53, p <0.0001). Secondary outcomes including all-cause mortality (16.3% vs 24.9%, p = 0.007), intensive care unit admission (14.7% vs 29.0%, p <0.001), intubation (6.4% vs 18.6%, p <0.001), and noninvasive ventilation (18.6% vs 27.5%, p = 0.007) occurred less frequently, and length of stay was shorter (6 vs 7 days, p <0.001) in patients on than those not on preadmission OAC. A higher CHA2DS2-VASc score was associated with an increased risk of thrombotic events. In conclusion, among patients with baseline AF who were hospitalized with COVID-19, those on preadmission OAC had lower rates of death, arterial and venous thrombotic events, and less severe COVID-19.


Тема - темы
Atrial Fibrillation , Atrial Flutter , COVID-19 , Stroke , Thrombosis , Administration, Oral , Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Atrial Flutter/drug therapy , COVID-19/complications , COVID-19/epidemiology , Hospital Mortality , Hospitalization , Humans , Risk Assessment , Risk Factors , Stroke/epidemiology , Thrombosis/epidemiology , Thrombosis/etiology , Thrombosis/prevention & control
12.
Future Cardiol ; 18(9): 743-754, 2022 09.
Статья в английский | MEDLINE | ID: covidwho-1933500

Реферат

Compared with face-to-face consultations, telemedicine has many advantages, including more efficient use of healthcare resources, partial relief of the burden of care, reduced exposure to COVID-19, treatment adjustment, organization of more efficient healthcare circuits and patient empowerment. Ensuring optimal anticoagulation in atrial fibrillation patients is mandatory if we want to reduce the thromboembolic risk. Of note, telemedicine is an excellent option for the long-term management of atrial fibrillation patients. Moreover, direct oral anticoagulants may provide an added value in telemedicine (versus vitamin K antagonists), as it is not necessary to monitor anticoagulant effect or make continuous dosage adjustments. In this multidisciplinary consensus document, the role of telemedicine in anticoagulation of this population is discussed and practical recommendations are provided.


Тема - темы
Atrial Fibrillation , COVID-19 , Stroke , Telemedicine , Administration, Oral , Anticoagulants , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , COVID-19/complications , Humans
14.
Antimicrob Agents Chemother ; 66(7): e0059022, 2022 07 19.
Статья в английский | MEDLINE | ID: covidwho-1909571

Реферат

Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is an oral carbapenem prodrug being developed for the treatment of serious bacterial infections. The active moiety, tebipenem, has broad-spectrum activity against common Enterobacterales pathogens, including extended-spectrum-ß-lactamase (ESBL)-producing multidrug-resistant strains. This study evaluated the intrapulmonary pharmacokinetics (PK) and epithelial lining fluid (ELF) and alveolar macrophage (AM) concentrations of tebipenem relative to plasma levels in nonsmoking, healthy adult subjects. Thirty subjects received oral TBP-PI-HBr at 600 mg every 8 h for five doses. Serial blood samples were collected following the last dose. Each subject underwent one standardized bronchoscopy with bronchoalveolar lavage (BAL) 1, 2, 4, 6, or 8 h after the fifth dose of TBP-PI-HBr. The tebipenem area under the concentration-time curve for the 8-h dosing interval (AUC0-8) values in plasma, ELF, and AMs were calculated using the mean concentration at each BAL sampling time. Ratios of AUC0-8 values for total ELF and AMs to those for unbound plasma were determined, using a plasma protein binding value of 42%. Mean values ± standard deviations (SD) of tebipenem maximum (Cmax) and minimum (Cmin) total plasma concentrations were 11.37 ± 3.87 mg/L and 0.043 ± 0.039 mg/L, respectively. Peak tebipenem concentrations in plasma, ELF, and AMs occurred at 1 h and then decreased over 8 h. Ratios of tebipenem AUC0-8 values for ELF and AMs to those for unbound plasma were 0.191 and 0.047, respectively. Four (13.3%) subjects experienced adverse events (diarrhea, fatigue, papule, and coronavirus disease 2019 [COVID-19]); all resolved, and none were severe or serious. Tebipenem is distributed into the lungs of healthy adults, which supports the further evaluation of TBP-PI-HBr for the treatment of lower respiratory tract bacterial infections caused by susceptible pathogens. (This study has been registered at ClinicalTrials.gov under identifier NCT04710407.).


Тема - темы
Anti-Bacterial Agents , COVID-19 , Administration, Oral , Adult , Anti-Bacterial Agents/pharmacokinetics , Bronchoalveolar Lavage Fluid , Carbapenems/metabolism , Humans , Lung/metabolism , Monobactams/metabolism
15.
Croat Med J ; 63(3): 287-294, 2022 Jun 22.
Статья в английский | MEDLINE | ID: covidwho-1898169

Реферат

In patients with COVID-19, thromboinflammation is one of the main causes of morbidity and mortality, which makes anticoagulation an integral part of treatment. However, pharmacodynamic and pharmacokinetic properties of direct oral anticoagulants (DOACs) limit the use of this class of anticoagulants in COVID-19 patients due to a significant interference with antiviral agents. DOACs use in COVID-19 hospitalized patients is currently not recommended. Furthermore, patients already on oral anticoagulant drugs should be switched to heparin at hospital admission. Nevertheless, outpatients with a confirmed diagnosis of COVID-19 are recommended to continue prior DOAC therapy. More studies are required to clarify the pathogenesis of COVID-19-induced derangement of the coagulation system in order to recommend an appropriate anticoagulant treatment.


