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Fully automated synthetic chemistry would substantially change the field by providing broad on-demand access to small molecules. However, the reactions that can be run autonomously are still limited. Automating the stereospecific assembly of Csp3-C bonds would expand access to many important types of functional organic molecules1. Previously, methyliminodiacetic acid (MIDA) boronates were used to orchestrate the formation of Csp2-Csp2 bonds and were effective building blocks for automating the synthesis of many small molecules2, but they are incompatible with stereospecific Csp3-Csp2 and Csp3-Csp3 bond-forming reactions3-10. Here we report that hyperconjugative and steric tuning provide a new class of tetramethyl N-methyliminodiacetic acid (TIDA) boronates that are stable to these conditions. Charge density analysis11-13 revealed that redistribution of electron density increases covalency of the N-B bond and thereby attenuates its hydrolysis. Complementary steric shielding of carbonyl π-faces decreases reactivity towards nucleophilic reagents. The unique features of the iminodiacetic acid cage2, which are essential for generalized automated synthesis, are retained by TIDA boronates. This enabled Csp3 boronate building blocks to be assembled using automated synthesis, including the preparation of natural products through automated stereospecific Csp3-Csp2 and Csp3-Csp3 bond formation. These findings will enable increasingly complex Csp3-rich small molecules to be accessed via automated assembly.
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The immunological effects of exclusive enteral nutrition (EEN) in the treatment of active Crohn's disease (CD) are yet to be unveiled. The present study investigated changes in peripheral blood mononuclear cell profiles in children with active CD following 8-week treatment with EEN. In nine children, EEN significantly decreased the number and frequency of circulating effector memory CD8+ T cells re-expressing CD45RA, with corresponding increases observed in the frequency of circulating central and effector memory CD8+ T cells. These signals were conserved when looking at a subgroup of patients who achieved remission, and another who demonstrated the highest level of compliance to EEN. We speculate that the increases in circulating central and effector memory CD8+ T cells may be related to the extensive microbiome-modifying effects of EEN dampening immune response within the gastrointestinal tract.
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Doença de Crohn , Nutrição Enteral , Leucócitos Mononucleares , Humanos , Doença de Crohn/terapia , Doença de Crohn/imunologia , Doença de Crohn/sangue , Nutrição Enteral/métodos , Criança , Masculino , Feminino , Adolescente , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Linfócitos T CD8-Positivos/imunologia , Microbioma GastrointestinalRESUMO
BACKGROUND: A significant body of literature has interrogated the critical role of diet in the development and management of inflammatory bowel disease (IBD). SUMMARY: This review provides a summary and critical appraisal of the literature in this area, focussing on four distinct themes: nutritional epidemiology, animal and in vitro experiments, enteral nutrition, and food-based dietary therapies. KEY MESSAGES: Nutritional epidemiology and data from experiments in animals indicate that a western-type diet pattern is associated with increased risk of IBD onset. However, these findings have not been consistently replicated in the dietary management of IBD. Exclusive enteral nutrition (EEN) is the only dietary therapy with reproducible evidence of efficacy in the management of active Crohn's disease (CD). Use of EEN may also be useful for improving perioperative outcomes in CD, and as an adjuvant therapy to biologic therapy. Several dietary therapies for CD and ulcerative colitis have been proposed in the literature, but replication in well-controlled studies is needed before their routine use enters the clinical setting. Precision nutritional therapy might be an attractive therapeutic paradigm in a heterogenous disease like IBD. However, no recommendations for personalised dietary therapy can currently be made, and it is imperative we unravel the complex interplay between diet and gut inflammation before we are able to do so. Undoubtedly, diet is of critical importance in the development and management of IBD. However, the exact mechanism by which diet causes gut inflammation is still elusive, and dietary guidance is difficult to formulate.
