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BACKGROUND: In MONARCH 2, the addition of abemaciclib to fulvestrant significantly improved both progression-free survival (PFS) and overall survival (OS) in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) with disease progression on prior endocrine therapy. In MONARCH 3, the addition of abemaciclib to a nonsteroidal aromatase inhibitor (NSAI) as initial therapy for HR+, HER2- ABC significantly improved PFS. Here, we present the prespecified final OS results for MONARCH 3. PATIENTS AND METHODS: MONARCH 3 is a randomized, double-blind, phase III study of abemaciclib plus NSAI (anastrozole or letrozole) versus placebo plus NSAI in postmenopausal women with HR+, HER2- ABC without prior systemic therapy in the advanced setting. The primary objective was investigator-assessed PFS; OS was a gated secondary endpoint, and chemotherapy-free survival was an exploratory endpoint. RESULTS: A total of 493 women were randomized 2 : 1 to receive abemaciclib plus NSAI (n = 328) or placebo plus NSAI (n = 165). After a median follow-up of 8.1 years, there were 198 OS events (60.4%) in the abemaciclib arm and 116 (70.3%) in the placebo arm (hazard ratio, 0.804; 95% confidence interval 0.637-1.015; P = 0.0664, non-significant). Median OS was 66.8 versus 53.7 months for abemaciclib versus placebo. In the subgroup with visceral disease, there were 113 OS events (65.3%) in the abemaciclib arm and 65 (72.2%) in the placebo arm (hazard ratio, 0.758; 95% confidence interval 0.558-1.030; P = 0.0757, non-significant). Median OS was 63.7 months versus 48.8 months for abemaciclib versus placebo. The previously demonstrated PFS benefit was sustained, and chemotherapy-free survival numerically improved with the addition of abemaciclib. No new safety signals were observed. CONCLUSIONS: Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS (intent-to-treat population: 13.1 months; subgroup with visceral disease: 14.9 months) in patients with HR+ HER2- ABC; however, statistical significance was not reached.
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Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Inhibidores de la Aromatasa , Bencimidazoles , Neoplasias de la Mama , Letrozol , Receptor ErbB-2 , Receptores de Estrógenos , Receptores de Progesterona , Humanos , Femenino , Aminopiridinas/administración & dosificación , Aminopiridinas/uso terapéutico , Bencimidazoles/administración & dosificación , Bencimidazoles/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inhibidores , Método Doble Ciego , Letrozol/administración & dosificación , Letrozol/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico , Inhibidores de la Aromatasa/administración & dosificación , Persona de Mediana Edad , Anciano , Receptores de Progesterona/metabolismo , Receptores de Estrógenos/metabolismo , Anastrozol/uso terapéutico , Anastrozol/administración & dosificación , Adulto , Anciano de 80 o más Años , Supervivencia sin ProgresiónRESUMEN
Objective: To evaluate the application of whole exome sequencing (WES) in the diagnosis of hereditary eye diseases. Methods: A total of 24 patients who came to the Obstetrics and Gynecology Hospital of Fudan University for reproductive genetic counseling from December 2020 to December 2023 with the main complaint of congenital eye disorders were included in this study. All cases had no known infections or exposure to known teratogenic drugs, karyotype and chromosome microarray analysis (CMA) abnormalities. Genomic DNA was extracted from the peripheral blood of the probands and their family members and tested for WES. Among them, three individual WES and 21 Trio WES were performed. Potential pathogenic sites were screened and analyzed by Sanger sequencing. For RPGRIP1:c.1611+26G>A site, minigene vector was constructed and RT-qPCR was performed to detect the effect of mRNA splicing. Results: A total of 24 families were collected in this study, of which 20 yielded positive results, achieving a diagnosis rate of 83.3% (20/24). The results involved 21 genes and identified 30 distinct variants, 19 of which were new variants reported. Prenatal diagnostic analysis of family 3 revealed that the fetus carried a c.6970G>T heterozygous nonsense mutation in the PRPF8 gene. The results of RT-PCR with the minigene vector at the non-classical splice site in family 24 indicated that the transcription product of the mutant plasmid was partially retained 104 bp in intron 12, resulting in a p.Glu538Valfs*12 alteration of the protein. Conclusions: The high detection rate of WES in the diagnosis of hereditary eye diseases further supports the advantages of its application as an important molecular detection tool for determining the etiology of hereditary eye diseases.