Тема - темы
COVID-19 , Thrombosis , Administration, Oral , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Inflammation , Pharmacogenetics
16.
Curr Opin Neurol ; 34(3): 286-294, 2021 06 01.
Статья в английский | MEDLINE | ID: covidwho-1895869

Реферат

PURPOSE OF REVIEW: Using highly effective (HE) compounds right from the beginning of disease-modifying immunotherapy (DMT) in people with multiple sclerosis (pwMS) has gained popularity among clinicians and pwMS alike. We discuss the most recent evidence supporting this approach, and whether any of the associated risks should stop us adopting it as a default strategy. RECENT FINDINGS: With the addition of injectable ofatumumab, and the two oral sphingosine one phosphate modulators siponimod and ozanimod, ten HE DMTs are now available for pwMS, though variation in licensing status and cost may limit their use in some healthcare environments. Real World evidence based on large MS registry data suggests the superiority of early HE DMT over a slow treatment escalation approach; delaying HE DMT leads to more rapid and often irreversible disability accrual. Mechanistically, B-cell depletion, particularly memory B-cell suppression, is a common denominator closely associated with DMT efficacy. SUMMARY: The concept that HE DMTs are necessarily associated with a high risk of adverse effects, is no longer supported by the evidence. The rather predictable and manageable risk profile of most HE DMTs should lower the threshold for clinicians to discuss such treatment with pwMS as a first line approach.


Тема - темы
Multiple Sclerosis , Administration, Oral , Humans , Immunologic Factors/therapeutic use , Immunotherapy , Multiple Sclerosis/drug therapy , Treatment Outcome
17.
J Ethnopharmacol ; 296: 115472, 2022 Oct 05.
Статья в английский | MEDLINE | ID: covidwho-1895183

Реферат

ETHNOPHARMACOLOGICAL RELEVANCE: Xuanfei Baidu prescription, consisting of 13 Chinese medicines, was formulated by academicians Boli Zhang and Professor Qingquan Liu based on their experience in first-line clinical treatment of COVID-19. Xuanfei Baidu granules (XFBD granules) are a proprietary Chinese medicine preparation developed based on Xuanfei Baidu prescription. It is recommended for the treatment of patients with the common wet toxin and lung stagnation syndrome of COVID-19. However, the pharmacokinetic characteristics of its major bioactive components in rats under different physiological and pathological conditions are unclear. MATERIALS AND METHODS: A rapid and sensitive analytical method, ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS/MS), was developed and applied to 24 major bioactive components in normal and ARDS rats after oral administration of XFBD granules. We studied the metabolic process of XFBD granules in vivo to compare the differences in pharmacokinetic parameters between normal and model metabolic processes. RESULTS: This method was successfully applied to the pharmacokinetic investigation of 24 major components of XFBD granules following oral administration in normal and ARDS rats. Eight components, including ephedrine and amygdalin, were more highly absorbed and had shorter Tmax values than the model group; the absorption of six components, such as rhein, decreased in ARDS rats, and there was no significant difference in the absorption of ten components, such as verbenalin and naringin, between the normal and ARDS rats. The results showed that the peak times of other analytes were very short, and 80% of these target constituents were eliminated in both normal and ARDS rats within 6 h except for liquiritigenin and 18ß-glycyrrhetinic acid. CONCLUSIONS: In this study, a rapid and sensitive UPLC-MS/MS analytical method was developed and applied to 24 major bioactive components in normal and ARDS rats after the oral administration of XFBD granules. This will serve to form the basis for further studies on the pharmacokinetic-pharmacodynamic correlation of XFBD granules.


Тема - темы
COVID-19 , Drugs, Chinese Herbal , Respiratory Distress Syndrome , Administration, Oral , Animals , Chromatography, High Pressure Liquid/methods , Chromatography, Liquid/methods , Rats , Rats, Sprague-Dawley , Tandem Mass Spectrometry/methods
18.
Int J Environ Res Public Health ; 19(11)2022 05 26.
Статья в английский | MEDLINE | ID: covidwho-1892852

Реферат

Isotretinoin (ISO) is an oral prescription-only retinoid, well known for its acne-treating effect. However, it affects a substantial number of human cell types, causing a broad spectrum of adverse effects. The purpose of this study is to establish the isotretinoin therapy adverse events among human clinical trials and their prevalence. Two authors (J.K., J.L.) systematically performed the literature review and assessment from December 2021-February 2022. Three databases (PubMed, ClinicalTrials, and Cochrane Library) were searched using the following terms: "isotretinoin acne vulgaris" for published studies in English from 1980-2021. Finally, 25 randomized controlled clinical trials (RCTs) and five open-label clinical trials provided 3274 acne vulgaris suffering patients. Isotretinoin therapy affects almost all of the systems in the human body, causing numerous adverse events. However, they mainly concern mild mucocutaneous conditions (severe cases are rare) and represent individual responses to a drug. In addition, all adverse events are reversible and can be avoided by specific preparations.


