Optimization of solid oral dosage form administration to patients with swallowing difficulties: An integrative review.

AIM: To appraise and synthesize research investigating optimizing the administration of solid oral dosage forms (SODFs) to adults with swallowing difficulties. DESIGN: An integrative review. METHODS: An electronic search was conducted on Medical Literature Analysis and Retrieval System Online (Public Medline interface), Elsevier SciVerse Scopus and Scientific Electronic Library Online (updated February 2023). Restriction regarding the publication date was not considered for the inclusion of records. Studies addressing risks, general aspects, recommendations about patient postural adjustments, swallowing techniques, swallowing aids and aspects of concealment of SODFs were included. RESULTS: Fifty-three records published between 2002 and 2021 were included. The main administration risks were aspiration, asphyxia and solid oral dosage form-induced oral/oesophageal mucosal lesions. The most frequent general aspect reported was administering one oral dosage form at a time. The sitting position was the most patient postural adjustment mentioned. The most frequently reported solid oral dosage form swallowing technique was the lean-forward method for capsules. Solid oral dosage form swallowing aids cited: tongue and throat lubricant and solid oral dosage form coating device, swallowing cup and swallowing straw. CONCLUSION: The literature data on administering SODFs for adults with swallowing difficulties were appraised and synthesized. Some aspects, for example, not administering SODFs simultaneously, can make swallowing safer. Postural adjustments and solid oral dosage form swallowing aids are important to avoid administration risks. Swallowing SODFs can be easier if learned by techniques. Liquid and food are helpful as vehicles, and several of these have been listed. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: By optimizing the contributing factors of administering oral pharmacotherapy, the nurse can use appropriate practices to improve patient safety. Additionally, knowing and establishing the administration aspects are reasonable steps for standardizing care for patients with swallowing oral dosage form difficulties. IMPACT: This study addressed administering SODFs to adult patients with swallowing difficulties. The administration of SODFs to adult patients with swallowing difficulties can be optimized if only one oral dosage form at a time is administrated and if patient postural adjustments, swallowing techniques and swallowing aids are used. This investigation will impact the care of patients with swallowing difficulties. REPORTING METHOD: The authors declare they adhered to the relevant EQUATOR guidelines and report following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Effectiveness of Calcitonin Gene-Related Peptide Monoclonal Antibodies in the Prevention of Migraine: A Systematic Review and Meta-Analysis of Observational Cohort Studies.

BACKGROUND AND OBJECTIVE: Migraine is a neurological disorder characterized by episodes of moderate-to-severe headache. The emergence of drugs derived from monoclonal antibodies specific for the calcitonin gene has brought forth a therapeutic option for patients in whom the traditional treatments have failed. This study aimed to evaluate the clinical effectiveness of calcitonin gene-related peptide antibodies in the prevention of migraine through a systematic review and meta-analysis of observational cohort studies. METHODS: A literature search for evidence was performed in electronic databases for observational studies that evaluated adult patients with migraine receiving calcitonin gene-related peptide receptor antagonists (e.g. erenumab, fremanezumab, galcanezumab and eptinezumab) and reported effectiveness outcomes (mean reduction in monthly migraine/headache days, and proportion of patients with 50% or greater reduction in migraine/headache days). RESULTS: During the screening process, 47 records were included for data extraction and qualitative and quantitative analyses. The overall rate of patients with a reduction of at least 50% of mean monthly migraine days was 54% (95% CI 49-59%), and overall mean monthly migraine reduction was about 7.7 days (95% CI 8.4-7.0 days). Regarding the outcome ≥ 50% reduction in mean monthly headache reduction, the overall rate of patients with a reduction of at least 50% was 57% (95% CI 48-64%), and the overall mean monthly headache reduction was approximately 8.8 days (95% CI 10.1-7.5 days). Subgroup analyses considering the drug treatment used and type of migraine were consistent with previous results. CONCLUSIONS: The use of calcitonin gene-related peptide antibodies in real-world studies to prevent migraine demonstrates promising effectiveness outcomes, in agreement with those reported in previously published randomized clinical trial reports.

Cost of Illness in Patients With COVID-19 Admitted in Three Brazilian Public Hospitals.