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Secuenciación del Exoma , Enfermedades Hereditarias del Ojo , Humanos , Enfermedades Hereditarias del Ojo/genética , Enfermedades Hereditarias del Ojo/diagnóstico , Femenino , Diagnóstico Prenatal/métodos , Mutación , LinajeRESUMEN
BACKGROUND: Though the CXCR2 chemokine receptor is known to play a key role in cancer growth and response to therapy, a direct link between expression of CXCR2 in tumor progenitor cells during induction of tumorigenesis has not been established. METHODS: To characterize the role of CXCR2 during melanoma tumorigenesis, we generated tamoxifen-inducible tyrosinase-promoter driven BrafV600E/Pten-/-/Cxcr2-/- and NRasQ61R/INK4a-/-/Cxcr2-/- melanoma models. In addition, the effects of a CXCR1/CXCR2 antagonist, SX-682, on melanoma tumorigenesis were evaluated in BrafV600E/Pten-/- and NRasQ61R/INK4a-/- mice and in melanoma cell lines. Potential mechanisms by which Cxcr2 affects melanoma tumorigenesis in these murine models were explored using RNAseq, mMCP-counter, ChIPseq, and qRT-PCR; flow cytometry, and reverse phosphoprotein analysis (RPPA). RESULTS: Genetic loss of Cxcr2 or pharmacological inhibition of CXCR1/CXCR2 during melanoma tumor induction resulted in key changes in gene expression that reduced tumor incidence/growth and increased anti-tumor immunity. Interestingly, after Cxcr2 ablation, Tfcp2l1, a key tumor suppressive transcription factor, was the only gene significantly induced with a log2 fold-change greater than 2 in these three different melanoma models. CONCLUSIONS: Here, we provide novel mechanistic insight revealing how loss of Cxcr2 expression/activity in melanoma tumor progenitor cells results in reduced tumor burden and creation of an anti-tumor immune microenvironment. This mechanism entails an increase in expression of the tumor suppressive transcription factor, Tfcp2l1, along with alteration in the expression of genes involved in growth regulation, tumor suppression, stemness, differentiation, and immune modulation. These gene expression changes are coincident with reduction in the activation of key growth regulatory pathways, including AKT and mTOR.
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Melanoma , Proteínas Proto-Oncogénicas B-raf , Receptores de Interleucina-8B , Animales , Ratones , Carcinogénesis/genética , Línea Celular Tumoral , Transformación Celular Neoplásica , Melanoma/metabolismo , Proteínas Proto-Oncogénicas B-raf/genética , Receptores de Interleucina-8B/genética , Receptores de Interleucina-8B/metabolismo , Microambiente TumoralRESUMEN
PURPOSE: To provide real-life data on azole treatment outcomes and the role of surgery in the current management of invasive fungal rhinosinusitis complicated by orbitocranial fungal infection (OCFI). METHODS: Data was collected retrospectively from a chart review from four participating centers and a systematic literature review. The study group included patients with OCFI treated with azole antifungals. The control cases were treated with other antifungal agents. The cranial and orbital involvement degree was staged based on the imaging. The extent of the surgical resection was also classified to allow for inter-group comparison. RESULTS: There were 125 patients in the azole-treated group and 153 in the control group. Among the patients with OCFI cranial extension, 23% were operated on in the azole-treated group and 18% in the control group. However, meninges and brain resection were performed only in the controls (11% of patients) and never in the azole antifungals group. Orbital involvement required surgery in 26% of azole-treated cases and 39% of controls. Despite a more aggressive cranial involvement, azole-treated patients' mortality was significantly lower than in controls, with an OCFI-specific mortality rate of 21% vs. 52%. A similar, though not statistically significant, trend was found for the extent of the orbital disease and surgery. CONCLUSION: Despite less aggressive surgical intervention for cranial involvement, OCFI patients treated with azoles had a higher survival rate. This finding suggests we may improve morbidity with a more conservative surgical approach in conjunction with azole treatment. The same trend is emerging for orbital involvement.
