Chronic neutropenia in childhood: experience of a tertiary center

Abstract Objective: To assess the prevalence of chronic neutropenia (CN) and the clinical profile of patients with CN aged up to 18 years, followed in the pediatric hematology, rheumatology, or immunology outpatient clinic of a tertiary medical center from May 1, 2018, to 30 April 2019. Methods: Retrospective observational study carried out by collecting data from the patient's medical charts. CN was defined as absolute neutrophil count (ANC) below 1.5 × 109/L lasting over three months. Autoimmune neutropenia (AIN) was defined by clinical criteria and an over twofold increase in ANC after glucocorticoid stimulation. AIN was considered secondary when associated with autoimmune or immunoregulatory disorders. Wilcoxon and Fisher's exact tests were used to compare variables; the significance level was 5 %. Results: A total of 1,039 patients were evaluated; 217 (20 %) presented CN. Twenty-one (2 %) had AIN, classified as primary in 57 % of the cases. The average age at the onset of symptoms was 38.6 months. During follow-up, patients had 4.2 infections on average; frequency was higher among patients with secondary AIN (p = 003). Isolated neutropenia occurred in 43 % of the patients with AIN. Neutropenia resolved in eight (38 %) of the 21 patients with AIN within 19.6 months on average. Eight patients with secondary AIN met the criteria for Inborn Errors of Immunity. Conclusion: AIN prevalence was 2 %. Most cases were first evaluated by a pediatric immunologist or rheumatologist rather than a pediatric hematologist. This study highlights the need for a multidisciplinary approach involving a pediatric immunologist, rheumatologist, and hematologist.

Development and evaluation of a mixed reality model for training the retrosigmoid approach.

INTRODUCTION: The use of simulation has the potential to accelerate the learning curves and increase the efficiency of surgeons. However, there is currently a scarcity in models dedicated to skull base surgical approaches. Thus, the objective of this study was to develop a cost-effective mixed reality system consisting of an ultrarealistic physical model and augmented reality (AR) and evaluate its use in training surgeons on the retrosigmoid approach. MATERIALS AND METHODS: The virtual models were developed from images of patients with vestibular schwannoma. The tumor was mirrored to allow bilateral approaches and the model has drawers for repositioning structures, allowing reuse of the material and cost reduction. Pre and post-test assessments were applied to ten residents and young neurosurgeons, divided into control and test groups. Only the control group was exposed to the model. The difference in scores obtained by participants before and after exposure to the models was considered for analysis and participants in the control group answered self-satisfaction questionnaires. RESULTS: The mean differences were 4.80 in the control group (95%CrI = 1.08-9.79) and 5.43 in the test group (95%CrI = 1.67-8.20). The average score of the self-satisfaction questionnaires was 24.0 (23-25). CONCLUSION: The ultrarealistic model efficiently allowed retromastoid access to the cerebellopontine angle. A tendency towards greater gains in performance in the group exposed to the model was verified. Scores from the self-satisfaction questionnaires demonstrated that participants considered the model relevant for neurosurgical training and increased confidence among surgeons.

Personalized lung care: Bronchopulmonary dysplasia risk prediction tool tailored for neonates born in resource-limited settings.

PURPOSE: Predicting bronchopulmonary dysplasia (BPD) to assess the risk-benefit of therapy is necessary considering the side effects of medications. We developed and validated an instrument for predicting BPD and compared it with an instrument currently used for neonates born in a Brazilian hospital. METHODS: This was a retrospective cohort study of patients born between 2016 and 2020 with a gestational age (GA) between 23 and 30 weeks. Predictive equations were elaborated using methods of component variable selection collected on the 14th day of life; 70% of the sample was randomly selected for the construction of risk prediction equations and the remaining 30% for their validation, application, and comparison with the National Institute of Child Health and Human Development (NICHD) instrument. The sensitivity, specificity, and predictive values of the equations were calculated. RESULTS: The equation that used variables with p < 5% in Fisher's exact test presented the best results: specificity of 98% and positive predictive value of 93% and could be used for BPD prediction of all small-for-gestational-age (SGA) infants. The NICHD calculator applied to our population had a specificity of 93% and a positive predictive value of 75% and could not be applied to extremely SGA infants. CONCLUSION: Our tool can predict the risk of BPD on the 14th day of life, has higher specificity and positive predictive value to our population than the NICHD instrument, and can be suitable for SGA infants. The results must be confirmed by applying it to other populations to validate our tool.

