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Background: Poor discharge planning can lead to increases in adverse drug events, hospital readmissions, and costs. Prior research has identified the pharmacist as an integral part of the discharge process. Objectives: To gain patients' perspectives on the discharge process and what they would like pharmacists to do to ensure a successful discharge. Methods: Twenty patients discharged from tertiary care hospitals were interviewed after discharge. A phenomenological approach was used to conduct this qualitative study. Results: Five main themes were identified from the patient interviews: interactions with health care professionals, importance of discharge documentation, importance of seamless care, comprehensive and patient-specific medication counselling, and patients' preference for involvement and communication at all stages of hospital stay. Conclusions: Although participants generally reported positive interactions with health care providers at discharge, several areas for improvement were identified, particularly in terms of communication, discharge documentation, and continuity of care. A list of recommendations aligning with patient preferences is provided for clinicians.
Contexte: Une mauvaise planification du congé hospitalier peut entraîner une augmentation des événements indésirables liés aux médicaments, des réadmissions et des coûts. Des recherches antérieures ont reconnu le pharmacien comme faisant partie intégrante du processus associé au congé de l'hôpital. Objectifs: Recueillir le point de vue des patients sur le processus relatif au congé et sur ce qu'ils aimeraient que les pharmaciens fassent pour assurer la réussite de celui-ci. Méthodologie: Vingt patients d'hôpitaux de soins tertiaires ont été interrogés après leur congé. Cette étude qualitative a été menée en adoptant une approche phénoménologique. Résultats: Cinq thèmes principaux ont émergé à partir des entretiens avec les patients: les interactions avec les professionnels de la santé, l'importance de la documentation au moment du congé, l'importance de soins continus, des conseils complets et spécifiques au patient en matière de médication, et la préférence des patients pour l'implication et la communication à toutes les étapes de leur séjour à l'hôpital. Conclusions: Bien que les participants aient généralement signalé des interactions positives avec les prestataires de soins de santé au moment de leur congé, plusieurs domaines d'amélioration ont été dépistés, notamment sur les plans de la communication, de la documentation au moment du congé et de la continuité des soins. Une liste de recommandations alignées sur les préférences des patients est fournie aux cliniciens.
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Localized cutaneous neurofibromas (cNFs) are benign tumors that arise in the dermis of patients affected by neurofibromatosis type 1 syndrome. cNFs are benign lesions: they do not undergo malignant transformation or metastasize. Nevertheless, they can cover a significant proportion of the body, with some individuals developing hundreds to thousands of lesions. cNFs can cause pain, itching, and disfigurement resulting in substantial socio-emotional repercussions. Currently, surgery and laser desiccation are the sole treatment options but may result in scarring and potential regrowth from incomplete removal. To identify effective systemic therapies, we introduce an approach to establish and screen cNF organoids. We optimized conditions to support the ex vivo growth of genomically diverse cNFs. Patient-derived cNF organoids closely recapitulate cellular and molecular features of parental tumors as measured by immunohistopathology, methylation, RNA sequencing, and flow cytometry. Our cNF organoid platform enables rapid screening of hundreds of compounds in a patient- and tumor-specific manner.