OBJECTIVES: The severity and transmissibility of COVID-19 justifies the need to identify the factors associated with its cost of illness (CoI). This study aimed to identify CoI, cost predictors, and cost drivers in the management of patients with COVID-19 from hospital and Brazil's Public Health System (SUS) perspectives. METHODS: This is a multicenter study that evaluated the CoI in patients diagnosed of COVID-19 who reached hospital discharge or died before being discharged between March and September 2020. Sociodemographic, clinical, and hospitalization data were collected to characterize and identify predictors of costs per patients and cost drivers per admission. RESULTS: A total of 1084 patients were included in the study. For hospital perspective, being overweight or obese, being between 65 and 74 years old, or being male showed an increased cost of 58.4%, 42.9%, and 42.5%, respectively. From SUS perspective, the same predictors of cost per patient increase were identified. The median cost per admission was estimated at US$359.78 and US$1385.80 for the SUS and hospital perspectives, respectively. In addition, patients who stayed between 1 and 4 days in the intensive care unit (ICU) had 60.9% higher costs than non-ICU patients; these costs significantly increased with the length of stay (LoS). The main cost driver was the ICU-LoS and COVID-19 ICU daily for hospital and SUS perspectives, respectively. CONCLUSIONS: The predictors of increased cost per patient at admission identified were overweight or obesity, advanced age, and male sex, and the main cost driver identified was the ICU-LoS. Time-driven activity-based costing studies, considering outpatient, inpatient, and long COVID-19, are needed to optimize our understanding about cost of COVID-19.

Análise dos custos diretos e indiretos da COVID-19 em um hospital brasileiro / Analysis of the direct and indirect costs of COVID-19 in a Brazilian hospital

Objetivo: Avaliar os custos diretos na perspectiva hospitalar e do Sistema Único de Saúde (SUS), bem como os custos indiretos de pacientes hospitalizados por COVID-19. Métodos: Estudo observacional com coleta de dados por micro e macrocusteio, realizado com pacientes admitidos por COVID-19 em um hospital paulista (março a setembro de 2020). Custos indiretos foram obtidos pelos métodos de capital humano e de anos de vida ajustados pela incapacidade (DALY). Análises de Mann-Whitney e regressão linear foram realizadas. Resultados: Foram incluídos 158 indivíduos com mediana de idade de 57 anos (IIQ 42-68 anos). A mediana de custo da internação na perspectiva do SUS e hospitalar foi de, respectivamente, R$ 2.009,46 (IIQ: R$ 1.649,11; R$ 4.847,36), principalmente devido à unidade de terapia intensiva (UTI), e R$ 19.055,91 (IIQ: R$ 8.399,47; R$ 38.438,00), principalmente devido a recursos humanos. Tempo total de internação (p < 0,001), óbito (p < 0,001) e ventilação invasiva (p < 0,001) foram preditores de aumento de custo. Foi identificada perda de 381,5 DALY e perda de produtividade de 128 anos, equivalente a US$ 855.307. Conclusão: Os principais direcionadores de custo foram recursos humanos e UTI. Entretanto, na perspectiva da sociedade, foi identificado o maior impacto devido à perda de produtividade e DALY. Tempo de hospitalização foi um dos grandes contribuidores do custo, e esse fator pode estar atrelado a gravidade da doença e protocolos de cuidado ao paciente.

Objective: To evaluate the direct costs from the hospital and Unified Health System (SUS) perspective, as well as the indirect costs of patients hospitalized by COVID-19. Methods: Observational study with data collection by micro- and macro-costing, carried out with patients hospitalized in a hospital in São Paulo (March-September 2020). Indirect costs were obtained using human capital and disability-adjusted life years (DALY) methods. Mann-Whitney and linear regression analyzes were performed. Results: 158 individuals were included, with a median age of 57 years (IQR 42-68 years). The median cost of admission in the SUS and hospital perspective was, respectively, R$ 2,009.46 (IQR: R$ 1,649.11; R$ 4,847.36), mainly due to the intensive care unit (ICU) and R$ 19,055.91 (IQR: R$ 8,399.47; R$ 38,438.00), mainly due to human resources. The total length of stay in hospital (p < 0.001), death (p < 0.001) and invasive ventilation (p < 0.001) were predictors of cost increase.