Risk factors and mortality of candidemia in a children's public hospital in Sao Paulo, Brazil.

Candida bloodstream infections in children are of special concern in neonatal and pediatric intensive care and patients with comorbidities. This study aimed to estimate the incidence and risk factors associated with mortality in candidemia cases occurring in a public children's hospital in Ribeirao Preto, Brazil. It is a retrospective transversal study. Every patient under the age of 18 admitted to the study facility from January 1, 2013, to December 31, 2019, was considered potentially eligible to be included if they had candidemia. We collected clinical data from medical records. We included 113 blood cultures yielding positive results for Candida. The incidence rate was 2.12 per 1000 admissions. The most common Candida species was Candida parapsilosis. Septic shock during the candidemia episode was the only clinical outcome associated with a relative risk-adjusted (RRa) of 2.77 with an interval >1 (1.12-6.85). Our findings show that the incidence rate and mortality rates of candidemia are in line with those in other children's services in Brazil. We found a global mortality rate of 28.31% (32/113) from candidemia episodes. We highlight the predominance of non-albicans Candida species including C. parapsilosis. Septic shock was the most important factor showing a significant risk of mortality.

Nutritional status and age at menarche in Amazonian students.

OBJECTIVES: Age at menarche (MA) is a proxy for biological maturation and a parameter of socioeconomic changes. Worldwide, anticipation of menarche is associated with nutritional transition and excess weight. The objective of this study was to evaluate the MA in Amazonian students and its association with nutritional status, ethnicity, and socioeconomic level. METHODS: Cross-sectional study with 1,017 students aged 6 to 17 living in the city of Manaus, Brazil. MA was analyzed by status quo and recall; its association with body mass index (BMI), race, socioeconomic status, and adult height was examined. RESULTS: 559 (51.9%) participants had already experienced menarche. In 91.7%, menarche occurred between 10 and 14 years of age; the mean age at the onset of menarche was 11.9 years. Overweight (11.6 years) and obese (11.4 years) participants reached menarche earlier than those with normal weight (12 years) and lean (12.7 years) participants. The associations between MA and nutritional status showed that overweight and obesity are risk factors for the early occurrence of menarche. MA was not associated with socioeconomic status/parental education or race. However, excess weight was associated with earlier MA in all races and social classes. The adult height was slightly lower in girls with menarche before 12 years old (157.9 vs 159.4 cm). CONCLUSION: Regardless of socioeconomic level or ethnicity, excess weight was associated with earlier menarche in Amazonian students.

High Incidence Rates of Early-onset Bacterial Sepsis in Infants Born in Two Brazilian Maternities: A 15-Year Retrospective Analysis.

