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1.
Sci Total Environ ; 930: 172785, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38677414

RESUMO

Island coastal zones are often mistakenly perceived as "ecological desert". Actually, they harbour unique communities of organisms. The biodiversity on islands is primarily influenced by the effects of area and isolation (distance from the mainland), which mainly focused on plants and animals, encompassing studies of entire islands. However, the application of area and isolation effects to soil microorganisms on island beaches across the intertidal zones remains largely unexplored. We hypothesized that island area and isolation shape soil bacterial communities by regulating soil properties on island beaches, due to the fact that local soil properties might be strongly influenced by land-use, which may vary among islands of different sizes and isolations. To test this hypothesis, we conducted a study on 108 plots spanning 4 intertidal zones on 9 representative island beaches within Zhoushan Archipelago, eastern China. We employed one-way ANOVA and Tukey's honestly significant difference (HSD) test to assess the differences in diversity, composition of soil bacterial communities and soil properties among intertidal zones. Redundancy analysis and structural equation modelling (SEM) were used to examine the direct and indirect impacts of beach area and isolation on soil bacterial communities. Our findings revealed that the area and isolation did not significantly influence soil bacterial diversity and the relative abundance of dominant soil bacterial phyla. However, soil nitrogen (soil N), phosphorus (soil P), organic carbon (SOC), available potassium content (soil AK), and electrical conductivity (soil EC) showed significant increases with the area and isolation. As the tidal gradient increased on beaches, soil bacterial OTU richness, Chao 1, and relative abundance of Planctomycetota and Crenarchaeota decreased, while relative abundance of other soil bacterial phyla increased. We found that influences of island area and isolation shape soil bacterial communities on beaches by regulating soil properties, particularly soil moisture, salinity, and nutrients, all of which are also influenced by area and isolation. Island with larger areas and in lower intertidal zones, characterized by higher soil water content (SWC), soil EC, and soil AK, exhibited greater soil bacterial diversity and fewer dominant soil bacterial phyla. Conversely, in the higher intertidal zones with vegetation containing higher soil N and SOC, lower soil bacterial diversity and more dominant soil bacterial phyla were observed. These findings have the potential to enhance our new understanding of how island biogeography in interpreting island biome patterns.


Assuntos
Bactérias , Biodiversidade , Microbiologia do Solo , Solo , Solo/química , China , Ilhas , Microbiota , Monitoramento Ambiental , Nitrogênio/análise , Praias , Ecossistema
2.
Clin Infect Dis ; 75(5): 786-794, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34996113

RESUMO

BACKGROUND: GSK3640254 (GSK'254) is a next-generation human immunodeficiency virus type 1 (HIV-1) maturation inhibitor with pharmacokinetics (PK) supporting once-daily therapy. METHODS: This phase IIa double-blind (sponsor-unblinded), randomized, placebo-controlled, adaptive study evaluated antiviral effect, safety, tolerability, and PK of once-daily GSK'254 monotherapy administered with food (moderate-fat meal) in HIV-1-positive, treatment-naive adults. In part 1, participants received GSK'254 10 or 200 mg for 10 days. In part 2, participants received GSK'254 40, 80, or 140 mg for 7 days, modified from 10 days by a protocol amendment to decrease potential for resistance-associated mutations (RAMs). The primary endpoint was maximum change from baseline in HIV-1 RNA. RESULTS: Maximum changes in HIV-1 RNA of -0.4, -1.2, -1.0, -1.5, and -2.0 log10 occurred with GSK'254 10, 40, 80, 140, and 200 mg, respectively. Regardless of dosing duration, doses ≥40 mg resulted in ≥1-log10 declines in HIV-1 RNA. Plasma PK was generally dose proportional to 140 mg but non-proportional between 140 and 200 mg. Four participants in the 200-mg group developed RAMs on day 11 in part 1, 1 with phenotypic resistance. No RAMs occurred in part 2. Adverse events (AEs) were reported by 22 (65%) participants; headache was the most common (n = 4). Two non-drug-related serious AEs occurred. All AEs were of mild-to-moderate intensity, except for 2 grade 3 non-drug-related AEs in 1 participant. CONCLUSIONS: This monotherapy study established a dose-antiviral response relationship for GSK'254. No safety or tolerability concerns were noted. These results supported dose selection for the ongoing phase IIb study (ClinicalTrials.gov: NCT04493216). CLINICAL TRIALS REGISTRATION: NCT03784079.