Efficacy and safety of immunotherapies for the treatment of high-grade gliomas: a systematic review and meta-analysis

Background/Aim: High-grade gliomas are aggressive brain neoplasms usually refractory to treatment. Recently new treatment approaches have emerged, including immunotherapies. Hence, the aim of the present study was to evaluate the efficacy and safety of immunotherapies in adult patients with high-grade gliomas. Methods: Searches were performed in three databases for relevant studies published until December 2020. Title and abstract screening, full-text review, data extraction, and risk of bias assessment were performed independently by two reviewers. Risk of bias assessment was performed according to the revised Cochrane risk-of-bias tool for randomized trials (RoB 2). Meta-analyses were performed with Review Manager software (version 5.4.1), using risk ratio and 95% confidence intervals as measure of effect, the Mantel-Haenszel method, and random effects models. The quality of evidence assessment was conducted according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Nineteen studies were included in the systematic review, of which 15 reported comparable data for meta-analyses. The outcomes assessed in the meta-analyses were overall survival (OS) and progression-free survival (PFS), with subgroups at 6, 12, and more than 12 months. No statistical differences were observed between immunotherapy and conventional treatment, except for the OS subgroup over 12 months. The certainty on the evidence was moderate. Conclusion: There was no evidence of an additional benefit of immunotherapy compared to standard treatment in the synthesis of results from clinical trials. Further high-quality clinical trials are needed to improve the quality of evidence concerning immunotherapies for the treatment of high-grade gliomas.

Cost-Effectiveness of Molecular Method Diagnostic for Rapid Detection of Antibiotic-Resistant Bacteria.

OBJECTIVES: This study aimed to perform a cost-effectiveness analysis (CEA) of the molecular diagnostic method (MM) associated with conventional diagnostic method (CM) compared with the CM alone, for the detection of resistant profile in bacteremia, from the perspective of the Brazilian Public Health System, in intensive care units setting. METHODS: The clinical parameters regarding methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Gram-negative bacteria (CRGNB), and vancomycin-resistant Enterococcus spp. (VRE) infections were collected from searches on PubMed, Scopus, and SciELO, using specific keywords. Data on direct medical costs to treat these infections were collected according to Brazilian Public Health System perspective from Brazilian databases, in tables of 2018 to 2019. CEA was performed after building a dynamic model, which was calibrated and validated according to international recommendations. The incremental cost-effectiveness ratio of the MM + CM compared with the CM was calculated using the outcomes "avoided death" and "avoided resistant infections." One-way sensitivity analyses were performed. RESULTS: This CEA demonstrated that the MM + CM was dominant in all scenarios. Estimates showed that for MRSA, CRGNB, and VRE infections, every avoided death would lead to savings of Brazilian real (R$) 4.9 million ($937 301), R$2.2 million ($419 899), and R$1.3 million ($248 919), respectively. The same infections assessed by avoided resistant infections savings were projected to be R$24 964 ($4686), R$40 260 ($7558), and R$23 867 ($4480). CONCLUSIONS: MM leads to cost reduction and increased benefits, optimizing the use of financial resources on the health system in the intensive care unit setting, in bacteremia caused by MRSA, CRGNB, and VRE.

Solid Oral Dosage Forms Use in Adults with Neurological Disorders and Swallowing Difficulties: A Scoping Review.

Swallowing difficulties affects the deglutition of solid oral dosage forms (SODFs) and it is a common problem among neurological disorders. Interventions may improve the use of SODFs in healthcare settings. The aim of this study was to map the available research about the interventions aiming the effective and safe use of SODFs in adults with neurological disorders and swallowing difficulties and to identify potential literature gaps in this scientific field. A scoping review was carried out based on Joanna Briggs Institute guidelines and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, in PubMed, Scopus, and SciELO databases (March 2021). Peer-reviewed observational studies assessed the effectiveness and safety of SODFs in adults with neurological disorders and swallowing difficulties in the healthcare organizations setting were included. 11 studies were included (three case reports, two mixed-methods intervention studies, and six analytic studies). The frequency of women ranged from 49 to 67%, and the age from 57 to 91 years. Most studies (n = 7) included elderly patients, Parkinson (n = 6) and dementia (n = 3). Medication review was the most frequently reported intervention, 35% (9/26). In most studies, interventions were targeted to patients during hospitalization (n = 7) and performed by physicians (n = 8). At least 20 different outcomes were evaluated in the studies. Implementing specific protocols for using SODFs aimed at the swallowing difficulties of this population is not a common practice. Additional studies on interventions aimed at optimizing SODFs are needed to support the safety and efficacy of oral therapy in this patient group.

