Clinical-laboratory characteristics predictive of COVID-19 severity: a prospective hospital cohort, in Pernambuco, Northeast Brazil.

OBJECTIVE: To describe the clinical-laboratory profile and analyze the factors associated with the severity of COVID-19. METHODS: A prospective cohort study involving patients with COVID-19 admitted to a tertiary hospital in Recife, Brazil. All cases were confirmed by RT-PCR and classified according to severity criteria. A descriptive statistical analysis of the population's characteristics was conducted. Risk factors associated with the outcome of the case according to severity were analyzed by calculating the odds ratio (OR) using the general equation estimation (GEE) model. RESULTS: Among the 75 cases included, 64% were female, and 62.7% were aged 65 years or older. The median length of stay was 9 days (6 - 14). Hypertension (65.3%) and Diabetes Mellitus (36%) were the most frequent comorbidities. Severe forms of COVID-19 constituted 41.3% of the sample. The factors associated with severity were a history of asthma (OR=4.58, 95%CI:1.13 - 18.7), report of anorexia (OR=1, 12, 95%CI:1.01-1.24), and laboratory changes that included elevated platelets (OR=1.00, 95% CI:1.00-1.01), elevated D'Dimer (OR=1, 26, 95% CI:1.04-1.52), elevated aspartate aminotransferase (OR=1.00, 95% CI:1.00-1.01), and gamma-glutamyl transferase (OR=1.22, IC95 %:0.98-1.51), hypernatremia (OR=1.31, 95%CI:1.12-1.52), and hyperkalemia (OR=1.21, 95% CI:1.04-1.41). CONCLUSION: Multisystemic involvement with a tendency for thrombophilia, electrolyte disturbances, and hepatic aggression, reflected by laboratory changes, were factors associated with the severity of COVID-19.

Survival and mortality profile among people living with HIV in a cohort in the Northeastern region of Brazil.

Conditions related to the acquired immune deficiency syndrome (AIDS) are still a significant cause of morbidity and mortality among people living with HIV (PLHIV). Longer survival in this population were reported to increase the risk of developing noncommunicable chronic diseases (NCDs). This study aimed to estimate the survival and causes of death according to age group and sex among PLHIV monitored at two referral centers in the Northeastern Brazil. This is a prospective, retrospective cohort with death records from 2007 to 2018, based on a database that registers causes of death using the International Classification of Disease (ICD-10), which were subsequently coded following the Coding Causes of Death in HIV (CoDe). A total of 2,359 PLHIV participated in the study, with 63.2% being men, with a follow-up period of 13.9 years. Annual mortality rate was 1.46 deaths per 100 PLHIV (95% CI: 1.33 - 1.60) with a frequency of 20.9%. Risk of death for men increased by 49% when compared to women, and the risk of death in PLHIV increased by 51% among those aged 50 years and over at the time of diagnosis. It was observed that 73.5% accounted for AIDS-related deaths, 6.9% for non-AIDS defining cancer, 6.3% for external causes, and 3.2% for cardiovascular diseases. Among the youngest, 97.2% presented an AIDS-related cause of death. Highest frequency of deaths from neoplasms was among women and from external causes among men. There is a need for health services to implement strategies ensuring greater adherence to treatment, especially among men and young people. Moreover, screening for chronic diseases and cancer is essential, including the establishment of easily accessible multidisciplinary care centers that can identify and address habits such as illicit drug use and alcoholism, which are associated with violent deaths.

Feeding characteristics and growth among children with prenatal exposure to Zika virus with and without microcephaly in the microcephaly epidemic research group pediatric cohort.

OBJECTIVE: To describe the feeding characteristics and growth of children with prenatal exposure to Zika virus (ZIKV) from birth to 48 months. DESIGN: Using data from the prospective Microcephaly Epidemic Research Group Pediatric Cohort (MERG-PC), children without microcephaly born to mothers with evidence of ZIKV infection during pregnancy (ZIKV-exposed children without microcephaly) and children with Zika-related microcephaly were compared using repeated cross-sectional analyses within the following age strata: birth; 1 to 12; 13 to 24; 25 to 36; and 37 to 48 months. The groups were compared in relation to prematurity, birth weight, breastfeeding, alternative feeding routes, dysphagia and anthropometric profiles based on the World Health Organization Anthro z-scores (weight-length/height, weight-age, length/height-age and BMI-age). RESULTS: The first assessment included 248 children, 77 (31.05%) with microcephaly and 171 (68.95%) without microcephaly. The final assessment was performed on 86 children. Prematurity was 2.35 times higher and low birth weight was 3.49 times higher in children with microcephaly. The frequency of breastfeeding was high (> 80%) in both groups. On discharge from the maternity hospital, the frequency of children requiring alternative feeding route in both groups was less than 5%. After 12 months of age, children with microcephaly required alternative feeding route more often than children without microcephaly. In children with microcephaly, the z-score of all growth indicators was lower than in children without microcephaly. CONCLUSIONS: Children with Zika-related microcephaly were more frequently premature and low birth weight and remained with nutritional parameters, i.e., weight-for-age, weight-for-length/height and length/height-for-age below those of the children without microcephaly.

