Genomic surveillance and serological profile of SARS-CoV-2 variants circulating in Macaé and nearby cities, southeastern Brazil.

Introduction: A characteristic of the COVID-19 pandemic has been the sequential emergence and global dissemination of SARS-CoV-2 variants, noted for their enhanced transmission efficiency. These variants with mutations in the Spike glycoprotein (S-glycoprotein), which interacts with ACE2 receptors in human cells is critical for infection, affects the transmissibility of the virus, which is a matter of great concern for public health. Objective: This research analyses the effects these variants on a cohort of vaccinated and naturally infected individuals from the cities of Macaé-RJ, Rio das Ostras-RJ, and Campos dos Goytacazes-RJ, Brazil, from March 2021 to March 2023. Methods: This investigation encompasses the Alpha (B.1.1.7), Gamma (P.1), Delta (B.1.617.2, B.1.671.3), and Omicron (BQ.1, BQ.1.1 sublines, and BF.7) variants, focusing on their genomic surveillance and implications for the disease's epidemiology. The experimental analysis included a control group (vaccinated and uninfected subjects), and an infected group (post-vaccinated subjects). Samples from nasopharyngeal swabs underwent viral detection via RT-qPCR for diagnosis confirmation. RNase H-dependent RT-qPCR (rhAmp-PCR) and third-generation sequencing were used to detect SARS-CoV-2 variants. Anti-S-glycoprotein immunoglobulins were also evaluated for vaccinated infected and noninfected volunteers. Symptoms from infected individuals were compiled in order to reveal patterns of clinical signs associated with viral infection. Results: The study included 289 participants, with infections identified by Gamma (n = 44), Delta (n = 189), and Omicron (n = 56) variants. The prevalent symptoms among the naturally infected participants were cough, fever, sore throat, headache, and runny nose. For Omicron, cognitive symptoms such as memory loss and concentration issues were reported. Interestingly, the infected vaccinated group had higher anti-S-glycoprotein IgM production (n = 28, 0.2833 ± 0.09768 OD) compared to the uninfected vaccinated group (n = 14, 0.1035 ± 0.03625 OD). Conversely, anti-S-glycoprotein IgG production was higher in the control group (n = 12, 1.770 ± 0.1393 OD) than in the infected vaccinated group (n = 26, 1.391 ± 0.1563 OD). Conclusion: This comprehensive study enables monitoring of predominant variants and their correlation with clinical cases, providing valuable insights for public health. Our research group continues to survey circulating variants, contributing to the global understanding of the pandemic.

Genetic Modifiers of Sickle Cell Anemia Phenotype in a Cohort of Angolan Children.

The aim of this study was to identify genetic markers in the HBB Cluster; HBS1L-MYB intergenic region; and BCL11A, KLF1, FOX3, and ZBTB7A genes associated with the heterogeneous phenotypes of Sickle Cell Anemia (SCA) using next-generation sequencing, as well as to assess their influence and prevalence in an Angolan population. Hematological, biochemical, and clinical data were considered to determine patients' severity phenotypes. Samples from 192 patients were sequenced, and 5,019,378 variants of high quality were registered. A catalog of candidate modifier genes that clustered in pathophysiological pathways important for SCA was generated, and candidate genes associated with increasing vaso-occlusive crises (VOC) and with lower fetal hemoglobin (HbF) were identified. These data support the polygenic view of the genetic architecture of SCA phenotypic variability. Two single nucleotide polymorphisms in the intronic region of 2q16.1, harboring the BCL11A gene, are genome-wide and significantly associated with decreasing HbF. A set of variants was identified to nominally be associated with increasing VOC and are potential genetic modifiers harboring phenotypic variation among patients. To the best of our knowledge, this is the first investigation of clinical variation in SCA in Angola using a well-customized and targeted sequencing approach.

Working Together to Improve Type 2 Diabetes Care: A Participatory Design Project to Address Identified Needs of People With Diabetes and Their Health-care Professionals.

