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1.
Respir Investig ; 62(4): 710-716, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38823190

RESUMO

The number of older people with impaired swallowing function increases with aging population. Aspiration pneumonia is one of the most cases of pneumonia developing among older people. As aspiration pneumonia may develop as a result of age-related deterioration, it is crucial to consider it as an unavoidable event with aging. While pneumonia is diagnosed based on respiratory symptoms and radiological features, the lung involvement of aspiration pneumonia may be undetectable via a frontal chest radiograph in some cases. Bacterial profiles show the predominance of drug-resistant bacteria, such as Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), but isolated bacteria from respiratory samples do not necessarily indicate causative pathogens. Furthermore, there is no evidence regarding treatment superiority using broad-spectrum antibiotics compared with narrow-spectrum antibiotics. Even if isolated pathogens are a causative factor for pneumonia among older patients, the use of broad-spectrum antibiotics covering the bacteria may not improve their outcomes. Therefore, we propose a treatment strategy independent of the risk of drug resistance focusing on the discrimination of patients who are unlikely to respond to broad-spectrum antibiotics. An aspiration risk is associated with increased in-hospital mortality in patients with pneumonia, which could also lead to a greater risk of poor long-term outcomes with increased 1-year mortality. Advance care planning is now recognized as a process for communication and medical decision-making across the life course. This approach would be widely recommended for older people with aspiration risk.

2.
Geriatrics (Basel) ; 9(2)2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38525743

RESUMO

BACKGROUNDS: It remains unclear if antibiotics should be used for the treatment of acute aspiration bronchitis to prevent the development of pneumonia. This study aimed to assess the associations between the use of antibiotics and the development of pneumonia among patients with acute aspiration bronchitis. METHODS: We retrospectively reviewed consecutive patients with acute aspiration bronchitis aged ≥75 years. Acute aspiration bronchitis was defined as a condition with aspiration risk, high fever (body temperature, ≥37.5 °C), respiratory symptoms, and the absence of evidence of pneumonia. RESULTS: There was no significant difference in the incidence of pneumonia between patients treated with and without antibiotics for acute aspiration bronchitis (6/44, 14% vs. 31/143, 22%; p = 0.242). Lower estimated glomerular filtration rate (adjusted odds ratio, 0.956; 95% confidence interval, 0.920-0.993) was significantly associated with the development of pneumonia. CONCLUSIONS: Antibiotic administration should not be routinely recommended to prevent pneumonia following acute aspiration bronchitis, and patients with decreased renal function should be closely monitored. A randomized controlled trial is necessary to validate these results.

3.
Cureus ; 16(1): e51724, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38318593

RESUMO

Pneumocystis jirovecii pneumonia (PCP) is the most common opportunistic infection in patients with human immunodeficiency virus (HIV), but it may develop in patients without HIV, whose immune system is suppressed by anticancer or immunosuppressive agents even when indicating normal counts of CD4+ T cells. Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma, which is believed not to cause immunosuppressive conditions unless it develops leukosis or metastasis or is treated with anticancer drugs or systemic immunosuppressants. Here, we report a case of PCP in a patient with localized MF not receiving immunosuppressive treatment. The patient, a woman in her 70s, presented with persistent dyspnea. High-resolution computed tomography (HRCT) showed diffuse ground-glass opacities in both lungs. Bronchoalveolar lavage fluid was positive for P. jirovecii. Moreover, the cytomegalovirus antigenemia test was positive, whereas tests for anti-HIV and antihuman T-cell lymphotropic virus antibodies were negative. The patient was treated with trimethoprim-sulfamethoxazole, prednisolone, and ganciclovir, which gradually improved the symptoms and diminished diffuse ground-glass opacities on HRCT. This case exemplifies a rare presentation of PCP with mild MF that was not treated with chemotherapy or immunosuppressants. The possible mechanisms for the development of PCP are discussed.

