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1.
Gels ; 9(10)2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37888372

RESUMO

The purpose of the current study was to prepare and evaluate a citronella oil-loaded microemulsion-based micro-emulgel for the treatment of Candida albicans. The primary objective was to use the skin to transfer hydrophobic medications into the bloodstream. The formulation included cinnamon oil as an antifungal oil and citronella oil as an active pharmaceutical ingredient, respectively. Tween 80 and PEG 200 were used as the surfactant and co-surfactant, respectively, to create phase diagrams. Carbopol 940, one of the frequently used polymers, was investigated for its ability to prepare gel formulations. The optimized (F3) batch contained the highest percentage (87.05 ± 0.03%) of drug content and, according to the statistics provided, had the highest drug release rate of around 87.05% within 4 h. The Korsmeyer-Peppas model with n value of 0.82, which is in the range 0.5-1, had the highest r2 value, indicating that release following non-Fickian/anomalous diffusion provided a better dimension for all of the formulations. The optimized (F3) formulation had stronger antifungal activity in comparison to other formulations. This leads to the conclusion that citronella oil can be made into a micro-emulgel, which may improve its release in aqueous systems while maintaining a high level of drug release at the target site.

2.
Future Oncol ; 19(38): 2505-2516, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37671641

RESUMO

WHAT IS THIS SUMMARY ABOUT?: This is a summary of results from a phase 3 clinical study called HIMALAYA. HIMALAYA looked at treatment with one dose of a medication called tremelimumab combined with multiple doses of a medication called durvalumab (the STRIDE regimen) or multiple doses of durvalumab alone. These treatments were compared with a medication called sorafenib in participants with unresectable hepatocellular carcinoma (HCC). HCC is a type of liver cancer that is difficult to treat because it is often diagnosed when it is unresectable, meaning it can no longer be removed with surgery. Sorafenib has been the main treatment for unresectable HCC since 2007. However, people who take sorafenib may experience side effects that can reduce their quality of life, so alternative medicines are being trialed. Tremelimumab and durvalumab are types of drugs called immunotherapies, and they both work in different ways to help the body's immune system fight cancer. WHAT WERE THE RESULTS OF THE STUDY?: Participants who took STRIDE lived longer than participants who took sorafenib, whilst participants who took durvalumab alone lived a similar length of time as participants who took sorafenib. Participants who took STRIDE or durvalumab had a lower relative risk of experiencing worsening in their quality of life than participants who took sorafenib. The side effects that participants who received STRIDE or durvalumab experienced were expected for these types of treatments and could mostly be managed. WHAT DO THE RESULTS OF THE STUDY MEAN?: Overall, STRIDE is more effective than sorafenib for people with unresectable HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Sorafenibe/uso terapêutico , Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
3.
J Clin Exp Hepatol ; 13(4): 691-697, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37440936

RESUMO

The liver is well known for its immunotolerance, but rejection without immunosuppression is frequently encountered post liver transplantation, especially in humans.1 Indeed, the amount of immunosuppression required post liver transplant is less compared to other organ transplants like kidney, heart, and intestine.2 Reports of successful weaning of immunosuppression have been reported but are not practiced for fear of unwanted alloimmune response leading to rejection. Life-long immunosuppression is needed in most patients for graft survival but is associated with side effects like renal dysfunction, metabolic abnormalities, or risk of de novo malignancies. Also, the appropriate dose of immunosuppression to achieve adequate graft function and prevention of toxicities is very important. One shoe does not fit all. There are significant individual variations in response and side effect profile. Also, the level of immunosuppression varies with the underlying liver disease like autoimmune disease requires higher immunosuppression. Thus, monitoring the adequate immunosuppression with the minimization of drug toxicity is imperative post-transplant. Unfortunately, the current methods for immunosuppression monitoring rely on testing the immunosuppressive drug levels rather than the immune system activity. We have discussed the concept of alloreactivity, available methods of immunosuppression and drug monitoring and investigational methods in this review.