BACKGROUND: Data on the burden and etiology of neonatal early-onset bacterial sepsis (EOBS) in low-to-middle-income countries are scarce. Surveillance is critical for optimizing prevention and treatment strategies. We aimed to estimate the incidence of EOBS in 2 large Brazilian cohorts of neonates. METHODS: Data were retrospectively obtained from 33,794 neonates born between 2009 and 2017 at low-risk (n = 17,981) and high-risk maternity centers (n = 15,813). Blood cultures were taken within 72 hours of life from neonates with perinatal risk factors for EOBS or suspected EOBS. A positive blood culture for a pathogenic microorganism and a compatible clinical evolution confirmed the diagnosis of EOBS. RESULTS: One-third of the infants born from high-risk and 18.5% from low-risk maternities were investigated for EOBS. Overall, EOBS was more incident in neonates born in the high-risk facilities [66 cases or 4.2/1000 (95% CI: 3.2-5.3)] than in the low-risk facilities [24 cases or 1.3/1000 (95% CI: 0.9-2.0)]. The incidence rate of EOBS increased with decreasing gestational age (<32 weeks: 20.5/1000; 32-36 weeks: 5.6/1000; ≥37 weeks: 1.5/1000). Group B Streptococcus (GBS) was the agent more frequently identified in high-risk and low-risk maternities: 1.8/1000 (95% CI: 1.1-2.4) and 0.4/1000 (95% CI: 0.2-0.9), respectively. EOBS's overall case fatality rate was 17.8% for all the agents and 22% for GBS. CONCLUSIONS: EOBS remains unacceptably high and is frequently fatal in preterm and term infants cared for in high- or low-risk maternities. Because GBS has emerged as the most frequent causative agent, preventive strategies are urgently needed.

Quality of Life Assessment in Patients with Surgically Treated Parasagittal Meningiomas.

AIM: To assess quality of life (QoL) in patients with parasagittal meningiomas (PSM), and to identify the risk factors for different levels of QoL. MATERIAL AND METHODS: Patients were contacted and interviewed via telephone. A total of 136 patients with PSM underwent surgery at our institution between 1984 and 2020. Among them, 45 had agreed to participate in the research. The scales utilized included the Functional Assessment of Cancer Therapy General (FACT-G), Brain (FACT-Br), and Meningioma (FACT-MNG). Medical records were also reviewed. RESULTS: The mean KPS was 93.3 (70-100). Overall, the mean scores for the FACT-G, FACT-Br, and FACT-MNG scales were 98.4/108 (55-108; SD: 12.9), 179.3/200 (98-200; SD: 22.4), and 219.3 (119-248; SD: 29.7). Considerable variability in scales scores was observed among those with the same KPS score. Preoperative KPS score was significantly associated with both FACT-Br [-21.64; 95% CrI (-34.04, -9.59)] and FACT-MNG [-31.88; 95% CrI (-47.24, -15.25)]. Preoperative KPS was identified as a risk factor for QoL impairment. CONCLUSION: Variability in the scale scores among those with the same KPS score highlights the importance of structured assessment. Moreover, KPS may overlook impairments in QoL. To date, this has been the first study to assess QoL in PSM patients.

Chronic neutropenia in childhood: experience of a tertiary center.

OBJECTIVE: To assess the prevalence of chronic neutropenia (CN) and the clinical profile of patients with CN aged up to 18 years, followed in the pediatric hematology, rheumatology, or immunology outpatient clinic of a tertiary medical center from May 1, 2018, to 30 April 2019. METHODS: Retrospective observational study carried out by collecting data from the patient's medical charts. CN was defined as absolute neutrophil count (ANC) below 1.5 × 109/L lasting over three months. Autoimmune neutropenia (AIN) was defined by clinical criteria and an over twofold increase in ANC after glucocorticoid stimulation. AIN was considered secondary when associated with autoimmune or immunoregulatory disorders. Wilcoxon and Fisher's exact tests were used to compare variables; the significance level was 5 %. RESULTS: A total of 1,039 patients were evaluated; 217 (20 %) presented CN. Twenty-one (2 %) had AIN, classified as primary in 57 % of the cases. The average age at the onset of symptoms was 38.6 months. During follow-up, patients had 4.2 infections on average; frequency was higher among patients with secondary AIN (p = 003). Isolated neutropenia occurred in 43 % of the patients with AIN. Neutropenia resolved in eight (38 %) of the 21 patients with AIN within 19.6 months on average. Eight patients with secondary AIN met the criteria for Inborn Errors of Immunity. CONCLUSION: AIN prevalence was 2 %. Most cases were first evaluated by a pediatric immunologist or rheumatologist rather than a pediatric hematologist. This study highlights the need for a multidisciplinary approach involving a pediatric immunologist, rheumatologist, and hematologist.

