Methodological quality and clinical recommendations of guidelines on the management of dyslipidaemias for cardiovascular disease risk reduction: a systematic review and an appraisal through AGREE II and AGREE REX tools.

BACKGROUND: Clinical practice guidelines (CPGs) are statements to assist practitioners and stakeholders in decisions about healthcare. Low methodological quality guidelines may prejudice decision-making and negatively affect clinical outcomes in non-communicable diseases, such as cardiovascular diseases worsted by poor lipid management. We appraised the quality of CPGs on dyslipidemia management and synthesized the most updated pharmacological recommendations. METHODS: A systematic review following international recommendations was performed. Searches to retrieve CPG on pharmacological treatments in adults with dyslipidaemia were conducted in PubMed, Scopus, and Trip databases. Eligible articles were assessed using AGREE II (methodological quality) and AGREE-REX (recommendation excellence) tools. Descriptive statistics were used to summarize data. The most updated guidelines (published after 2019) had their recommendations qualitatively synthesized in an exploratory analysis. RESULTS: Overall, 66 guidelines authored by professional societies (75%) and targeting clinicians as primary users were selected. The AGREE II domains Scope and Purpose (89%) and Clarity of Presentation (97%), and the AGREE-REX item Clinical Applicability (77.0%) obtained the highest values. Conversely, guidelines were methodologically poorly performed/documented (46%) and scarcely provided data on the implementability of practical recommendations (38%). Recommendations on pharmacological treatments are overall similar, with slight differences concerning the use of supplements and the availability of drugs. CONCLUSION: High-quality dyslipidaemia CPG, especially outside North America and Europe, and strictly addressing evidence synthesis, appraisal, and recommendations are needed, especially to guide primary care decisions. CPG developers should consider stakeholders' values and preferences and adapt existing statements to individual populations and healthcare systems to ensure successful implementation interventions.

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.

Bioactive compounds as potential angiotensin-converting enzyme II inhibitors against COVID-19: a scoping review.

OBJECTIVE AND DESIGN: The current study aimed to summarize the evidence of compounds contained in plant species with the ability to block the angiotensin-converting enzyme 2 (ACE-II), through a scoping review. METHODS: PubMed and Scopus electronic databases were used for the systematic search and a manual search was performed RESULTS: Studies included were characterized as in silico. Among the 200 studies retrieved, 139 studies listed after the exclusion of duplicates and 74 were included for the full read. Among them, 32 studies were considered eligible for the qualitative synthesis. The most evaluated class of secondary metabolites was flavonoids with quercetin and curcumin as most actives substances and terpenes (isothymol, limonin, curcumenol, anabsinthin, and artemisinin). Other classes that were also evaluated were alkaloid, saponin, quinone, substances found in essential oils, and primary metabolites as the aminoacid L-tyrosine and the lipidic compound 2-monolinolenin. CONCLUSION: This review suggests the most active substance from each class of metabolites, which presented the strongest affinity to the ACE-II receptor, what contributes as a basis for choosing compounds and directing the further experimental and clinical investigation on the applications these compounds in biotechnological and health processes as in COVID-19 pandemic.

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.

The naturally-derived alkaloids as a potential treatment for COVID-19: A scoping review.

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has a high mortality rate and transmissibility. In this context, medicinal plants have attracted attention due to the wide availability and variety of therapeutic compounds, such as alkaloids, a vast class with several proven pharmacological effects, like the antiviral and anti-inflammatory activities. Therefore, this scoping review aimed to summarize the current knowledge of the potential applicability of alkaloids for treating COVID-19. A systematic search was performed on PubMed and Scopus, from database inception to August 2021. Among the 63 eligible studies, 65.07% were in silico model, 20.63% in vitro and 14.28% clinical trials and observational studies. According to the in silico assessments, the alkaloids 10-hydroxyusambarensine, cryptospirolepine, crambescidin 826, deoxynortryptoquivaline, ergotamine, michellamine B, nigellidine, norboldine and quinadoline B showed higher binding energy with more than two target proteins. The remaining studies showed potential use of berberine, cephaeline, emetine, homoharringtonine, lycorine, narciclasine, quinine, papaverine and colchicine. The possible ability of alkaloids to inhibit protein targets and to reduce inflammatory markers show the potential for development of new treatment strategies against COVID-19. However, more high quality analyses/reviews in this field are necessary to firmly establish the effectiveness/safety of the alkaloids here described.