4.
J Infect Chemother ; 30(2): 129-133, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37769992

RESUMO

INTRODUCTION: It has not been fully elucidated that nutritional parameters affect the change of activities of daily living (ADL) during pneumonia treatment. This study assessed the impact of nutritional status, including erector spinae muscle (ESM) size on ADL changes from admission to discharge among older patients with community-acquired pneumonia (CAP). METHODS: We retrospectively included patients (age: ≥65 years) who were admitted to the hospital for CAP and underwent chest computed tomography (CT) on admission. ADL was evaluated using the Barthel index, and patients were divided into the maintained or improved ADL group and the declined ADL group from admission through discharge. The ESM cross-sectional area was measured on a single-slice CT image. Logistic regression models were applied for assessing factors associated with changes in ADL. RESULTS: A total of 523 patients hospitalized for CAP (median age 86 years) were evaluated. The declined group had significantly higher ADL levels on admission, a greater frequency of smoking history and malignancy, and a lower frequency of cerebrovascular disease and dementia. No significant difference in ESM size was observed between the groups. Multivariate analysis revealed that higher ADL levels on admission (odds ratio 1.034, interquartile range 1.026-1.043) and malignancy (3.002, 1.150-7.836) were associated with a decline in ADL, whereas cerebrovascular disease (0.579, 0.373-0.900) was related to improvement or maintenance of ADL. CONCLUSIONS: Although nutritional status might not affect the change of ADL among older patients hospitalized with pneumonia, a cerebrovascular disease history may be a good predictor for ADL improvement.


Assuntos
Transtornos Cerebrovasculares , Neoplasias , Pneumonia , Humanos , Idoso de 80 Anos ou mais , Idoso , Atividades Cotidianas , Alta do Paciente , Estudos Retrospectivos
5.
Pathogens ; 12(11)2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-38003795

RESUMO

PURPOSE: As the number of patients with Mycobacterium avium complex lung disease is significantly increasing worldwide, several studies have focused on the prognostic factors associated with the disease. This systematic review investigated the factors associated with mortality among patients with Mycobacterium avium complex lung disease. METHODS: Two investigators independently identified studies that were designed to determine risk factors for mortality in patients with Mycobacterium avium complex lung disease from PubMed, the Cochrane Register of Control Trial database, and EMBASE (accessed on 25 November 2022). RESULTS: Of the 1133 titles and abstracts screened, 54 full texts were selected for review, and 15 studies were finally included in this systematic review. The most commonly studied risk factors were advanced age and low body mass index (11 studies for each), followed by male sex (8 studies), hypoalbuminemia (5 studies), and cavity (5 studies). In each study, these factors were mostly associated with increased all-cause mortality among patients with Mycobacterium avium complex lung disease as confirmed via multivariate analysis. CONCLUSIONS: Advanced age, male sex, low body mass index, hypoalbuminemia, and cavity are likely to be the common risk factors for all-cause mortality among patients with Mycobacterium avium complex lung disease, suggesting that patients with these factors need to be carefully monitored.

6.
Cureus ; 15(10): e47921, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37905163

RESUMO

BACKGROUND: Individuals with swallowing dysfunction in their 50s and 60s may be at risk for aspiration pneumonia as they age. The association of background and lifestyle with swallowing dysfunction for those in their 50s and 60s has not been fully studied. This study aimed to clarify the relationship between lifestyle and swallowing function in this group. PATIENTS AND METHODS: We targeted physicians in their 50s and 60s as participants. The repetitive saliva swallowing test (RSST) was used to evaluate swallowing function, and self-reported questionnaires about their lifestyle were administered. The associations between RSST scores and participants' backgrounds and lifestyles were analyzed. RESULTS: This study included 310 participants, who were divided into two groups: 162 in the low RSST group and 148 in the high RSST group. The low RSST group had significantly shorter daily conversation times and a lower incidence of hyperlipidemia than the high RSST group. On multivariate analysis, less than three hours of daily conversation time was independently related to lower RSST scores (adjusted odds ratio: 1.863; 95% confidence interval: 1.167-2.974). CONCLUSIONS: Shorter conversation time may serve as a predictor of impaired swallowing function, potentially increasing the risk of aspiration pneumonia in the future.