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Neurofibroma , Organoides , Neoplasias Cutâneas , Humanos , Organoides/patologia , Neoplasias Cutâneas/patologia , Neurofibroma/patologia , Neurofibroma/cirurgia , Neurofibromatose 1/patologiaRESUMO
PURPOSE: Claudin-6 (CLDN6) is expressed at elevated levels in multiple human cancers including ovarian and endometrial malignancies, with little or no detectable expression in normal adult tissue. This expression profile makes CLDN6 an ideal target for development of a potential therapeutic antibody-drug conjugate (ADC). This study describes the generation and preclinical characterization of CLDN6-23-ADC, an ADC consisting of a humanized anti-CLDN6 monoclonal antibody coupled to monomethyl auristatin E (MMAE) via a cleavable linker. EXPERIMENTAL DESIGN: A fully humanized anti-CLDN6 antibody was conjugated to MMAE resulting in the potential therapeutic ADC, CLDN6-23-ADC. The antitumor efficacy of CLDN6-23-ADC was assessed for antitumor efficacy in CLDN6-positive (CLDN6+) and -negative (CLDN6-) xenografts and patient-derived xenograft (PDX) models of human cancers. RESULTS: CLDN6-23-ADC selectively binds to CLDN6, versus other CLDN family members, inhibits the proliferation of CLDN6+ cancer cells in vitro, and is rapidly internalized in CLDN6+ cells. Robust tumor regressions were observed in multiple CLDN6+ xenograft models and tumor inhibition led to markedly enhanced survival of CLDN6+ PDX tumors following treatment with CLDN6-23-ADC. IHC assessment of cancer tissue microarrays demonstrate elevated levels of CLDN6 in 29% of ovarian epithelial carcinomas. Approximately 45% of high-grade serous ovarian carcinomas and 11% of endometrial carcinomas are positive for the target. CONCLUSIONS: We report the development of a novel ADC, CLDN6-23-ADC, that selectively targets CLDN6, a potential onco-fetal-antigen which is highly expressed in ovarian and endometrial cancers. CLDN6-23-ADC exhibits robust tumor regressions in mouse models of human ovarian and endometrial cancers and is currently undergoing phase I study.
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Neoplasias do Endométrio , Imunoconjugados , Camundongos , Animais , Humanos , Feminino , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , Anticorpos Monoclonais Humanizados , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêutico , Modelos Animais de Doenças , Neoplasias do Endométrio/tratamento farmacológico , Linhagem Celular TumoralRESUMO
OBJECTIVES: The COVID-19 vaccine is currently being administered worldwide to address the ongoing pandemic. Although these vaccines have proven effective in preventing severe disease, the level of immunity required to prevent respiratory mucosal infection remains less well understood. Therefore, it is desirable to develop a noninvasive screening strategy such as oral fluid to monitor secreted antibodies longitudinally as potential surrogates of mucosal immunity. METHODS: We evaluated the anti-spike protein antibodies in gingival crevicular fluid (GCF) and saliva and compared them to immune responses in the blood of 50 healthy health care workers following 2 doses of intramuscular Pfizer/BioNTech-BNT162b2 vaccine. RESULTS: The antibodies to SARS-CoV-2 spike and subdomain proteins (RBD, S1, S2, and NTD) were significantly higher in serum than oral fluids but showed a greater detection rate and higher median titres in GCF than saliva. For all tested SARS-CoV-2 antigens, IgG in GCF (as opposed to saliva) showed a more significant and stronger correlation with IgG in serum. Serum-neutralising antibodies (Nab) titres also displayed a significant and stronger correlation with anti-spike protein and their subdomains in GCF than saliva. Interestingly, the time post-second dose of vaccine and sex had a similar influence on IgG in serum and GCF. However, interferon (IFN)-γ-producing T-cell responses showed no association with SARS-Cov-2 IgG antibodies in serum, GCF, or saliva and neutralisation antibodies in serum. The correlation matrix of all measured parameters grouped serum and GCF IgG parameters separately from salivary IgG parameters indicating that GCF better represents the humoural response in serum than saliva. CONCLUSIONS: Within limitations, we propose that GCF could be a less invasive alternative to serum and more appropriate than saliva to detect antibody responses by current COVID-19 vaccines if the GCF collection procedure could be standardised. Further research is needed to investigate the suitability of GCF for community immune surveillance for vaccines.