OBJECTIVES: Diabetes care in Australia is often fragmented and provider-centred, resulting in suboptimal care. Innovative solutions are needed to bridge the evidence-practice gap, and technology can facilitate the redesign of type 2 diabetes care. We used Participatory Design to increase the chances of fulfilling stakeholders' needs. Using this method, we explored solutions aimed at redesigning diabetes care, focussing on the previously identified needs. METHODS: The Participatory Design project was guided by stakeholders' contributions. Stakeholders of this project included people with type 2 diabetes, health-care professionals, technology developers, and researchers. Information uncovered at each step influenced the next: 1) identification of needs, 2) generation of solutions, and 3) testing of solutions. Here, we present steps 2 and 3. In step 2, we presented previously identified issues and elicited creative solutions. In step 3, we obtained stakeholders' feedback on the solutions from step 2, presented as care pathways. RESULTS: Suggested solutions included a multidisciplinary wellness centre, a mobile app, increased access to education, improved care coordination, increased support for general practitioners, and a better funding model. The revised care pathways featured accessible community resources, a tailored self-management and educational app, a care coordinator, a digital dashboard, and specialized support for primary care to deal with complex cases. CONCLUSIONS: Using a Participatory Design, we successfully identified multiple innovative solutions with the potential to improve person-centred and integrated type 2 diabetes care in Australia. These solutions will inform the implementation and evaluation of a redesigned care model by our team.

Influence of cigarette smoking on the Index of Cardiac Electrophysiological Balance in apparently healthy Angolans.

Background: Tobacco use accelerates atherosclerosis and is one of the predictors of death from ischemic heart disease, arrhythmias, heart failure, and sudden death. A new non-invasive parameter, the Index of Cardiac Electrophysiological Balance (iCEB) between depolarization and repolarization of the action potential, was considered a new biomarker for the identification of patients at increased arrhythmic risk. Objectives: We aimed to evaluate the iCEB in apparently healthy Angolans with habitual cigarette smoking compared to non-smokers. Subjects and methods: Data were obtained from the CardioBengo study, a cross-sectional community-based study in which a random sample of individuals aged between 15 and 84 years was selected. In total, 214 apparently healthy subjects, 102 smokers, and 112 non-smokers in the same age group were included in the final analysis. Results: The average age of the participants was 42.17 ± 13.04 years old and 26.6% of the sample was female. Smoking subjects had higher iCEB and corrected Index of Cardiac Electrophysiological Balance (iCEBc) values compared with non-smoking controls (4.39 vs. 4.25; p = 0.024, respectively), and (4.74 vs. 4.57; p = 0.030, respectively). Conclusions: In summary, iCEB and iCEBc were significantly higher in habitual smokers than in nonsmokers, which represents an increased risk of ventricular arrhythmogenesis in healthy habitual smokers. To the best of our knowledge, this is the first study performed in Africa to evaluate iCEB in smokers, making this type of study very important in low- and middle-income countries in the context of epidemiological transition.

The efficient role of sodium alginate-based biodegradable dressings for skin wound healing application: a systematic review.

Injuries and damage to the skin can be caused by different reasons throughout human life. The use of sodium alginate in tissue dressing has been highly studied due to its intrinsic properties, including its degradation rate and biocompatibility, and the capacity of supporting tissue proliferation. The aim of this paper is to demonstrate evidences, through a systematic review method, to support the application of sodium alginate as a curative and as a potential accelerator in the healing of skin wounds. Four databases were used to develop this systematic review: Science Direct, PubMed, Scielo and Scopus. The time interval established for the search was from January 2016 to October 2023. After applying the exclusion and inclusion criteria, each selected article was evaluated and it was observed that the improvement of the mechanical properties of sodium alginate when correctly processed and crosslinked were evident. However, the increase of crosslinking affects as the wettability and the swelling of the biomaterials can cause limitations in mechanical properties and hidrophilic behavior. To achieve the ideal dressing, it is necessary to apply the optimal concentration of crosslinking and other substances, which can damage its hidrophilic characteristic. Thus, it was concluded that sodium alginate has every caracteristic desirable to develop an effective and safe dressing.

Bismuth Subcitrate, Metronidazole and Tetracycline - A Rare Cause of Drug-Induced Liver Injury.