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Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Animais , Humanos , Doenças Inflamatórias Intestinais/terapia , Dieta/efeitos adversos , Doença de Crohn/terapia , Colite Ulcerativa/terapia , InflamaçãoRESUMO
Dockstore (https://dockstore.org/) is an open source platform for publishing, sharing, and finding bioinformatics tools and workflows. The platform has facilitated large-scale biomedical research collaborations by using cloud technologies to increase the Findability, Accessibility, Interoperability and Reusability (FAIR) of computational resources, thereby promoting the reproducibility of complex bioinformatics analyses. Dockstore supports a variety of source repositories, analysis frameworks, and language technologies to provide a seamless publishing platform for authors to create a centralized catalogue of scientific software. The ready-to-use packaging of hundreds of tools and workflows, combined with the implementation of interoperability standards, enables users to launch analyses across multiple environments. Dockstore is widely used, more than twenty-five high-profile organizations share analysis collections through the platform in a variety of workflow languages, including the Broad Institute's GATK best practice and COVID-19 workflows (WDL), nf-core workflows (Nextflow), the Intergalactic Workflow Commission tools (Galaxy), and workflows from Seven Bridges (CWL) to highlight just a few. Here we describe the improvements made over the last four years, including the expansion of system integrations supporting authors, the addition of collaboration features and analysis platform integrations supporting users, and other enhancements that improve the overall scientific reproducibility of Dockstore content.
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Biologia Computacional/métodos , Disseminação de Informação , Internet , Software , Fluxo de Trabalho , Computação em Nuvem , Biologia Computacional/educação , Visualização de Dados , Humanos , National Heart, Lung, and Blood Institute (U.S.) , National Human Genome Research Institute (U.S.) , Reprodutibilidade dos Testes , Estados UnidosRESUMO
BACKGROUND: Prognosis of patients with multiple myeloma (MM) who have relapsed on or become refractory to immunomodulators and bortezomib is poor, and treatment options are limited. While pomalidomide plus low-dose dexamethasone (POM/DEX) has demonstrated efficacy in clinical trials, real-world evidence is scarce. PATIENTS AND METHODS: POSEIDON was a prospective non-interventional study designed to evaluate effectiveness, safety and quality of life (QoL) of POM/DEX in patients with relapsed or refractory MM (R/RMM) pretreated with at least two prior therapy lines including both lenalidomide and bortezomib in real world in Germany. Patients received POM/DEX according to physicians' choice. Data were analyzed descriptively. RESULTS: Between 2014 and 2017, 151 patients were enrolled, 144 patients with a median of three prior therapy lines qualified for effectiveness analysis. Median age was 73.2 years. Median progression-free and overall survival were 6.3 months [95% confidence interval (CI) 5.2, 8.6] and 12.9 months [95% CI 10.6, 15.1]. Most frequent grade 3/4 adverse events were leukopenia (8.2%), pneumonia (7.5%) and anemia (5.5%). QoL was maintained after start of POM/DEX. CONCLUSION: The results of POSEIDON support the effectiveness and safety of POM/DEX in R/RMM patients pretreated with lenalidomide and bortezomib and highlight the clinical value of the POM/DEX regimen in the real-world setting. Registered at clinicaltrials.gov (NCT02075996).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona , Gerenciamento Clínico , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Humanos , Lenalidomida , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Qualidade de Vida , Recidiva , Retratamento , Resultado do TratamentoRESUMO
BACKGROUND: There is a clinical need to develop biomarkers of small bowel damage in coeliac disease and Crohn's disease. This study evaluated intestinal fatty acid binding protein (iFABP), a potential biomarker of small bowel damage, in children with coeliac disease and Crohn's disease. METHODS: The concentration iFABP was measured in plasma and urine of children with ulcerative colitis, coeliac disease, and Crohn's disease at diagnosis and from the latter two groups after treatment with gluten free diet (GFD) or exclusive enteral nutrition (EEN), respectively. Healthy children (Controls) were also recruited. RESULTS: 138 children were recruited. Plasma but not urinary iFABP was higher in patients with newly diagnosed coeliac disease than Controls (median [Q1, Q3] coeliac disease: 2104 pg/mL 1493, 2457] vs Controls: 938 pg/mL [616, 1140], p = 0.001). Plasma or urinary iFABP did not differ between patients with coeliac on GFD and Controls. Baseline iFABP in plasma decreased by 6 months on GFD (6mo GFD: 1238 pg/mL [952, 1618], p = 0.045). By 12 months this effect was lost, at which point 25% of patients with coeliac disease had detectable gluten in faeces, whilst tissue transglutaminase IgA antibodies (TGA) continued to decrease. At diagnosis, patients with Crohn's disease had higher plasma iFABP levels than Controls (EEN Start: 1339 pg/mL [895, 1969] vs Controls: 938 pg/mL [616, 1140], p = 0.008). iFABP did not differ according to Crohn's disease phenotype. Induction treatment with EEN tended to decrease (p = 0.072) iFABP in plasma which was no longer different to Controls (EEN End: 1114 pg/mL [689, 1400] vs Controls: 938 pg/mL [616, 1140], p = 0.164). Plasma or urinary iFABP did not differ in patients with ulcerative colitis from Controls (plasma iFABP, ulcerative colitis: 1309 pg/mL [1005, 1458] vs Controls: 938 pg/mL [616, 1140], p = 0.301; urinary iFABP ulcerative colitis: 38 pg/mg [29, 81] vs Controls: 53 pg/mg [27, 109], p = 0.605). CONCLUSIONS: Plasma, but not urinary iFABP is a candidate biomarker with better fidelity in monitoring compliance during GFD than TGA. The role of plasma iFABP in Crohn's disease is promising but warrants further investigation. TRIAL REGISTRATION: Clinical Trials.gov, NCT02341248. Registered on 19/01/2015.