Assuntos
Infecções por HIV , HIV-1 , Adulto , Antivirais/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , RNA/farmacologia , RNA/uso terapêutico
3.
Clin Pharmacol Drug Dev ; 9(8): 972-977, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32558338

RESUMO

GSK2838232 is a novel, potent HIV-1 maturation inhibitor for use in regimen-based combination antiretroviral therapy from a once-daily oral dose boosted with a pharmacoenhancer (ritonavir or cobicistat). This phase 1 study in healthy participants was conducted in 2 parts. Part 1 (n = 14) assessed the relative bioavailability of single doses of a 200-mg GSK2838232 tablet and capsule formulation boosted with 100 mg ritonavir in fed and fasted (tablet-only) subjects. Part 2 (n = 10) assessed the pharmacokinetics of repeated 500-mg once-daily doses of GSK2838232 without a pharmacoenhancing boosting agent. In part 1, GSK2838232 demonstrated comparable bioavailability following a single dose of 200 mg GSK2838232 as capsule and tablet formulations in combination with ritonavir (RTV) under fed conditions, with lower intrasubject variability observed for the tablet formulation. In part 2, following administration of 500 mg GSK2838232 once daily for 11 days under fed conditions, Cmax , AUC0-τ , and Cτ showed a small degree of accumulation (1.2- to 1.3-fold) of GSK2838232. The median tmax was approximately 4 hours on both day 1 and day 11 when given with food. The mean t½ was approximately 23 hours on day 11. Steady-state concentrations were achieved by day 3 with a geometric mean steady-state Cτ on day 11 of 28 ng/mL. The tablet formulation was generally well tolerated as a single 200-mg dose with RTV under fed and fasted conditions and following administration of multiple daily doses (11 days) of 500 mg unboosted.


Assuntos
Fármacos Anti-HIV/farmacocinética , Infecções por HIV/tratamento farmacológico , Triterpenos Pentacíclicos/farmacocinética , Ritonavir/administração & dosagem , Administração Oral , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/sangue , Área Sob a Curva , Disponibilidade Biológica , Relação Dose-Resposta a Droga , Esquema de Medicação , Composição de Medicamentos , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Jejum/efeitos adversos , Feminino , Interações Alimento-Droga , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Triterpenos Pentacíclicos/administração & dosagem , Triterpenos Pentacíclicos/sangue , Segurança , Comprimidos
4.
Clin Infect Dis ; 71(5): 1255-1262, 2020 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31769793

RESUMO

BACKGROUND: GSK2838232 is a second-generation, potent, small-molecule, oral human immunodeficiency virus type 1 (HIV-1) maturation inhibitor for once-daily administration boosted with a pharmacoenhancer. METHODS: The phase 2a, proof-of-concept study was an open-label, adaptive dose-ranging design. Safety, pharmacokinetics, and efficacy of GSK2838232 boosted by cobicistat were evaluated in individuals with HIV-1 infection. The study participants (N = 33) received GSK2838232 once daily across a range of doses (20-200 mg) with cobicistat 150 mg for 10 days. RESULTS: GSK2838232 was safe and well tolerated with no clinically meaningful changes in safety parameters or adverse events. Exposure (maximum concentration and area under the concentration-time curve from time zero to the concentration at 24 hours postdose) increased 2- to 3-fold with repeated dosing in an approximately dose-proportional manner, reaching steady-state by day 8 with a half-life (t½) from 16.3 to 19.2 hours. Clearance and t½ values were not dependent on dose. Viral load declined from baseline with all GSK2838232 doses. Mean maximum declines from baseline to day 11 in HIV-1 RNA log10 copies/mL with the 20-mg, 50-mg, 100-mg, and 200-mg cohorts were -0.67, -1.56, -1.32, and -1.70, respectively. CD4+ cell counts increased at doses ≥50 mg. CONCLUSIONS: GSK2838232 with cobicistat was well tolerated and exhibited efficacy as a short-term monotherapy in participants with HIV-1. This positive proof-of-concept study supports the continued development of GSK2838232 for the treatment of HIV as part of combination antiretroviral therapy. CLINICAL TRIALS REGISTRATION: NCT03045861.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Humanos , Triterpenos Pentacíclicos , Carga Viral
5.
J Clin Pharmacol ; 55(9): 1042-50, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25857714