Drug-induced liver injury (DILI) is a liver condition caused by any drug or toxic substance. The spectrum of DILI manifestations can range from asymptomatic elevation of liver enzymes to acute liver failure. Antibiotics are one of the major causes of DILI. The authors report the case of a 37-year-old male with nausea, right hypochondrium pain and fever with history of bismuth subcitrate, metronidazole and tetracycline combination treatment in the previous five days. DILI was suspected and other aetiologies of acute hepatitis were excluded such as viral, autoimmune or even haemochromatosis and Wilson's disease. Liver biopsy was performed, being compatible with the diagnosis of DILI; DILI is a diagnosis of exclusion. Bismuth subcitrate, metronidazole and tetracycline combination treatment is a rare cause of DILI. LEARNING POINTS: Bismuth subcitrate, metronidazole and tetracycline in combination is a rare cause of drug-induced liver injury (DILI).DILI is an exclusion diagnosis.Liver biopsy has an important role in the diagnosis of DILI.

Ocular repercussions in COVID-19 patients: structural changes of the retina and choroid.

BACKGROUND: Neurotropic capabilities of SARS-COVs allow viruses to reach the central nervous system by hematogenous neuronal dissemination. The human retina, as an extension of the Central Nervous System, may have some neurodegenerative and/or vascular modifications related to COVID-19. OBJECTIVES: To evaluate choroidal and inner neural layers in participants previously recovered from COVID-19 compared to the control group using optical coherence tomography. METHODS: With a cross-sectional approach, the sample (n = 96), constituted by patients who have recovered from COVID-19 (n = 56) and healthy participants control group (n = 40) were ophthalmologically characterized. The neurodegenerative and vascular histological assessment was performed using SD-OCT and the mean thickness was measured in Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. Retinal nerve fiber layer, Ganglion cell layer and subfoveal choroidal thickness were obtained through semi-automatic measurement. RESULTS: A total of 40 controls (27 women [67.5%]) and 56 COVID-19 participants (34 women [60.8%]) were included in this first report. There were retinal thickness significant differences in nearly all inner ETDRS subfields: nasal 3 mm (p = .025), I3 (p = .049), and temporal 3 mm (p = .009). Also, a decrease in neural layers was found in the nasal 3 mm (p = .049) and temporal 3 mm (p = .029) during ganglion cell layer assessment. The peripapillary retinal nerve fiber layer thickness was thinner in the COVID-19 group in superior temporal (p = .019), nasal (p = .002), inferior temporal (p = .046) and global (p = .014). Concerning the subfoveal choroidal measurement, an increase was observed in the COVID-19 group (p = .002). CONCLUSION: Participants who had recovered from COVID-19 showed a non-glaucomatous neuropathy trend pattern. We found differences closer to the classic description of the "bow-tie" observed in other neurological as compressive neuropathies at the chiasma location. OCT assessment also showed an increase in choroidal thickness as a result of vascular changes.

Effects of auriculotherapy on anxiety and biomarkers in Primary Health Care: a clinical trial.

OBJECTIVE: to assess the effects of auriculotherapy on anxiety and brain-derived neurotrophic factor (BDNF), neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) serum levels in adults assisted in Primary Health Care. METHODS: a pre-experimental pilot clinical trial. Information was obtained from 19 patients using the State-Trait Anxiety Inventory (STAI) and analysis of BDNF, NSE and S100B serum levels. RESULTS: the pre-intervention anxiety score in the IDATE-Trait was 52.11±6.691 (CV 12.84%) and the assessment after auriculotherapy was significantly lower (43.72±8.141; CV 18.62%; P=0.0007). S100B levels were significantly reduced after auriculotherapy (from 64.03±72.18 to 54.03±68.53 pg/mL; CV 126.8%; P=0.0023). CONCLUSION: auriculotherapy effectively reduced anxiety levels. It proved to be safe and easy to apply, allowing nurses to perform this technique autonomously. A reduction of S100B was also evidenced, demonstrating possible prevention of neuronal damage.

Assessing Adherence to Vaccination, Social Distancing and Other Preventive Behaviors by Patients With Mental Disorders in the Context Of Covid-19 Pandemic: A Scoping Review Protocol.