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Vacina BNT162 , COVID-19 , Humanos , Vacinas contra COVID-19 , COVID-19/prevenção & controle , SARS-CoV-2 , Imunoglobulina G , Imunidade , Anticorpos AntiviraisRESUMO
Background and Aims: Due to increasing knowledge of the "gut-liver axis", there has been growing interest regarding the use of fecal microbiota transplant in the management of chronic liver disease. There are limited data available and current guidelines are mostly based on expert opinions. We aim to perform the first systematic review investigating safety and efficacy of fecal microbiota transplant particularly among high-risk decompensated cirrhosis patient populations. Methods: Literature search was performed using variations of the keywords "fecal microbiota transplant" and "cirrhosis" on PubMed/Medline from inception to 3 October 2021. The resulting 116 articles were independently screened by two authors. In total, 5 qualifying studies, including 2 randomized control trials and 3 retrospective case series, were found to meet established eligibility criteria and have adequate quality of evidence to be included in this review. Results: Of the total 58 qualifying patients, there were 2 deaths post fecal microbiota transplant, 1 of which could not rule out being related (1.7%). Among the remaining 56 participants, 8 serious adverse events were reported, of which 2 could not rule out being related (3.6%). The success rate of fecal microbiota transplantation in treating recurrent Clostridioides difficile infection among patients with decompensated cirrhosis was 77.8%. The success rate when used as investigational treatment for hepatic encephalopathy was 86.7%, with multiple studies reporting clinically significant improvement in encephalopathy testing scores. Conclusions: We found a marginally higher rate of deaths and serious adverse events from fecal microbiota transplant in our patient population compared with the average immunocompetent population, where it was previously found to have 0 deaths and SAE rate of 2.83%. The efficacy when used for recurrent C.difficile infection was 77.8% and 87% in the decompensated cirrhotic and general populations, respectively. Studies on efficacy in novel treatment of hepatic encephalopathy have been promising. This study concludes that fecal microbiota transplant use in decompensated cirrhosis patients should be used with caution and preferably be limited to research purposes until better data are available.
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OBJECTIVE: Assess the ability of an antimicrobial drug-releasing resin adhesive, containing octenidine dihydrochloride (OCT)-silica co-assembled particles (DSPs), to enhance the biostability and preserve the interfacial fracture toughness (FT) of composite restorations bonded to dentin. Enzyme-catalyzed degradation compromises the dental restoration-tooth interface, increasing cariogenic bacterial infiltration. In addition to bacterial ingress inhibition, antimicrobial-releasing adhesives may exhibit direct interfacial biodegradation inhibition as an additional benefit. METHODS: Mini short-rod restoration bonding specimens with total-etch adhesive with/without 10% wt. DSPs were made. Interfacial fracture toughness (FT) was measured as-manufactured or post-incubation in simulated human salivary esterase (SHSE) for up to 6-months. Effect of OCT on SHSE and whole saliva/bacterial enzyme activity was assessed. Release of OCT outside the restoration interface was assessed. RESULTS: No deleterious effect of DSPs on initial bonding capacity was observed. Aging specimens in SHSE reduced FT of control but not DSP-adhesive-bonded specimens. OCT inhibited SHSE degradation of adhesive monomer and may inhibit endogenous proteases. OCT inhibited bacterial esterase and collagenase. No endogenous collagen breakdown was detected in the present study. OCT increased human saliva degradative esterase activity below its minimum inhibitory concentration towards S. mutans (MIC), but inhibited degradation above MIC. OCT release outside restoration margins was below detection. SIGNIFICANCE: DSP-adhesive preserves the restoration bond through a secondary enzyme-inhibitory effect of released OCT, which is virtually confined to the restoration interface microgap. Enzyme activity modulation may produce a positive-to-negative feedback switch, by increasing OCT concentration via biodegradation-triggered release to an effective dose, then subsequently slowing degradation and degradation-triggered release.
