Dabigatran for stroke prevention in real life in a sample of population from Turkey: D-SPIRIT registry.

OBJECTIVE: The D-SPIRIT registry is designed to investigate the safety and effectiveness of dabigatran etexilate in patients with atrial fibrillation in routine clinical practice. METHODS: D-SPIRIT is the first national, multicenter, prospective, observational, postmarketing registry that investigates the usage of dabigatran in real life. A total of 326 noveloral anticoagulant-eligible patients with atrial fibrillation who have been taking dabigatran etexilate therapy for stroke prevention at least 6 months from 9 different centers were enrolled into the registry. Patients were followed up for 2 years to evaluate the effectiveness and safety of the treatment. All adverse clinical events including bleeding, thromboembolic events, stroke, systemic embolism, transient ischemic attack, myocardial infarction, and all-cause death were recorded. RESULTS: The mean age was 71.1±9.6 years, and 57.4% of the study participants were female. The mean CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack [TIA], vascular disease, age 65-74 years, sex category) score was 3.4±1.6. The cumulative adverse clinical events rate was 6.30% per year. The rate for embolic events including TIA, ischemic stroke, and peripheral embolism was 1.26% per year. The rate for major bleeding was 2.20% per year, and the mortality rate was 0.94% per year. CONCLUSION: This registry obtained an important overview of the current safety and effectiveness of the dabigatran etexilate in Turkey. Our results indicate similar rates of thromboembolic and bleeding events with pivotal phase 3 trial and other real-life registries. However, rate of undertreatment usage of dabigatran etexilate in real life was found to be considerable.

Heart failure with preserved ejection fraction, atrial fibrillation, and increased NT­proBNP levels : An emergent clinical dilemma.

BACKGROUND: The co-presence of atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) may cause some diagnostic difficulties, because AF itself is associated with elevated levels of N­terminal pro-B-type natriuretic peptide (NT-proBNP). In the present study we aimed to investigate NT-proBNP levels of patients with HFpEF and AF. METHODS: This was a retrospective cohort study. Outpatient data were reviewed through the hospital data management system. Consecutive patients with the diagnosis of HFpEF and AF, who had at least one NT-proBNP measurement, were included in the study. RESULTS: The study population comprised 235 patients. Median NT-proBNP levels were 1242 pg/ml in the stable phase and 2321.5 pg/ml during decompensation. NT-proBNP was correlated positively with age, CHA2DS2 and CHA2DS2VASc scores, left atrial diameter (LAD), tricuspid annulus diameter, and systolic pulmonary artery pressure but negatively correlated with left ventricular ejection fraction (LVEF) and hemoglobin level. The change in NT-proBNP was positively correlated with heart rate and LAD. CONCLUSION: Patients with HFpEF and AF have higher levels of NT-proBNP, which may exceed the upper limits defined in guidelines. This study underlines the importance of measuring NT-proBNP levels in the stable phase and proposes a rule-in level for the decompensated phase.

Clinical characteristics and in-hospital outcomes of acute decompensated heart failure patients with and without atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) and heart failure (HF) are common cardiovascular diseases. The impact of AF on in-hospital outcomes in acute decompensated heart failure (ADHF) is controversial. The aim of this study is to determine the prevalence of AF among hospitalized patients with ADHF and describe the clinical characteristics and in-hospital outcomes of these patients with and without AF. METHODS: We examined the multicenter, observational data from the real-life data of hospitalized patients with HF: Journey HF-TR study in Turkey that studied the clinical characteristics and in-hospital outcomes of hospitalized patients with ADHF between September 2015 and September 2016. RESULTS: Of the 1,606 patients hospitalized with ADHF, 626 (39%) had a history of AF or developed new-onset AF during hospitalization. The patients with AF were older (71±12 vs. 65±13 years; p<0.001) and more likely to have a history of hypertension, valvular heart disease, and stroke. The AF patients were less likely to have coronary artery disease and diabetes. In-hospital adverse event rates and length of in-hospital stay were similar in ADHF patients, both with and without AF. In-hospital all-cause mortality rate was higher in patients with AF than in patients without AF, although the difference was not statistically significant (8.9% vs. 6.8%; p=0.121). CONCLUSION: AF has been found in more than one-third of the patients hospitalized with ADHF, and it has varied clinical features and comorbidities. The presence of AF is not associated with increased adverse events or all-cause mortality during the hospitalization time.

Epidemiology and clinical characteristics of hospitalized elderly patients for heart failure with reduced, mid-range and preserved ejection fraction.