4.
J Clin Pharmacol ; 63(11): 1221-1231, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37300457

RESUMO

A novel single-dose regimen of 300 mg tremelimumab in combination with durvalumab (STRIDE) has demonstrated a favorable benefit-risk profile in the phase 1/2 Study 22 trial (in patients with unresectable hepatocellular carcinoma, uHCC) and in the phase 3 HIMALAYA study. The current analysis evaluated the population pharmacokinetics (PopPK) of tremelimumab and durvalumab, and the exposure-response (ER) relationship for efficacy and safety of STRIDE in patients with uHCC. Previous PopPK models for tremelimumab and durvalumab were updated using data from previous studies in various cancers combined with data from Study 22 and HIMALAYA. Typical population mean parameters and associated inter- and intra-individual variability were assessed, as was the influence of covariates. Individual exposure metrics were derived from the individual empirical Bayes estimates as drivers for ER analysis related to efficacy and safety from HIMALAYA. The observed pharmacokinetics of tremelimumab in uHCC were well described by a 2-compartment model with both linear and time-dependent clearance. All identified covariates changed tremelimumab PK parameters by <25%, and thus had minimal clinical relevance; similar results were obtained from durvalumab PopPK analysis. None of tremelimumab or durvalumab exposure metrics were significantly associated with overall survival (OS), progression-free survival (PFS), or adverse events. Baseline aspartate aminotransferase and neutrophil-to-lymphocyte ratio (NLR) were associated with OS (P < .001) by the Cox proportional hazards model. No covariate was identified as a significant factor for PFS. No dose adjustment for tremelimumab or durvalumab is needed based on PopPK covariate analyses or ER analyses. Our findings support the novel STRIDE dosing regimen in patients with uHCC.

5.
Health Aff (Millwood) ; 42(3): 424-432, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36877896

RESUMO

The COVID-19 pandemic created a large, sudden unmet public health need for rapid access to safe and effective treatments. Against this backdrop, policy makers and researchers have looked to drug repurposing-using a drug previously approved for one indication to target a new indication-as a means to accelerate the identification and development of COVID-19 treatments. Using detailed data on US clinical trials initiated during the pandemic, we examined the trajectory and sources of drug repurposing initiatives for COVID-19. We found a rapid increase in repurposing efforts at the start of the pandemic, followed by a transition to greater de novo drug development. The drugs tested for repurposing treat a wide range of indications but were typically initially approved for other infectious diseases. Finally, we documented substantial variation by trial sponsor (academic, industry, or government) and generic status: Industry sponsorship for repurposing occurred much less frequently for drugs with generic competitors already on the market. Our findings inform drug repurposing policy for both future emerging diseases and drug development in general.


Assuntos
COVID-19 , Reposicionamento de Medicamentos , Humanos , Pandemias , Desenvolvimento de Medicamentos , Pessoal Administrativo
7.
Basic Clin Pharmacol Toxicol ; 133(4): 295-300, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36585032

RESUMO

An elusive problem in the adhesion G protein-coupled receptor (AGPCR) field is full understanding of the activation mechanisms of the 33-member receptor class. With the recent solution of active-state structures of nearly one quarter of AGPCRs, clarity has been brought to how AGPCRs are activated in response to endogenous full agonists. AGPCRs are self-activated via a tethered peptide agonist (TA) that transitions from a concealed or encrypted location to a decrypted state that binds to a typical GPCR orthosteric binding pocket. Here, we summarize the key milestones that led to the discovery of the AGPCR TA activation mechanism and discuss how extracellular shear forces may initiate TA decryption in physiological contexts. We compare the new active-state AGPCR structures and note that the orthosteric site-engaged TAs adopt a remarkably similar partial α-helical hook-like conformation, despite divergence of overall receptor similarity. Further, we contrast the TA-bound AGPCR structures to a partially active AGPCR structure to highlight the transitions AGPCRs may undergo during activation. Finally, we provide commentary on the validity of alternative AGPCR activation mechanisms.