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Doença Celíaca , Colite Ulcerativa , Doença de Crohn , Colite Ulcerativa/genética , Doença de Crohn/tratamento farmacológico , Nutrição Enteral , Proteínas de Ligação a Ácido Graxo , HumanosRESUMO
ABSTRACT: It remains unclear whether suboptimal response to exclusive enteral nutrition (EEN) in some children with Crohn disease (CD) is explained by poor compliance. The present study measured faecal gluten immunogenic peptides (GIP), a biomarker of gluten intake, in 45 children (3- 17âyears) with CD, and explored associations with faecal calprotectin (FC) levels at 33 and 54âdays of EEN. FC decreased in patients with undetectable GIP at both 33 and 54âdays of EEN (mean decrease, 33âdays: -743âmg/kg, 54âdays: -1043âmg/kg, Pâ <â0.001) but not in patients who had detectable levels. At EEN completion, patients with undetectable GIP had a lower FC by 717âmg/kg compared with patients with a positive GIP result (Pâ=â0.042) and demonstrated a greater decline from baseline FC (-69% vs +5%, Pâ=â0.011). Poorer response to EEN is explained in part by diminished compliance. Faecal GIP might be useful as proxy biomarker of EEN compliance.
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Doença de Crohn , Complexo Antígeno L1 Leucocitário , Cooperação do Paciente , Biomarcadores , Criança , Doença de Crohn/dietoterapia , Nutrição Enteral , Glutens , Humanos , Indução de RemissãoRESUMO
OBJECTIVES: To evaluate the efficacy of standard and optimized infliximab induction dosing in attaining corticosteroid (CS) free clinical remission at week 52 and the effect that post-induction trough levels have on long-term outcome. METHODS: Inflammatory bowel disease (IBD) patients ≤18 years commenced on infliximab between August 1, 2016, and August 1, 2018, from Vancouver, Canada, and Glasgow, Scotland, were included. The Glasgow cohort followed standard induction while the Vancouver cohort undertook induction optimization based on clinical, biomarker, and proactive infliximab trough levels. Baseline characteristics and laboratory values were documented. RESULTS: In total, 140 children were included [median age 14.1 years (interquartile range (IQR) 12.0-16.0)]; 54% male. CS-free clinical remission at week 52 was higher in the optimized group compared to the standard cohort [65/78 (83%) vs. 32/62 (52%), P < 0.001]. Combined CS-free clinical and biomarker remission (CRP < 5 mg/L) was also higher in the optimized compared to the standard cohort [65/78 (83%) vs 25/62 (40%), P < 0.001]. The median post-induction trough level was higher in children who were in CS-free clinical remission at week 52 [3.6 mg/L (1.5-7.1)] vs. those who were not [2.0 mg/L (0.8-4.1), P = 0.04]. The odds of attaining a therapeutic post-induction trough level were almost 4-fold higher in the optimized group than the standard cohort (OR 3.97, 95% CI: 1.89-8.68, P < 0.001). CONCLUSIONS: Standard infliximab induction resulted in less favorable long-term outcomes for pediatric IBD patients. Optimizing induction using clinical, biomarker, and proactive trough levels resulted in higher post-induction trough levels and a greater odds of attaining long-term clinical remission.