7.
Medicine (Baltimore) ; 102(34): e34858, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37653769

RESUMO

BACKGROUND: 5-aminolevulinic acid (5-ALA), a natural amino acid that is marketed alongside sodium ferrous citrate (SFC) as a functional food, blocks severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proliferation in vitro and exerts anti-inflammatory effects. In this phase II open-label, prospective, parallel-group, randomized trial, we aimed to evaluate the safety and efficacy of 5-ALA in patients with mild-to-moderate coronavirus disease 2019. METHODS: This trial was conducted in patients receiving 5-ALA/SFC (250/145 mg) orally thrice daily for 7 days, followed by 5-ALA/SFC (150/87 mg) orally thrice daily for 7 days. The primary endpoints were changes in SARS-CoV-2 viral load, clinical symptom scores, and 5-ALA/SFC safety (adverse events [AE] and changes in laboratory values and vital signs). RESULTS: A total of 50 patients were enrolled from 8 institutions in Japan. The change in SARS-CoV-2 viral load from baseline was not significantly different between the 5-ALA/SFC (n = 24) and control (n = 26) groups. The duration to improvement was shorter in the 5-ALA/SFC group than in the control group, although the difference was not significant. The 5-ALA/SFC group exhibited faster improvement rates in "taste abnormality," "cough," "lethargy," and "no appetite" than the control group. Eight AEs were observed in the 5-ALA/SFC group, with 22.7% of patients experiencing gastrointestinal symptoms (decreased appetite, constipation, and vomiting). AEs occurred with 750/435 mg/day in 25.0% of patients in the first phase and with 450/261 mg/day of 5-ALA/SFC in 6.3% of patients in the second phase. CONCLUSION: 5-ALA/SFC improved some symptoms but did not influence the SARS-CoV-2 viral load or clinical symptom scores over 14 days. The safety of 5-ALA/SFC in this study was acceptable. Further evaluation using a larger sample size or modified method is warranted.


Assuntos
Ácido Aminolevulínico , COVID-19 , Humanos , Ferro , Fosfatos , Estudos Prospectivos , SARS-CoV-2
9.
Open Forum Infect Dis ; 10(8): ofad418, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37577113

RESUMO

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening infectious disease for which no effective treatment strategy has been established. Although corticosteroids (CSs) are widely administered to patients with SFTS, their efficacy remains uncertain. This study aimed to assess the impact of CS therapy on the in-hospital mortality of patients with SFTS. Methods: In this nationwide observational study using the Japanese Diagnosis Procedure Combination database, patients hospitalized for SFTS from April 2013 to March 2021 were reviewed. We compared patients who were treated with CSs to those who were treated without them after propensity score matching to adjust for their background, disease severity, and combination therapy. Results: We included 494 patients with SFTS, and 144 pairs of them were analyzed after propensity score matching. No significant difference in the 30-day mortality (19% vs 15%, P = .272) and the number of survival days (log-rank test, P = .392) was found between the CS treatment group and the non-CS treatment group. However, in subgroup analyses, the CS treatment group tended to have better survival among patients with impaired consciousness on admission and/or shock status within 7 days after admission. Conclusions: CS therapy does not seem effective for all patients with SFTS; however, the impact might be altered by disease severity assessed by the consciousness level and shock status. A large-scale interventional study is required to determine its efficacy, especially for critically ill patients with SFTS.

10.
Microbiol Spectr ; 11(4): e0490822, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37314340

RESUMO

Nontuberculous mycobacterial infections are generally believed to be independently acquired from the environment. Although person-to-person transmission of nontuberculous mycobacteria, especially Mycobacterium abscessus subsp. massiliense, is a serious concern among individuals with cystic fibrosis (CF), evidence of its spread among patients without CF has never been established. We unexpectedly found a number of M. abscessus subsp. massiliense cases among patients without CF in a hospital. This study aimed to define the mechanism of M. abscessus subsp. massiliense infection among patients who were ventilator dependent and without CF who had progressive neurodegenerative diseases in our long-term care wards from 2014 to 2018 during suspected nosocomial outbreaks. We conducted whole-genome sequencing of M. abscessus subsp. massiliense isolates from 52 patients and environmental samples. Potential opportunities for in-hospital transmission were analyzed using epidemiological data. M. abscessus subsp. massiliense was isolated from one air sample obtained near a patient without CF who was colonized with M. abscessus subsp. massiliense but not from other potential sources. Phylogenetic analysis of the strains from these patients and the environmental isolate revealed clonal expansion of near-identical M. abscessus subsp. massiliense isolates, with the isolates generally differing by fewer than 22 single nucleotide polymorphisms (SNPs). Approximately half of the isolates differed by fewer than nine SNPs, indicating interpatient transmission. Whole-genome sequencing revealed a potential nosocomial outbreak among patients who were ventilator dependent and without CF. IMPORTANCE The isolation of M. abscessus subsp. massiliense from the air, but not from environmental fluid samples, may suggest airborne transmission. This was the first report to demonstrate person-to-person transmission of M. abscessus subsp. massiliense, even among patients without CF. M. abscessus subsp. massiliense may spread among patients who are ventilator dependent without CF through direct or indirect in-hospital transmission. The current infection control measures should address potential transmission among patients without CF, particularly in facilities that treat patients who are ventilator dependent and patients with preexisting chronic pulmonary diseases, such as CF.