Assuntos
Peptídeos , Receptores Acoplados a Proteínas G , Adesão Celular , Relação Estrutura-Atividade , Receptores Acoplados a Proteínas G/metabolismo , Domínios e Motivos de Interação entre Proteínas
8.
Indian J Ophthalmol ; 70(10): 3710-3712, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36190079

RESUMO

A 32-year-old male with no known systemic illness presented with unilateral Purtscher-like retinopathy in his left eye 2 weeks after recovering from a severe COVID-19 infection. Fundus examination revealed areas of intraretinal whitening and few cotton wool spots. Multimodal imaging findings were consistent with embolic occlusion of capillaries seen in Purtscher-like retinopathy. The case highlights the effect of virus-directed coagulation cascade activation leading to unilateral microvasculopathy in our patient. The case adds to the spectrum of COVID-19 retinopathy and presses that retina screening strategies should be established for patients suffering from or recovering from severe COVID-19 infection.


Assuntos
COVID-19 , Papiledema , Doenças Retinianas , Adulto , COVID-19/complicações , Angiofluoresceinografia/métodos , Fundo de Olho , Humanos , Masculino , Doenças Retinianas/diagnóstico , Doenças Retinianas/etiologia
9.
JMIR Res Protoc ; 11(8): e36741, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36006689

RESUMO

BACKGROUND: Heart failure (HF) is a prevalent chronic disease and is associated with increases in mortality and morbidity. HF is a leading cause of hospitalizations and readmissions in the United States. A potentially promising area for preventing HF readmissions is continuous remote patient monitoring (CRPM). OBJECTIVE: The primary aim of this study is to determine the feasibility and preliminary efficacy of a CRPM solution in patients with HF at NorthShore University HealthSystem. METHODS: This study is a feasibility study and uses a wearable biosensor to continuously remotely monitor patients with HF for 30 days after discharge. Eligible patients admitted with an HF exacerbation at NorthShore University HealthSystem are being recruited, and the wearable biosensor is placed before discharge. The biosensor collects physiological ambulatory data, which are analyzed for signs of patient deterioration. Participants are also completing a daily survey through a dedicated study smartphone. If prespecified criteria from the physiological data and survey results are met, a notification is triggered, and a predetermined electronic health record-based pathway of telephonic management is completed. In phase 1, which has already been completed, 5 patients were enrolled and monitored for 30 days after discharge. The results of phase 1 were analyzed, and modifications to the program were made to optimize it. After analysis of the phase 1 results, 15 patients are being enrolled for phase 2, which is a calibration and testing period to enable further adjustments to be made. After phase 2, we will enroll 45 patients for phase 3. The combined results of phases 1, 2, and 3 will be analyzed to determine the feasibility of a CRPM program in patients with HF. Semistructured interviews are being conducted with key stakeholders, including patients, and these results will be analyzed using the affective adaptation of the technology acceptance model. RESULTS: During phase 1, of the 5 patients, 2 (40%) were readmitted during the study period. The study completion rate for phase 1 was 80% (4/5), and the study attrition rate was 20% (1/5). There were 57 protocol deviations out of 150 patient days in phase 1 of the study. The results of phase 1 were analyzed, and the study protocol was adjusted to optimize it for phases 2 and 3. Phase 2 and phase 3 results will be available by the end of 2022. CONCLUSIONS: A CRPM program may offer a low-risk solution to improve care of patients with HF after hospital discharge and may help to decrease readmission of patients with HF to the hospital. This protocol may also lay the groundwork for the use of CRPM solutions in other groups of patients considered to be at high risk. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36741.

10.
Comput Intell Neurosci ; 2022: 3675821, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35795743

RESUMO

According to OWASP 2021, cross-site scripting (XSS) attacks are increasing through specially crafted XML documents. The attacker injects a malicious payload with a new pattern and combination of scripts, functions, and tags that deceits the existing security mechanisms in web services. This paper proposes an approach, GeneMiner, encompassing GeneMiner-E to extract new features and GeneMiner-C for classification of input payloads as malicious and nonmalicious. The proposed approach evolves itself to the changing patterns of attack payloads and identifies adversarial XSS attacks. The experiments have been conducted by collecting data from open source and generating various combinations of scripts, functions, and tags using an incremental genetic algorithm. The experimental results show that the proposed approach effectively detects newly crafted malicious XSS payloads with an accuracy of 98.5%, which is better than the existing classification techniques. The approach learns variations in the existing attack sample space and identifies the new attack payloads with reduced efforts.