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Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Masculino , Criança , Adolescente , Feminino , Infliximab/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Doença de Crohn/tratamento farmacológico , Monitoramento de Medicamentos , Resultado do Tratamento , Doenças Inflamatórias Intestinais/tratamento farmacológico , Indução de Remissão , BiomarcadoresRESUMO
BACKGROUND: Patients with chronic conditions continue to face financial and system-related barriers to medication adherence. Pharmacy, provider, and payer-based financial and social incentive-based interventions may reduce these barriers and improve adherence. However, it is unclear how patient demographics and clinical characteristics influence the type of incentives preferred by patients. OBJECTIVES: To examine individuals' preference for financial versus social incentives and to explore the association between patient demographic and clinical characteristics with preferences for financial or social incentives. METHODS: A cross-sectional survey of a nationally representative sample of patients was conducted with Qualtrics panelists (N = 909). U.S. adults taking at least 1 prescription medication for a chronic condition were included. Survey items elicited participants' demographic characteristics, preference for financial or social incentives, self-reported medication adherence, number of prescribed medications, and number of chronic conditions. Bivariate associations between patient characteristics and incentive preferences were tested using t and chi-square tests. Logistic regression was performed to determine patient characteristics associated with participants' preference for incentives. RESULTS: When compared with those who were adherent to medications, individuals who were nonadherent were less likely to prefer financial incentives over social incentives (adjusted odds ratio [OR] 0.55 [95% CI 0.31-0.98]). Patient income, sex, and ethnicity were also associated with preferences for financial incentives. Those earning less than $50,000 per year were less likely to prefer financial incentives compared with social incentives (adjusted OR 0.44 [0.24-0.79]). Females were more likely to prefer financial incentives (adjusted OR 1.98 [1.16-3.37]). Hispanic/Latinos were less likely to prefer financial incentives compared to non-Hispanics/non-Latinos (adjusted OR 0.51 [0.29-0.89]). CONCLUSION: Preferences for medication adherence incentives differed on the basis of adherence status and patients' demographic characteristics. Findings have implications for how incentive-based interventions can be structured to target certain patient groups.
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Assistência Farmacêutica , Farmácias , Adulto , Estudos Transversais , Feminino , Humanos , Adesão à Medicação , MotivaçãoRESUMO
OBJECTIVE: The association of continuity of care (COC) among providers and mortality risk for breast cancer patients with comorbidities is not sufficiently studied. DESIGN: A retrospective cohort study using the 2006-2014 Surveillance, Epidemiology and End Results (SEER)-Medicare data. PARTICIPANTS: Newly diagnosed female breast cancer patients (n = 57,578) with comorbidities (hypertension, hyperlipidemia, and/or diabetes). METHODS: All-cause mortality was assessed annually for up to 5 years. COC was estimated using the Bice-Boxerman index, which included: 1) specialty COC capturing continuity of visits to the same provider type (Primary Care Physicians, Oncologists, and Other specialists) and 2) individual COC capturing continuous care to the same provider regardless of provider specialty. Cox proportional hazards models estimated the hazard ratio (HR) of all-cause mortality across quartile of the COC index. RESULTS: Mortality was positively associated with advanced tumor stages and number of comorbidities (p < 0.05). Patients with high specialty COC (4th vs. 1st quartile, HR 1.34, 95%CI 1.29-1.40) had higher risks of mortality compared with those with low specialty COC. However, patients with high individual COC (4th vs. 1st quartile, HR 0.53, 95%CI 0.51-0.54) had lower risks of mortality compared to those with low individual COC. CONCLUSION: Receiving care from fewer providers is associated with lower mortality and from fewer types of provider is associated with higher mortality. The results might be confounded by uncontrolled factors and provoke the need for alternative patient care models that recognize the balance between appropriate subspecialties and minimizing the fragmentation of care within and across subspecialties.