The COVID-19 pandemic has emerged as a worldwide public health crisis, leading to significant disruptions in societal behaviors and norms. Within the affected population, individuals with mental health disorders are considered a vulnerable group, experiencing higher infection rates and poorer outcomes. These adverse outcomes can be attributed to various factors, including inadequate adherence to vaccination and other preventive measures. To address this issue, this study aims to present the research protocol for a scoping review that will comprehensively examine the literature on the adherence of individuals with mental disorders to preventive behaviors during the COVID-19 pandemic. The scoping review will adhere to the methodological guidelines outlined by the Joanna Briggs Institute and will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. A comprehensive search for published literature containing original data will be conducted in the Embase, MEDLINE, PsycINFO, and Web of Science databases. The search strategy will be developed based on the Population, Concept, and Context inclusion criteria. Two authors will independently screen titles, abstracts, and full texts for inclusion and extract relevant data. The findings of the review will be presented using descriptive statistics, including tables, charts, and flow diagrams, to elucidate the key concepts of interest.

Suicide in veterinary medicine: A literature review.

Veterinarians are commonly exposed to occupational stressors, including excessive workload and financial constraints. These stressors can lead to psychological distress, which typically results in mental health disorders such as depression, anxiety, and burnout and can even culminate in suicide attempts or suicide deaths. Risk factors associated with poor mental health and high rates of suicide in veterinary practitioners include continuous exposure to challenging scenarios, such as interpersonal conflicts, performing euthanasia, and easy access to lethal means of suicide, such as opioids and anesthetics. The previous studies highlight the urgent need for a better understanding of predisposing factors, mental health-related improvements in the professional environment, and the subsequent establishment of primary mental health-related care policies. Effective ways to promote mental health and prevent suicide may include social support, resilience, developing coping skills, promoting a healthy work environment, and discouraging perfectionist behaviors. This review aimed to summarize findings in studies that have investigated mental health and suicide in veterinarians and veterinary students and highlight measures that could be implemented as options for mental health promotion and suicide prevention.

Plain radiography has a role to play in current clinical practice in Western Switzerland.

AIM: The aim of the study was to investigate the current role of conventional radiography examinations in Western Switzerland and the main clinical indications required to justify the use of this imaging examination. METHODS: Ethical approval was obtained from Vaud Ethics committee (Ref 2020-00311). An online questionnaire was specifically designed and implemented on the data collection tool LimeSurvey composed of two parts: a) to characterise the participants' profile and their institutions and b) 169 projections for the different anatomical area (upper and lower limbs, pelvis, skull, spine, thorax, abdomen) were presented to collect data about the frequency and main clinical indications. Statistical analysis was performed using the software IBM SPSS® (Statistical Package for the Social Sciences) version 26. RESULTS: Radiographers from 60% (26/43) of the invited institutions participated in this survey, mainly from Vaud region. The upper and lower limbs were the most commonly examined by using conventional radiography mainly for trauma and degenerative disorders. The thorax was also an anatomical area commonly explored by X-rays, so were the spine (cervical and lumbar lateral). The skull radiographs were rarely performed in clinical practice and some of the projections were not being used, namely Hirtz, Tangential Nose Bones, Worms and Caldwell's views. CONCLUSIONS: Plain radiography is being used in clinical practice mainly for appendicular skeleton studies and for trauma and degenerative pathologies. Adaptations in radiographers' education and training and other healthcare professionals are needed to provide the judicious use of data that radiographs can give to better manage the patients' imaging pathway.

Correction: The Efficacy, Safety, and Efficiency of the Off-Label Use of Bevacizumab in Patients Diagnosed With Age-Related Macular Degeneration: Protocol for a Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.2196/38658.].

Composite lipid emulsion use and essential fatty acid deficiency in pediatric patients with intestinal failure with high parenteral nutrition dependence: A retrospective cohort study.