Assuntos
Algoritmos , Segurança Computacional
11.
Indian J Ophthalmol ; 70(4): 1412-1415, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35326069

RESUMO

The coagulation abnormalities and thromboembolic complications of coronavirus 2 (SARS-CoV-2) are now a well-established fact. The hypercoagulable state, the tendency for thromboembolism, and a cytokine surge state have been the exclusive reasons for multiorgan failure and other morbidities that have been regularly reported in COVID-19 patients. Ocular involvement in patients with active disease and those who have recovered is uncommon but not rare. We report a case series of four patients with CRVO, BRVO, CRAO, and vitreous hemorrhage in patients with proven COVID-19 infection and no other systemic ailments. The case series also tries to correlate the elevated D-dimer values, which signify a plausible prothrombotic state with the vaso-occlusive phenomenon in the retina leading to significant visual morbidity.


Assuntos
COVID-19 , Oclusão da Veia Retiniana , COVID-19/complicações , Humanos , Retina , Oclusão da Veia Retiniana/complicações , SARS-CoV-2
13.
Retin Cases Brief Rep ; 16(6): 793-798, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33181802

RESUMO

PURPOSE: To study the efficacy of swept source optical coherence tomography angiography (SSOCTA) to longitudinally follow-up patients with extrafoveal polyps post-laser photocoagulation and anti-vascular endothelial growth factor injection. METHODS: Observational case series. Four patients diagnosed as polypoidal choroidal vasculopathy with extrafoveal polyps on multimodal imaging were followed up serially on SSOCT, en face and cross-sectional SSOCTA at a month and then 3 monthly for a year. Indocyanine green angiography was repeated at 4 months and 1 year. RESULTS: Anatomical regression of extrafoveal polyps was documented on a combination of en face and cross-sectional SSOCTA, 3 months post-laser photocoagulation and anti-vascular endothelial growth factor. Regression of polyps was maintained at the 12-month follow-up visit in all cases. Changes in branching vascular network morphology post-treatment were well-delineated on en face SSOCTA. Swept source optical coherence tomography angiography findings correlated well with the gold standard indocyanine green angiography. CONCLUSION: Swept source optical coherence tomography angiography is an effective noninvasive imaging modality to diagnose and longitudinally follow-up extrafoveal polyps postintervention. Laser photocoagulation with anti-vascular endothelial growth factor achieved regression of polyps in all cases and this was maintained over 12 months.


Assuntos
Neovascularização de Coroide , Pólipos , Humanos , Corioide/patologia , Neovascularização de Coroide/diagnóstico , Estudos Transversais , Angiofluoresceinografia/métodos , Verde de Indocianina , Pólipos/diagnóstico , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
14.
Appl Clin Inform ; 12(5): 1161-1173, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34965606

RESUMO

OBJECTIVE: We report on our experience of deploying a continuous remote patient monitoring (CRPM) study soft launch with structured cascading and escalation pathways on heart failure (HF) patients post-discharge. The lessons learned from the soft launch are used to modify and fine-tune the workflow process and study protocol. METHODS: This soft launch was conducted at NorthShore University HealthSystem's Evanston Hospital from December 2020 to March 2021. Patients were provided with non-invasive wearable biosensors that continuously collect ambulatory physiological data, and a study phone that collects patient-reported outcomes. The physiological data are analyzed by machine learning algorithms, potentially identifying physiological perturbation in HF patients. Alerts from this algorithm may be cascaded with other patient status data to inform home health nurses' (HHNs') management via a structured protocol. HHNs review the monitoring platform daily. If the patient's status meets specific criteria, HHNs perform assessments and escalate patient cases to the HF team for further guidance on early intervention. RESULTS: We enrolled five patients into the soft launch. Four participants adhered to study activities. Two out of five patients were readmitted, one due to HF, one due to infection. Observed miscommunication and protocol gaps were noted for protocol amendment. The study team adopted an organizational development method from change management theory to reconfigure the study protocol. CONCLUSION: We sought to automate the monitoring aspects of post-discharge care by aligning a new technology that generates streaming data from a wearable device with a complex, multi-provider workflow into a novel protocol using iterative design, implementation, and evaluation methods to monitor post-discharge HF patients. CRPM with structured escalation and telemonitoring protocol shows potential to maintain patients in their home environment and reduce HF-related readmissions. Our results suggest that further education to engage and empower frontline workers using advanced technology is essential to scale up the approach.