Manifestações oculares da artrite reumatoide e positividade de autoanticorpos: uma revisão sistemática / Ocular manifestations of rheumatoid arthritis and autoantibodies positivity: a systematic review

Contexto: As manifestações oculares da artrite reumatoide representam cerca de 40% das manifestações extra-articulares, acarretando comprometimento da qualidade de vida. O fator reumatoide e o anticorpo contra peptídeos citrulinados cíclicos são marcadores sorológicos para diagnóstico laboratorial da doença. Objetivo: Identificar as principais manifestações oculares da artrite reumatoide e a sua relação com a positividade do fator reumatoide e anticorpo contra peptideos citrulinados cíclicos, através de uma revisão sistemática. Métodos: Uma revisão sistemática foi conduzida nas bases de dados: PubMed, Scopus, Web of Science e SciELO, até janeiro de 2018. Critérios de inclusão e exclusão foram aplicados e dados dos estudos selecionados foram extraídos e organizados em tabelas e gráficos. Avaliação metodológica e análise estatística, incluindo duas meta-análises, foram realizadas. Os estudos selecionados foram armazenados no Software Endnote X8 versão student (Serial Number: 3151802521 e Product Key: L899B-8N8FJ-SX9JW-BEQ58-U9HCD). Análises estatísticas foram realizadas com o Software Review Manager versão 5.3 (software gratuito). Resultados: Dos 1.985 estudos encontrados através da busca em bases de dados, quatro estudos foram incluídos. A síndrome sicca e síndrome de Sjögren secundária representaram cerca de 50% das manifestações oculares. Meta-análises aplicadas em dois estudos não identificaram associação de risco estatisticamente significativa entre o anticorpo contra peptideos citrulinados cíclicos e fator reumatoide e o desenvolvimento de manifestações oculares. Conclusão: As manifestações oculares da Artrite Reumatoide correspondem à significativa parcela das manifestações extra-articulares. No entanto, não foram constatadas associação de risco entre autoanticorpos e tais manifestações. [au]

Background: Ocular involvement represents about 40% of extra-articular manifestations of Rheumatoid Arthritis, pointing to impairment in patients' quality of life. Anti-cyclic citrullinated peptide antibody and rheumatoid factor are serological markers to laboratorial diagnosis of disease. Objective: Identify main ocular manifestations of Rheumatoid Arthritis and its relationship between positivity of rheumatoid factor and anti-cyclic citrullinated peptide antibody, through a Systematic Review of literature. Methods: Systematic Review was conducted on database search, including: PubMed, Scopus, Web of Science and SciELO until January, 2018. Inclusion and exclusion criteria were applied and data of select studies were extracted and organized in tables and graphics. Methodological appraisal and statistical analysis, including meta-analyses, were performed. Selected studies were stored in software Endnote X8 student (Serial Number: 3151802521 e Product Key: L899B-8N8FJ-SX9JW-BEQ58-U9HCD). Statistical analyses were performed with Review Manager software version 5.3 (free software). Results: From 1,985 studies found by database search, four studies were selected and analyzed. Sicca syndrome and secondary Sjögren's syndrome represented about 50% of ocular manifestations. Meta-analyses applied in two studies demonstrated no statistical significative risk association between anti-cyclic citrullinated peptide and development of ocular manifestations. Conclusion: From extra-articular manifestations of Rheumatoid Arthritis, ocular manifestations correspond to a significative amount. Nevertheless, there were no statistical significative risk association between autoantibodies and these manifestations. [au]

Safety of Antiretroviral Therapy in the Treatment of HIV/AIDS in Children: Systematic Review and Meta-analysis.

The safety of using different antiretroviral therapies (ART) in pediatric HIV/AIDS patients is not well-established. Therefore, this study aimed to assess the safety of ART in children. A systematic review of randomized clinical trials (RCTs) was conducted to assess the safety of ART used by pediatric patients living with HIV/AIDS. The electronic search was conducted in PubMed and Scopus, in addition to a manual search. Studies were included if they assessed the safety of ART compared to placebo or another ART. Direct and indirect meta-analyses were conducted regarding safety outcomes. The systematic review included 21 RCTs. The studies included more than 5500 participants, and age ranged from 3 months to 18 years. The drugs evaluated were nucleoside reverse transcriptase inhibitors (NRTI); non-NRTI; and protease inhibitors. The predominant route of infection was vertical. Direct meta-analyses were performed for the outcomes sleep disorders, hepatobiliary disorders, respiratory disorders, hypertransaminasemia, neutropenia, hospitalization, and death. For these outcomes, no statistically significant differences were found. Indirect meta-analyses were performed for the outcomes anemia, gastrointestinal disorders, liver disorders, severe adverse events (AE), AE that led to changes in treatment, fever, and skin manifestations. However, no statistically significant differences were found for these outcomes. In this study, non-significant differences were detected in the safety of different ART used in pediatric individuals. The choice of appropriate therapy should be based on its efficacy and the individual characteristics of each patient.