Assuntos
Infecção Hospitalar , Fibrose Cística , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Humanos , Mycobacterium abscessus/genética , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Fibrose Cística/microbiologia , Filogenia , Infecção Hospitalar/epidemiologia , Micobactérias não Tuberculosas , Ventiladores Mecânicos
11.
J Infect Chemother ; 29(7): 688-692, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37011836

RESUMO

INTRODUCTION: Acid-fast bacillus (AFB) is a major pathogen that causes noncystic fibrosis bronchiectasis requiring multidrug chemotherapy. Bronchoscopic bronchial wash is performed to determine the causative pathogens of bronchiectasis; but, predictive factors for AFB isolation have not been fully elucidated. This study aimed to determine the factors associated with AFB isolation from bronchial wash samples. METHODS: This was a single-center, cross-sectional study. Patients undergoing bronchoscopic bronchial wash for bronchiectasis were included, whereas those who did not undergo high-resolution computed tomography (HRCT); had acute pneumonia, interstitial lung disease, and a positive polymerase chain reaction result but a negative culture result for AFB; or in whom a guide sheath was used for suspected lung cancer were excluded. Binomial logistic regression was used to analyze the factors associated with a positive culture for AFB. RESULTS: Of the 96 included cases, AFB isolation was observed in the bronchial wash fluid of 26 patients (27%). No smoking history, a positive result for antiglycopeptidolipid (GPL)-core IgA antibody, and the presence of tree-in-bud appearance, multiple granular and nodular images on HRCT were more commonly observed in patients with AFB isolation than in those without. In the multivariate analysis, the tree-in-bud appearance (odds ratio, 4.223; 95% CI, 1.046-17.052) and anti-GPL core IgA antibody (odds ratio, 9.443; 95% CI, 2.206-40.421) were significantly associated with AFB isolation. CONCLUSIONS: The tree-in-bud appearance on HRCT is likely to predict AFB isolation independent of anti-GPL core IgA antibody results. Bronchoscopic bronchial wash should be recommended for bronchiectasis with multiple granulomas on HRCT.


Assuntos
Bacillus , Bronquiectasia , Doenças Pulmonares Intersticiais , Humanos , Estudos Transversais , Fibrose
12.
Cureus ; 15(2): e35565, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37007317

RESUMO

Pneumocystis jirovecii pneumonia (PCP) typically presents with diffuse ground-glass attenuation (GGA) in both lungs on high-resolution CT (HRCT). While other radiological features, including cysts and air-space consolidation, may be found, the absence of GGA has a high negative predictive value for PCP in patients with AIDS. We report a case of PCP in a male patient who visited our hospital with a subacute, non-productive cough. He had never been diagnosed with an HIV infection. Although his HRCT scan revealed multiple centrilobular nodules without GGA, Pneumocystis jirovecii was detected in the bronchoalveolar lavage (BAL), and no other additional pathogens were identified. The patient was diagnosed with PCP associated with AIDS after a high plasma HIV-RNA titer and low CD4+ cell count were confirmed. Physicians need to be aware of this atypical radiological presentation of PCP associated with AIDS.

13.
Respir Investig ; 61(2): 181-185, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36720183

RESUMO

Although studies have investigated the factors associated with psychological post-COVID-19 symptoms, the impact of marital status on symptom development has not been fully determined. This study conducts a questionnaire survey to investigate the association between marital status and the proportion of patients with post-COVID-19 symptoms in 749 cases as valid responses. Depressive state and memory impairment were more frequently seen in the no-spouse group when each symptom was compared according to marital status. Particularly in individuals in the 40s who had minor COVID-19 illness, this trend was noted. Single patients with mild COVID-19 illness may need proactive psychological support.