Assuntos
Assistência ao Convalescente , Insuficiência Cardíaca , Insuficiência Cardíaca/diagnóstico , Ambiente Domiciliar , Humanos , Monitorização Fisiológica , Alta do Paciente , Estudos Prospectivos
16.
J Indian Prosthodont Soc ; 21(2): 116-124, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33938861

RESUMO

Aim: Early crestal bone loss (ECBL) has been observed regardless of the absence of possible etiologic factors for bone loss during the healing phase and before the second-stage implant surgery. The purpose of this systematic review and meta-analysis was to correlate the possible association of interleukin-1 (IL-1) gene polymorphisms and ECBL (bone loss before the second-stage surgery) around dental implants. Settings and Design: Systematic review and meta-analysis following PRISMA guidelines. Materials and Methods: Considering the inclusion criteria, an electronic search by using specific keywords of three databases PubMed [("Dental" OR "oral") AND ("Implants*") AND ("gene polymorphism" OR "genotype" AND ("IL-1" OR "interleukins")], Cochrane library [implant AND (biomarker or cytokine), interleukin-1 or IL-1 AND implants], and EMBASE [("gene polymorphisms"/de OR "interleukins"/cytokine exp OR "biomarker":ti,ab,kw) AND ("dental implantation"/de OR "oral implant")] and manual search from 1995 till March 2020 was made by 2 independently calibrated reviewers. ACROBAT-NRSI, Version 1.0.0 and Review Manager, Version 5.3, computer software were used for the risk of bias assessment and to conduct the meta-analysis respectively. Statistical Analysis Used: Cochran's Q test and I2 statistics. Results: Of 38 articles which were found eligible for full-text screening, two articles fulfilled the inclusion criteria and hence were included in the meta-analysis. The I2 statistic and Q-test values of the included studies revealed acceptable homogeneity for studied three IL-1 gene polymorphisms (IL-1A-889: I2 = 0%, IL-1B - 511: I2 = 0%, IL-1B+3954: I2 = 24%). Forest plot of association between IL-1B-511 gene and ECBL revealed a significant association between 2/2 genotype of IL-1B-511 gene and an increased risk of ECBL (OR = 0.23, 95% CI = 0.09-0.58, Pheterogeneity = 0.68, I2 = 0%, and P = 0.002). Results of the IL-1A-889 and IL-1B+3954 gene revealed no significant associations between any genotype of these genes with risk of ECBL. Conclusions: There is an evidence of the association of IL-1B-511 (2/2) genetic polymorphisms and increased ECBL in the individuals of Asian ethnicity (OR = 0.23, P = 0.002).


Assuntos
Perda do Osso Alveolar , Implantes Dentários , Implantes Dentários/efeitos adversos , Genótipo , Humanos , Interleucinas , Polimorfismo Genético
17.
Kidney Int Rep ; 6(4): 995-1002, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33912749