INTRODUCTION: Elderly patients hospitalized with heart failure (HF) have high mortality rates and requires specific evidence based theraphy, however there are few studies which have focused on patients older than 80 years hospitalized with HF. The aim of the present study is to evaluate the overall clinical characteristics, management, and in-hospital outcomes of elderly patients hospitalized with HF. METHODS: Journey-HF study was conducted in 37 different centers in Turkey and recruited 1606 patients who were hospitalized with HF between September 2015 and September 2016. In this study, clinical profile of patients ≥ 80 years old and 65-79 years old hospitalized with HF were described and compared based on EF-related classification: HFrEF (HF with reduced ejection fraction), HFmrEF (HF with mid-range ejection fraction) and HFpEF (HF with preserved ejection fraction). RESULTS: A total of 1034 elder patients (71.6% 65-79 years old and 28.4% ≥80 years old) were recruited. Of the 65-79 years old patients 67.4% had HFrEF, 16.2% had HFmrEF and 16.3% had HFpEF. Among patients ≥80 years old 61.6% had HFrEF, 15.6% had HmrEF and 22.8% had HFpEF. When compared with patients with HFrEF and HFmrEF, patients ≥80 years old with HFpEF were more likely to be older, have atrial fibrilation (AF), and less likely to have diabetes mellitus (DM), coronary artery disease (CAD) or to be recieving an angiotensin-converting enzyme inhibitor (ACEi) or beta blocker theraphy. When compared to patients 65-79 years old with HFpEF, patients ≥80 years with HFpEF had a higher rate of AF and less likely DM. Acute coronary syndrome was the most common precipitant factor for hospitalization in both age groups with HFrEF group. Arrhythmia was a major precipitant factor for hospitalization of patients ≥80 years old with HFpEF. Non-compliance with theraphy was a major problem of patients ≥80 years old with HFrEF. CONCLUSION: Elderly patients with HFrEF, HFmrEF and HFpEF each had characterized unique patient profiles and the guideline recommended medications were less likely to be used in these patient populations. In hospital mortality rate is worrisome and reflects a need for more specific tretment strategy.

Resistant hypertension in elderly: a clinical manifestation of heart failure with preserved ejection fraction? retrospective single-center analysis.

Background: Resistant hypertension (RHT) is defined as high blood pressure despite three antihypertensive medications one being a diuretic. RHT is a common clinical problem and as a subgroup has not been studied widely. The present study has investigated patient demographics and if the RHT might be a clinical presentation of heart failure with preserved ejection fraction (HFPEF) in elderly. Method: The outpatient data between January and June 2015 of Izmir Kemalpasa State hospital's hypertension specialty clinic has been reviewed retrospectively. The patients with pseudo-RHT are excluded. Among 957 patients, 68 patients have been identified as true RHT with a left ventricle ejection fraction ≥50%. HFPEF is defined according to the latest guideline. Instead of a common cut-off level for NT-proBNP, age and gender-related cut-off levels have been used. Results: The mean age was 63.24 ± 12.05 years. Among 68 patients, 49 were female. While only 3 patients in younger group (8.8%) had elevated levels of NT-proBNP, 22 of older RHT patients (64.7%) had high levels. NT-proBNP levels were disproportionally high in elderly (p < 0.001) and high levels in RHT patients were related to a larger left atrial diameter (p < 0.001). Conclusion: The underlying mechanism might be different in RHT according to age. Hypervolemia might be the key factor in older RHT patients but not in younger patients. The current study suggests RHT in elderly can be a clinical presentation of HFPEF, and they should be investigated and treated accordingly. Because of single-center results and limited patients, further studies are needed.

Design and rationale of dabigatran's stroke prevention in real life in Turkey (D-SPIRIT).

OBJECTIVE: The D-SPIRIT registry is designed to investigate the safety and efficacy of dabigatran etexilate in patients with nonvalvular atrial fibrillation (NVAF) and to collect data on outcomes in clinical practice. METHODS: The D-SPIRIT is a national, prospective, observational, post-marketing registry involving patients with NVAF who have been taking dabigatran etexilate therapy for stroke prevention for a minimum of 6 months prior to enrollment. The registry will collect and analyze data from routine care, enrolling up to 600 patients in 9 centers. Patients will be followed up for 2 years to evaluate effectiveness and safety. A sample size of 600 subjects is proposed based on the following assumptions; Two-sided significance level of 0.05 (1-sided significance level of 0.025), ischemic stroke incidence rate of 0.768%-1.111%, hemorrhagic stroke incidence rate of 0.109%-0.130%, transient ischemic attack incidence rate of 0.722%-0.623%, therapy discontinuation incidence rate of 40% at day 730, and duration of enrollment period of 12 months with non-uniformed enrollment rate. Ethics approval was given by Dokuz Eylül University Ethics Committee of Clinical Research (2014/54) and approved by the Turkish Ministry of Health. CONCLUSION: Potential results of D-SPIRIT registry will add data from clinical practice to those from the RE-LY trial to expand knowledge of dabigatran etexilate treatment in patients with NVAF.