RESUMO

JNJ-56914845 (GSK2336805) is a hepatitis C virus nonstructural protein 5A inhibitor under development for the treatment of chronic hepatitis C (CHC) infection. This open-label, parallel-group, 2-part study evaluated the pharmacokinetics and safety of a single oral 60 mg dose of JNJ-56914845 in 4 cohorts: healthy, mild, moderate, and severe hepatic impairment (n = 8/cohort). Severity of hepatic impairment was categorized using Child-Pugh score, and the healthy subjects were matched for age, sex, body mass index, and smoking status to the moderate hepatic impairment cohort. JNJ-56914845 plasma AUC0-∞ was 26%, 52%, and 45% lower in subjects with mild, moderate, and severe hepatic impairment, respectively, relative to healthy subjects with no difference in half-life among the groups. The apparent oral clearance and volume of distribution were higher in subjects with hepatic impairment. The lower plasma concentrations were largely explained by decreased plasma protein binding in hepatically impaired subjects. One subject with severe hepatic impairment had 2 non-drug-related serious adverse events: an esophageal bleed requiring hospitalization, encephalopathy. Although hepatically impaired subjects have lower exposures than healthy matched controls, they had similar or slightly higher exposures than those observed in past studies of noncirrhotic, CHC patients, suggesting that no dose adjustments for hepatic impairment will be needed.


Assuntos
Antivirais/farmacocinética , Carbamatos/farmacocinética , Hepacivirus/metabolismo , Falência Hepática/metabolismo , Valina/análogos & derivados , Proteínas não Estruturais Virais/antagonistas & inibidores , Adulto , Área Sob a Curva , Carbamatos/efeitos adversos , Feminino , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Valina/efeitos adversos , Valina/farmacocinética
6.
Clin Pharmacol Drug Dev ; 3(5): 338-45, 2014 09.
Artigo em Inglês | MEDLINE | ID: mdl-27129005

RESUMO

This Phase I, randomized, open-label study evaluated the gastric pH-altering effects of omeprazole, a proton pump inhibitor, and the CYP3A enzyme/P-glycoprotein (Pgp)-inhibitory effects of ritonavir, an HIV protease inhibitor, on the pharmacokinetics and safety of the hepatitis C virus (HCV) non-structural protein 5A (NS5A) inhibitor GSK2336805 in healthy male and female subjects. Co-administration of GSK2336805 60 mg with omeprazole decreased GSK2336805 plasma AUC(0-∞) by 10% and Cmax by 18%; no marked effect was observed on t½ . Co-administration of GSK2336805 30 mg with ritonavir increased GSK2336805 plasma AUC(0-∞) by 52%, Cmax by 43%, and t½ by 40%; CL/F was decreased by 34%. All adverse events were minor in intensity. The gastric acid-suppressive effect of omeprazole had minimal impact on the extent and rate of GSK2336805 absorption in vivo; therefore, GSK2336805 may be co-administered with omeprazole without concern about lower GSK2336805 exposures and compromised antiviral efficacy. The modest increases in AUC and Cmax following co-administration of GSK2336805 plus ritonavir suggest that GSK2336805 when given concomitantly with a single CYP3A/Pgp inhibiting drug will not likely require dose adjustment. Final dose recommendation will be based on GSK2336805 efficacy and safety profiles from Phase III trials in HCV-infected patients.