The trajectories of CD4 T lymphocytes over time in patients who have defaulted on treatment for tuberculosis in a cohort of people living with HIV, Recife/PE.

BACKGROUND: The CD4 T lymphocyte count in people living with HIV (PLHIV) is a predictor for the progression of the disease (AIDS), survival and response to antiretroviral treatment (ART). A CD4 T lymphocyte count of less than 200 cells/mm3 is indicative of a greater risk for the onset of opportunistic diseases and death. Defaulting on treatment for tuberculosis (TB) may impact immune recovery in PLHIV who are taking ART. The aim of this study was to investigate an association of the CD4 lymphocyte with TB treatment Trajectory and with death. METHODS: A cohort of PLHIV over eighteen years of age and who were taking ART and who had defaulted on pulmonary TB treatment. Latent Class analysis was used to identify different trajectories of CD4 T lymphocyte counts over time. RESULTS: Latent class 1 (High CD4 trajectory) grouped individuals together who were characterized as maintaining a low probability (0 to 29%) of a CD4 count ≤ 200 cells/mm3over time, while latent class 2 (Low CD4 trajectory) grouped individuals together with a high probability (93% to 60%), and latent class 3 (Fluctuating CD4 trajectory), grouped individuals with a fluctuating probability (66% to 0%). The chance of defaulting on treatment earlier (≤ 90 days) was four times higher in latent class 2 (Low CD4 trajectory). Although there was no statistical significance, there was a higher frequency of deaths in this same latent class. CONCLUSION: Individuals with a high probability of a CD4 count ≤ 200 cells/ mm3 should be monitored in order to avoid treatment default and thereby prevent death. New studies should be conducted with a larger sample size and a longer follow-up time in PLHIV who initiated ART treatment early so as to support clinical decisions for a better understanding of immune behavior.

Survival and mortality profile among people living with HIV in a cohort in the Northeastern region of Brazil

ABSTRACT Conditions related to the acquired immune deficiency syndrome (AIDS) are still a significant cause of morbidity and mortality among people living with HIV (PLHIV). Longer survival in this population were reported to increase the risk of developing noncommunicable chronic diseases (NCDs). This study aimed to estimate the survival and causes of death according to age group and sex among PLHIV monitored at two referral centers in the Northeastern Brazil. This is a prospective, retrospective cohort with death records from 2007 to 2018, based on a database that registers causes of death using the International Classification of Disease (ICD-10), which were subsequently coded following the Coding Causes of Death in HIV (CoDe). A total of 2,359 PLHIV participated in the study, with 63.2% being men, with a follow-up period of 13.9 years. Annual mortality rate was 1.46 deaths per 100 PLHIV (95% CI: 1.33 - 1.60) with a frequency of 20.9%. Risk of death for men increased by 49% when compared to women, and the risk of death in PLHIV increased by 51% among those aged 50 years and over at the time of diagnosis. It was observed that 73.5% accounted for AIDS-related deaths, 6.9% for non-AIDS defining cancer, 6.3% for external causes, and 3.2% for cardiovascular diseases. Among the youngest, 97.2% presented an AIDS-related cause of death. Highest frequency of deaths from neoplasms was among women and from external causes among men. There is a need for health services to implement strategies ensuring greater adherence to treatment, especially among men and young people. Moreover, screening for chronic diseases and cancer is essential, including the establishment of easily accessible multidisciplinary care centers that can identify and address habits such as illicit drug use and alcoholism, which are associated with violent deaths.

Hematological Changes during Seven Days of Hospitalization in Patients with Acute Myocardial Infarction. / Alterações Hematológicas durante um Período de Sete Dias de Internação em Pacientes com Infarto Agudo do Miocárdio.

BACKGROUND: Acute myocardial infarction is a major cause of mortality worldwide, and atherosclerotic plaque formation is the main pathophysiological mechanism, which results in chronic inflammation that induces erythrocyte maturation and may cause an increase in the red cell distribution width (RDW) index. OBJECTIVE: Evaluate the role of the anisocytosis index in patients with acute myocardial infarction in both types of infarctions as a predictor of severity. METHODS: Patients were included in the study according to the inclusion/exclusion criteria, following the hospital routine based on their clinical and laboratory history. Statistical analyzes were performed according to each variable. All conclusions were drawn considering the significance level of 5%. RESULTS: During the follow-up period, in the 349 patients analyzed, the mortality rate was associated with the variables RDW (CV) and RDW (SD), in those patients who died, an increase was noted, as demonstrated in the multivariate model, for the effects of an acute ST elevation myocardial infarction and the RDW, adjusted for confounding factors (p-value = 0.03 and 0.04). In contrast, the total number of erythrocytes (p-value = 0.00) and hemoglobin (p-value = 0.03) showed a decrease during severe patients' hospitalization. CONCLUSION: The anisocytosis index was a predictive factor of mortality and can be used as an indicator of worse prognosis in patients with acute myocardial infarction.