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Antifúngicos , Micosis , Humanos , Antifúngicos/uso terapéutico , Azoles/uso terapéutico , Pruebas de Sensibilidad Microbiana , Micosis/tratamiento farmacológico , Micosis/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Revisiones Sistemáticas como AsuntoRESUMEN
Sixteen patients with recurrent high-grade glioma who were treated by domestic magnetic resonance-guided laser interstitial thermotherapy (MRgLITT) in the Neurosurgery Department of Xuanwu Hospital of Capital Medical University from 1st January 2021 to 31st December 2021 were prospectively included, with 11 males and 5 females, and aged 27-74 (50±16) years. The duration of surgery, the rate of ablation after surgery, and perioperative complications were assessed. The patients were followed up every 3 months to assess survival and progression. A total of 5 WHO grade â ¢ patients and 11 WHO grade â £ patients were included. The operation time was 144 (109, 176) min, 28 targeted lesions were detected, and the ablation rate [M (Q1, Q3)] was 91.0% (87.4%, 93.3%). After surgery, 2 patients (2/16) had decreased limb muscle strength, and no perioperative death or other serious complications occurred. The median time to a complete response was 12 (5, 14) months in WHO Grade â ¢ patients, and one died 12 months after surgery, while the median time to a complete response was 3 (1, 8) months in 11 WHO Grade â £ patients, with a total of 8 deaths at the last follow-up. Therefore, domestic MRgLITT has certain efficacy and safety in the treatment of recurrent high-grade glioma, providing a new option for patients with recurrent glioma.
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Glioma , Hipertermia Inducida , Femenino , Masculino , Humanos , Imagen por Resonancia Magnética , Rayos Láser , Espectroscopía de Resonancia MagnéticaRESUMEN
Severe acute dichlorvos poisoning is characterized by rapid onset, swift disease progression and serious complications. It frequently involves multiple organ failure (central, respiratory and circulatory systems), severe acidosis, and rare occurrences of gastric perforation. When secondary gastric perforation occurs, treatment becomes difficult and the prognosis of patients is poor. Thus, early and sufficient gastrointestinal decontamination is crucial. This article presented two cases of gastric perforation secondary to dichlorvos poisoning and discussed the causes of gastric perforation, as well is clinical diagnostic and treatment methods.
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Diclorvos , Insuficiencia Multiorgánica , HumanosRESUMEN
The effectiveness of different treatment processes on assimilable organic carbon (AOC) removal and bacterial diversity variations was evaluated in a water treatment plant. The van der Kooij technique was applied for AOC analysis and responses of bacterial communities were characterized by the metagenomics assay. Results show that the AOC concentrations were about 93, 148, 43, 51, 37, and 38 µg acetate-C/L in effluents of raw water basin, preozonation, rapid sand filtration (RSF), ozonation, biofiltration [biological activated carbon (BAC) filtration], and chlorination (clear water), respectively. Increased AOC concentrations were observed after preozonation, ozonation, and chlorination units due to the production of biodegradable organic matters after the oxidation processes. Results indicate that the oxidation processes were the main causes of AOC formation, which resulted in significant increases in AOC concentrations (18-59% increment). The AOC removal efficiencies were 47, 28, and 60% in the RSF, biofiltration, and the whole system, respectively. RSF and biofiltration were responsible for the AOC treatment and both processes played key roles in AOC removal. Thus, both RSF and biofiltration processes would contribute to AOC treatment after oxidation. Sediments from the raw water basin and filter samples from RSF and BAC units were collected and analyzed for bacterial communities. Results from scanning electron microscope analysis indicate that bacterial colonization was observed in filter materials. This indicates that the surfaces of the filter materials were beneficial to bacterial growth and AOC removal via the adsorption and biodegradation mechanisms. Next generation sequencing analyses demonstrate that water treatment processes resulted in the changes of bacterial diversity and community profiles in filters of RSF and BAC. According to the findings of bacterial composition and interactions, the dominant bacterial phyla were Proteobacteria (41% in RSF and 56% in BAC) followed by Planctomycetes and Acidobacteria in RSF and BAC systems, which might affect the AOC biodegradation efficiency. Results would be useful in developing AOC treatment and management processes in water treatment plants.