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Anti-Infecciosos , Colagem Dentária , Dente , Antibacterianos , Resinas Compostas , Cimentos Dentários , Dentina , Adesivos Dentinários , Esterases , Humanos , Teste de Materiais , Cimentos de ResinaRESUMO
In this review, we examine the pharmacokinetics and clinically relevant drug interactions of the newer generation direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C, specifically sofosbuvir/velpatasvir (Epclusa®), sofosbuvir/velpatasvir/voxilaprevir (Vosevi®), glecaprevir/pibrentasvir (Maviret®), and elbasvir/grazoprevir (Zepatier®). We searched MEDLINE (1948-January 2020), Embase (1964-January 2020), Google, and GoogleScholar using the terms pharmacokinetics, drug interaction, drug metabolism, sofosbuvir, velpatasvir, Epclusa, voxilaprevir, Vosevi, glecaprevir, pibrentasvir, Maviret, elbasvir, grazoprevir, and Zepatier, from inception to January 13, 2020. The search was limited to randomized controlled trials, in vitro studies, prospective and retrospective human studies, drug monographs, abstracts, and conference proceedings. All relevant published literature on pharmacokinetic and pharmacodynamic interactions involving DAAs were reviewed and the data extracted. Numerous clinically relevant drug-drug interactions (DDIs) were identified with the newer generation DAAs and commonly prescribed drugs. NS3/4A protease inhibitors are more likely to be involved in DDIs, followed by NS5A inhibitors and NS5B polymerase inhibitor. The majority of clinically relevant DDIs are predictable, according to known pharmacokinetic, pharmacodynamics, and physicochemical properties of DAAs; however, in select cases, unpredictable DDIs do occur. As expected, many drug interactions exist between newer generation DAAs and commonly prescribed medications. While the majority of clinically relevant interactions are predictable, many require therapeutic dose adjustment or careful selection of non-interacting drugs. In select cases, severe and unpredictable drug interactions can occur. Clinicians should consult hepatitis C virus pharmacotherapy experts and tertiary drug interaction resources when initiating DAA therapy in patients taking other medications.
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Recently, California (CA) pharmacists' scope of practice has expanded to include independently prescribing self-administered hormonal contraceptives, nicotine replacement therapy medications, travel health medications, routine vaccinations, naloxone hydrochloride, and HIV preexposure and postexposure prophylaxis. However, previous reports indicate that practicing within this expanded scope has remained limited. Therefore, a 26-item, web-based survey was emailed to CA community pharmacists to assess pharmacists' knowledge, intent, and barriers to prescribing and billing for these patient care services. A total of 216 chain, supermarket-based, independent, mass merchant, and health-system outpatient pharmacists were included. The primary services provided and medications prescribed are for vaccinations and naloxone. Most pharmacists agree that engagement in and implementation of new strategies to enhance patients' access to care is important. Common barriers include patient unawareness of pharmacist-provided services, lack of payment for services, and difficulty incorporating services within pharmacy workflow. Pharmacists are confident in their ability to provide patient care services but are less knowledgeable and confident about billing for them. Enhancing promotion of pharmacist-provided services to patients, developing strategies to efficiently incorporate them into the workflow, and payment models can help overcome barriers to providing these services.
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BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) is used in recurrent Clostridioides difficile infections. However, protocols are facility dependent, and one variable is whether pre-procedural proton pump inhibitors (PPIs) are given. In theory, PPIs reduce acidity and protect the transplanted microbiome for the most potent dose. We conducted a systematic review to study the effect of PPIs on FMT delivered by upper gastrointestinal (GI) routes. METHODS: We searched Pubmed/Medline, Cochrane Library, Embase, Scopus, and Web of Science through December 16, 2018 using variations of keywords "fecal microbiota transplant" and "Clostridium difficile infection." Two authors independently reviewed 4210 results and found 11 qualifying studies with data on upper GI FMT, use of PPIs, and the rate of treatment failure at follow-up. RESULTS: Of 233 included patients, treatment failure occurred in 20.6% of those with use of PPIs versus 22.6% in the group without (relative risk 0.91; confidence interval 0.56-1.50). Limitations include the lack of studies directly comparing outcomes based on use of PPIs and inability to control for possible confounders such as chronic PPI use, amount of stool transplanted, and pre-FMT antibiotics. CONCLUSIONS: We did not find evidence supporting a clinically significant benefit from routine use of PPIs in FMT protocol. It is possible that the theoretical benefit from improved survival of transplanted microbiota is offset by negative effects on the microbiome. We suggest that routine use of PPIs in upper GI FMT be reconsidered. Further investigation is needed to optimize protocols for safety and efficacy.