RESUMO

INTRODUCTION: Rabbit antithymocyte globulin (rATG) dosing strategies for induction in pediatric kidney transplantation vary between centers. It is not known whether a lower rATG induction dose provides safe and effective immunosuppression compared with a "standard" higher dose. METHODS: We performed a retrospective multicenter study of all isolated first-time kidney transplant recipients <21 years old who received rATG induction between 1 January 2010 and 31 December 2014 at 9 pediatric centers. An a priori cutoff of a 4.5-mg/kg cumulative rATG dose was used to identify low (≤ 4.5 mg/kg) and standard (> 4.5 mg/kg) exposure groups. Outcomes examined included 12 months posttransplant graft function (estimated glomerular filtration rate [eGFR]); the occurrence of acute rejection, donor-specific antibody (DSA), neutropenia, and viral infection (cytomegalovirus [CMV], Epstein-Barr virus [EBV], and BK virus); and 24-month outcomes of posttransplant lymphoproliferative disorder (PTLD) occurrence and patient and graft survival. RESULTS: Two hundred thirty-five patients were included. Baseline features of the low and standard rATG dose groups were similar. By 12 months, the rATG dose group had no significant impact on the occurrence of neutropenia, positive DSA, or viral polymerase chain reaction (PCR). Graft function was similar. Acute rejection rates were similar at 17% (low dose) versus 19% (standard dose) (P = 0.13). By 24 months, graft survival (96.4% vs. 94.6%) and patient survival (100% vs. 99.3%) were similar between the low- and standard-dose groups (P = 0.54 and 0.46), whereas the occurrence of PTLD trended higher in the standard-dose group (0% vs. 2.6%, P = 0.07). CONCLUSION: A low rATG induction dose ≤ 4.5 mg/kg provided safe and effective outcomes in this multicenter low immunologic risk pediatric cohort. Prospective studies are warranted to define the optimal rATG induction dose in pediatric kidney transplantation.

18.
New Gener Comput ; 39(3-4): 583-597, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33642663

RESUMO

COVID-19 (also known as SARS-COV-2) pandemic has spread in the entire world. It is a contagious disease that easily spreads from one person in direct contact to another, classified by experts in five categories: asymptomatic, mild, moderate, severe, and critical. Already more than 66 million people got infected worldwide with more than 22 million active patients as of 5 December 2020 and the rate is accelerating. More than 1.5 million patients (approximately 2.5% of total reported cases) across the world lost their life. In many places, the COVID-19 detection takes place through reverse transcription polymerase chain reaction (RT-PCR) tests which may take longer than 48 h. This is one major reason of its severity and rapid spread. We propose in this paper a two-phase X-ray image classification called XCOVNet for early COVID-19 detection using convolutional neural Networks model. XCOVNet detects COVID-19 infections in chest X-ray patient images in two phases. The first phase pre-processes a dataset of 392 chest X-ray images of which half are COVID-19 positive and half are negative. The second phase trains and tunes the neural network model to achieve a 98.44% accuracy in patient classification.

19.
J Crohns Colitis ; 15(6): 938-949, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-33599720

RESUMO

BACKGROUND AND AIMS: Ontamalimab, a fully-human monoclonal antibody targeting MAdCAM-1, induced remission in patients with moderate-to-severe ulcerative colitis [UC] in the TURANDOT study. We aimed to assess long-term safety, tolerability, and efficacy of ontamalimab in TURANDOT II. METHODS: TURANDOT II was a phase 2, multicentre, open-label [OL] study in patients with moderate-to-severe UC who completed TURANDOT on placebo or ontamalimab (NCT01771809). Patients were randomised to 75 mg or 225 mg ontamalimab every 4 weeks for 72 weeks [OL1]. The dosage could be increased to 225 mg from Week 8 at the investigator's discretion. All patients then received 75 mg every 4 weeks for 72 weeks [OL2], followed by 6-month safety follow-up. The primary objective was safety, measured by adverse events [AEs], serious AEs [SAEs], and AEs leading to withdrawal. Mucosal healing [MH; centrally read endoscopy] was assessed. RESULTS: Of 330 patients, 180 completed OL1; 94 escalated to 225 mg; 127 completed OL2. Overall, 36.1% experienced drug-related AEs. The most common SAE [10.0%] was worsening/ongoing UC; 5.5% of patients had serious infections, the most common being gastroenteritis [0.9%]. One death and four cancers [all unrelated to ontamalimab] occurred. No PML [progressive multifocal leukoencephalopathy]/lymphoproliferative disorders occurred. Geometric mean high-sensitivity C-reactive protein [hsCRP] and faecal calprotectin decreased across OL1 in both dose groups. The proportion of patients assigned to placebo in TURANDOT achieving MH increased from 8.8% [6/68] at baseline to 35.3% at Week 16 [24/68; non-responder imputation]. The corresponding increase in the ontamalimab group was from 23.3% [61/262] to 26.7% [70/262]. CONCLUSIONS: Ontamalimab was well tolerated up to 144 weeks in patients with moderate-to-severe UC, with good safety and efficacy.