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Objective: To examine the outcomes of Tiantan first-aid protocol on critically ill patients with primary central nervous system lymphoma (PCNSL). Methods: The clinical data of 18 patients with PCNSL who were treated according to Tiantan first-aid protocol at Department of Neurosurgery,Beijing Tiantan Hospital, Capital Medical University from November 2019 to December 2021 were retrospectively analyzed. There were 9 males and 9 females, aged (56.9±11.1)years (range: 29 to 77 years). The median Karnofsky performance status(KPS) score at admission was 40 (range: 20 to 60). Three patients were mild coma, 3 were lethargy and 12 were conscious. The mean midline shift was 0.7 cm (range: 0 to 1.8 cm). After admission, all patients were treated according to the plan of rapid biopsy, rapid routine pathology and rapid salvage chemotherapy. The treatment procedures, clinical and radiographic outcomes, KPS score and adverse reactions of patients after chemotherapy were collected. Results: All of the 18 patients completed the first-aid treatment. The median duration from admission to the biopsy was 1 day (range: 0 to 5 days), from biopsy to routine pathological diagnosis was 1 day (range: 1 to 4 days) and from routine pathology to salvage chemotherapy was 1 day (range: 0 to 4 days). All the patients were pathologically confirmed with diffuse large B cell lymphoma, 1 patient was double-hit lymphoma. Seventeen patients underwent clinical remission and 1 died of cardiac dysfunction. The successful salvage rate was 17/18. Radiologically, complete remission was observed in 1 case, partial remission in 16 cases, and stable disease in 1 case. The median KPS score at discharge was 60 (range: 30 to 80). The mild gastrointestinal, hematological and hepatic adverse effects were observed after chemotherapy. Conclusion: Tiantan first-aid protocol is effective for critically ill patients with PCNSL, which has the merit to be popularly used and improved.
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Neoplasias del Sistema Nervioso Central , Linfoma , Sistema Nervioso Central , Neoplasias del Sistema Nervioso Central/terapia , Enfermedad Crítica , Femenino , Humanos , Linfoma/terapia , Masculino , Estudios RetrospectivosRESUMEN
Chlorfenapyr is a moderately dangerous insecticide widely used in agriculture. The mortality of acute poisoning patients is high, and there is no effective treatment. This paper retrospectively analyzes the clinical data of two cases of compound chlorfenapyr poisoning. The main symptoms of the patients were high fever, sweating, gradual coma, increased creatine kinase and myoglobin, with delayed poisoning symptoms. Despite comprehensive treatment, both patients died eventually. It indicated that chlorfenapyr was highly toxic and had a high mortality. In addition to routine symptomatic treatment for patients with acute poisoning, blood purification treatment should be actively carried out in the early stage.
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Insecticidas , Piretrinas , Agricultura , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: The ItchyQoL is an itch-specific patient-reported outcome measure used to assess quality of life in patients with chronic pruritus (CP). OBJECTIVES: We aimed to assess and extend the psychometric properties of the ItchyQoL using classical test theory (CTT) and item response theory (IRT). METHODS: Item characteristic curves were analysed to investigate whether the response categories were functioning optimally. Confirmatory factor analyses were carried out on the ItchyQoL prior to and after rescoring of the response categories. We conducted a Rasch analysis for the ItchyQoL with revised response options and assessed the mean fit residuals in addition to the assumptions of unidimensionality and local independence. RESULTS: In total, 551 patients with CP from nine European countries completed the 22 items of the ItchyQoL. IRT analysis supported the revision of response options from five points to three. This revision was supported by excellent structural validity using CTT. The overall fit to the Rasch model was adequate. Unidimensionality was supported by the ItchyQoL overall scale and by the single subscales; however, local independence was violated in eight cases. CONCLUSIONS: We suggest a revision of the response categories of the ItchyQoL from a 5-point to a 3-point scale. When this revision was applied, the ItchyQoL showed excellent structural validity according to CTT and IRT/Rasch. The calculation of an overall ItchyQoL sum score is allowed.