Diagnosis and prediction of COVID-19 severity: can biochemical tests and machine learning be used as prognostic indicators?

OBJECTIVE: This study aimed to implement and evaluate machine learning based-models to predict COVID-19' diagnosis and disease severity. METHODS: COVID-19 test samples (positive or negative results) from patients who attended a single hospital were evaluated. Patients diagnosed with COVID-19 were categorised according to the severity of the disease. Data were submitted to exploratory analysis (principal component analysis, PCA) to detect outlier samples, recognise patterns, and identify important variables. Based on patients' laboratory tests results, machine learning models were implemented to predict disease positivity and severity. Artificial neural networks (ANN), decision trees (DT), partial least squares discriminant analysis (PLS-DA), and K nearest neighbour algorithm (KNN) models were used. The four models were validated based on the accuracy (area under the ROC curve). RESULTS: The first subset of data had 5,643 patient samples (5,086 negatives and 557 positives for COVID-19). The second subset included 557 COVID-19 positive patients. The ANN, DT, PLS-DA, and KNN models allowed the classification of negative and positive samples with >84% accuracy. It was also possible to classify patients with severe and non-severe disease with an accuracy >86%. The following were associated with the prediction of COVID-19 diagnosis and severity: hyperferritinaemia, hypocalcaemia, pulmonary hypoxia, hypoxemia, metabolic and respiratory acidosis, low urinary pH, and high levels of lactate dehydrogenase. CONCLUSION: Our analysis shows that all the models could assist in the diagnosis and prediction of COVID-19 severity.

Analysis of completeness for spontaneous reporting of disease-modifying therapies in multiple sclerosis.

Introduction: Considering the need for effective postmarketing surveillance of disease-modifying therapies (DMTs) in multiple sclerosis (MS), we analyzed the potential of the spontaneous reports for safety signal detection, verifying the completeness of the reports in the FDA Adverse Event Reporting System (FAERS).Methods: All reports with DMTs for MS considered the primary suspect cause of ADRs and registered between January 2004 and June 2019 were selected. The vigiGrade completeness score was applied and reports with a score greater than 0.80 were considered well documented. Descriptive statistical analysis and comparisons of well-documented reports by DMTs were performed.Results: A total of 297,926 reports were analyzed. The lowest completeness rates were observed for type of report (13.5%), dose (62.7%), and time from treatment start to the ADR (79.0%). Overall, 80.8% of reports were classified as well documented and those related to natalizumab had the highest proportion (92.4%, p < 0.001), while the lowest was observed for reports sent in 2017 (53.1%, p < 0.001) and for teriflunomide (48.5%, p < 0.001).Conclusions: The high proportion of well-documented reports for DMTs indicates that they can be a valuable source for safety signal detection. A more careful analysis should be performed for data from the groups identified with low completeness to avoid the disclosure of spurious results.

Evaluation of the epidemiological aspects and the impact of COVID-19 on tuberculosis notifications in São Paulo

Objective: This study aimed to analyze the incidence and epidemiological profile of tuberculosis (TB) cases registered in a region of the State of São Paulo (SP) and to assess the impact of COVID19 on TB incidence and completeness of notifications. Methods: This is a retrospective crosssectional study analyzing reports of adult patients with TB, who were notified in the TB-Web from January 2010 to December 2020. Sociodemographic (e.g. sex, race and scholarity) and clinical variables (e.g., clinical form, types of cases and comorbidities) were collected and analyzed. The completeness of TB notifications and the impact of COVID-19 on TB notifications were evaluated, considering the year of 2020. The study was reported following Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cross-sectional studies [CAAE 33166620.0.0000.0102]. Results: A total of 1,509 notifications were included, with a mean incidence of 48.5/100,000 inhabitants. The median age was 42 years, most notification included males (71%), were of white race (42%) and had the pulmonary form of TB (85%). In assessing the impact of the pandemic on notifications in 2020, there was a decrease of 36% in the number of TB notifications, with an emphasis between July and August, which was the peak period of COVID-19 cases in the region. No change in the completeness of TB notifications was observed in this period. Conclusions: Results indicate the clinical and epidemiological profile in a region of SP between 2010 and 2020. The pandemic led to a decrease in the number of TB notifications but did not change the completeness of notifications.