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Neoplasias da Mama , Doenças Cardiovasculares , Idoso , Neoplasias da Mama/terapia , Continuidade da Assistência ao Paciente , Feminino , Humanos , Medicare , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: Paediatric acute severe colitis (ASC) management during the novel SARS-CoV-2/COVID-19 pandemic is challenging due to reliance on immunosuppression and the potential for surgery. We aimed to provide COVID-19-specific guidance using the European Crohn's and Colitis Organisation/European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines for comparison. DESIGN: We convened a RAND appropriateness panel comprising 14 paediatric gastroenterologists and paediatric experts in surgery, rheumatology, respiratory and infectious diseases. Panellists rated the appropriateness of interventions for ASC in the context of the COVID-19 pandemic. Results were discussed at a moderated meeting prior to a second survey. RESULTS: Panellists recommended patients with ASC have a SARS-CoV-2 swab and expedited biological screening on admission and should be isolated. A positive swab should trigger discussion with a COVID-19 specialist. Sigmoidoscopy was recommended prior to escalation to second-line therapy or colectomy. Methylprednisolone was considered appropriate first-line management in all, including those with symptomatic COVID-19. Thromboprophylaxis was also recommended in all. In patients requiring second-line therapy, infliximab was considered appropriate irrespective of SARS-CoV-2 status. Delaying colectomy due to SARS-CoV-2 infection was considered inappropriate. Corticosteroid tapering over 8-10 weeks was deemed appropriate for all. After successful corticosteroid rescue, thiopurine maintenance was rated appropriate in patients with negative SARS-CoV-2 swab and asymptomatic patients with positive swab but uncertain in symptomatic COVID-19. CONCLUSION: Our COVID-19-specific adaptations to paediatric ASC guidelines using a RAND panel generally support existing recommendations, particularly the use of corticosteroids and escalation to infliximab, irrespective of SARS-CoV-2 status. Consideration of routine prophylactic anticoagulation was recommended.
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Anticoagulantes/uso terapêutico , COVID-19 , Colectomia/métodos , Colite Ulcerativa , Doença de Crohn , Infliximab/uso terapêutico , Metilprednisolona/uso terapêutico , Adolescente , COVID-19/epidemiologia , COVID-19/terapia , Criança , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/terapia , Doença de Crohn/epidemiologia , Doença de Crohn/terapia , Humanos , Imunossupressores/classificação , Imunossupressores/uso terapêutico , Administração dos Cuidados ao Paciente/métodos , Administração dos Cuidados ao Paciente/normas , Administração dos Cuidados ao Paciente/tendências , Guias de Prática Clínica como Assunto , Risco Ajustado/métodos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Sigmoidoscopia/métodos , Reino UnidoRESUMO
BACKGROUND AND AIMS: It is not clear whether alterations in the intestinal microbiota of children with celiac disease (CD) cause the disease or are a result of disease and/or its treatment with a gluten-free diet (GFD). METHODS: We obtained 167 fecal samples from 141 children (20 with new-onset CD, 45 treated with a GFD, 57 healthy children, and 19 unaffected siblings of children with CD) in Glasgow, Scotland. Samples were analyzed by 16S ribosomal RNA sequencing, and diet-related metabolites were measured by gas chromatography. We obtained fecal samples from 13 children with new-onset CD after 6 and 12 months on a GFD. Relationships between microbiota with diet composition, gastrointestinal function, and biomarkers of GFD compliance were explored. RESULTS: Microbiota α diversity did not differ among groups. Microbial dysbiosis was not observed in children with new-onset CD. In contrast, 2.8% (Bray-Curtis dissimilarity index, P = .025) and 2.5% (UniFrac distances, P = .027) of the variation in microbiota composition could be explained by the GFD. Between 3% and 5% of all taxa differed among all group comparisons. Eleven distinctive operational taxonomic units composed a microbe signature specific to CD with high diagnostic probability. Most operational taxonomic units that differed between patients on a GFD with new-onset CD vs healthy children were associated with nutrient and food group intake (from 75% to 94%) and with biomarkers of gluten ingestion. Fecal levels of butyrate and ammonia decreased during the GFD. CONCLUSIONS: Although several alterations in the intestinal microbiota of children with established CD appear to be effects of a GFD, specific bacteria were found to be distinct biomarkers of CD. Studies are needed to determine whether these bacteria contribute to pathogenesis of CD.