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Infecções por Clostridium/microbiologia , Infecções por Clostridium/terapia , Transplante de Microbiota Fecal , Fezes/microbiologia , Trato Gastrointestinal/microbiologia , Inibidores da Bomba de Prótons/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Resultados Negativos , Resultado do TratamentoRESUMO
Invasive pneumococcal infection is a major cause of morbidity and mortality worldwide despite the availability of pneumococcal vaccines. The aim of this study was to re-evaluate the clinical syndromes, prognostic factors and outcomes for pneumococcal disease in adults and children in Singapore during the period before and after the introduction of the pneumococcal vaccine. We retrospectively analyzed a large cohort of patients admitted to the four main public hospitals in Singapore with S. pneumoniae infection between 1997 and 2013. A total of 889 (64% of all isolates identified in the clinical laboratories) cases were included in the analysis; 561 (63.1%) were adult (≥16 years) cases with a median age of 62 years and 328 (36.9%) were paediatric cases with a median age of 3 years. Bacteraemic pneumonia was the most common syndrome in both groups (69.3% vs. 44.2%), followed by primary bacteraemia without pneumonia (14.3% vs. 13.4%), meningitis (6.4% vs. 7.6%) and non-bacteraemic pneumonia (5.2% vs. 21%). The major serotypes in adults were 3, 4, 6B, 14, 19F and 23F whereas in children they were 14, 6B and 19F, accounting both for nearly half of pneumococcal disease cases. No particular serotype was associated with mortality or severity of the pneumococcal disease. Overall mortality rate was 18.5% in adults and 3% in children. Risk factors for mortality included acute cardiac events in adults, meningitis in children and critical illness and bilateral pulmonary infiltrates in both adults and children. Penicillin resistance was not associated with increased mortality. Our results agree with global reports that the course of pneumococcal disease and its clinical outcome were more severe in adults than in children. The main serotypes causing invasive disease were mostly covered by the vaccines in use. The high mortality rates reflect an urgent need to increase vaccination coverage in both adults and children to tackle this vaccine-preventable infection.
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Resistência às Penicilinas , Vacinas Pneumocócicas/administração & dosagem , Pneumonia Pneumocócica/mortalidade , Pneumonia Pneumocócica/prevenção & controle , Streptococcus pneumoniae , Vacinação , Adolescente , Adulto , Fatores Etários , Idoso , Bacteriemia/mortalidade , Bacteriemia/prevenção & controle , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Singapura/epidemiologia , Taxa de SobrevidaRESUMO
Objective: To review the evidence for trimethoprim-sulfamethoxazole (TMP-SMX), clindamycin, doxycycline, and minocycline in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Data Source: MEDLINE, PubMed, EMBASE, Google, Google Scholar, Cochrane Central Register of Controlled Trials from 1946 to May 20, 2019. The search was performed with the keywords methicillin-resistant Staphylococcus aureus, MRSA, Staphylococcus aureus, pneumonia, trimethoprim, sulfamethoxazole drug combination, trimethoprim, sulfamethoxazole, TMP-SMX, co-trimoxazole, clindamycin, doxycycline, and minocycline. Data Extraction: Studies reporting the use of the above antibiotics for MRSA pneumonia treatment with clinical outcomes were included. Search parameters were limited to English language and human studies only. Data Synthesis: The search yielded 16 relevant articles: 6 TMP-SMX, 8 clindamycin, zero doxycycline, and 2 minocycline. For TMP-SMX, prospective randomized trials showed variable results; however, these studies were not specifically designed to assess MRSA pneumonia treatment. Retrospective studies with clindamycin suggested that it could be used as monotherapy or in combination with other anti-MRSA antibiotics. There was no evidence for doxycycline use, but 2 small retrospective reviews appeared to support minocycline as a treatment option. Relevance to Patient Care and Clinical Practice: These antibiotics are often used in clinical practice as potential treatment options for MRSA pneumonia. This article reviews the evidence for the clinical efficacy and safety of these agents. Conclusions: There are limited data to support use of TMP-SMX, clindamycin, doxycycline, or minocycline in MRSA pneumonia treatment. Randomized controlled trials are required to determine the effectiveness of these antibiotics. Clinicians should base their decision to use these agents on a case-by-case basis depending on clinical status and susceptibility results.