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Medición de Resultados Informados por el Paciente , Calidad de Vida , Humanos , Psicometría , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
BACKGROUND: Defecation is a complex process and up to 25% of the population suffer from symptoms of defecatory dysfunction. For functional testing, diagnostics, and therapy of anorectal disorders, it is important to know the optimal defecation position. is The aim of this study was to evaluate defecation pressure patterns in side lying, seated and squatting defecation positions in normal subjects using a simulated stool device called Fecobionics. METHODS: The Fecobionics expulsion parameters were assessed in an interventional study design conducted from May 29 to December 9 2019. Subjects were invited to participate in the study through advertisement at The Chinese University of Hong Kong. The Fecobionics device consisted of a core containing pressure sensors at the front (caudal end) and rear (cranial end) and a polyester-urethane bag spanning most of the core length which also contained sensors. The Fecobionics bag was distended to 50 ml in the rectum of normal subjects (no present and past symptoms of defecatory disorders, no prior abdominal surgery, medication or chronic diseases). Studies were done in side lying (left lateral recumbent position), seated (hip flexed 90°) and squatting position (hip flexed 25°). Pressure endpoints including the rear-front pressure diagram and defecation indices were compared between positions. RESULTS: Twelve subjects (6 females/6 males, mean age 26.3 ± 2.6 [19.0-48.0] years) were included and underwent the planned procedures. The resting anal pressure for side lying and seated positions were 33.1 ± 4.1 cmH2O and 37.1 ± 4.0 cmH2O (p > 0.3). The anal squeeze pressure for side lying and seated positions were 98.4 ± 6.9 cmH2O and 142.3 ± 16.4 cmH2O (p < 0.05). The expulsion duration for the side lying, seated and squatting positions were 108.9 ± 8.3 s, 15.0 ± 2.1 s and 16.1 ± 2.9 s, respectively (p < 0.01 between lying and the two other positions). The maximum evacuation pressure for seated and squatting were 130.1 ± 12.4 cmH2O and 134.0 ± 11.1 cmH2O (p > 0.5). Rear-front pressure diagrams and distensibility indices demonstrated distinct differences in pressure patterns between the side lying position group and the other positions. CONCLUSIONS: The delay in expelling the Fecobionics device in the lying position was associated with dyssynergic pressure patterns on the device. Quantitative differences were not found between the seated and squatting position. Trial Registration http://www.clinicaltrials.gov Identifier: NCT03317938.
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Estreñimiento , Enfermedades del Recto , Adulto , Canal Anal , Defecación , Femenino , Humanos , Masculino , Manometría , Recto , Adulto JovenRESUMEN
Objective: To investigate the safety and short-term efficacy of domestic magnetic resonance-guided laser interstitial thermotherapy (MRgLITT) in the treatment of drug-resistant epilepsy. Methods: Patients with drug-resistant epilepsy treated with a domestic MRgLITT system in the Department of Neurosurgery, Xuanwu Hospital, Capital Medical University from October 2020 to April 2021 were prospectively enrolled. The damage volume ratio was assessed immediately after surgery, and perioperative complications were recorded and followed up. The clinical safety and short-term efficacy were evaluated using the Engel classification. Results: A total of 22 patients were included, including 12 males and 10 females, aged from 3 to 45 years old [(24±13) years]. There were 5 cases of medial temporal lobe epilepsy (MTLE), 3 cases of hypothalamic hamartoma (HH), 7 cases of focal cortical dysplasia (FCD), and 7 cases of other types, respectively. The mean operation time and blood loss was (173±49) min and (3.7±1.6) ml. The postoperative length of hospital stay was (5.5±1.8) days, and the average damage volume ratio was 92.6%. Among them, only 2 patients (FCD of the parietal lobe) showed transient contralateral limb weakness, without any serious complications such as symptomatic intracranial hemorrhage and cerebral infarction. The follow-up time was 14 to 168 days. There were 13 Engel class â cases (59.1%), 2 Engel class â ¡ cases (9.1%), 2 Engel class â ¢ cases (9.1%) and 5 Engel class â £ cases (22.7%), respectively. Short-term incident-free rates were MTLE 5/5and FCD4/7, respectively. Conclusion: Domestic MRgLITT system is stable, reliable and safe in the treatment of drug-refractory epilepsy, and has better short-term efficacy in MTLE and FCD patients.