Assuntos
Antivirais/farmacocinética , Carbamatos/farmacocinética , Inibidores do Citocromo P-450 CYP3A/administração & dosagem , Citocromo P-450 CYP3A/metabolismo , Absorção Gastrointestinal , Hepacivirus/efeitos dos fármacos , Omeprazol/administração & dosagem , Inibidores de Proteases/farmacocinética , Inibidores da Bomba de Prótons/administração & dosagem , Ritonavir/administração & dosagem , Valina/análogos & derivados , Proteínas não Estruturais Virais/antagonistas & inibidores , Adolescente , Adulto , Idoso , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/sangue , Área Sob a Curva , Biotransformação , Carbamatos/administração & dosagem , Carbamatos/efeitos adversos , Carbamatos/sangue , Inibidores do Citocromo P-450 CYP3A/efeitos adversos , Interações Medicamentosas , Feminino , Meia-Vida , Voluntários Saudáveis , Hepacivirus/enzimologia , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , New York , Omeprazol/efeitos adversos , Inibidores de Proteases/administração & dosagem , Inibidores de Proteases/efeitos adversos , Inibidores de Proteases/sangue , Inibidores da Bomba de Prótons/efeitos adversos , Ritonavir/efeitos adversos , Valina/administração & dosagem , Valina/efeitos adversos , Valina/sangue , Valina/farmacocinética , Proteínas não Estruturais Virais/metabolismo , Adulto Jovem
7.
Clin Pharmacol Drug Dev ; 3(6): 439-48, 2014 11.
Artigo em Inglês | MEDLINE | ID: mdl-27129119

RESUMO

This first-time-in-human, randomized, double-blind, placebo-controlled, dose-escalation study assessed the safety, tolerability, pharmacokinetics, and antiviral activity of GSK2485852, a hepatitis C virus (HCV) NS5B inhibitor, in 27 chronically infected HCV genotype-1 subjects. Subjects received GSK2485852 70, 420, and 70 mg with a moderate fat/caloric meal. Safety, pharmacokinetics, antiviral activity, HCV genotype/phenotype, and interleukin 28B genotype were evaluated. A statistically significant reduction in HCV ribonucleic acid (RNA) was observed after a single dose of 420 mg GSK2485852 (-1.33 log10 IU/mL) compared with placebo (-0.09 log10 IU/mL) at 24 hours post-dose. Subjects receiving 70 mg GSK2485852 were exposed to concentrations above the protein-adjusted 90% effective concentration for a short time; none experienced a significant decline in HCV RNA (-0.47 log10 copies/mL). GSK2485852 was readily absorbed; however, the observed geometric mean maximum plasma concentration (Cmax ) and area under the curve (AUC) values were significantly lower than expected due to a higher-than-predicted-oral clearance. Co-administration with food reduced the AUC and Cmax of GSK2485852 by 40% and 70%, respectively. Two metabolites were detected in human blood with one having approximately 50% higher concentrations than those of the parent. GSK2485852 was well-tolerated and exhibited antiviral activity after a single 420 mg dose in HCV subjects.


Assuntos
Antivirais/administração & dosagem , Antivirais/farmacocinética , Ácidos Borônicos/administração & dosagem , Ácidos Borônicos/farmacocinética , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Inibidores de Proteases/administração & dosagem , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacocinética , Proteínas não Estruturais Virais/antagonistas & inibidores , Adolescente , Adulto , Idoso , Antivirais/efeitos adversos , Ácidos Borônicos/efeitos adversos , Método Duplo-Cego , Feminino , Interações Alimento-Droga , Genótipo , Hepacivirus/enzimologia , Hepacivirus/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/genética , Humanos , Interferons , Interleucinas/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Inibidores de Proteases/efeitos adversos , Inibidores de Proteases/farmacocinética , RNA Viral/sangue , Sulfonamidas/efeitos adversos , Resultado do Tratamento , Estados Unidos , Carga Viral , Proteínas não Estruturais Virais/metabolismo , Adulto Jovem
8.
Pharmacotherapy ; 33(7): 701-9, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23553534