Assuntos
COVID-19 , Humanos , Depressão/diagnóstico , Depressão/psicologia , Estado Civil , Inquéritos e Questionários , Ansiedade/diagnóstico
14.
Intern Med ; 62(14): 2043-2050, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-36476547

RESUMO

Objective Although extended-spectrum ß-lactamase (ESBL)-producing bacteria are a global threat, as they may cause respiratory infection, the factors associated with the isolation of these bacteria from sputum remain unclear. We therefore explored the factors related to ESBL-producing Klebsiella pneumoniae and Escherichia coli isolated from sputum samples. Methods This study included consecutive patients admitted to our department from 2010 to 2021 with K. pneumoniae or E. coli isolated from their sputum. The patients were categorized into ESBL-producing and non-ESBL-producing groups, and the factors associated with ESBL-producing bacteria isolation were assessed using a binomial logistic regression analysis. Results We included 82 patients, and ESBL-producing pathogens were isolated from 23 (28%). The usage rates of cephem [odds ratio (OR) 4.000, 95% confidence interval (CI) 1.402-11.409, p=0.010], quinolone (OR 2.961, 95% CI 1.097-7.996, p=0.032), and macrolide (OR 4.273, 95% CI 1.518-12.028, p=0.006) in the past year were significantly higher in the ESBL-producing group than in the non-ESBL-producing group. The multivariate analysis revealed that the applications of cephem (adjusted OR: 4.130, 95% CI: 1.233-13.830, p=0.021) and macrolide (adjusted OR: 6.365, 95% CI: 1.922-21.077, p=0.002) was independently associated with the isolation of ESBL-producing bacteria. Conclusion A history of cephem and macrolide use can be considered a risk factor for ESBL-producing bacteria isolation from sputum samples. Physicians need to consider these risk factors when determining antibiotics for the treatment of patients with respiratory infections.


Assuntos
Infecções por Escherichia coli , Infecções por Klebsiella , Humanos , Escherichia coli , Enterobacteriaceae , Infecções por Klebsiella/tratamento farmacológico , beta-Lactamases , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Escherichia coli/tratamento farmacológico , Fatores de Risco , Klebsiella pneumoniae , Bactérias
15.
Respir Investig ; 61(1): 1-4, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36400689

RESUMO

The pathogenesis of eosinophilic pneumonia is currently poorly understood, and this disease has not been reported in twins since 1983. Herein, we report a case of acute eosinophilic pneumonia in twins, which appeared to be triggered by initial smoking at different times by both patients. One patient resumed smoking after recovering from eosinophilic pneumonia, with no observed recurrence. This study discussed the possibility of an association between susceptibility to eosinophilic pneumonia and genetic factors in twins.


Assuntos
Eosinofilia Pulmonar , Humanos , Eosinofilia Pulmonar/etiologia , Doença Aguda , Fumar
16.
J Infect Chemother ; 29(1): 55-60, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36162646

RESUMO

BACKGROUND: Although the 2019 American Thoracic Society and Infectious Diseases Society of America guidelines for community-acquired pneumonia (CAP) recommend the use of antibiotics with Pseudomonas aeruginosa coverage for patients with prior sputum isolation of P. aeruginosa, further research is needed to confirm its clinical outcomes. This study aimed to assess the impact of the use of antibiotics with P. aeruginosa coverage on mortality in elderly CAP patients with sputum isolation of P. aeruginosa. METHODS: We retrospectively included consecutive elderly patients who were hospitalized for CAP and P. aeruginosa-positive sputum culture. The association between the use of antibiotics with P. aeruginosa coverage and 28-day mortality was assessed based on propensity score to reduce selection bias. RESULTS: A total of 216 patients were included, and 68 (31%) of them were treated with antibiotics with P. aeruginosa coverage. The number of patients treated with antibiotics with P. aeruginosa coverage was significantly higher among nonsurvivors than among survivors. After adjustment using propensity score, the association between the use of antibiotics with P. aeruginosa coverage and the 28-day mortality was found to be statistically nonsignificant (odds ratio 2.182, 95% confidence interval 0.732-6.508, p = 0.162). CONCLUSIONS: The use of antibiotics with P. aeruginosa coverage in elderly CAP patients with sputum isolation of P. aeruginosa did not improve their prognosis. A randomized control study is required to identify cases that should be treated with antibiotics covering P. aeruginosa.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Humanos , Estados Unidos , Idoso , Pseudomonas aeruginosa , Estudos Retrospectivos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Pneumonia/tratamento farmacológico , Antibacterianos/uso terapêutico , Prognóstico
18.
Cureus ; 14(9): e29095, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36249614