FUNDAMENTO: O infarto agudo do miocárdio é uma das principais causas de mortalidade em todo o mundo e a formação de placa aterosclerótica é o principal mecanismo fisiopatológico, que resulta em inflamação crônica e induz a maturação eritrocitária, podendo causar aumento no índice de amplitude de distribuição dos glóbulos vermelhos (RDW). OBJETIVO: Avaliar o papel do índice de anisocitose em pacientes com infarto agudo do miocárdio em ambos os tipos de infarto como preditor de gravidade. MÉTODOS: Os pacientes foram incluídos no estudo de acordo com os critérios de inclusão e exclusão, seguindo a rotina hospitalar baseada na história clínica e laboratorial. As análises estatísticas foram realizadas de acordo com cada variável. Chegou-se a todas as conclusões considerando o nível de significância de 5%. RESULTADOS: Durante o período de acompanhamento, nos 349 pacientes analisados, a taxa de mortalidade esteve associada às variáveis RDW (CV) e RDW (SD). Nos pacientes que foram a óbito, notou-se aumento, conforme demonstrado no modelo multivariado, nos efeitos de um infarto agudo do miocárdio com supradesnivelamento do segmento ST e RDW, ajustado para fatores de confusão (valor-p = 0,03 e 0,04). Em contrapartida, o número total de eritrócitos (valor-p = 0,00) e hemoglobina (valor-p = 0,03) apresentou diminuição durante a internação de pacientes graves. CONCLUSÃO: O índice de anisocitose foi fator preditivo de mortalidade e pode ser utilizado como indicador de pior prognóstico em pacientes com infarto agudo do miocárdio.

Interferon-gamma gene diplotype (AA-rs2069716 / AG-rs2069727) may play an important role during secondary outcomes of severe dengue in Brazilian patients.

Dengue is a global and growing health threat, especially in Southeast Asia, West Pacific and South America. Infection by the dengue virus (DENV) results in dengue fever, which can evolve to severe forms. Cytokines, especially interferons, are involved in the immunopathogenesis of dengue fever, and so may influence the disease outcomes. The aim of this study was to investigate the association between severe forms of dengue and two single nucleotide polymorphisms (SNPs) in the interferon-gamma gene (IFNG): A256G (rs2069716) and A325G (rs2069727). We included 274 patients infected with DENV serotype 3: 119 cases of dengue without warning signs (DWoWS), and 155 with warning signs (DWWS) or severe dengue (SD). DNA was extracted, and genotyped with Illumina Genotyping Kit or real time PCR (TaqMan probes). We estimated the adjusted Odds Ratios (OR) by multivariate logistic regression models. When comparing with the ancestral AA/AA diplotype (A256G/A325G), we found a protective association of the AA/AG against DWWS/SD among patients with secondary dengue (OR 0.51; 95% IC 0.24-1.10, p = 0.085), adjusting for age and sex. The variant genotype at locus A325G of the IFNG, in combination with the ancestral genotype at locus A256G, can protect against severe clinical forms of secondary dengue in Brazilian DENV3-infected patients.

Longitudinal evolution of electroencephalogram (EEG): Findings over five years of follow-up in children with Zika-related microcephaly from the Microcephaly Epidemic Research Group Pediatric Cohort (2015-2020).

OBJECTIVE: To assess the longitudinal evolution of EEG findings in children with Zika related-microcephaly (ZRM) and to evaluate the associations of these patterns with the children's clinical and neuroimaging characteristics. METHODS: As part of the follow-up of the Microcephaly Epidemic Research Group Pediatric Cohort (MERG-PC) in Recife, Brazil, we performed serial EEG recordings in a subgroup of children with ZRM to evaluate changes in background rhythms and epileptiform activity (EA). Latent class analysis was used to identify patterns in the evolution of EA over time; clinical and neuroimaging findings were compared across the identified groups. RESULTS: Out of the 72 children with ZRM who were evaluated during 190 EEGs/videoEEGs, all participants presented with abnormal background activity, 37.5% presented with an alpha-theta rhythmic activity, and 25% presented with sleep spindles, which were less commonly observed in children with epilepsy. EA changed over time in 79.2% of children, and three distinct trajectories were identified: (i) multifocal EA over time, (ii) no discharges/focal EA evolving to focal/multifocal EA, and (iii) focal/multifocal EA evolving to epileptic encephalopathy patterns (e.g., hypsarrhythmia or continuous EA in sleep). The multifocal EA over time trajectory was associated with periventricular and thalamus/basal ganglia calcifications, brainstem and corpus callosum atrophy and had less focal epilepsy, whereas the children in the trajectory which evolved to epileptic encephalopathy patterns had more frequently focal epilepsy. SIGNIFICANCE: These findings suggest that, in most children with ZRM, trajectories of changes in EA can be identified and associated with neuroimaging and clinical features.