Cost-effectiveness of amphotericin B formulations in the treatment of systemic fungal infections.

Amphotericin formulations, indicated for invasive fungal infections (IFIs), vary in effectiveness, safety and costs. In Brazil, only the conventional formulation is provided by the Public Health System. The aim of this study was to perform a cost-effectiveness analysis comparing conventional amphotericin B (CAB), liposomal amphotericin B (LAB) and amphotericin B lipid complex (ABLC). Therefore, a decision tree was developed. The model began with high-risking patients on suspicion or confirmation of IFI. The analysis was conducted under the perspective of the Brazilian Public Health System. Model health states were defined according to medication use and clinical evolution. Clinical efficacy (cure) and transition probabilities were derived from the literature. Resource use was estimated from Brazilian data. Time horizon followed the maximum treatment time determined in the patient information leaflets (3 or 6 weeks). One-way and probabilistic-sensitivity analyses were conducted. The conventional formulation was the most cost-effective. No dominance was observed; however, high incremental cost-effectiveness ratios were obtained for LAB (USD 313 130) and ABLC (USD 1 711 280). Sensitivity analyses demonstrated the robustness of the results. CAB is the most cost-effective treatment, followed by LAB and ABLC. Although CAB presents critical safety aspects, the high acquisition costs of the other formulations prevent their large-scale use in Brazil.

Fluconazole Doses Used for Prophylaxis of Invasive Fungal Infection in Neonatal Intensive Care Units: A Network Meta-Analysis.

OBJECTIVES: To evaluate the safety and efficacy of different doses of fluconazole used for invasive prophylaxis of fungal infection in neonates. STUDY DESIGN: A systematic search was conducted with PubMed, Scopus, and Web of Science. A manual search was performed as well. Only randomized controlled trials of neonates in a neonatal intensive care unit (NICU) who received fluconazole prophylaxis for invasive fungal infection, regardless of the dose or therapeutic regimen, were included in this review. Data on baseline characteristics, outcomes incidence of proven invasive Candida infection, overall mortality, and invasive Candida infection-related mortality were extracted. RESULTS: Eleven studies were included in the review, with fluconazole doses of 3, 4, or 6?mg/kg. When the incidence of invasive Candida and invasive Candida-related mortality were considered as outcomes, the 3 and 6?mg/kg fluconazole doses were found to be statistically superior to placebo (OR, 5.48 [95% credible interval, 1.81-18.94] and 2.63 [1.18-7.02], respectively, and 15.32 [1.54-54.31] and 9.14 [1.26-142.7], respectively), but data for the 3 doses were not statistically significantly different. CONCLUSIONS: Use of the lowest fluconazole dose (3?mg/kg) should be recommended for Candida prophylaxis in neonates, given that increasing the fluconazole dose is not associated with higher efficacy and has greater potential for toxicity and increased cost.

Novel COVID-19 biomarkers identified through multi-omics data analysis: N-acetyl-4-O-acetylneuraminic acid, N-acetyl-L-alanine, N-acetyltriptophan, palmitoylcarnitine, and glycerol 1-myristate.