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Clindamicina/uso terapêutico , Terapia Combinada/métodos , Doxiciclina/uso terapêutico , Minociclina/uso terapêutico , Pneumonia/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Clindamicina/farmacologia , Doxiciclina/farmacologia , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Minociclina/farmacologia , Estudos Retrospectivos , Combinação Trimetoprima e Sulfametoxazol/farmacologiaRESUMO
We conducted a systematic review to identify the use and effectiveness of clinical interventions to prevent or mitigate weight gain in patients using systemic corticosteroids. We independently searched nine bibliometric databases for reviews and longitudinal studies published up to 26 October 2018, and assessed the quality of studies meeting inclusion criteria. We identified 3893 records and screened 3037 eligible studies, read four full-texts and extracted data from three randomized control trials. Two studies examined a diet-only intervention for weight management, while one study examined a mixed intervention for diet and exercise. Overall, existing evidence is of poor quality and based on small feasibility studies of either paediatric leukaemia or female lupus patients, which suggested divergent effects of lifestyle interventions on weight, body mass index or waist circumference. Current evidence suggests a state of clinical equipoise that deserves greater research attention given the prevalent use of corticosteroids for treating a variety of chronic conditions. Robust high-quality longitudinal studies to decipher preventive strategies of steroid-induced weight gain must be prioritized in research and policy to improve patient care and prevent further obesity-related disease burden.
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Corticosteroides/administração & dosagem , Obesidade/tratamento farmacológico , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Obesidade/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Redução de Peso/efeitos dos fármacos , Adulto JovemRESUMO
INTRODUCTION: Autoimmune hepatitis (AIH) is a cause of chronic liver disease. It is usually suspected based on clinical presentation and laboratory findings, but the diagnosis relies on the presence of specific autoantibodies and characteristic histology. Other unexplained findings should always prompt investigation for coexisting syndromes. CASE PRESENTATION: The patient is a 60-year-old Hispanic female with a history of mild asthma presented with exertional and pleuritic chest pain with weight loss, arthralgia, subjective fever, and night sweats for the last 3 months. Given the nonspecific nature of the presentation, further workup was pursued. Laboratory results indicated pancytopenia, elevated INR, and positive autoimmune panel including ANA, anti-chromatin, anti-histone, and rheumatoid factor as well as abnormal C3 and C4. Subsequent liver biopsy with interface hepatitis lead to a diagnosis of AIH with concurrent systemic lupus erythematosus suspected. CONCLUSION: The diagnostic work up for AIH is multimodal and aims to differentiate other etiologies such as congestive hepatopathy, iron overload, viral hepatitis, and other autoimmune liver diseases. In this particular case, unusual clinical and laboratory findings led to diagnosis of the overlap syndrome. Treatment for both was necessary to prevent further progression of disease.
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Autoanticorpos , Hepatite A , Hepatite Autoimune , Hidroxicloroquina/administração & dosagem , Fígado/patologia , Lúpus Eritematoso Sistêmico , Prednisona/administração & dosagem , Fator Reumatoide/sangue , Antirreumáticos/administração & dosagem , Artralgia/diagnóstico , Artralgia/etiologia , Autoanticorpos/sangue , Autoanticorpos/classificação , Biópsia/métodos , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Diagnóstico Diferencial , Feminino , Hepatite A/diagnóstico , Hepatite A/imunologia , Hepatite A/fisiopatologia , Hepatite A/terapia , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/imunologia , Hepatite Autoimune/fisiopatologia , Hepatite Autoimune/terapia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/terapia , Pessoa de Meia-Idade , Administração dos Cuidados ao Paciente/métodos , Resultado do TratamentoRESUMO