RESUMO

STUDY OBJECTIVE: To assess the effect of a therapeutic and supratherapeutic intravenous dose of the neuraminidase inhibitor zanamivir on QT and rate-corrected QT intervals. DESIGN: Randomized, placebo-controlled, single-dose, four-period, balanced crossover study. SETTING: Clinical research unit. SUBJECTS: Forty healthy adults were randomized to receive intravenous zanamivir at two dose levels, oral moxifloxacin, and placebo; 38 subjects completed all four study treatments. INTERVENTION: Subjects were randomized to receive a single intravenous dose of zanamivir 600 mg (therapeutic dose) with oral moxifloxacin placebo, a single intravenous dose of zanamivir 1200 mg (supratherapeutic dose) with oral moxifloxacin placebo, oral moxifloxacin 400 mg (positive control) with intravenous zanamivir placebo, or intravenous zanamivir placebo with oral moxifloxacin placebo. Subjects crossed over to all other treatments, with each treatment separated by a 7-day washout period. MEASUREMENTS AND MAIN RESULTS: Zanamivir pharmacokinetics were dose proportional; the pharmacokinetic exposure from zanamivir 1200 mg was 2 times higher than that from 600 mg, the maximum dose under clinical evaluation. For both 600-mg and 1200-mg doses of intravenous zanamivir, the upper limit of the 90% confidence interval (CI) for the placebo-adjusted mean change from baseline of the QT interval corrected for heart rate using Fridericia's formula (ΔΔQTcF) was less than 10 msec at all time points. The sensitivity of the study to detect modest increases in QT interval was established with the positive control, moxifloxacin. The maximum ΔΔQTcF value for zanamivir 1200 mg was 1.73 msec (90% CI -0.40 to 3.87 msec), which was observed within 30 minutes after dosing, and 11.21 msec (90% CI 8.81-13.60) for moxifloxacin, observed at 4 hours after dosing. No relationship was observed between zanamivir serum concentration and ΔΔQTcF. Zanamivir was generally well tolerated, with very few adverse events; none were serious or severe. CONCLUSION: Intravenous zanamivir does not affect cardiac repolarization. Accordingly, treatment with intravenous zanamivir does not require additional cardiac monitoring beyond the standard of care.


Assuntos
Antivirais/administração & dosagem , Síndrome do QT Longo/induzido quimicamente , Zanamivir/administração & dosagem , Administração Oral , Adulto , Antivirais/efeitos adversos , Antivirais/farmacocinética , Compostos Aza/efeitos adversos , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Eletrocardiografia , Feminino , Fluoroquinolonas , Frequência Cardíaca/efeitos dos fármacos , Humanos , Infusões Intravenosas , Masculino , Moxifloxacina , Quinolinas/efeitos adversos , Fatores de Tempo , Adulto Jovem , Zanamivir/efeitos adversos , Zanamivir/farmacocinética
9.
Hum Psychopharmacol ; 28(6): 594-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24519693