Evaluation of the behavioral, histopathological, and immunohistochemical effects resulting from ventriculosubcutaneous shunt obstruction in kaolin-induced hydrocephalus in rats.

PURPOSE: Hydrocephalus is a brain disease prevalent in the pediatric population that presents complex pathophysiology and multiple etiologies. The best treatment is still ventricular shunting. Mechanical obstruction is the most frequent complication, but the resulting pathological effects are still unknown. OBJECTIVE: Evaluation and comparison of clinical, histopathological, and immunohistochemical aspects in the acute phase of experimental hydrocephalus induced by kaolin, after treatment with adapted shunt, and after shunt obstruction and posterior disobstruction. METHODS: Wistar rats aged 7 days were used and divided into 4 groups: control group without kaolin injection (n = 6), untreated hydrocephalic group (n = 5), hydrocephalic group treated with ventriculosubcutaneous shunt (DVSC) (n = 7), and hydrocephalic group treated with shunt, posteriorly obstructed and disobstructed (n = 5). The animals were submitted to memory and spatial learning evaluation through the Morris water maze test. The rats were sacrificed at 28 days of age and histological analysis of the brains was performed with luxol fast blue, in addition to immunohistochemical analysis in order to evaluate reactive astrocytosis, inflammation, neuronal labeling, and apoptotic activity. RESULTS: The group with shunt obstruction had worse performance in memory tests. Reactive astrocytosis was more evident in this group, as was the inflammatory response. CONCLUSIONS: Obstruction of the shunt results in impaired performance of behavioral tests and causes irreversible histopathological changes when compared to findings in the group with treated hydrocephalus, even after unblocking the system. The developed model is feasible and efficient in simulating the clinical context of shunt dysfunction.

Normocephalic Children Exposed to Maternal Zika Virus Infection Do Not Have a Higher Risk of Neurodevelopmental Abnormalities around 24 Months of Age than Unexposed Children: A Controlled Study.

Although very few controlled studies are available, in utero Zika virus (ZIKV)-exposed children are considered at risk for neurodevelopmental abnormalities. We aimed to identify whether there is an excess risk of abnormalities in non-microcephalic children born to mothers with confirmed ZIKV infection compared with ZIKV-unexposed children from the same population. In a cross-sectional study nested in two larger cohorts, we compared 324 ZIKV-exposed children with 984 unexposed controls. Outcomes were assessed using the Bayley Screening Test III applied around 24 months of age. Relative risks for classifying children as emergent or at-risk for neurodevelopmental delay in at least one of five domains were calculated, adjusting for covariates. In four of the five domains, few children were classified as emergent (4-12%) or at-risk (0.3-2.16%) but for the expressive communication domain it was higher for emergent (19.1-42.9%). ZIKV-exposed children were half as frequently classified as emergent, including after adjusting for covariates [RR = 0.52 (CI 95% 0.40; 0.66)]. However, no difference was detected in the at-risk category [RR = 0.83 (CI 95% 0.48; 1.44)]. Normocephalic children exposed to the Zika virus during pregnancy do not have a higher risk of being classified as at risk for neurodevelopmental abnormalities at two years of age.

Type I and type IIb autoimmune chronic spontaneous urticaria: Using common clinical tools for endotyping patients with CSU.