Objective: To evaluate the effects of switching from ticagrelor or prasugrel to clopidogrel in acute coronary syndrome (ACS) patients managed with percutaneous coronary intervention on major adverse cardiovascular events (MACEs) and bleeding. Data Sources: We searched MEDLINE, EMBASE, CENTRAL, bibliographies of relevant articles, and clinicaltrials.gov for eligible articles published from inception to January 27, 2019. Study Selection and Data Extraction: We included randomized controlled trials (RCTs) and cohort and case-control studies that reported on ≥1 outcome of interest. Primary outcomes were MACE and major bleeding, and the secondary outcome was any bleeding. Data Synthesis: From 483 articles, we included 7 relevant studies (2 RCTs, 5 cohort studies) at high/unclear risk of bias. Random-effects meta-analysis revealed inconclusive effects on MACE (hazard ratio [HR] = 1.00, 95% CI = 0.59-1.68; I2 = 82%), major bleeding (HR = 0.51; 0.19-1.35; I2 = 91%), and any bleeding (HR = 0.64; 0.38-1.07; I2 = 85%). Similar nonsignificant results were obtained in secondary analyses evaluating risk ratios. Relevance to Patient Care and Clinical Practice: Ticagrelor and prasugrel, are now considered preferred therapy over clopidogrel in patients with ACS. Switching from these potent P2Y12 inhibitors to clopidogrel is commonly performed to reduce bleeding risk, other adverse effects, or costs. Current best-available evidence is inconclusive regarding the effects of switching to clopidogrel on the risk of MACE and bleeding. Overall, studies were underpowered to detect clinically important differences. Conclusions: Until adequately powered trials demonstrate an advantage to switching to clopidogrel from prasugrel or ticagrelor, clinicians may consider this approach as clinically indicated on an individual, case-by-case basis.
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Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Hemorragia/induzido quimicamente , Humanos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Cloridrato de Prasugrel/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Ticagrelor/administração & dosagem , Resultado do TratamentoRESUMO
Tumor organoids maintain cell-cell interactions, heterogeneity, microenvironment, and drug response of the sample they originate from. Thus, there is increasing interest in developing tumor organoid models for drug development and personalized medicine applications. Although organoids are in principle amenable to high-throughput screenings, progress has been hampered by technical constraints and extensive manipulations required by current methods. Here we introduce a miniaturized method that uses a simplified geometry by seeding cells around the rim of the wells (mini-rings). This allows high-throughput screenings in a format compatible with automation as shown using four patient-derived tumor organoids established from two ovarian and one peritoneal high-grade serous carcinomas and one carcinosarcoma of the ovary. Using our automated screening platform, we identified personalized responses by measuring viability, number, and size of organoids after exposure to 240 kinase inhibitors. Results are available within a week from surgery, a timeline compatible with therapeutic decision-making.
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Neoplasias/tratamento farmacológico , Organoides/efeitos dos fármacos , Medicina de Precisão/métodos , Inibidores de Proteínas Quinases/uso terapêutico , Técnicas de Cultura de Tecidos/métodos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Neoplasias/patologia , Organoides/patologia , Reprodutibilidade dos Testes , Microambiente Tumoral/efeitos dos fármacosAssuntos
Estudos de Equivalência como Asunto , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Interpretação Estatística de Dados , Humanos , Preparações Farmacêuticas/administração & dosagem , Projetos de Pesquisa/normas , Revisões Sistemáticas como Assunto , Equivalência TerapêuticaRESUMO
Patients with abdominopelvic cancers are at increased risk of venous thromboembolism (VTE) due to their malignancy. We evaluated outcomes and the rate of VTE in patients undergoing abdominopelvic surgery for malignancy with preoperative epidural analgesia without postoperative chemical VTE prophylaxis. A retrospective review between 2009 and 2015 identified 285 patients with malignancy who underwent abdominopelvic surgery by a single surgeon (AWS). Lower extremity venous duplex scans (VDS) were performed preoperatively and before discharge. Demographics, procedures, and VTE outcomes were reviewed. The median age was 66 years. The average operative time was 315 minutes. All patients ambulated on postoperative day (POD) one or two. Epidural catheters (ECs) were removed on postoperative day four or five. No patient received VTE prophylaxis while an epidural catheter was in place. Preoperative lower extremity VDS revealed above-knee deep vein thrombosis (DVT) in seven patients (2.5%). Postoperative lower extremity VDS revealed acute DVT in 24 patients (8.4%): nine (3.2%) above-knee and 15 (5.2%) below-knee. The nine patients with above-knee DVT were anticoagulated after epidural removal. No patient developed a pulmonary embolism. Our data suggest that patients undergoing major open operations with epidural analgesia have low rates of DVT and may obviate the need for chemical prophylaxis. However, larger studies are required to determine the overall effects of epidural analgesia on the development of DVTs postoperatively.