Тема - темы
Acne Vulgaris , Isotretinoin , Acne Vulgaris/drug therapy , Administration, Oral , Humans , Isotretinoin/adverse effects
19.
Int J Clin Pract ; 2022: 7325060, 2022.
Статья в английский | MEDLINE | ID: covidwho-1886811

Реферат

Background: Most evidence regarding anticoagulation and COVID-19 refers to the hospitalization setting, but the role of oral anticoagulation (OAC) before hospital admission has not been well explored. We compared clinical outcomes and short-term prognosis between patients with and without prior OAC therapy who were hospitalized for COVID-19. Methods: Analysis of the whole cohort of the HOPE COVID-19 Registry which included patients discharged (deceased or alive) after hospital admission for COVID-19 in 9 countries. All-cause mortality was the primary endpoint. Study outcomes were compared after adjusting variables using propensity score matching (PSM) analyses. Results: 7698 patients were suitable for the present analysis (675 (8.8%) on OAC at admission: 427 (5.6%) on VKAs and 248 (3.2%) on DOACs). After PSM, 1276 patients were analyzed (638 with OAC; 638 without OAC), without significant differences regarding the risk of thromboembolic events (OR 1.11, 95% CI 0.59-2.08). The risk of clinically relevant bleeding (OR 3.04, 95% CI 1.92-4.83), as well as the risk of mortality (HR 1.22, 95% CI 1.01-1.47; log-rank p value = 0.041), was significantly increased in previous OAC users. Amongst patients on prior OAC only, there were no differences in the risk of clinically relevant bleeding, thromboembolic events, or mortality when comparing previous VKA or DOAC users, after PSM. Conclusion: Hospitalized COVID-19 patients on prior OAC therapy had a higher risk of mortality and worse clinical outcomes compared to patients without prior OAC therapy, even after adjusting for comorbidities using a PSM. There were no differences in clinical outcomes in patients previously taking VKAs or DOACs. This trial is registered with NCT04334291/EUPAS34399.


Тема - темы
Atrial Fibrillation , COVID-19 , Thromboembolism , Administration, Oral , Anticoagulants/adverse effects , Atrial Fibrillation/drug therapy , COVID-19/drug therapy , Hemorrhage/chemically induced , Hospitalization , Hospitals , Humans , Prognosis , Registries , Thromboembolism/prevention & control
20.
J Clin Invest ; 132(9)2022 05 02.
Статья в английский | MEDLINE | ID: covidwho-1883373

Реферат

BACKGROUNDHyaluronan (HA), an extracellular matrix glycosaminoglycan, has been implicated in the pathophysiology of COVID-19 infection, pulmonary hypertension, pulmonary fibrosis, and other diseases, but is not targeted by any approved drugs. We asked whether hymecromone (4-methylumbelliferone [4-MU]), an oral drug approved in Europe for biliary spasm treatment that also inhibits HA in vitro and in animal models, could be repurposed as an inhibitor of HA synthesis in humans.METHODSWe conducted an open-label, single-center, dose-response study of hymecromone in healthy adults. Subjects received hymecromone at 1200 (n = 8), 2400 (n = 9), or 3600 (n = 9) mg/d divided into 3 doses daily, administered orally for 4 days. We assessed safety and tolerability of hymecromone and analyzed HA, 4-MU, and 4-methylumbelliferyl glucuronide (4-MUG; the main metabolite of 4-MU) concentrations in sputum and serum.RESULTSHymecromone was well tolerated up to doses of 3600 mg/d. Both sputum and serum drug concentrations increased in a dose-dependent manner, indicating that higher doses lead to greater exposures. Across all dose arms combined, we observed a significant decrease in sputum HA from baseline after 4 days of treatment. We also observed a decrease in serum HA. Additionally, higher baseline sputum HA levels were associated with a greater decrease in sputum HA.CONCLUSIONAfter 4 days of exposure to oral hymecromone, healthy human subjects experienced a significant reduction in sputum HA levels, indicating this oral therapy may have potential in pulmonary diseases where HA is implicated in pathogenesis.TRIAL REGISTRATIONClinicalTrials.gov NCT02780752.FUNDINGStanford Medicine Catalyst, Stanford SPARK, Stanford Innovative Medicines Accelerator program, NIH training grants 5T32AI052073-14 and T32HL129970.


Тема - темы
Hyaluronic Acid , Hymecromone , Administration, Oral , COVID-19 , Europe , Extracellular Matrix/metabolism , Humans , Hyaluronic Acid/metabolism , Hymecromone/administration & dosage , Hymecromone/adverse effects
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