Possíveis desfechos de longo prazo da Covid-19: uma revisão sistemática de escopo / Possible long-term outcomes of Covid-19: a systematic scoping review

Objetivo: mapear os possíveis desfechos de longo prazo da COVID-19 no mundo. Métodos: em acordo com as recomendações do Joanna Briggs Institute, foi realizada uma revisão sistemática de escopo de estudos experimentais e observacionais com busca nas bases de dados PubMed e Scopus, complementada por busca manual. Resultados: de 5.325 registros, 121 atenderam aos critérios de elegibilidade, os quais incluíram 1.638 recuperados da COVID-19. Foram identificados 52 potenciais desfechos de longo prazo da COVID-19, principalmente disfunção olfatória (n=605), disfunção gustativa (n=372), dispneia (n=233) e lesões pulmonares (n=225). Entre os cuidados de longo prazo, destacam-se início de terapia medicamentosa, terapia de substituição renal e amputação. Conclusão: foram mapeados 52 possíveis desfechos de longo prazo da COVID-19 e recomendações de continuação de cuidados, que variaram de manifestações leves a graves com duração menor ou igual a um mês e maior que um mês.

Objective: to map these possible long-term outcomes of COVID-19 worldwide. Methods: In accordance with the recommendations of the Joanna Briggs Institute, a systematic scoping review of experimental and observational studies was carried out with a search in PubMed and Scopus databases, complemented by manual search. Results: Of 5,325 records, 121 met eligibility criteria, which included 1,638 recovered from COVID-19. Fifty-two (52) potential long-term outcomes of COVID-19 were identified, mainly olfactory dysfunction (n=605), taste dysfunction (n=372), dyspnea (n=233) and lung injuries (n=225). Long-term care included initiation of drug therapy, renal replacement therapy and amputation. Conclusion: Fifty-two (52) possible long-term outcomes of COVID-19 and recommendations for continued care were mapped, ranging from mild to severe manifestations lasting less than or equal to one month and greater than one month.

Fecal microbiota transplantation in inflammatory bowel disease patients: A systematic review and meta-analysis.

OBJECTIVES: Current evidence on fecal microbiota transplantation for inflammatory bowel disease is inconclusive. We conducted a systematic review to gather evidence on the efficacy and safety of fecal microbiota transplantation for inflammatory bowel disease. METHODS: Systematic searches were conducted in PubMed, Scopus, and Web of Science. Clinical remission was considered as the primary endpoint. Pairwise meta-analyses were performed for the randomized controlled studies (Mantel Haenszel, random effects model). Proportion meta-analyses, accounting for weighted pooled rates reported in the interventional studies, were conducted using the mixed effects model. Subgroup analyses considering the type of stool, donor type, and disease subtype were also performed. Cumulative meta-analyses to assess further needs of evidence were conducted. RESULTS: Sixty studies were included, from which 36 could be synthesized in the quantitative analyses. Pairwise meta-analyses of six controlled trials showed significant differences in favor of fecal microbiota transplantation compared with placebo (clinical remission: RR 1.70 [95% CI 1.12, 2.56]; clinical response: RR 1.68 [95% CI 1.04, 2.72]). An overall clinical remission of 37%, overall clinical response of 54%, and a prevalence of 29% of adverse events were found for the interventional studies. Frozen fecal material and universal donors were related to better efficacy outcomes. In addition, Crohn's disease patients seemed to benefit more from the procedure. CONCLUSIONS: The comparative analyses demonstrated that frozen fecal material from universal donors may be related to a higher rate of clinical remission, especially for Crohn's disease.

Outcome measures for disease-modifying therapies in relapsing multiple sclerosis randomized clinical trials: a scoping review protocol.