Impact of the COVID-19 pandemic on the mental health of frontline healthcare workers in a highly affected region in Brazil.

BACKGROUND: The COVID-19 pandemic had a major impact on the mental health of healthcare workers (HCWs), especially in low and middle-income countries, which had to face additional political, social, and economic challenges. We thus aimed to assess the prevalence of mental health outcomes and the associated factors in HCWs treating COVID-19 patients in one of the most affected regions in Brazil. METHODS: We used the Respondent-Driven Sampling method to assess the risks of COVID-19 infection and symptoms of mental disorders in nurses, nursing technicians, and physicians who worked on the frontline in the metropolitan region of Recife. 865 healthcare workers completed a survey regarding sociodemographic data, work-related risks, and symptoms of mental disorders - SRQ-20 for common mental disorders (CMD); AUDIT-C for problematic alcohol use; GAD-7 for anxiety; PHQ-9 for depression; PCL-5 for post-traumatic stress disorder (PTSD). Gile's successive sampling estimator was used to produce the weighted estimates by professional category. A Poisson regression model with robust variance was used to analyze factors associated with a positive screening for CMD. We will present the results of a cross-sectional analysis of the mental health outcomes after the first peak of COVID-19 - from August 2020 to February 2021. RESULTS: The prevalence ratios for a positive screening for CMD were 34.9% (95% CI: 27.8-41.9) in nurses, 28.6% (95% CI: 21.3-36.0) in physicians, and 26.6% (95% CI: 16.8-36.5) in nursing technicians. Nurses presented a higher prevalence of depressive symptoms (23%). Positive screening for problematic alcohol use (10.5 to14.0%), anxiety (10.4 to 13.3%), and PTSD (3.3 to 4.4%) were similar between the professional categories. The main factors associated with CMD in nurses and physicians were related to an intrinsic susceptibility to mental illness, such as previous or family history of psychiatric disorder, and female sex. Among nurse technicians, work-related factors, such as accidents with biological material, presented the strongest association with CMD. CONCLUSION: The mental health of HCWs fighting COVID-19 in Recife was severely affected. It is crucial that healthcare services provide adequate working conditions and psychological support, investing in programs to promote and protect HCWs mental health.

Risk of adverse outcomes in offspring with RT-PCR confirmed prenatal Zika virus exposure: An individual participant data meta-analysis of 13 cohorts in the Zika Brazilian Cohorts Consortium.

Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%.

Heart rate variability as a predictor of mechanical ventilation weaning outcomes.

BACKGROUND: Delays in the mechanical ventilation (MV) weaning process increase mortality. The spontaneous breathing test is the gold standard to assess weaning and extubation success, although it has approximately 85% accuracy. Studies have demonstrated a correlation between decreased heart rate variability (HRV) and weaning failure. OBJECTIVES: To assess the usefulness of HRV as a predictor of MV weaning outcomes. METHODS: Cross-sectional analytical study in adults of both sexes on MV in intensive care unit (ICU) stay. Patients were divided into weaning success and failure groups. Clinical data were collected, and HRV records were obtained with a heart rate monitor. RESULTS: The study included 68 individuals - 91.1% in the weaning success group and 8.9% in the failure group. All HRV indices analyzed in both groups were lower than the reference values. No statistical difference was found in the mean RR interval (RRi), the standard deviation of the NN interval (SDNN), and the square root of the mean squared differences of successive NN intervals (RMSSD) between the groups. The weaning failure group had a significant increase in LF (41 vs. 69.4) and LF/HF ratio (0.685 vs. 2.6) and a significant decrease in HF (58.85 vs. 30.2). CONCLUSIONS: HRV measure with spectral analysis can be a good predictor of MV weaning failure. Integrating this assessment tool in ICU to predict weaning outcomes could provide more precise prognoses and more adequate assistance quality.

Adherence to antiretroviral therapy and factors associated with non-adherence: a cohort study at two referral services in Brazil.