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Epilepsia Refractaria , Hipertermia Inducida , Terapia por Láser , Preparaciones Farmacéuticas , Adolescente , Adulto , Niño , Preescolar , Epilepsia Refractaria/cirugía , Femenino , Humanos , Rayos Láser , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of hepatocellular carcinoma (HCC) was published in 2018, and covered the diagnosis, management, treatment and follow-up of early, intermediate and advanced disease. At the ESMO Asia Meeting in November 2018 it was decided by both the ESMO and the Taiwan Oncology Society (TOS) to convene a special guidelines meeting immediately after the Taiwan Joint Cancer Conference (TJCC) in May 2019 in Taipei. The aim was to adapt the ESMO 2018 guidelines to take into account both the ethnic and the geographic differences in practice associated with the treatment of HCC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with intermediate and advanced/relapsed HCC representing the oncology societies of Taiwan (TOS), China (CSCO), India (ISMPO) Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Singapore (SSO). The voting was based on scientific evidence, and was independent of the current treatment practices, the drug availability and reimbursement situations in the individual participating Asian countries.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Asia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , China , Humanos , India , Japón , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Malasia , Oncología Médica , República de Corea , TaiwánRESUMEN
Although testing is widely regarded as critical to fighting the COVID-19 pandemic, what measure and level of testing best reflects successful infection control remains unresolved. Our aim was to compare the sensitivity of two testing metrics - population testing number and testing coverage - to population mortality outcomes and identify a benchmark for testing adequacy. We aggregated publicly available data through 12 April on testing and outcomes related to COVID-19 across 36 OECD (Organization for Economic Development) countries and Taiwan. Spearman correlation coefficients were calculated between the aforementioned metrics and following outcome measures: deaths per 1 million people, case fatality rate and case proportion of critical illness. Fractional polynomials were used to generate scatter plots to model the relationship between the testing metrics and outcomes. We found that testing coverage, but not population testing number, was highly correlated with population mortality (rs = -0.79, P = 5.975 × 10-9vs. rs = -0.3, P = 0.05) and case fatality rate (rs = -0.67, P = 9.067 × 10-6vs. rs = -0.21, P = 0.20). A testing coverage threshold of 15-45 signified adequate testing: below 15, testing coverage was associated with exponentially increasing population mortality; above 45, increased testing did not yield significant incremental mortality benefit. Taken together, testing coverage was better than population testing number in explaining country performance and can serve as an early and sensitive indicator of testing adequacy and disease burden.
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Prueba de COVID-19/estadística & datos numéricos , COVID-19/epidemiología , COVID-19/mortalidad , Salud Global , Organización para la Cooperación y el Desarrollo Económico/estadística & datos numéricos , SARS-CoV-2 , HumanosRESUMEN
Lactococcosis [Lactococcus garvieae (LG)] is one of the most prevalent bacterial diseases affecting grey mullet (Mugil cephalus) aquaculture. Therefore, the present research evaluated the efficacy of formalin-killed LG vaccine with an oil-based adjuvant in grey mullet under laboratory and field trials. The laboratory evaluation for LG vaccine and its cross-protection upon challenge in grey mullet found that single-dose immunization of formalin-killed LG with adjuvant resulted in 91.4% and 100% relative per cent survival (RPS) when challenged with homologous and heterologous strains. The levels of specific antibody titre and lysozyme activity increased significantly in the vaccinated group. Immune gene expression at 24 hr after challenge showed an increase in levels of pro-inflammatory and anti-inflammatory cytokines. A parallel field trial experiment was conducted to investigate the long-term effectiveness of the LG vaccine. Results demonstrated that at one month and three months post-immunization with heterologous strain, 100% RPS was recorded in the vaccinated group. The findings suggested that the formalin-inactivated LG vaccine strain (S3) protected grey mullet against LG infection for a period of three months.