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Analgesia Epidural , Neoplasias do Sistema Digestório/cirurgia , Neoplasias Pélvicas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Tromboembolia Venosa/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Most dental resin composite restorations are replacements for failing restorations. Degradation of the restoration-tooth margins by cariogenic bacteria results in recurrent caries, a leading cause for restoration failure. Incorporating antimicrobial agents in dental adhesives could reduce interfacial bacterial count and reduce recurrent caries rates, inhibit interfacial degradation, and prolong restoration service life, while minimizing systemic exposure. Direct addition of antimicrobial compounds into restorative materials have limited release periods and could affect the integrity of the material. Attempts to incorporate antimicrobial within mesoporous silica nanoparticles showed theoretical promise due to their physical robustness and large available internal volume, yet yielded short-term burst release and limited therapeutic payload. We have developed novel broad-spectrum antimicrobial drug-silica particles co-assembled for long-term release and high payload incorporated into dental adhesives. The release of the drug, octenidine dihydrochloride, is modulated by the oral degradative environment and mathematically modeled to predict effective service life. Steady-state release kills cariogenic bacteria, preventing biofilm formation over the adhesive surface, with no toxicity. This novel material could extend dental restoration service life and may be applied to other long-term medical device-tissue interfaces for responsive drug release upon bacterial infection. STATEMENT OF SIGNIFICANCE: This study describes a novel dental adhesive that includes a broad-spectrum antimicrobial drug-silica co-assembled particles for long-term antimicrobial effect. The release of the drug, octenidine dihydrochloride, is modulated by the oral degradative environment and mathematically modeled to predict effective release throughout the service life of the restoration. Steady-state drug-release kills caries-forming bacteria, preventing biofilm formation over the adhesive surface, without toxicity. This novel material could extend dental restoration service life and may be applied to other long-term medical device-tissue interfaces for responsive drug release upon bacterial infection. Since recurrent cavities (caries) caused by bacteria are the major reason for dental filling failure, this development represents a significant contribution to the biomaterials field in methodology and material performance.
Assuntos
Resinas Acrílicas , Antibacterianos , Biofilmes , Resinas Compostas , Cimentos Dentários , Modelos Biológicos , Poliuretanos , Resinas Acrílicas/química , Resinas Acrílicas/farmacocinética , Antibacterianos/química , Antibacterianos/farmacocinética , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Linhagem Celular , Resinas Compostas/química , Resinas Compostas/farmacocinética , Cimentos Dentários/química , Cimentos Dentários/farmacocinética , Humanos , Nanopartículas/química , Poliuretanos/química , Poliuretanos/farmacocinética , Porosidade , Dióxido de Silício/químicaRESUMO
BACKGROUND: The goal of the study was to investigate the current clinical practices among oncologic surgeons regarding cytoreductive surgery (CRS) with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: From September to October 2016, an online questionnaire surveyed the oncologic surgeons by email. The questionnaire included 20 multiple-choice questions of the following: eligibility for the CRS with HIPEC procedure, perioperative staging and surgery skill, assessment of residual tumors, and method used for intraperitoneal HIPEC. RESULTS: The response rate was 16% (34/217). The majority of respondents (68%) worked at a university hospital. All respondents indicated that mesenteric invasion is the most crucial factor affecting treatment decision. Most surgeons (79%) used the Sugarbaker's staging system to intraoperatively measure the extent of peritoneal invasion. The methods used to measure the extent of miliary pattern of residual tumor spread, and the amount of residual tumor after electrocauterization varied among the surgeons. Most responders (65%) used the closed system of HIPEC. CONCLUSIONS: Despite the fact that CRS HIPEC is the standard treatment for PSM, the clinical practices are very different according to each clinical situation. Nevertheless, mesenteric invasion was found to be the most important factor impacting the treatment decision-making by the majority of responders.