BACKGROUND: Reports of essential fatty acid deficiency (EFAD) in patients receiving parenteral nutrition (PN) and a composite lipid (mixed oil intravenous lipid emulsion [MO ILE]) are predominantly when managed by lipid restriction. The objective of this study was to determine the prevalence of EFAD in patients with intestinal failure (IF) who are PN dependent without lipid restriction. METHODS: We retrospectively evaluated patients, ages 0-17 years, followed by our intestinal rehabilitation program between November 2020 and June 2021 with PN dependency index (PNDI) of >80% on a MO ILE. Demographic data, PN composition, PN days, growth, and plasma fatty acid profile were collected. A plasma triene-tetraene (T:T) ratio >0.2 indicated EFAD. Summary statistics and Wilcoxon rank sum test evaluated to compare between PNDI category and ILE administration (grams/kilograms/day). P < 0.05 was considered significant. RESULTS: Twenty-six patients (median age, 4.1 years [interquartile range (IQR) = 2.4-9.6]) were included. The median duration of PN was 1367 days (IQR = 824-3195). Sixteen patients had a PNDI of 80%-120% (61.5%). Fat intake for the group was 1.7 g/kg/day (IQR = 1.3-2.0). The median T:T ratio was 0.1 (IQR = 0.1-0.2) with no values >0.2. Linoleic and arachidonic acid were low in 85% and 19% of patients, respectively; however, Mead acid was normal in all patients. CONCLUSION: This report is the largest to date on the EFA status of patients with IF on PN. These results suggest that, in the absence of lipid restriction, EFAD is not a concern when using MO ILEs in children receiving PN for IF.

Immunoglobulin A as a Key Immunological Molecular Signature of Post-COVID-19 Conditions.

COVID-19 has infected humans worldwide, causing millions of deaths or prolonged symptoms in survivors. The transient or persistent symptoms after SARS-CoV-2 infection have been defined as post-COVID-19 conditions (PCC). We conducted a study of 151 Brazilian PCC patients to analyze symptoms and immunoglobulin profiles, taking into account sex, vaccination, hospitalization, and age. Fatigue and myalgia were the most common symptoms, and lack of vaccination, hospitalization, and neuropsychiatric and metabolic comorbidities were relevant to the development of PCC. Analysis of serological immunoglobulins showed that IgA was higher in PCC patients, especially in the adult and elderly groups. Also, non-hospitalized and hospitalized PCC patients produced high and similar levels of IgA. Our results indicated that the detection of IgA antibodies against SARS-CoV-2 during the course of the disease could be associated with the development of PCC and may be an immunological signature to predict prolonged symptoms in COVID-19 patients.

Experience of practicing obstetrician-gynecologists in a surgical training program in total laparoscopic hysterectomy.

BACKGROUND: Advanced surgical techniques, such as total laparoscopic hysterectomy, are often challenging to acquire beyond fellowship training programs for practicing obstetrician-gynecologists. A lack of formative data currently exist for continuing medical education programs, limiting our understanding of how improvement in surgical skills and training programs occur. OBJECTIVE: This study aimed to investigate how practicing obstetrician-gynecologists acting as trainees experience a program that aims to teach them total laparoscopic hysterectomy, and to assess whether their surgical skills improve according to data from formative assessment tools and qualitative data from open-ended survey questions and in-depth interviews. STUDY DESIGN: We report a process analysis of formative data collected during a pilot implementation trial of a surgical training program targeting practicing obstetrician-gynecologists. Eleven consultant obstetrician-gynecologists and 4 experienced surgical mentors participated in 4 hospitals in Queensland, Australia. Total laparoscopic hysterectomy was performed in 700 patients over the course of the study. A total laparoscopic hysterectomy surgical mentorship training program of 10 training days with up to 3 total laparoscopic hysterectomy procedures per day was performed. Both the obstetrician-gynecologists and the surgical mentor completed a formative assessment questionnaire analyzing the trainee's performance after each surgical procedure. Mentors were formatively assessed by the Structured Training Trainer Assessment Report (STTAR) and at the completion of the study by the mini-STTAR, a summative assessment of quality of mentorship. Obstetrician-gynecologists, mentors, hospital leaders, and surgical administrative staff participated in qualitative interviews about the training program. RESULTS: Over time, there was a demonstrated improvement in trainee performance reported by both mentors and trainees in all competency assessment tool domains as the case number increased, with mentors consistently rating trainees' performance higher than the trainees themselves. Most trainees were satisfied with their mentor in all 31 areas during formative assessment, and at the end of the training, structure, attributes, and role modeling were all rated high (average score >4.5; range, 3.79-5.00), whereas training behavior was rated slightly lower at 4.1 (range, 3.79-4.45). Qualitative interviews demonstrated that the trainees found the training to be a beneficial, hands-on experience. CONCLUSION: Formative assessment clearly documented improvement in surgical skills during a total laparoscopic hysterectomy training program for consultant obstetrician-gynecologists.