This cohort study evaluated non-adherence to antiretrovirals at referral services in Pernambuco, Brazil, 2016/2017, through self-report. A generalized mixed-effects model for binary outcomewas used. We assessed 542 participants with an adherence rate of 85.50%. A greater chance of non-adherence was associated with:a low/moderate level of nicotine dependence (OR = 2.79, p = 0.00, IC = 1.44-5.41); ≥7 tablets/day (OR = 6.14, p = 0.00, IC = 3.42-11.02); LPV/r (OR = 1.49, p = 0.6, IC = 0.98-2.26), ddI (OR = 3.34, p = 0.03, IC = 1.12-9.97), ABC (OR = 4.02, p = 0.05, IC = 1.01-16.03), RAL (OR = 2.49, p = 0.01, IC = 1.32-4.70) and DTG (OR = 4.65, p = 0.01, IC = 1.42-15.16); 6-10 year seropositive diagnosis (OR = 2.17, p = 0.01, IC = 1.20-3.92) and symptoms of depression (OR = 1.55, p = 0.03, IC = 1.03-2.33). Protective factors for non-adherence weres: ≥50 years (OR = 0.67, p = 0.06, IC = 0.45-1.01), secondary/higher education (OR = 0.48, p = 0.00, IC = 0.34-0.70), embarrassment at health service (OR = 0.49, p = 0.04, IC = 0.24-0.97), good understanding of antiretrovirals (OR = 0.62, p = 0.03, IC = 0.40-0.96), adverse event (OR = 0.74, p = 0,06, IC = 0.54-1.01), use of TDF (OR = 0.62, p = 0.01, IC = 0.43-0.90), NVP (OR = 0.41, p = 0.05, IC = 0.71-1.00) and EFZ (OR = 0.48, p = 0.01, IC = 0.29-0.80) and good knowledge of HIV/AIDS/ART. (OR = 0.67, p = 0.07, IC = 0.43-1.04). Variables with stronger association were those linked to ART. Systematic use of self-report adherence is recommended for priority groups.

Alterações Hematológicas durante um Período de Sete Dias de Internação em Pacientes com Infarto Agudo do Miocárdio / Hematological Changes during Seven Days of Hospitalization in Patients with Acute Myocardial Infarction

Resumo Fundamento O infarto agudo do miocárdio é uma das principais causas de mortalidade em todo o mundo e a formação de placa aterosclerótica é o principal mecanismo fisiopatológico, que resulta em inflamação crônica e induz a maturação eritrocitária, podendo causar aumento no índice de amplitude de distribuição dos glóbulos vermelhos (RDW). Objetivo Avaliar o papel do índice de anisocitose em pacientes com infarto agudo do miocárdio em ambos os tipos de infarto como preditor de gravidade. Métodos Os pacientes foram incluídos no estudo de acordo com os critérios de inclusão e exclusão, seguindo a rotina hospitalar baseada na história clínica e laboratorial. As análises estatísticas foram realizadas de acordo com cada variável. Chegou-se a todas as conclusões considerando o nível de significância de 5%. Resultados Durante o período de acompanhamento, nos 349 pacientes analisados, a taxa de mortalidade esteve associada às variáveis RDW (CV) e RDW (SD). Nos pacientes que foram a óbito, notou-se aumento, conforme demonstrado no modelo multivariado, nos efeitos de um infarto agudo do miocárdio com supradesnivelamento do segmento ST e RDW, ajustado para fatores de confusão (valor-p = 0,03 e 0,04). Em contrapartida, o número total de eritrócitos (valor-p = 0,00) e hemoglobina (valor-p = 0,03) apresentou diminuição durante a internação de pacientes graves. Conclusão O índice de anisocitose foi fator preditivo de mortalidade e pode ser utilizado como indicador de pior prognóstico em pacientes com infarto agudo do miocárdio.

Abstract Background Acute myocardial infarction is a major cause of mortality worldwide, and atherosclerotic plaque formation is the main pathophysiological mechanism, which results in chronic inflammation that induces erythrocyte maturation and may cause an increase in the red cell distribution width (RDW) index. Objective Evaluate the role of the anisocytosis index in patients with acute myocardial infarction in both types of infarctions as a predictor of severity. Methods Patients were included in the study according to the inclusion/exclusion criteria, following the hospital routine based on their clinical and laboratory history. Statistical analyzes were performed according to each variable. All conclusions were drawn considering the significance level of 5%. Results During the follow-up period, in the 349 patients analyzed, the mortality rate was associated with the variables RDW (CV) and RDW (SD), in those patients who died, an increase was noted, as demonstrated in the multivariate model, for the effects of an acute ST elevation myocardial infarction and the RDW, adjusted for confounding factors (p-value = 0.03 and 0.04). In contrast, the total number of erythrocytes (p-value = 0.00) and hemoglobin (p-value = 0.03) showed a decrease during severe patients' hospitalization. Conclusion The anisocytosis index was a predictive factor of mortality and can be used as an indicator of worse prognosis in patients with acute myocardial infarction.