This study aims to apply machine learning models to identify new biomarkers associated with the early diagnosis and prognosis of SARS-CoV-2 infection.Plasma and serum samples from COVID-19 patients (mild, moderate, and severe), patients with other pneumonia (but with negative COVID-19 RT-PCR), and healthy volunteers (control) from hospitals in four different countries (China, Spain, France, and Italy) were analyzed by GC-MS, LC-MS, and NMR. Machine learning models (PCA and PLS-DA) were developed to predict the diagnosis and prognosis of COVID-19 and identify biomarkers associated with these outcomes.A total of 1410 patient samples were analyzed. The PLS-DA model presented a diagnostic and prognostic accuracy of around 95% of all analyzed data. A total of 23 biomarkers (e.g., spermidine, taurine, L-aspartic, L-glutamic, L-phenylalanine and xanthine, ornithine, and ribothimidine) have been identified as being associated with the diagnosis and prognosis of COVID-19. Additionally, we also identified for the first time five new biomarkers (N-Acetyl-4-O-acetylneuraminic acid, N-Acetyl-L-Alanine, N-Acetyltriptophan, palmitoylcarnitine, and glycerol 1-myristate) that are also associated with the severity and diagnosis of COVID-19. These five new biomarkers were elevated in severe COVID-19 patients compared to patients with mild disease or healthy volunteers.The PLS-DA model was able to predict the diagnosis and prognosis of COVID-19 around 95%. Additionally, our investigation pinpointed five novel potential biomarkers linked to the diagnosis and prognosis of COVID-19: N-Acetyl-4-O-acetylneuraminic acid, N-Acetyl-L-Alanine, N-Acetyltriptophan, palmitoylcarnitine, and glycerol 1-myristate. These biomarkers exhibited heightened levels in severe COVID-19 patients compared to those with mild COVID-19 or healthy volunteers.

Female representation among editorial boards of social, clinical, and educational pharmacy journals.

BACKGROUND: Recent studies on editorial team members of healthcare journals have been showing disparities in this distribution. However, there are limited data with respect to pharmacy journals. Thus, the aim of this study was to investigate the distribution of women among editorial board members of social, clinical, and educational pharmacy research journals around the globe. METHODS: A cross-sectional study was conducted between September and October 2022. Data were extracted from Scimago Journal & Country Rank and Clarivate Analytics Web of Science Journal Citation Reports The top 10 journals in each region of the world (continents) were analyzed. Editorial board members were categorized into four groups and determined based on information available on the journal's website. The sex was classified in binary form through name and photography, the personal and institutional web pages, or the Genderize program. RESULTS: A total of 45 journals were identified in the databases, of which 42 of them were analyzed. We identified 1482 editorial board members with only 527 (35.6%) being female. Analyzing the subgroups, there were 47 total editors-in-chief, 44 total co-editors, 272 associate editors, and 1119 editorial advisors. Of these, 10 (21.27%), 21 (47.72%), 115 (42.27%), and 381 (34.04%) were female, respectively. Only 9 journals (21.42%) presented more females among their editorial board members. CONCLUSION: A notable sex disparity among social, clinical, and educational pharmacy journals' editorial board members was identified. Efforts should be made to involve more female sex in their editorial teams.

Mapping the characteristics, methodological quality and standards of reporting of network meta-analyses on antithrombotic therapies: An overview.

BACKGROUND: Although a large number of network meta-analyses (NMAs) in the field of cardiology are available, little is known about their methodological quality. We aimed to map the characteristics and critically appraised the standards of conduct and evidence reporting of NMAs assessing antithrombotic therapies for the treatment or prophylaxis of heart diseases and cardiac surgical procedures. METHODS: We systematically searched PubMed and Scopus to identify NMAs comparing the clinical effects of antithrombotic therapies. Overall characteristics of the NMAs were extracted and their reporting quality and methodological quality were evaluated using the PRISMA-NMA checklist and AMSTAR-2, respectively. RESULTS: We found 86 NMAs published between 2007 and 2022. Comparisons among direct-acting oral anticoagulants were available in 61 (71%) NMAs. Although around 75% of NMAs stated that they followed international guidelines for conduct and reporting, only one third provided a protocol/register. Complete search strategies and publication bias assessment were lacking in around 53% and 59% of studies, respectively. Most NMAs (n = 77, 90%) provided supplemental material; however, only 5 (6%) made the complete raw data available. Network diagrams were depicted in most studies (n = 67, 78%), yet network geometry was described in only 11 (12.8%) of them. Mean adherence to the PRISMA-NMA checklist was 65.1 ± 16.5%. AMSTAR-2 assessment showed 88% of the NMAs had critically low methodological quality. CONCLUSION: Although there is a wide diffusion of NMA-type studies on antithrombotics for heart diseases, their methodological and reporting quality remains suboptimal. This may reflect fragile clinical practices due to misleading conclusions from critically low-quality NMAs.