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Vacunas Bacterianas/inmunología , Enfermedades de los Peces/prevención & control , Infecciones por Bacterias Grampositivas/veterinaria , Lactococcus/inmunología , Smegmamorpha/inmunología , Adyuvantes Inmunológicos/farmacología , Animales , Acuicultura , Vacunas Bacterianas/farmacología , Enfermedades de los Peces/inmunología , Infecciones por Bacterias Grampositivas/inmunología , Infecciones por Bacterias Grampositivas/prevención & control , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/farmacologíaRESUMEN
BACKGROUND: Candidaemia is associated with high mortality. Variables associated with mortality have been published previously, but not developed into a risk predictive model for mortality. We sought to describe the current epidemiology of candidaemia in Australia, analyse predictors of 30-day all-cause mortality, and develop and validate a mortality risk predictive model. METHODS: Adults with candidaemia were studied prospectively over 12 months at eight institutions. Clinical and laboratory variables at time of blood culture-positivity were subject to multivariate analysis for association with 30-day all-cause mortality. A predictive score for mortality was examined by area under receiver operator characteristic curves and a historical data set was used for validation. RESULTS: The median age of 133 patients with candidaemia was 62 years; 76 (57%) were male and 57 (43%) were female. Co-morbidities included underlying haematologic malignancy (n = 20; 15%), and solid organ malignancy in (n = 25; 19%); 55 (41%) were in an intensive care unit (ICU). Non-albicans Candida spp. accounted for 61% of cases (81/133). All-cause 30-day mortality was 31%. A gastrointestinal or unknown source was associated with higher overall mortality than an intravascular or urologic source (p < 0.01). A risk predictive score based on age > 65 years, ICU admission, chronic organ dysfunction, preceding surgery within 30 days, haematological malignancy, source of candidaemia and antibiotic therapy for ≥10 days stratified patients into < 20% or ≥ 20% predicted mortality. The model retained accuracy when validated against a historical dataset (n = 741). CONCLUSIONS: Mortality in patients with candidaemia remains high. A simple mortality risk predictive score stratifying patients with candidaemia into < 20% and ≥ 20% 30-day mortality is presented. This model uses information available at time of candidaemia diagnosis is easy to incorporate into decision support systems. Further validation of this model is warranted.
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Candidemia/mortalidad , Anciano , Antifúngicos/uso terapéutico , Australia/epidemiología , Candida/clasificación , Candida/genética , Candida/aislamiento & purificación , Candidemia/tratamiento farmacológico , Candidemia/epidemiología , Candidemia/microbiología , Femenino , Neoplasias Hematológicas/complicaciones , Hospitalización/estadística & datos numéricos , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Factores de RiesgoRESUMEN
BACKGROUND: Chronic pruritus (CP) is a frequently occurring symptom in inflammatory dermatoses, causing a high burden and limitations to health-related quality of life (HRQoL). OBJECTIVE: The ItchyQoL was developed to assess the impairment to HRQoL in patients with CP. However, it has only been validated in English and German. Here, we report the validation in several languages across Europe. METHODS: After professional translation, the versions of ItchyQoL were digitized for use as a tablet application. Validation was performed in clinics for dermatology in Austria, France, Germany, Italy, Poland, Russia, Spain, Switzerland and Turkey. RESULTS: Five hundred and thirty-five patients with either contact dermatitis, chronic prurigo - nodular type, psoriasis vulgaris, lichen planus or mycosis fungoides/Sézary syndrome and with CP ≥ 3 on the numerical rating scale were included. ItchyQoL showed a high level of consistency (Cronbach's-α, all: 0.95) and test-retest reliability (intraclass correlation: 0.91). It strongly correlated with the Dermatology Life Quality Index (r = 0.72, P < 0.001) and moderately correlated with itch intensity scales in the study population (visual analogue scale r = 0.46; numerical rating scale r = 0.51; verbal rating scale r = 0.51, for all: P < 0.001). CONCLUSION: ItchyQoL is now also validated in French, Italian, Polish, Russian, Spanish and Turkish and can be used in clinical trials in countries speaking these languages.