Background: Mechanisms triggering the pathogenesis of chronic spontaneous urticaria (CSU) have been identified as type I autoallergic (which is associated with IgE antibodies against autoantigens) and type IIb autoimmune (which is driven by autoantibodies to FceR1 and/or IgE). Objective: Our aim was to define presumptive endotypes in patients with CSU by using tests amenable to use in routine clinical practice. Methods: A retrospective analysis of the medical records of 394 patients with CSU with or without chronic inducible urticaria or angioedema was performed. Patients were assigned to 1 of 4 groups as follows: (1) type I endotype of CSU, if they presented at least 1 of the following: allergic disease, total IgE level of at least 40UI/mL, and positive result of skin tests to inhalant allergen(s), (2) type IIb endotype of CSU, if they presented at least 1 of following: autoimmune disease, low total IgE level less than 40 IU/mL, positive autologous serum skin test result, positive for antinuclear antibodies in a titer of at least 1:160, and elevated level of anti-thyroid peroxidase, (3) overlap of type I/type IIb endotypes of CSU, if they presented with at least 1 marker of both type I and type IIb, and (4) non-type I/type IIb endotype of CSU, if they presented with none of the markers of type I or type IIb. Results: The mean age at onset of symptoms was 34 years; 82.2% of those with CSU were female, and angioedema and chronic inducible urticaria were found in 74.8% and 31.9% of patients, respectively. Of the patients with CSU, 38% presented with the type I endotype and 51% presented with type I/type IIb overlap, whereas 9% presented with the type IIb endotype and 2% presented with the non-type I/type IIb endotype. Eosinopenia was associated with type IIb and type I/type IIb overlap as opposed to the type I and non-type I/type IIb endotypes (P = .02). Conclusions: Most patients with CSU presented with features of the type 1 (autoallergic) endotype, whether associated with type IIb (autoimmune) endotype or not.

Effect of manual hyperinflation with versus without positive end-expiratory pressure on dynamic compliance in pediatric patients following congenital heart surgery: A randomized controlled trial.

BACKGROUND: We aimed to compare the effect of manual hyperinflation with versus without positive end-expiratory pressure (PEEP) on dynamic compliance of the respiratory system in pediatric patients undergoing congenital heart surgery; to assess the safety of the technique in this population. METHODS: This was a randomized controlled trial conducted at the pediatric intensive care unit (PICU) of a tertiary-care hospital. Patients admitted to the PICU following cardiac surgery and receiving postoperative mechanical ventilation were randomized to the experimental or control group. Patients in the experimental group (n = 14) underwent manual hyperinflation with a PEEP valve set at 5 cm H2O, once daily, during the first 48 hours after surgery. Patients allocated to the control group (n = 16) underwent manual hyperinflation without PEEP, at the same time points. Lung mechanics was assessed before (T0) and 5 minutes (T5) after manual hyperinflation. The primary endpoint was dynamic compliance. Secondary outcomes included oxygen saturation index, duration of mechanical ventilation, length of stay, 28-day mortality and safety. RESULTS: Demographic and clinical characteristics were comparable in both groups. There was no significant difference in dynamic compliance between times in each group (Day 1: (mean) 0.78 vs 0.81 and 0.70 vs 0.77; Day 2: 0.85 vs 0.78 and 0.67 vs 0.68 mL/kg/cm H2O, in experimental and control groups, respectively; P > .05). Mean deltas of dynamic compliance were not significantly different between groups. The proportion of patients extubated <72 hours after surgery was similar in experimental and control groups (43% vs 50%, respectively; P = .73). Oxygen saturation index, length of stay, and 28-day mortality were not significantly different between groups. None of the patients had hemodynamic instability. CONCLUSIONS: Manual hyperinflation was safe and well tolerated in pediatric patients following surgery for congenital heart disease. No significant change in dynamic compliance of the respiratory system or in oxygenation was observed with the use of manual hyperinflation with or without PEEP in this population.

Continuous interstitial glucose monitoring for term newborns: analysis of the first day of life.