Naringenin-4'-glucuronide as a new drug candidate against the COVID-19 Omicron variant: a study based on molecular docking, molecular dynamics, MM/PBSA and MM/GBSA.

This study aimed to identify natural bioactive compounds (NBCs) as potential inhibitors of the spike (S1) receptor binding domain (RBD) of the COVID-19 Omicron variant using computer simulations (in silico). NBCs with previously proven biological in vitro activity were obtained from the ZINC database and analyzed through virtual screening, molecular docking, molecular dynamics (MD), molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA), and molecular mechanics/generalized Born surface area (MM/GBSA). Remdesivir was used as a reference drug in docking and MD calculations. A total of 170,906 compounds were analyzed. Molecular docking screening revealed the top four NBCs with a high affinity with the spike (affinity energy <-7 kcal/mol) to be ZINC000045789238, ZINC000004098448, ZINC000008662732, and ZINC000003995616. In the MD analysis, the four ligands formed a complex with the highest dynamic equilibrium S1 (mean RMSD <0.3 nm), lowest fluctuation of the complex amino acid residues (RMSF <1.3), and solvent accessibility stability. However, the ZINC000045789238-spike complex (naringenin-4'-O glucuronide) was the only one that simultaneously had minus signal (-) MM/PBSA and MM/GBSA binding free energy values (-3.74 kcal/mol and -15.65 kcal/mol, respectively), indicating favorable binding. This ligand (naringenin-4'-O glucuronide) was also the one that produced the highest number of hydrogen bonds in the entire dynamic period (average = 4601 bonds per nanosecond). Six mutant amino acid residues formed these hydrogen bonds from the RBD region of S1 in the Omicron variant: Asn417, Ser494, Ser496, Arg403, Arg408, and His505. Naringenin-4'-O-glucuronide showed promising results as a potential drug candidate against COVID-19. In vitro and preclinical studies are needed to confirm these findings.Communicated by Ramaswamy H. Sarma.

Chemical Constituents, Anticancer and Anti-Proliferative Potential of Limonium Species: A Systematic Review.

Limonium species represent a source of bioactive compounds that have been widely used in folk medicine. This study aimed to synthesize the anticancer and anti-proliferative potential of Limonium species through a systematic review. Searches were performed in the electronic databases PubMed/MEDLINE, Scopus, and Scielo and via a manual search. In vivo or in vitro studies that evaluated the anticancer or anti-proliferative effect of at least one Limonium species were included. In total, 942 studies were identified, with 33 articles read in full and 17 studies included for qualitative synthesis. Of these, 14 (82.35%) refer to in vitro assays, one (5.88%) was in vivo, and two (11.76%) were designed as in vitro and in vivo assays. Different extracts and isolated compounds from Limonium species were evaluated through cytotoxic analysis against various cancer cells lines (especially hepatocellular carcinoma-HepG2; n = 7, 41.18%). Limonium tetragonum was the most evaluated species. The possible cellular mechanism involved in the anticancer activity of some Limonium species included the inhibition of enzymatic activities and expression of matrix metalloproteinases (MMPs), which suggested anti-metastatic effects, anti-melanogenic activity, cell proliferation inhibition pathways, and antioxidant and immunomodulatory effects. The results reinforce the potential of Limonium species as a source for the discovery and development of new potential cytotoxic and anticancer agents. However, further studies and improvements in experimental designs are needed to better demonstrate the mechanism of action of all of these compounds.

Flavonoid as possible therapeutic targets against COVID-19: a scoping review of in silico studies.

OBJECTIVES: This scoping review aims to present flavonoid compounds' promising effects and possible mechanisms of action on potential therapeutic targets in the SARS-CoV-2 infection process. METHODS: A search of electronic databases such as PubMed and Scopus was carried out to evaluate the performance of substances from the flavonoid class at different stages of SARS-CoV-2 infection. RESULTS: The search strategy yielded 382 articles after the exclusion of duplicates. During the screening process, 265 records were deemed as irrelevant. At the end of the full-text appraisal, 37 studies were considered eligible for data extraction and qualitative synthesis. All the studies used virtual molecular docking models to verify the affinity of compounds from the flavonoid class with crucial proteins in the replication cycle of the SARS-CoV-2 virus (Spike protein, PLpro, 3CLpro/ MPro, RdRP, and inhibition of the host's ACE II receptor). The flavonoids with more targets and lowest binding energies were: orientin, quercetin, epigallocatechin, narcissoside, silymarin, neohesperidin, delphinidin-3,5-diglucoside, and delphinidin-3-sambubioside-5-glucoside. CONCLUSION: These studies allow us to provide a basis for in vitro and in vivo assays to assist in developing drugs for the treatment and prevention of COVID-19.