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Doença Celíaca/diagnóstico , Dieta Livre de Glúten/efeitos adversos , Disbiose/diagnóstico , Microbioma Gastrointestinal , Estudos de Casos e Controles , Doença Celíaca/microbiologia , Criança , Disbiose/microbiologia , Fezes/microbiologia , Feminino , Voluntários Saudáveis , Humanos , Masculino , EscóciaRESUMO
BACKGROUND: The anti-inflammatory effect of exclusive enteral nutrition on the gut of children with Crohn's disease is rapidly lost after food reintroduction. This study assessed disease dietary triggers following successful treatment with exclusive enteral nutrition. METHODS: Nutrient intake, dietary patterns and dietary biomarkers in faeces (gluten immunogenic peptides, undigestible starch, short chain fatty acids) were assessed in 14 children with Crohn's disease during early food reintroduction, following exclusive enteral nutrition. Groups above (Group A) and below (Group B) the median levels of faecal calprotectin after food reintroduction were assigned for comparative analysis. RESULTS: Intakes of fibre, gluten-containing cereals and red and processed meat were significantly higher in Group A than Group B; (median [Q1, Q3], g/day; Fibre: 12.1 [11.2, 19.9] vs. 9.9 [7.6, 12.1], p = 0.03; Red and processed meat: 151 [66.7, 190] vs. 63.3 [21.7, 67], p = 0.02; gluten-containing cereals: 289 [207, 402] vs. 203 [61, 232], p = 0.035). A diet consisting of cereals and meat products was predictive (92% accuracy) of higher faecal calprotectin levels after food reintroduction. In faeces, butyrate levels, expressed as absolute concentration and relative abundance, were higher in Group A than Group B by 28.4 µmol/g (p = 0.015) and 6.4% (p = 0.008), respectively. Levels of gluten immunogenic peptide and starch in faeces did not differ between the two groups. CONCLUSIONS: This pilot study identified potential dietary triggers of gut inflammation in children with Crohn's disease after food reintroduction following treatment with exclusive enteral nutrition. TRIAL REGISTRATION: Clinical trials.gov registration number: NCT02341248; Clinical trials.gov URL: https://clinicaltrials.gov/ct2/show/NCT02341248 (retrospectively registered).
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Doença de Crohn , Nutrição Enteral , Criança , Doença de Crohn/terapia , Dieta , Humanos , Inflamação , Projetos Piloto , Indução de RemissãoRESUMO
OBJECTIVES: The aim of the study was to assess the efficacy, safety and side-effect profile of ferric carboxymaltose (FCM) for correcting IDA in children and adolescents in paediatric gastroenterology, hepatology, and nutrition. METHOD: This was a retrospective study of all gastroenterology patients <18 years who had FCM (October 2015 to October 2017). Haematological and biochemical parameters were recorded pre-infusion, at 4 weeks, 3 months, 6 months, and 1 year post-infusion. Recognised side-effects were documented. RESULTS: Sixty-six children received FCM during this period. Data was analysed on 61 children, 5 excluded because of inadequate data. The median age at administration was 14 years (IQR 7). Thirty-two (52%) were boys. Twenty-six (42%) were <14 years old. Seven (11.5%) were <5 years old. Seventeen (28%) were switched from oral iron supplements to FCM. The median dose of FCM delivered was 19âmg/kg. The median haemoglobin increased from 108 to 126âg/L at 1 month post-infusion (P value <0.00001). The mean cell volume also improved from 80 to 84âfL at 1 month post-infusion (P valueâ=â0.0007). Forty-eight (94%) children corrected their anaemia after receiving FCM. Two patients (3%) reported side-effects with skin bruising and staining. CONCLUSIONS: FCM appears to be effective in correcting IDA in children across a wide range of gastroenterology indications and all ages. It is effective and generally well tolerated including in very young patients. Potential side-effects can be avoided by careful monitoring during infusions.
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Anemia Ferropriva , Gastroenterologia , Adolescente , Anemia Ferropriva/tratamento farmacológico , Criança , Pré-Escolar , Compostos Férricos/efeitos adversos , Humanos , Infusões Intravenosas , Masculino , Maltose/análogos & derivados , Estudos RetrospectivosRESUMO
ABSTRACT: The use of thiopurine therapy in Epstein-Barr virus (EBV)-naïve inflammatory bowel disease (IBD) patients remains controversial due to a risk of EBV-associated complications. We evaluated EBV status and outcomes within our paediatric IBD population over an 8-year period; finding that 217 of 409 (53%) screened patients were seropositive for EBV at IBD diagnosis; that thiopurines were used in 189 of 217 (87%) seropositive and 159 of 192 (83%) seronegative patients (Pâ=â0.22); and that 7 of 192 (4%) previously seronegative patients subsequently tested positive for EBV with 6 of 7 (86%) patients having concurrently recorded thiopurine use. All six patients continued thiopurine with/without a period of cessation; no EBV-associated lymphoproliferative disorders/serious complications were recorded within our cohort. A significant proportion of our patients would not receive thiopurine therapy should their use be avoided in EBV-negative patients (47%) or seronegative males (30%). The small but significant risks of thiopurine treatment must be balanced against the potential benefits of successful IBD management; further research into this is required.