OBJECTIVE: Glycaemia in newborns changes significantly after birth; however, little is known about these changes. The objective was to describe continuous interstitial glucose values in term newborns who were exclusively breast fed on the first day of life. DESIGN: We studied 159 newborns with appropriate weights for gestational age, who were exclusively breast fed on the first day of life, using a continuous glucose monitoring device that calculates interstitial glucose every 5 min. The device was removed after 24 hours, and the results were analysed using the R program, which provides the minimum, maximum, median and a standard curve with centiles. RESULTS: At the second hour of life, the moment in which the sensor started to identify the newborn's glycaemia, interstitial glucose levels were 2.59-4.43 mmol/L (46.7-79.9 mg/dL). The median interstitial glucose level of the newborns during the first day of life was 3.33±0.48 mmol/L (60±8.6 mg/dL). Interstitial glucose levels dropped until the sixth hour of life, reaching 2.19-3.95 mmol/L (39.5-71.1 mg/dL), and then increased again. The maximum values were found at the 20th and 21st hours of life, which were 2.81-4.64 mmol/L (50.6-83.6 mg/dL). CONCLUSION: The interstitial glucose during the first 24 hours of life declined until the sixth hour of life, then increased around the 20th hour and remained stable until the end of the first day of life.

Long-term seizure outcome and mobility after surgical treatment for Rasmussen encephalitis in children: A single-center experience.

OBJECTIVE: Rasmussen Encephalitis (RE) is a rare inflammatory neurodegenerative disease associated with refractory seizures, hemiparesis, and cognitive deterioration, due to lateralized cortical atrophy. Hemispheric surgery (hemispherotomy) is the mainstay of treatment, but its unavoidable motor deficits and lack of long-term data regarding seizure outcomes can make patients and families apprehensive to undergo this procedure. The present study aimed at analyzing the results of surgical treatment for RE from a motor and epilepsy standpoint, and mitigate such concerns. METHODS: Clinical and operative data were retrospectively collected from medical records of pharmacoresistant patients treated with functional hemispherectomy at a tertiary reference center for epilepsy surgery, during a 24-year period (1996-2020). Variables such as age of epilepsy onset, seizure semiology, seizure frequency, immunomodulatory therapy, age at surgery, duration of epilepsy, surgical procedures and complications, number of medications used preoperatively and postoperatively were described and statistically analyzed. RESULTS: Forty-three (43) patients were included in this study. Mean age of epilepsy onset was 6.14 years, the average interval between epilepsy onset and hemispherotomy was 2.21 years. and the mean age at surgery was 8.28 years. Thirty patients (69.7%) were Engel I at their last follow-up, of whom 23 (56.4%) were Engel Ia, within a mean follow-up of 11.3 years. Duration of epilepsy, seizure frequency, and age at surgery, among others, did not correlate with seizure outcome, except the use of immunotherapy which led to worse outcomes (p < .05). Also, after surgery, motor functionality was significantly recovered (i.e., most patients returned to their previous status) with time. SIGNIFICANCE: This study tackled some issues regarding the surgical treatment of this disease, particularly showing that hemispherotomy is safe and leads to potentially recoverable disability of motor functions while providing high rates of effective and long-lasting seizure control; therefore, early surgical indication should be warranted once medical refractoriness has been established.

Cytomegalovirus Active Infection in Critically Ill Children.

OBJECTIVE: To describe the epidemiology, clinical characteristics and outcomes of children with cytomegalovirus (CMV) active infection in the pediatric intensive care unit (PICU) and to investigate risk factors for mortality. METHODS: This was a retrospective cohort study of patients who had CMV DNA detected in blood samples and/or tracheal aspirates by polymerase chain reaction (PCR) during stay at 2 PICUs of a university hospital. Suspected cases without etiological confirmation and patients with laboratory-confirmed CMV infection before PICU admission were excluded. RESULTS: Demographic, clinical and outcome data were collected from medical records. From January 1, 2012, to December 31, 2019, 4748 children were admitted to the PICUs. Thirty-five (0.74%; 95% CI 0.51%-1.02%) had laboratory-confirmed CMV active infection; 71.4% were immunocompromised and 11 (31.4%) died. Patients who died were older than those who survived (median age 65 vs. 5.5 months, respectively; P = 0.048), and they received antiviral therapy for a shorter time (median 12 vs. 23 days, respectively; P = 0.001). The main causa mortis was septic shock (82%) and in most deceased patients (73%) the last CMV PCR before death was positive. PELOD score >6 was a risk factor for death (RR 2.96; 95% CI 1.07-8.21). Viral load in blood had a poor ability for the prediction of death (area under the receiver operating characteristic curve 0.62; 95% CI 0.37-0.84). CONCLUSIONS: The incidence of CMV active infection during PICU stay was 0.74% in an upper-middle income country with a high CMV seroprevalence. PELOD score higher than 6 was a risk factor for death. No association was observed between CMV viral load and mortality.