Diagnosis and prognosis of COVID-19 employing analysis of patients' plasma and serum via LC-MS and machine learning.

OBJECTIVE: To implement and evaluate machine learning (ML) algorithms for the prediction of COVID-19 diagnosis, severity, and fatality and to assess biomarkers potentially associated with these outcomes. MATERIAL AND METHODS: Serum (n = 96) and plasma (n = 96) samples from patients with COVID-19 (acute, severe and fatal illness) from two independent hospitals in China were analyzed by LC-MS. Samples from healthy volunteers and from patients with pneumonia caused by other viruses (i.e. negative RT-PCR for COVID-19) were used as controls. Seven different ML-based models were built: PLS-DA, ANNDA, XGBoostDA, SIMCA, SVM, LREG and KNN. RESULTS: The PLS-DA model presented the best performance for both datasets, with accuracy rates to predict the diagnosis, severity and fatality of COVID-19 of 93%, 94% and 97%, respectively. Low levels of the metabolites ribothymidine, 4-hydroxyphenylacetoylcarnitine and uridine were associated with COVID-19 positivity, whereas high levels of N-acetyl-glucosamine-1-phosphate, cysteinylglycine, methyl isobutyrate, l-ornithine and 5,6-dihydro-5-methyluracil were significantly related to greater severity and fatality from COVID-19. CONCLUSION: The PLS-DA model can help to predict SARS-CoV-2 diagnosis, severity and fatality in daily practice. Some biomarkers typically increased in COVID-19 patients' serum or plasma (i.e. ribothymidine, N-acetyl-glucosamine-1-phosphate, l-ornithine, 5,6-dihydro-5-methyluracil) should be further evaluated as prognostic indicators of the disease.

A multivariate analysis of risk factors associated with death by Covid-19 in the USA, Italy, Spain, and Germany.

Aim: Our aim was to investigate the risk factors associated with death from COVID-19 in four countries: The USA, Italy, Spain, and Germany. Subject and methods: We used data from the Institute for Health Metrics and Evaluation with projection information from January-August 2020. A multivariate analysis of logistic regression was performed. The following factors were analyzed (per day): number of beds needed for the hospital services, number of intensive care units (ICU) beds required, number of ventilation devices, number of both hospital and ICU admissions due to COVID-19. Nagelkerke's R2 coefficient of determination was used to evaluate the model's predictive ability. The quality of the model's fit was assessed by the Hosmer-Lemeshow and the chi-square tests. Results: Among the evaluated countries, Italy presented greater need for ICU beds/day (≤ 98; OR = 2315.122; CI 95% [334.767-16,503.502]; p < 0.001) and daily ventilation devices (≤ 118; OR = 1784.168; CI 95% [250.217-12,721.995]; p < 0.001). It is expected that both Italy and Spain have a higher ICU admission rate due to COVID-19 (n = 14/day). Spain will need more beds/day (≤ 357; OR = 146.838; CI 95% [113.242-190.402]; p  < 0.001) and probably will have a higher number of daily hospital admissions (n = 48/day). All the above-mentioned factors have an important impact on patients' mortality due to COVID-19 in all four countries. Conclusions: Further investments in hospitals' infrastructure, as well as the development of innovative devices for patient's ventilation, are paramount to fight the pandemic in the USA, Italy, Spain, and Germany.

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.

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.

Risk factors associated with delay in diagnosis and mortality in patients with COVID-19 in the city of Rio de Janeiro, Brazil.