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Prurito/diagnóstico , Prurito/psicología , Calidad de Vida/psicología , Enfermedades de la Piel/patología , Enfermedades de la Piel/psicología , Adulto , Anciano , Estudios Transversales , Europa (Continente) , Femenino , Humanos , Cooperación Internacional , Masculino , Persona de Mediana Edad , Psicometría , Medición de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
A mechanical approach is needed for understanding anorectal function and defecation. Fecal continence is achieved by several interacting mechanisms including anatomical factors, anorectal sensation, rectal compliance, stool consistency, anal muscle strength, motility, and psychological factors. The balance is easily disturbed, resulting in symptoms such as fecal incontinence and constipation. Novel technologies have been developed in recent years for studying anorectal function. Especially, the Fecobionics device, a simulated feces, has gained attention recently. This facilitates new analysis of anorectal mechanical function. In this study, a theoretical model is developed to analyze anorectal mechanophysiological data generated by the Fecobionics device. Theoretical approaches can enhance future interdisciplinary research for unraveling defecatory function, sensory-motor disorders, and symptoms. This is a step in the direction of personalized treatment for gastrointestinal disorders based on optimized subtyping of anorectal disorders.
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A total of 1 685 school-age children selected from Hangzhou received lung function testing to evaluate the short-term effects of air pollution on their lung function. The results showed that in every 10 µg/m(3) increase of average concentration of PM(2.5) and PM(10) on the day of the test and the day before the test,peak expiratory flow (PEF) decreased 0.039 (95%CI: 0.012-0.067) L/s and 0.031 (95% CI:0.011-0.051) L/s,respectively. When the average concentration of SO(2) increased 10 µg/m(3) on the day of test and the day prior to the test, PEF and 75% of the forced vital capacity that has not been exhaled (MEF(75)) decreased 0.437 (95%CI: 0.217-0.658) L/s and 0.396 (95%CI: 0.180-0.613) L/s. After being adjusted for NO(2),with every 10 µg/m(3) increase of average concentration of PM(2.5) and PM(10) on the day of the test and the day before the test,PEF and MEF(75) decreased 0.056 (95%CI: 0.028-0.085), 0.053(95%CI: 0.027-0.081) and 0.047 (95%CI: 0.026-0.068) L/s,0.044 (95%CI: 0.023-0.065) L/s on the day before the test, respectively. The results indicate that air pollution have short-term and lag effects on lung function of school-age children in Hangzhou.
Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Pulmón , Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/efectos adversos , Niño , China , Humanos , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Material Particulado , Pruebas de Función Respiratoria , Capacidad VitalRESUMEN
Objective: Comparison of the permeability between the rabbit cornea and sclera ex vivo by determining the concentration of gatifloxacin using LC-MS/MS method, which may provide the basis for a new route of drug administration. Methods: Experimental study. The permeability of the cornea and sclera in healthy male New Zealand rabbits was evaluated by using Franz diffusion pool. We chose both gatifloxacin ophthalmic solution and gel as the test drugs, and calculated the cumulative permeation amounts (Qn), apparent permeability coefficient(P(app)). Results: The linear range of gatifloxacin was 5-1 000 ng/ml. The intra-day and inter-day precision was 1.7% -2.8% and 1.0% - 2.3%. Q(n) and P(app) of gatifloxacin ophthalmic solution in cornea and sclera ex vivo were 177.57, 517.52 µg/cm(2) and 4.34, 12.51 cm/s respectively, whereas that of gatifloxacin ophthalmic gel were 151.87, 411.05 µg/cm(2) and 3.66, 9.21 cm/s. Conclusion: This validated method could be applied to determine the gatifloxacin. The cumulative permeation amounts and apparent permeability coefficient of sclera are significantly higher than that of cornea for both ophthalmic solution and gel, suggesting that the development of a new route of drug administration based on sclera may have potential advantage. (Chin J Ophthalmol, 2019, 55: 928-932).