A data-driven approach to manage type 2 diabetes mellitus through digital health: The Klivo Intervention Program protocol (KIPDM).

BACKGROUND: Digital therapeutics, an emerging type of medical approach, is defined as evidence-based therapeutic interventions through qualified software programs that help prevent, manage, or treat chronic diseases such as type 2 diabetes mellitus (T2DM), which has high social and economic burden. Klivo, a startup certified by the Brazilian Society of Diabetes, developed the first digital therapeutic product for managing T2DM in Brazil, reaching 21 of 24 states. Klivo has continuously been improving its model of behavior change on the basis of an intensive lifestyle intervention method that addresses individuals' needs-the Klivo Intervention Program for T2DM (KIPDM). To test the most recent version of the KIPDM, we will evaluate the ongoing management of daily life habits in patients with T2DM by measuring clinically significant outcomes. To improve the transparency of further results, here we will present the study protocol and detail the plan for the research project, including the study design and the analysis strategies. METHODS: The KIPDM will be sponsored by health plans and healthcare provider organizations and will be free for patients (adults aged ≥ 18 years and <65 years; and glycated hemoglobin ≥ 7%). The program will be based on a 6-month management process that will supervise patients remotely. The program will include educational classes via the Klivo app, text messages, or e-mails. Evaluation will include objectively assessing clinical, laboratory, and behavioral outcomes such as health-related quality of life, mental health, medication adherence, and healthcare utilization. For this, validated electronic questionnaires will be available through the Klivo app. The primary outcome will be glycated hemoglobin (HbA1c) values. The secondary outcome will be time in target blood glucose range (TIR) estimated by capillary glycemia. Other outcomes of interest will be evaluated at baseline and stipulated time points (3 and 6 months after the start of the program). EXPECTED OUTCOMES: KIPDM patients should present improved HbA1c and TIR along the intervention as compared to baseline values. Findings from this study will provide insights into the health improvement of T2DM and other cardiometabolic conditions such as hypertension, dyslipidemia, and obesity by using a digital therapeutic strategy. By analyzing the patient's health over time, this study will also contribute to understanding comorbidities associated with this chronic condition in the Brazilian population.

Growth phenotypes of very low birth weight infants for prediction of neonatal outcomes from a Brazilian cohort: comparison with INTERGROWTH

Abstract Objective: To assess the predictive value of selected growth phenotypes for neonatal morbidity and mortality in preterm infants < 30 weeks and to compare them with INTERGROWTH-21st (IG21). Methods: Retrospective analysis of data from the Brazilian Neonatal Research Network (BNRN) database for very low birth weight (VLBW) at 20 public tertiary-care university hospitals. Outcome: the composite neonatal morbidity and mortality (CNMM) consisted of in-hospital death, oxygen use at 36 weeks, intraventricular hemorrhage grade 3 or 4, and Bell stage 2 or 3 necrotizing enterocolitis. Selected growth phenotypes: small-for-gestational-age (SGA) defined as being < 3rd (SGA3) or 10th (SGA10) percentiles of BW, and large-for-gestational-age (LGA) as being > 97th percentile of BW. Stunting as being < 3rd percentile of the length and wasting as being < 3rd percentile of BMI. Single and multiple log-binomial regression models were fitted to estimate the relative risks of CNMM, comparing them to IG21. Results: 4,072 infants were included. The adjusted relative risks of CNMM associated with selected growth phenotypes were (BNRN/IG21): 1.45 (0.92-2.31)/1.60 (1.27-2.02) for SGA; 0.90 (0.55-1.47)/1.05 (0.55-1.99) for LGA; 1.65 (1.08-2.51)/1.58 (1.28-1.96) for stunting; and 1.48 (1.02-2.17) for wasting. Agreement between the two references was variable. The growth phenotypes had good specificity (>95%) and positive predictive value (70-90%), with poor sensitivity and low negative predictive value. Conclusion: The BNRN phenotypes at birth differed markedly from the IG21 standard and showed poor accuracy in predicting adverse neonatal outcomes.