RESUMO

OBJECTIVE: Although selective serotonin reuptake inhibitors are now established as first-line pharmacotherapy for social anxiety disorder (SAD), other agents with different mechanisms have shown promise in treating SAD. The aim of this study was to examine the efficacy and safety of tandospirone in treating adolescents with SAD. METHODS: Adolescent patients meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for SAD were randomly assigned (1:1) to open-label treatment with either tandospirone or sertraline for 8 weeks. The primary outcome measures were changes from baseline in the Hamilton Anxiety (HAM-A) scale and response using the Clinical Global Impression of Improvement (CGI-I) scale. RESULTS: The adjusted mean change in HAM-A scores from baseline was indicating a significant improvement over baseline in both treatment arms (p < 0.0001). The mean CGI-I scale score at week was with no significant difference between the two arms (p = 0.42). Rates of response were 48.6% for tandospirone and 55.6% for sertraline using the CGI-I. Response rates were 37.1% for tandospirone and 41.7% for sertraline using a HAM-A response criterion (≥50% reduction). The adjusted mean change in Social Phobia Inventory scores from baseline was indicating a significant improvement over baseline in both treatment arms (p < 0.0001). CONCLUSIONS: Tandospirone is safe and effective and appears non-inferior to sertraline for SAD in youths.


Assuntos
Ansiolíticos/uso terapêutico , Isoindóis/uso terapêutico , Transtornos Fóbicos/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Sertralina/uso terapêutico , Adolescente , Ansiolíticos/efeitos adversos , Feminino , Humanos , Isoindóis/efeitos adversos , Masculino , Piperazinas/efeitos adversos , Escalas de Graduação Psiquiátrica , Pirimidinas/efeitos adversos , Agonistas do Receptor de Serotonina/efeitos adversos , Agonistas do Receptor de Serotonina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Sertralina/efeitos adversos , Resultado do Tratamento , Adulto Jovem
10.
Int J Biostat ; 8(1)2012 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-23089807

RESUMO

A semi-parametric spatial model for spatial dependence is proposed in Poisson regressions to study the effects of risk factors on incidence outcomes. The spatial model is constructed through an application of reproducing kernels. A Bayesian framework is proposed to infer the unknown parameters. Simulations are performed to compare the reproducing kernel-based method with several commonly used approaches in spatial modeling, including independent Gaussian and CAR models. Compared with these models, the reproducing kernel-based method is easy to implement and more flexible in terms of the ability to model various spatial dependence patterns. To further demonstrate the proposed method, two real data applications are discussed: Scottish lip cancer data and Florida smoke-related cancer data.


Assuntos
Simulação por Computador , Estatística como Assunto/métodos , Teorema de Bayes , Humanos , Incidência , Cadeias de Markov , Distribuição Normal , Distribuição de Poisson , Análise de Regressão , Fatores de Risco , Análise Espacial
11.
Int J Gen Med ; 4: 597-606, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21887114

RESUMO

PURPOSE: Skin prick testing (SPT) is fundamental to the practice of clinical allergy identifying relevant allergens and predicting the clinical expression of disease. Wheal sizes on SPT are used to identify atopic cases, and the cut-off value for a positive test is commonly set at 3 mm. However, the measured wheal sizes do not solely reflect the magnitude of skin reaction to allergens, but also skin reactivity (reflected in the size of histamine reaction) and other random or non-random factors. We sought to estimate wheal sizes exclusively due to skin response to allergens and propose gender-specific cutoff points of atopy. METHODS: We developed a Bayesian method to adjust observed wheal sizes by excluding histamine and other factor effects, based on which revised cutoff points are proposed for males and females, respectively. The method is then applied to and intensively evaluated using a study population aged 18, at a location on the Isle of Wight in the United Kingdom. To evaluate the proposed approach, two sample t-tests for population means and proportion tests are applied. RESULTS: Four common aeroallergens, house dust mite (HDM), grass pollen, dog dander, and alternaria are considered in the study. Based on 3 mm cutoff, males tend to be more atopic than females (P-values are between 0.00087 and 0.062). After applying the proposed methods to adjust wheal sizes, our findings suggest that misclassifications of atopy occur more often in males. Revised allergen-specific cutoff values are proposed for each gender. CONCLUSION: To reduce the gender discrepancy, we may have two potentially convenient solutions. One way is to apply allergen-specific and gender-specific cutoff values following the proposed method. Alternatively, we can revise the concentration of allergens in the SPT solutions but keep the cutoff values unchanged, which may be more convenient to clinicians.

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