RESUMO

Although autoimmune pulmonary alveolar proteinosis (APAP) is more likely to be associated with infectious diseases, clinical case-based evidence is too limited to confirm this. We describe a case of a man in his late forties diagnosed with APAP nine years prior to the current presentation. A nodule in the right upper lobe gradually increased from 8 to 12 mm over a period of 6 months and was suspicious of malignancy. The pathological analyses revealed Aspergillus nodule without any malignant features. This study aims to report a case of Aspergillus nodule with APAP and discuss the differential diagnosis of solitary lung nodule developed in APAP.

19.
Cureus ; 14(10): e30335, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36263369

RESUMO

Although double masking provides better protection against COVID-19 than single masking, the exact number of masks needed to achieve the most significant protection has not been determined to date. The present study investigated the changes in leakage with the use of surgical masks in a healthy person in terms of the number of masks. When the number of masks reached the upper limit that could be worn on the ears, large plastic ear attachments were used for each ear. The leakage rate related to the use of a single mask was approximately 50%, and with two masks, it was significantly reduced to approximately 30%. However, the leakage rate increased to approximately 45% with the use of three and four masks. When more than four masks were worn, the rate gradually decreased. Conversely, the rate for three-seven masks was not significantly lower than that for two masks. Although individuals with large ears might be able to wear more than five masks, the use of more than two masks would not be significantly better than the use of two masks.

20.
BMC Med ; 20(1): 342, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36163020

RESUMO

BACKGROUND: In vitro drug screening studies have indicated that camostat mesilate (FOY-305) may prevent SARS-CoV-2 infection into human airway epithelial cells. This study was conducted to investigate whether camostat mesilate is an effective treatment for SARS-CoV-2 infection (COVID-19). METHODS: This was a multicenter, double-blind, randomized, parallel-group, placebo-controlled study. Patients were enrolled if they were admitted to a hospital within 5 days of onset of COVID-19 symptoms or within 5 days of a positive test for asymptomatic patients. Severe cases (e.g., those requiring oxygenation/ventilation) were excluded. Patients were enrolled, randomized, and allocated to each group using an interactive web response system. Randomization was performed using a minimization method with the factors medical institution, age, and underlying diseases (chronic respiratory disease, chronic kidney disease, diabetes mellitus, hypertension, cardiovascular diseases, and obesity). The patients, investigators/subinvestigators, study coordinators, and other study personnel were blinded throughout the study. Patients were administered camostat mesilate (600 mg qid; four to eight times higher than the clinical doses in Japan) or placebo for up to 14 days. The primary efficacy endpoint was the time to the first two consecutive negative tests for SARS-CoV-2. RESULTS: One-hundred fifty-five patients were randomized to receive camostat mesilate (n = 78) or placebo (n = 77). The median time to the first test was 11.0 days (95% confidence interval [CI]: 9.0-12.0) in the camostat mesilate group and 11.0 days (95% CI: 10.0-13.0) in the placebo group. Conversion to negative viral status by day 14 was observed in 45 of 74 patients (60.8%) in the camostat mesilate group and 47 of 74 patients (63.5%) in the placebo group. The primary (Bayesian) and secondary (frequentist) analyses found no significant differences in the primary endpoint between the two groups. No additional safety concerns beyond those already known for camostat mesilate were identified. CONCLUSIONS: Camostat mesilate did not substantially reduce the time to viral clearance, based on upper airway viral loads, compared with placebo for treating patients with mild to moderate SARS-CoV-2 infection with or without symptoms. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04657497. Japan Registry for Clinical Trials, jRCT2031200198.


Assuntos
Tratamento Farmacológico da COVID-19 , Teorema de Bayes , Método Duplo-Cego , Ésteres/efeitos adversos , Ésteres/uso terapêutico , Guanidinas/efeitos adversos , Guanidinas/uso terapêutico , Humanos , SARS-CoV-2 , Resultado do Tratamento
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