Portuguese Validation of the Unified Theory of Acceptance and Use of Technology Scale (UTAUT) to a COVID-19 Mobile Application: A Pilot Study.

The use of technology has proven to be a powerful tool in the fight against COVID-19 and its variants of concern (Gamma, Beta, Alpha, Delta, and Omicron). The urgency of responding to this worldwide pandemic has accelerated the development of monitoring systems and contact tracing applications. Without technology's contribution, the adverse effects on humanity economically, socially, and psychologically would be even more devastating. This study aimed to translate, adapt, and validate the Unified Theory of Acceptance and Use of Technology (UTAUT) model in a Portuguese university population, to evaluate adherence to a mobile application for tracking COVID-19. An observational cross-sectional study was developed using a sample with 1081 participants (71% female, 59.2% with ages between 16 and 24, and 78.2% of the respondent's university students). The Portuguese version model showed a good reliability (Cronbach's α = 0.82) and an acceptable overall adjustment to the sample under study (χ2/df = 3.732, CFI = 0.955, TLI = 0.944, RMSEA = 0.05, SRMR = 0.06); however, this model could be improved, as we proved. Since this is a pilot study, more studies are needed. The results indicated that the P-UTAUT can be improved for evaluating adherence to a COVID-19 mobile application.

Body Composition and Physical Activity in Pediatric Intestinal Failure On and Off Parenteral Nutrition.

OBJECTIVES: Data on the relationship between body composition (BC) and physical activity (PA) in children with intestinal failure (IF) are lacking. The objectives were to collect data on PA and BC in children with IF, both parenterally and enterally fed, and to assess the relationship between PA and BC. METHODS: Cross-sectional study in children 5-18 years with IF including those receiving parenteral nutrition (PN) and those fully enterally fed. PA levels were measured using accelerometry. BC was measured by dual-energy X-ray absorptiometry. Data were compared to age- and sex-matched population norms using t tests. Regression analysis assessed the relationship between BC and PA. RESULTS: Fifty-eight children with IF (38 males), mean (SD) age of 10.0 (3.5) years, 20 dependent on PN were included. Patients with IF had significantly fewer steps per day ( P ≤ 0.001) compared with literature controls, with a mean (SD) of 7,972 (3,008) and 11,749 (1,106), respectively. There were no significant differences between patients receiving PN and those enterally fed, but both groups were significantly less active than literature controls ( P < 0.001). Patients with IF had higher fat mass and lower fat-free mass compared to literature controls ( P = 0.008). PA had a significant effect on BC ( r2 = 0.32, P < 0.001). CONCLUSIONS: Children with IF, those receiving PN and those fully enterally fed, are at risk of decreased PA and altered BC. PA should be part of ongoing rehabilitation and management to optimize outcomes.