OBJECTIVE: The objective of the review is to explore randomized controlled trials on disease-modifying therapies for relapsing multiple sclerosis to identify and quantify the different outcome measures, instruments and definitions of efficacy, safety outcomes, health-related quality of life instruments and population subgroups. INTRODUCTION: A wide range of therapies are available for relapsing multiple sclerosis, as well as a wide range of outcome measures and definitions, which can be explained by the absence of a core outcome set for this disease. Establishing a core outcome set is fundamental for guiding future studies as they improve the consistency and relevance of new findings and enable the results of trials to be compared and combined. These features are especially important for relapsing multiple sclerosis due to the limited number of head-to-head studies on this disease. Although many systematic reviews and meta-analyses have focused on the efficacy and safety of disease-modifying therapies in relapsing multiple sclerosis, none have had the specific objective of mapping outcome measures. INCLUSION CRITERIA: This review will consider randomized controlled trials that explore populational subgroups, efficacy, safety outcomes, health-related quality of life instruments and their definitions in the context of disease-modifying therapies for adults with relapsing multiple sclerosis. METHODS: Electronic searches will be performed in PubMed, Scopus, the Cochrane Library, ClinicalTrials.gov, and JBI Evidence Synthesis with no time limit. Two researchers will independently select registries (screening and eligibility steps) and extract data on study characteristics, outcome measures, definitions and population subgroups. Data will be presented in graphical or tabular form, accompanied by a narrative summary.

Efficacy outcomes reported in trials of multiple sclerosis: A systematic scoping review.

BACKGROUND: This study aimed to map the outcome measures of clinical efficacy reported in Randomized Controlled Trials (RCT) to evaluate disease-modifying therapies (DMT) in patients with relapsing forms of multiple sclerosis (RMS). METHODS: A systematic scoping review was performed to identify RCT that assessed the efficacy of DMT in adult patients with RMS. Searches were conducted in PubMed, Scopus, and The Cochrane Controlled Register of Trials and complemented by manual search. A descriptive-quantitative analysis of the clinical efficacy outcomes with their respective definitions was performed. RESULTS: Of the 5,476 records identified, 226 were included. Among the included studies, 89% reported clinical efficacy outcomes, with 77 different outcomes identified, including five composite outcomes. A total of 36 different definitions for 'relapse' were identified. 'Annualized relapse rate' was the most prevalent single outcome (n = 56 studies). At the same time, the 'Proportion of patients with no evidence of radiological and clinic disease activity' was the most prevalent composite outcome (n = 14 studies) although with six different definitions. CONCLUSIONS: An absence of consensus on the clinical efficacy outcomes reported in RCT associated with a wide heterogeneity of definitions were identified. The mapped results of this research can be used as a basis for the definition of a core outcome set for clinical efficacy outcomes in adults with RMS.

Reliability in long-term clinical studies of disease-modifying therapies for relapsing-remitting multiple sclerosis: A systematic review.

BACKGROUND: Although relapsing-remitting multiple sclerosis (RRMS) has a chronic course, little information is known about the comparison between the disease-modifying therapies (DMT) for long-term outcomes. We aimed to conduct a systematic review of randomized clinical trial (RCT) extension and observational studies to examine the efficacy and safety of all available DMT for RRMS, compare the evidence with that derived from mid-term studies, and investigate whether the published long-term data are robust and reliable enough to inform clinical decision-making concerning RRMS treatment. METHOD: PubMed, Scopus, and manual searches were performed until October 2019. The clinical outcomes of long- and mid-term studies were compared. ROBINS-I was used to assess the methodological qualities of the long-term studies. PROSPERO number CRD42019123361. RESULTS: Nineteen long-term studies (9,018 participants) were included in the systematic review. All studies presented serious or critical risks of bias that were mainly due to confounding, selection, and missing data biases. The annualised relapse rates (ARR) observed in the long-term studies are lower (better) than those from the mid-term studies for most treatments. The main reason for this ARR decrease could be a selection bias for good responders in the long-term studies, since many studies show a loss of patients between the mid- and long-term phases. The safety profiles depend on the study, follow-up, report, and outcome (i.e., discontinuation or number of patients with at least one serious adverse event). CONCLUSION: The currently available long-term data for patients with RRMS exhibit serious or critical risks of bias that preclude robust comparisons between long-term studies. High quality comparative observational studies with long-term follow-ups or RCT extensions with intention-to-treat analyses are needed to support clinical and regulatory practice. Until reliable long-term evidence is available, neurologists should continue to base their conduct on mid-term studies, patient`s experience and, most importantly, patient`s needs and predictor factors, according to personalized medicine.