We investigated the predictors of delay in the diagnosis and mortality of patients with COVID-19 in Rio de Janeiro, Brazil. A cohort of 3,656 patients were evaluated (Feb-Apr 2020) and patients' sociodemographic characteristics, and social development index (SDI) were used as determinant factors of diagnosis delays and mortality. Kaplan-Meier survival analyses, time-dependent Cox regression models, and multivariate logistic regression analyses were conducted. The median time from symptoms onset to diagnosis was eight days (interquartile range [IQR] 7.23-8.99 days). Half of the patients recovered during the evaluated period, and 8.3% died. Mortality rates were higher in men. Delays in diagnosis were associated with male gender (p = 0.015) and patients living in low SDI areas (p < 0.001). The age groups statistically associated with death were: 70-79 years, 80-89 years, and 90-99 years. Delays to diagnosis greater than eight days were also risk factors for death. Delays in diagnosis and risk factors for death from COVID-19 were associated with male gender, age under 60 years, and patients living in regions with lower SDI. Delays superior to eight days to diagnosis increased mortality rates.

Safety of Treatments for ADHD in Adults: Pairwise and Network Meta-Analyses.

OBJECTIVE: The aim of the study was to analyze evidence comparing the profile of drugs used to treat ADHD in adult patients. METHOD: Systematic searches were conducted in electronic databases. Randomized, double-blind, parallel controlled trials that evaluated the safety of drugs in ADHD were included. The statistical analyses were conducted by pairwise meta-analyses and mixed treatment comparison (MTC). RESULTS: Ten ( n = 3006) trials were included in the analyses. We observed statistical differences for the following outcomes: decreased appetite between atomoxetine and placebo (odds ratio [OR] = 0.15, 95% credibility interval [CrI] = [0.05, 0.38]) and extended-release mixed amphetamine salts and placebo (OR = 0.06, 95% CrI = [0.00, 0.51]); insomnia between atomoxetine and placebo (OR = 0.48, 95% CrI = [0.27, 0.88]) and extended-release mixed amphetamine salts and placebo (OR = 0.23, 95% CrI = [0.06, 0.76]); sleepiness between atomoxetine and methylphenidate OROS (OR = 0.24, 95% CrI = [0.06, 0.97]); and decreased libido between atomoxetine and placebo (OR = 0.28, 95% CrI = [0.08, 0.90]). CONCLUSION: It was possible to generate evidence about the safety profile of different ADHD drugs.

Sustained Virological Response in Special Populations with Chronic Hepatitis C Using Interferon-Free Treatments: A Systematic Review and Meta-analysis of Observational Cohort Studies.

BACKGROUND AND OBJECTIVES: Hepatitis C treatment has changed considerably in recent years, and many interferon (IFN)-free therapies are now available. Considering the high rates of sustained virological response (SVR) presented by clinical trials for these treatments, high rates of effectiveness are also expected in real-world clinical practice. Hence, this study aimed to conduct a systematic review and meta-analysis of observational cohort studies to evaluate the clinical effectiveness and safety of IFN-free therapies for hepatitis C. METHODS: The search was performed in four electronic databases and included cohort studies that evaluated IFN-free schemes and provided data on SVR at 12 weeks after the end of treatment (SVR12) as the primary outcome. Overall and subgroup meta-analyses of patients' clinical conditions (e.g. co-infection with human immunodeficiency virus (HIV), cirrhosis, liver transplant, specific genotypes, and other conditions) were performed. RESULTS: Sixty-eight studies encompassing a total of 24,151 patients were included for quantitative and qualitative analyses, evaluating six treatments: sofosbuvir with ledipasvir, daclatasvir, or simeprevir; daclatasvir with asunaprevir; paritaprevir/ritonavir in combination with ombitasvir and dasabuvir; and sofosbuvir with ribavirin. The overall analysis showed SVR rates of 88-96% for all treatments except sofosbuvir combined with ribavirin, which had SVR rates of approximately 80%. The results of subgroup analyses showed that the genotype 3 virus appears to be the most difficult to treat. CONCLUSION: In order to choose the best treatment option, it is necessary to consider the patients' conditions and characteristics. In conclusion, the use of IFN-free therapies meets the high expectations created by clinical trials, including patients in special clinical conditions.