Interferon-gamma gene diplotype (AA-rs2069716 / AG-rs2069727) may play an important role during secondary outcomes of severe dengue in Brazilian patients

ABSTRACT Dengue is a global and growing health threat, especially in Southeast Asia, West Pacific and South America. Infection by the dengue virus (DENV) results in dengue fever, which can evolve to severe forms. Cytokines, especially interferons, are involved in the immunopathogenesis of dengue fever, and so may influence the disease outcomes. The aim of this study was to investigate the association between severe forms of dengue and two single nucleotide polymorphisms (SNPs) in the interferon-gamma gene (IFNG): A256G (rs2069716) and A325G (rs2069727). We included 274 patients infected with DENV serotype 3: 119 cases of dengue without warning signs (DWoWS), and 155 with warning signs (DWWS) or severe dengue (SD). DNA was extracted, and genotyped with Illumina Genotyping Kit or real time PCR (TaqMan probes). We estimated the adjusted Odds Ratios (OR) by multivariate logistic regression models. When comparing with the ancestral AA/AA diplotype (A256G/A325G), we found a protective association of the AA/AG against DWWS/SD among patients with secondary dengue (OR 0.51; 95% IC 0.24-1.10, p = 0.085), adjusting for age and sex. The variant genotype at locus A325G of the IFNG, in combination with the ancestral genotype at locus A256G, can protect against severe clinical forms of secondary dengue in Brazilian DENV3-infected patients.

Profile of judicialization in access to antineoplastic drugs and their costs: a cross-sectional, descriptive study based on a set of all lawsuits filed between 2016 and 2018 in a state in the Northeast Region of Brazil.

BACKGROUND: The judicialization of the acquisition of medication for healthcare is not restricted to Brazil but can also be found in other Latin American countries, despite the existence of a universal health system in the case of Brazil, the Unified Health System (known as the SUS). Right-to-medicines litigation has existed ever since the emergence of a high demand for treatment of Acquired Immuno-deficiency Syndrome (AIDS) but the current focus is on cancer. Pharmaceutical Assistance (PA) is the area within the SUS that is responsible for ensuring access to medication and the aim of this article is thus to draw up a profile of litigation related to PA in one economically significant state in the Northeast Region of Brazil, in terms of the following characteristics of lawsuits: the plaintiff filing the lawsuit; medical and health information; the cost of acquiring the requested medications; and the proportion accounted for by spending on antineoplastic drugs. METHODS: A cross-sectional, descriptive study was conducted of lawsuits filed between 2016 and 2018 at the Litigation Center of the State of Pernambuco Department of Health. RESULTS: A total of 2,947 lawsuits containing at least one requested medication were analyzed. The majority of the plaintiffs were male (51.7%); 49.8% of the requests originated in the Unified Health System (SUS), and plaintiffs were primarily patients in the Metropolitan region of the State capital, Recife. The most frequent cancers involved were those classified by the ICD as C61, C71 and C50. The median general expense on medications for the actions was U$1,734.94. Considering antineoplastic drugs alone, the cost exceeded U$7,500 per lawsuit over the three years, given that the median unit price for antineoplastic drugs is approximately US$65 compared to US$4 for non-antineoplastic drugs. CONCLUSION: The present study is of relevance to the field of public health and examines how a profile of such healthcare litigation can be used as a tool for managing and improving decision-making in times of economic austerity.

Characteristics of children of the Microcephaly Epidemic Research Group Pediatric Cohort who developed postnatal microcephaly.

The number of studies published on postnatal microcephaly in children with Congenital Zika Syndrome is small, clinical presentations vary and aspects of the evolution of these children remain unclarified. The present case series examined clinical characteristics and assessed the growth velocity of the head circumference, weight and height Z-scores in 23 children who developed postnatal microcephaly during follow-up in the Microcephaly Epidemic Research Group Pediatric Cohort. To estimate the change in the head circumference, weight and height Z-scores over time and compare the mean difference between sexes, we used multilevel mixed-effects linear regressions with child-specific random effects. Among these children, 60.9% (n = 14/23) presented with craniofacial disproportion, 60.9% (n = 14/23) with strabismus, 47.8% (n = 11/23) with early onset seizures, 47.8% (n = 11/23) with dysphagia and 43.5% (n = 10/23) with arthrogryposis. Of the 82.7% (n = 19/23) children who underwent neuroimaging, 78.9% (n = 15/19) presented with alterations in the central nervous system. Monthly growth velocity, expressed in Z-scores, of the head circumference was - 0.098 (95% CI % - 0.117 to - 0.080), of weight was: - 0.010 (95%-CI - 0.033 to 0.014) and of height was: - 0.023 (95%-CI - 0.046 to 0.0001). Postnatal microcephaly occurred mainly in children who had already presented with signs of severe brain damage at birth; there was variability in weight and height development, with no set pattern.

Risk of SARS-CoV-2 infection among front-line healthcare workers in Northeast Brazil: a respondent-driven sampling approach.