The Efficacy, Safety, and Efficiency of the Off-Label Use of Bevacizumab in Patients Diagnosed With Age-Related Macular Degeneration: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: Age-related macular degeneration (AMD) is recognized as the leading cause of vision loss in older people. Considering the phenomenon of aging societies worldwide, the prevalence of AMD is expected to increase gradually in the future. AMD can be divided into early, intermediate, and late stages, with the early and intermediate stages being mainly asymptomatic, and the late stage being classified as geographic atrophy, neovascular AMD, or both. Current pharmacological treatments for neovascular AMD include anti-vascular endothelial growth factor agents, such as ranibizumab, pegaptanib, and aflibercept. Additionally, it has been reported that the off-label use of intravitreally administered bevacizumab is effective. It is also lower cost than other agents, which makes it an interesting pharmacological approach. OBJECTIVE: This review aims to evaluate the efficacy, safety, and efficiency of bevacizumab for the treatment of neovascular AMD. METHODS: This review will only consider randomized controlled clinical trials that compare the use of bevacizumab with another pharmacological agent or a placebo in patients aged 50 years and older who are diagnosed with vascular AMD. It will exclude studies that include participants diagnosed with polypoidal choroidal vasculopathy or retinal angiomatous proliferation. To identify and select relevant articles, we will develop a highly sensitive search strategy and apply it in MEDLINE via the PubMed platform. Upon selection of the studies and analysis of the titles, abstracts, and full texts, the results will be presented according to the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The analysis and extraction of the data will be performed by 2 independent reviewers. Risk of bias will be evaluated with the Critical Appraisal Skills Programme (CASP) checklist. Finally, the same reviewers will also perform a quality assessment of the included studies with the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. RESULTS: The search strategy, after the application of the inclusion and exclusion criteria, identified 15 randomized clinical trials, which are currently being analyzed. This project has no funding and it has been developed by a multidisciplinary research team of pharmacologists and orthoptists. The study was initiated in May 2021 and it is expected to conclude by the end of 2023. CONCLUSIONS: This review will provide a synthesis of current information and underlying evidence about the off-label use of bevacizumab in neovascular AMD. It will provide a clearer vision of a possible new pharmacological approach, as well as the most suitable treatment designs, for the treatment of neovascular AMD. TRIAL REGISTRATION: PROSPERO CRD42021244931; https://tinyurl.com/p6m5ycpk. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38658.

Assessment of body composition in pediatric intestinal failure: A comparison study.

BACKGROUND: The objective of the study was to compare bioelectrical impedance analysis (BIA) and skinfolds with dual energy x-ray absorptiometry (DXA) in the assessment of body composition of children with intestinal failure. DXA is the reference method for body composition assessment in clinical settings. METHODS: Children aged 1-18 years with intestinal failure whohave DXA as part of routine clinical monitoring were eligible. BIA measured total body water on the same day as DXA. Skinfold measurements were taken at four sites: triceps, biceps, subscapular, and suprailiac. Percentage of fat mass (%FM) and fat-free mass (%FFM) were derived from resistance and reactance measured by BIA by using age-specific equations. Percentage of FM was calculated from skinfold measures by using age-specific equations. Data on patient characteristics, intestinal failure-related factors, and feeding method were collected. Paired t test examined differences in %FM and %FFM and Bland-Altman analysis determined the agreement between BIA, skinfolds, and DXA. Marginal linear model assessed the effect of age, sex, and feeding method on the difference in body composition obtained between DXA and BIA and between DXA and skinfolds. RESULTS: Sixty-eight children with intestinal failure, mean age 8.9 ± 4.2 years, were studied. There was no difference between %FFM and %FM obtained by DXA and BIA (P = 0.26), with a mean bias (95% CI) of -0.69 (-1.9 to 0.5) for %FFM. Sex and age were individually and jointly associated with the bias observed between DXA and BIA (P < 0.05). Skinfold and DXA measurements were significantly different (P < 0.05). CONCLUSIONS: BIA is an acceptable clinical tool for assessing body composition in pediatric intestinal failure.

Are Genetic Modifiers the Answer to Different Responses to Hydroxyurea Treatment?-A Pharmacogenetic Study in Sickle Cell Anemia Angolan Children.

Sickle cell anemia (SCA) is an inherited disease affecting the hemoglobin that is particularly common in sub-Saharan Africa. Although monogenic, phenotypes are markedly heterogeneous in terms of severity and life span. Hydroxyurea is still the most common treatment for these patients, and the response to treatment is highly variable and seems to be an inherited trait. Therefore, identifying the variants that might predict hydroxyurea response is important for identifying patients who will have a poorer or non-response to treatment, and the ones that are more prone to suffer from severe side effects. In the present pharmacogenetic study, we analyzed the exons of 77 genes described in the literature as potentially associated with hydroxyurea metabolism in Angolan children treated with hydroxyurea and evaluated the drug response considering fetal hemoglobin levels, other hematological and biochemical parameters, hemolysis, number of vaso-occlusive crises and hospitalizations. Thirty variants were identified in 18 of those genes as possibly associated with drug response, five of them in gene DCHS2. Other polymorphisms in this gene were also associated with hematological, biochemical and clinical parameters. Further research examining the maximum tolerated dose and fixed dose with a larger sample size is necessary to corroborate these findings.