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Infecções por Vírus Epstein-Barr , Doenças Inflamatórias Intestinais , Transtornos Linfoproliferativos , Criança , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/epidemiologia , Herpesvirus Humano 4 , Humanos , Imunossupressores/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , MasculinoRESUMO
WHAT IS KNOWN AND OBJECTIVES: Despite the large body of evidence demonstrating equivalent efficacy and safety for branded drugs and their generic counterparts, some patients and providers have the perception that generics may be less safe and effective than branded agents. Authorized generics (AGs) are a category of generic drugs defined by the United States Food and Drug Administration (FDA) as being the same as the brand-name drug without the brand's name on the label and which may have minor differences, such as tablet or capsule markings for identification. Studies in which AGs are considered along with other generics may increase our understanding of factors that may influence perceptions about generics and shed light on areas where education may be impactful. The objectives of this paper are to provide information about AGs, review studies in which they have been evaluated and explore the role that AGs may fill in the individualized treatment of patients. METHODS: A literature review was conducted on 30 September 2019 with follow-up search on 4 March 2020. The search was focussed on published papers and meeting abstracts that provided information on AGs with respect to medical and health outcomes of therapy as well as switching in individuals receiving branded, AG, or other generic agents. Information about patients' perceptions of generic medications and adherence to therapy was also included. Additional information, including relevant government sources, such as the FDA website and the Federal Trade Commission Report, was included as appropriate. RESULTS: The literature specific to AGs is limited, but available data clearly highlight the importance of patient perception of generics as well as medication appearance as factors that may affect adherence and potentially more frequent switchbacks to branded agents from generics or AGs. WHAT IS NEW AND CONCLUSION: To our knowledge, this is the first narrative review to provide a summary of the published evidence about AGs with respect to clinical and health outcomes and switching. There is a need for more research and education regarding the use of AGs in clinical practice if they are to become more recognized as a potential treatment choice for patients. Generic medications play an important role in the healthcare system, and AGs may be able to provide an option to meet the specific needs of individual patients.
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Medicamentos Genéricos/uso terapêutico , United States Food and Drug Administration/normas , Uso de Medicamentos , Medicamentos Genéricos/administração & dosagem , Medicamentos Genéricos/efeitos adversos , Excipientes/normas , Conhecimentos, Atitudes e Prática em Saúde , Recursos em Saúde/estatística & dados numéricos , Serviços de Saúde/estatística & dados numéricos , Humanos , Preferência do Paciente , Equivalência Terapêutica , Estados UnidosRESUMO
OBJECTIVES: Health disparities across different socioeconomic subgroups have been reported in previous studies. Mortality with potentially inappropriate medication (PIM) use may be subject to similar disparities. We aimed to assess the association between PIM use and all-cause mortality and the effect of disparity parameters (sex, race, income, education, and location of residence) on this relationship. METHODS: This longitudinal cohort study included 26,399 U.S. adults aged 45 years and older from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, of which 13,475 participants were aged 65 years and older (recruited 2003-2007). PIM use and drug-drug interactions (DDIs) were identified through the 2015 Beers Criteria and a clinically significant DDIs list by the American Family Physicians, respectively. Cox regression was used to assess disparities in mortality with PIM use, iteratively adjusting for disparity parameters and other covariates. The full models included interaction terms between PIM use and other covariates. A similar method was used for the analyses of disparities in mortality with DDIs. RESULTS: Approximately 87% of older adults used at least 1 drug listed in the Beers Criteria, and 3.8% of all participants used 2 or more drugs with DDIs. In the adjusted analysis, an increased risk of mortality was observed among whites with PIM use (hazard ratio [HR] = 1.27 [95% CI 1.10-1.47]). The higher mortality rate was observed among blacks without PIM use (1.34 [1.09-1.65]). Lower income and education were independent predictors for higher mortality. CONCLUSION: Racial differences in all-cause mortality with PIM use were observed. Further research is needed to better understand the contributing factors of such disparities to develop appropriate interventions.