OBJECTIVES: We assessed the prevalence of SARS-CoV-2 infection, personal protective equipment (PPE) shortages and occurrence of biological accidents among front-line healthcare workers (HCW). DESIGN, SETTING AND PARTICIPANTS: Using respondent-driven sampling, the study recruited distinct categories of HCW attending suspected or confirmed patients with COVID-19 from May 2020 to February 2021, in the Recife metropolitan area, Northeast Brazil. OUTCOME MEASURES: The criterion to assess SARS-CoV-2 infection among HCW was a positive self-reported PCR test. RESULTS: We analysed 1525 HCW: 527 physicians, 471 registered nurses, 263 nursing assistants and 264 physical therapists. Women predominated in all categories (81.1%; 95% CI: 77.8% to 84.1%). Nurses were older with more comorbidities (hypertension and overweight/obesity) than the other staff. The overall prevalence of SARS-CoV-2 infection was 61.8% (95% CI: 55.7% to 67.5%) after adjustment for the cluster random effect, weighted by network, and the reference population size. Risk factors for a positive RT-PCR test were being a nursing assistant (OR adjusted: 2.56; 95% CI: 1.42 to 4.61), not always using all recommended PPE while assisting patients with COVID-19 (OR adj: 2.15; 95% CI: 1.02 to 4.53) and reporting a splash of biological fluid/respiratory secretion in the eyes (OR adj: 3.37; 95% CI: 1.10 to 10.34). CONCLUSIONS: This study shows the high frequency of SARS-CoV2 infection among HCW presumably due to workplace exposures. In our setting, nursing assistant comprised the most vulnerable category. Our findings highlight the need for improving healthcare facility environments, specific training and supervision to cope with public health emergencies.

Co-circulation of Chikungunya Virus during the 2015-2017 Zika Virus Outbreak in Pernambuco, Brazil: An Analysis of the Microcephaly Epidemic Research Group Pregnancy Cohort.

Co-circulation of arthropod-borne viruses, particularly those with shared mosquito vectors like Zika (ZIKV) and Chikungunya (CHIKV), is increasingly reported. An accurate differential diagnosis between ZIKV and CHIKV is of high clinical importance, especially in the context of pregnancy, but remains challenging due to limitations in the availability of specialized laboratory testing facilities. Using data collected from the prospective pregnancy cohort study of the Microcephaly Epidemic Research Group, which followed up pregnant persons with rash during the peak and decline of the 2015-2017 ZIKV epidemic in Recife, Pernambuco, Brazil, this study aims to describe the geographic and temporal distribution of ZIKV and CHIKV infections and to investigate the extent to which ZIKV and CHIKV infections may be clinically differentiable. Between December 2015 and June 2017, we observed evidence of co-circulation with laboratory confirmation of 213 ZIKV mono-infections, 55 CHIKV mono-infections, and 58 sequential ZIKV/CHIKV infections (i.e., cases with evidence of acute ZIKV infection with concomitant serological evidence of recent CHIKV infection). In logistic regressions with adjustment for maternal age, ZIKV mono-infected cases had lower odds than CHIKV mono-infected cases of presenting with arthralgia (aOR, 99% CI: 0.33, 0.15-0.74), arthritis (0.35, 0.14-0.85), fatigue (0.40, 0.17-0.96), and headache (0.44, 0.19-1.90). However, sequential ZIKV/CHIKV infections complicated discrimination, as they did not significantly differ in clinical presentation from CHIKV mono-infections. These findings suggest clinical symptoms alone may be insufficient for differentiating between ZIKV and CHIKV infections during pregnancy and therefore laboratory diagnostics continue to be a valuable tool for tailoring care in the event of arboviral co-circulation.

Modeling of covariates predicting renal allograft failure within six months after transplantation / Modelagem das covariáveis preditivas para falência do enxerto renal até seis meses do transplante