Assuntos
Anticorpos Monoclonais Humanizados , Moléculas de Adesão Celular/antagonistas & inibidores , Colite Ulcerativa , Monitoramento de Medicamentos , Mucoproteínas/antagonistas & inibidores , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Proteína C-Reativa/análise , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/imunologia , Relação Dose-Resposta Imunológica , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/estatística & dados numéricos , Endoscopia Gastrointestinal/métodos , Endoscopia Gastrointestinal/estatística & dados numéricos , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/efeitos adversos , Humanos , Complexo Antígeno L1 Leucocitário/análise , Masculino , Resultado do Tratamento
20.
Nutrition ; 84: 111099, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33476997

RESUMO

OBJECTIVES: Malnutrition is predictor of morbidity and mortality in patients with cirrhosis. We investigated prevalence of malnutrition and factors affecting dietary intake in patients with cirrhosis. METHODS: Single-center cross-sectional observational study. A total of 251 patients with cirrhosis underwent dietary and nutritional assessment by subjective global assessment (SGA) and anthropometric measurement (dry body mass index, midarm circumference, midarm muscle circumference, triceps skinfold thickness, handgrip strength). Dietary intake was assessed in terms of total calories and protein intake, percentage of recommended intake, and per kilogram body weight per day. Factors influencing dietary intake were also assessed. RESULTS: Of 251 patients 199 (79%) were male and 52 (21%) were female (mean age, 51 ± 14 y, Child's A:B:C: 83:116:52). In SGA analysis 87 (35%) were well nourished (SGA-A), 106 (42%) were moderately nourished (SGA-B), and 58 (23%) were severely malnourished (SGA-C). Patients with Child's C score were severely malnourished compared with patients with Child's B and A scores. Midarm circumference, midarm muscle circumference, triceps skinfold thickness, and handgrip strength were significantly higher in SGA-A than SGA-B and SGA-C. Patients in SGA-A (1939 ± 479 kcal/d) consumed significantly higher calories than SGA-B (1494 ± 216 kcal/d) and SGA-C (1321 ± 213 kcal/d). Percentage of recommended calories intake (SGA-A [76%], SGA-B [61%], SGA-C [59%], P = 0.001) and calories/kg/d is also higher in SGA-A than SGA-B and SGA-C. The results with protein intake were similar (SGA-A [61 ± 14 gm/d], SGA-B [56 ± 7 gm/d], SGA-C [51 ± 9 gm/d], P = 0.001). Protein intake in g/kg/d is significantly lower in SGA-C (0.76 ± 0.22) than SGA-B (0.85 ± 0.2) and SGA-A (0.93 ± 0.2). A total of 61% patients were vegetarian, and 84% did not take evening snacks. Poor appetite (n = 68, 27%), early satiety (n = 75, 30%), abdominal fullness (n = 62, 25%), low-salt diet (n = 52, 21%), and social myth about diet 43(17%) were the common reasons for poor intake. Distension of abdomen, social myth about diet, and low sodium in diet were key factors affecting dietary intake in patients with cirrhosis and malnutrition. CONCLUSIONS: Malnutrition seen in 65% of patients. Total calories and protein intake was significantly low compared with recommendation even in well-nourished patients. Distension of abdomen, social myth about diet, and low sodium in diet were key factors affecting dietary intake in patients with cirrhosis and malnutrition.


Assuntos
Desnutrição , Avaliação Nutricional , Adulto , Idoso , Índice de Massa Corporal , Criança , Estudos Transversais , Ingestão de Alimentos , Feminino , Força da Mão , Humanos , Cirrose Hepática/complicações , Masculino , Desnutrição/epidemiologia , Desnutrição/etiologia , Pessoa de Meia-Idade , Estado Nutricional
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