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Lista de Medicamentos Potencialmente Inapropriados , Acidente Vascular Cerebral , Idoso , Humanos , Prescrição Inadequada , Estudos Longitudinais , Fatores Raciais , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
OBJECTIVE: To examine patient and caregiver opinions and "receptivity" regarding generic drug educational material in terms of content, format and design, delivery channel, and level of satisfaction. METHODS: Interviewer-administered surveys were conducted with patients and caregivers who were clients of a regional medication management program or pharmacy services clinic to gather perceptions about generic drugs and input on a generic drug educational handout developed by the U.S. Food and Drug Administration (FDA). Survey questions were developed by the investigators and pretested before use. Data were analyzed using descriptive statistics, and responses to open-ended questions were assessed using qualitative content analysis. Survey psychometrics were examined using exploratory factor analysis (EFA). RESULTS: Of the 100 survey participants, most (93%) had positive perceptions about generic drug safety and effectiveness after reading the handout. Most participants were satisfied or very satisfied with the handout's content (87%) as well as format and design (92%). However, more than 20% of participants were still unsure about the benefits and risks of generic drugs compared with those of brand drugs, and more than 15% were still unsure about which benefits and risks mattered most to them. The participants' preferred source for the handout was a pharmacy (49%) or doctor's office (27%). In an EFA of the survey instrument, 2 factors emerged related to the educational handout's content: (1) generic drug information, a 7-item factor (Cronbach alpha = 0.882); and (2) personal relevance, a 3-item factor (Cronbach alpha = 0.692). CONCLUSION: The findings indicate an overall positive "receptiveness" toward generic drug informational materials from patients and caregivers, which highlights the feasibility and importance of educational outreach programs about generic drugs targeted toward this population. Future studies may focus on more diverse populations and tailor materials to the needs of specific patient and caregiver subgroups and health literacy levels.
Assuntos
Cuidadores , Medicamentos Genéricos , Atitude , Estudos Transversais , Humanos , Inquéritos e Questionários , Estados Unidos , United States Food and Drug AdministrationRESUMO
Patients with comorbid mental health and chronic conditions often receive care from both psychiatrists and primary care physicians (PCPs). The introduction of multiple providers into the care process introduces opportunities for disruptions in care continuity. The purpose of this study was to explore psychiatrists' and PCPs' comfort prescribing, along with their comfort having other physician specialties prescribe medications for cardiometabolic, psychiatric, and neurological/behavioral conditions. This cross-sectional study utilized an online, validated, pilot-tested, anonymous survey to examine prescribing practices of psychiatrists and PCPs. Eligible participants included physicians with medical degrees, U.S. prescribing authority, and active patient care for ≥2 days/week. Outcomes of interest were physicians' self-comfort and cross-specialty comfort (other specialists prescribing mutual patients' medications) prescribing cardiometabolic, psychiatric, and neurological/behavioral medications. Comfort prescribing was measured using 7-point Likert scales. Discrepancies in comfort were analyzed using student's, one-sample, and paired t-tests. Multiple linear regressions examined associations between physician practice characteristics and physicians' comfort-level prescribing cardiometabolic and psychiatric medication categories. Among 50 psychiatrists and 50 PCPs, psychiatrists reported significantly lower self-comfort prescribing cardiometabolic medications (mean ± SD = 2.99 ± 1.63 vs. 6.77 ± 0.39, p < 0.001), but significantly higher self-comfort prescribing psychiatric medications (mean ± SD = 6.79 ± 0.41 vs. 6.00 ± 0.88, p < 0.001) and neurological/behavioral medications (mean ± SD = 6.48 ± 0.74 vs. 5.56 ± 1.68, p < 0.001) than PCPs. After adjusting for covariates, physician specialty was strongly associated with self-comfort prescribing cardiometabolic and psychiatric medication categories (both p < 0.001). Differences between self-comfort and cross-specialty comfort were identified. Because comfort prescribing medications differed by physician type, incorporating psychiatrists through collaborative methods with PCPs could potentially ensure comfort among physicians when initiating medications.
Assuntos
Papel do Médico , Médicos de Atenção Primária , Padrões de Prática Médica , Atenção Primária à Saúde , Psiquiatria , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The COVID-19 pandemic is putting unprecedented pressures on healthcare systems globally. Early insights have been made possible by rapid sharing of data from China and Italy. In the UK, we have rapidly mobilised inflammatory bowel disease (IBD) centres in order that preparations can be made to protect our patients and the clinical services they rely on. This is a novel coronavirus; much is unknown as to how it will affect people with IBD. We also lack information about the impact of different immunosuppressive medications. To address this uncertainty, the British Society of Gastroenterology (BSG) COVID-19 IBD Working Group has used the best available data and expert opinion to generate a risk grid that groups patients into highest, moderate and lowest risk categories. This grid allows patients to be instructed to follow the UK government's advice for shielding, stringent and standard advice regarding social distancing, respectively. Further considerations are given to service provision, medical and surgical therapy, endoscopy, imaging and clinical trials.