INTRODUCTION: Kidney transplantation (KT) is the renal replacement therapy (RRT) of choice for patients with chronic kidney disease (CKD). However, not every KT is successful and some patients persist on RRT. OBJECTIVE: To model a logistic regression with pre- and post-KT risk covariates capable of predicting secondary allograft dysfunction in need of RRT or reaching stage V of CKD until the first six months post-KT. METHODS: Cohort with KT recipients from Northeastern Brazil. Medical records of KT performed between 2011-2018 were analyzed. KT-recipients with insufficient data or who abandoned follow-up were excluded. The covariables analyzed were: demographic; infectious; pre- and post-KT comorbidities; panel reactive-antibodies; number of HLA mismatches; acute rejection episodes mediated by T-cell (ACR) or antibodies (AAR) six months after KT; and laboratory tests six months after KT. RESULTS: Covariates with higher risk for the analyzed outcomes six months after KT were: elderly KT recipients (OR:1.41; CI95%:1.01-1.99), time between onset of RRT and KT (ΔT-RRT&KT)>10years (OR:3.54; CI95%:1.27-9.87), diabetes mellitus (DM) pre-KT (OR:3.35; CI95%:1.51-7.46), pyelonephritis (OR:2.45; CI95%:1.24-4.84), polyomavirus nephropathy (OR:4.99; CI95%:1.87-13.3), AAS (OR:4.82; CI95%:1.35-17.2), 24h-proteinuria ≥300mg/24h (OR:5.05; CI95%:2.00-12.7) and serum calcium (Ca) <8.5mg/dL (OR:4.72; CI95%:2.00-11.1). The multivariate model presented an accuracy of 88.1% and the mean variance inflation factor is 1.81. CONCLUSION: Elderly-recipients, ΔT-RRT&KT>10 years, pre-KT DM, and post-KT aggressions until six months (pyelonephritis, polyomavirus nephropathy, ABMR, 24h-proteinuria≥300mg/24h, and Ca<8.5mg/dL) are associated with high predictive power for secondary allograft dysfunction in need of RRT or reaching CKD stage V until the first six months post-KT.

INTRODUÇÃO: Transplante renal (TR) é a terapia renal substitutiva (TRS) de escolha para pacientes com doença renal crônica (DRC). Entretanto, nem todo TR é bem-sucedido e alguns pacientes persistem em TRS. OBJETIVO: Modelar uma regressão logística com covariáveis de risco pré e pós-TR preditora da disfunção secundária do aloenxerto com necessidade de TRS ou alcance ao estágio V da DRC até os primeiros seis meses pós-TR. MÉTODOS: Coorte com receptores transplantados realizado em hospital no Nordeste brasileiro. Analisou-se registros médicos dos TR realizados entre 2011-2018. Receptores com dados insuficientes ou que abandonaram seguimento foram excluídos. Foram analisadas covariáveis: demográficas; infecciosas; comorbidades pré e pós-TR; painel de reatividade; incompatibilidades de HLA; episódios de rejeições agudas mediadas por células-T ou por anticorpos; exames laboratoriais seis meses pós-TR. RESULTADOS: Receptores idosos (OR:1,41; IC95%:1,01-1,99), tempo entre início da TRS e TR (∆T-TRS&TR)>10 anos (OR:3,54; IC95%:1,27-9,87), diabetes mellitus (DM) pré-TR (OR:3,35; IC95%:1,51-7,46), pielonefrite (OR:2,45; IC95%:1,24-4,84), nefropatia por poliomavírus (OR:4,99; IC95%:1,87-13,3), RAMA (OR:4,82; IC95%:1,35-17,2), proteinúria de 24h (Pt24h) ≥300mg/24h (OR:5,05; IC95%:2,00-12,7) e cálcio sérico (Ca)<8,5mg/dL (OR:4,72; IC95%:2,00-11,1) foram identificadas como covariáveis de maior risco para os desfechos analisados até seis meses pós-TR. O modelo multivariado apresentou acurácia de 88,1% e fator de inflação da variância médio de 1,81. CONCLUSÃO: Receptores idosos, ∆T-TRS&TR>10anos, DM pré-TR e agressões até seis meses pós-TR (pielonefrite, nefropatia por poliomavírus, RAMA, Pt24h≥300mg/24h e Ca<8,5mg/dL), apresentam alto poder preditivo para disfunção secundária do aloenxerto com necessidade de TRS ou alcance ao estágio V da DRC até os primeiros seis meses pós-TR.

Orthostatic changes in blood pressure and survival in elderly cardiopaths.

OBJECTIVE: The objective of this study was to analyze the association between orthostatic changes in blood pressure and mortality in elderly cardiopath patients. METHODS: A cohort of 455 elderly cardiopath patients, monitored at a referral outpatient cardiology clinic in Pernambuco, Brazil, from October 2015 to July 2018. The exposure groups were formed according to their orthostatic changes in blood pressure following the requirements of the Brazilian Guidelines for Hypertension. RESULTS: Orthostatic hypotension was present in 46 patients (10.1%), 91 had orthostatic hypertension (20%), and 318 had no orthostatic alterations (69.9%). There were 52 deaths during follow-up. The results demonstrated that there was no statistically significant association between orthostatic hypotension and overall mortality (HR 1.30; 95%CI 0.53-3.14; p=0.567) nor between orthostatic hypertension and overall mortality (HR 0.95; 95%CI 0.65-1.39; p=0.34). Survival in relation to the exposure groups presented no statistically significant difference (p=0.504). CONCLUSION: There was a low frequency of orthostatic hypotension and a mild high frequency of orthostatic hypertension when compared with previous studies, and no association was observed with overall mortality or with the survival time of elderly patients with heart disease.