Growth phenotypes of very low birth weight infants for prediction of neonatal outcomes from a Brazilian cohort: comparison with INTERGROWTH.

OBJECTIVE: To assess the predictive value of selected growth phenotypes for neonatal morbidity and mortality in preterm infants < 30 weeks and to compare them with INTERGROWTH-21st (IG21). METHOD: Retrospective analysis of data from the Brazilian Neonatal Research Network (BNRN) database for very low birth weight (VLBW) at 20 public tertiary-care university hospitals. OUTCOME: the composite neonatal morbidity and mortality (CNMM) consisted of in-hospital death, oxygen use at 36 weeks, intraventricular hemorrhage grade 3 or 4, and Bell stage 2 or 3 necrotizing enterocolitis. Selected growth phenotypes: small-for-gestational-age (SGA) defined as being < 3rd (SGA3) or 10th (SGA10) percentiles of BW, and large-for-gestational-age (LGA) as being > 97th percentile of BW. Stunting as being < 3rd percentile of the length and wasting as being < 3rd percentile of BMI. Single and multiple log-binomial regression models were fitted to estimate the relative risks of CNMM, comparing them to IG21. RESULTS: 4,072 infants were included. The adjusted relative risks of CNMM associated with selected growth phenotypes were (BNRN/IG21): 1.45 (0.92-2.31)/1.60 (1.27-2.02) for SGA; 0.90 (0.55-1.47)/1.05 (0.55-1.99) for LGA; 1.65 (1.08-2.51)/1.58 (1.28-1.96) for stunting; and 1.48 (1.02-2.17) for wasting. Agreement between the two references was variable. The growth phenotypes had good specificity (>95%) and positive predictive value (70-90%), with poor sensitivity and low negative predictive value. CONCLUSION: The BNRN phenotypes at birth differed markedly from the IG21 standard and showed poor accuracy in predicting adverse neonatal outcomes.

Impact of children with complex chronic conditions on costs in a tertiary referral hospital.

OBJECTIVES: To investigate the impact of complex chronic conditions on the use of healthcare resources and hospitalization costs in a pediatric ward of a public tertiary referral university hospital in Brazil. METHODS: This is a longitudinal study with retrospective data collection. Overall, three one-year periods, separated by five-year intervals (2006, 2011, and 2016), were evaluated. Hospital costs were calculated in three systematic samples of 100 patients each, consisting of patients with and without complex chronic conditions in proportion to their participation in the studied year. RESULTS: Over the studied period, the hospital received 2,372 admissions from 2,172 patients. The proportion of hospitalized patients with complex chronic conditions increased from 13.3% in 2006 to 16.9% in 2016 as a result of a greater proportion of neurologically impaired children, which rose from 6.6% to 11.6% of the total number of patients in the same period. Patients' complexity also progressively increased, which greatly impacted the use of healthcare resources and costs, increasing by 11.6% from 2006 (R$1,300,879.20) to 2011 (R$1,452,359.71) and 9.4% from 2011 to 2016 (R$1,589,457.95). CONCLUSIONS: Hospitalizations of pediatric patients with complex chronic conditions increased from 2006 to 2016 in a Brazilian tertiary referral university hospital, associated with an important impact on hospital costs. Policies to reduce these costs in Brazil are greatly needed.