Evaluation of the application of the Diabetes Quality of Life Questionnaire in patients with diabetes mellitus.

Objective Diabetes mellitus (DM) is a chronic disease with great impact on patients' quality of life (QoL). This variable can be measured using reliable, standardized, and validated instruments. The purpose of this study was to evaluate the application and reporting of the Diabetes Quality of Life Measure (DQOL) or the Diabetes Quality of Life for Youths Measure (DQOLY), an adapted version for young patients with DM. Materials and methods A systematic review of interventional and observational studies using the DQOL or DQOLY was performed. Searches were conducted in the electronic databases Medline, Scopus, Web of Science, Lilacs, and SciELO. Results After conducting the searches, 111 studies met the inclusion criteria and were included in the qualitative analysis. Of these, 32 studies were classified as interventional and 79 as observational, with 27,481 patients. The DQOL was applied in 82 studies, the DQOLY in another 27, and two studies used both instruments. DM was classified as type 1 DM in 69 studies and type 2 DM in 35 studies. Six studies included both patients. Improvement in patients' QoL after an intervention was observed in 13 interventional studies. Most of the studies (90%) provide a detailed description of the instrument and 52% the previous validation. The interpretation of the scores obtained varies among the studies, probably due to the differences inherent in cultural validations, translations, and adaptations. Conclusion The application of the instruments in clinical practice must be rigorously standardized and requires an accurate understanding of psychometric and statistical concepts. Arch Endocrinol Metab. 2020;64(1):59-65.

Evaluation of the application of the Diabetes Quality of Life Questionnaire in patients with diabetes mellitus

ABSTRACT Objective Diabetes mellitus (DM) is a chronic disease with great impact on patients' quality of life (QoL). This variable can be measured using reliable, standardized, and validated instruments. The purpose of this study was to evaluate the application and reporting of the Diabetes Quality of Life Measure (DQOL) or the Diabetes Quality of Life for Youths Measure (DQOLY), an adapted version for young patients with DM. Materials and methods A systematic review of interventional and observational studies using the DQOL or DQOLY was performed. Searches were conducted in the electronic databases Medline, Scopus, Web of Science, Lilacs, and SciELO. Results After conducting the searches, 111 studies met the inclusion criteria and were included in the qualitative analysis. Of these, 32 studies were classified as interventional and 79 as observational, with 27,481 patients. The DQOL was applied in 82 studies, the DQOLY in another 27, and two studies used both instruments. DM was classified as type 1 DM in 69 studies and type 2 DM in 35 studies. Six studies included both patients. Improvement in patients' QoL after an intervention was observed in 13 interventional studies. Most of the studies (90%) provide a detailed description of the instrument and 52% the previous validation. The interpretation of the scores obtained varies among the studies, probably due to the differences inherent in cultural validations, translations, and adaptations. Conclusion The application of the instruments in clinical practice must be rigorously standardized and requires an accurate understanding of psychometric and statistical concepts. Arch Endocrinol Metab. 2020;64(1):59-65

Targeting of intragraft reactive oxygen species by APP-103, a novel polymer product, mitigates ischemia/reperfusion injury and promotes the survival of renal transplants.

Inflammatory responses associated with ischemia/reperfusion injury (IRI) play a central role in alloimmunity and transplant outcomes. A key event driving these inflammatory responses is the burst of reactive oxygen species (ROS), with hydrogen peroxide (H2 O2 ) as the most abundant form that occurs as a result of surgical implantation of the donor organ. Here, we used a syngeneic rat renal transplant and IRI model to evaluate the therapeutic properties of APP-103, a polyoxalate-based copolymer molecule containing vanillyl alcohol (VA) that exhibits high sensitivity and specificity toward the production of H2 O2 . We show that APP-103 is safe, and that it effectively promotes kidney function following IRI and survival of renal transplants. APP-103 reduces tissue injury and IRI-associated inflammatory responses in models of both warm ischemia (kidney clamping) and prolonged cold ischemia (syngeneic renal transplant). Mechanistically, we demonstrate that APP-103 exerts protective effects by specifically targeting the production of ROS. Our data introduce APP-103 as a novel, nontoxic, and site-activating therapeutic approach that effectively ameliorates the consequences of IRI in solid organ transplantation.