Low pertussis antibody levels in maternal and umbilical cord blood samples in Turkey.

Pertussis continues to cause significant mortality and morbidity in many countries despite high vaccine coverage, especially among young infants. The aim of the study was to determine pertussis antibody levels in paired maternal and cord blood samples, to evaluate the placental transfer of these antibodies, and to assess whether newborn infants have adequate antibody levels against pertussis. Antibody titers to pertussis toxin (anti-PT) and filamentous hemagglutinin (anti-FHA) were measured by in-house enzyme linked immunosorbent assay (ELISA) in 251 paired maternal delivery and cord blood samples. Geometric mean concentrations (GMCs) of pertussis antibodies and cord:maternal GMC ratios were calculated. GMCs of maternal anti-PT and anti-FHA antibodies at delivery were 4.12 and 9.89 EU/ml, respectively. Cord GMCs were 133% and 131% of maternal delivery values for PT and FHA, respectively; demonstrating effective placental transfer. However, cord pertussis antibodies were at a low concentration; 5.49 EU/ml for PT and 12.73 EU/ml for FHA. Only 34.6% of infants had protective anti-PT levels (≥10 EU/ml) at birth. Anti-pertussis antibody concentrations were extremely low in pregnant women in Turkey where childhood pertussis vaccination coverage has been high for a long time. Despite effective placental antibody transfer, umbilical cord pertussis antibody concentrations are similarly low. A majority of young infants are vulnerable to pertussis infection until the onset of primary vaccinations. These data support the need for pertussis vaccination during pregnancy to prevent infant infection in Turkey.

Agreement of Mixed Venous Carbon Dioxide Tension (PvCO2) and Transcutaneous Carbon Dioxide (PtCO2) Measurements in Ventilated Infants.

BACKGROUND: Noninvasive transcutaneous carbon dioxide monitoring has been shown to be accurate in infants and children, limited data are available to show the usefulness and limitations of partial transcutaneous carbon dioxide tension (PtCO2) value. OBJECTIVES: The current study prospectively determines the effectiveness and accuracy of PtCO2 measurements in newborns. MATERIALS AND METHODS: Venous blood gas sampling and monitoring of the PtCO2 level (TCM TOSCA, Radiometer) were done simultaneously. All measurements are performed on mechanically ventilated infants. Partial venous carbon dioxide tension (PvCO2) values divided into three groups according to hypocapnia (Group 1: < 4.68 kPa), normocapnia (Group 2: 4.68-7.33 kPa), hypercapnia (Group 3: > 7.33 kPa) and then PvCO2 and PtCO2 data within each group were compared separately. RESULTS: A total of 168 measurements of each PvCO2 and PtCO2 data were compared in three separated groups simultaneously (13 in Group 1, 118 in Group 2, and 37 in Group 3). A bias of more than ± 0.7 kPa was considered unacceptable. PtCO2 was related to PvCO2 with acceptable results between the two measurements in hypocapnia (mean difference 0.20 ± 0.19 kPa) and normocapnia (0.002 ± 0.30 kPa) groups. On the other hand in hypercapnia group PtCO2 values were statistically significant (P < 0.001) and lower than PvCO2 data (mean difference 0.81 ± 1.19 kPa). CONCLUSIONS: PtCO2 measurements have generally good agreement with PvCO2 in hypocapnic and normocapnic intubated infants but there are some limitations especially with high level of CO2 tension. Monitoring of PtCO2 is generally a useful non-invasive indicator of PvCO2 in hypocapnic and normocapnic infants.

The effect of topical ointment on neonatal sepsis in preterm infants.

OBJECTIVE: To investigate the effects of topical ointment therapy on neonatal sepsis in premature infants. METHODS: A total of 197 premature infants≤34 weeks gestation were randomized to receive topical ointment (Aquaphor Original Emollient) or routine skin care group. Skin cultures were obtained on 3th, 7th and 14th day and blood cultures were obtained if sepsis was suspected clinically. Data included the maternal and neonatal characteristics, factors affecting the risk of sepsis and neonatal outcomes of both groups were collected. RESULTS: There were no significant differences in terms of gestational age, birth weight, gender, mode of delivery, multiple pregnancy and receiving antenatal corticosteroids between the study and control group. No statistically significant difference was found in the prevalence of sepsis, in the positive skin culture rates at any follow-up and in terms of the neonatal morbidities including patent ductus arteriosus and necrotizing enterocolitis between the groups. Although the rate of death was higher in the topical ointment group, no statistically significant difference was found between the groups. CONCLUSIONS: Our data suggests that applying topical ointment during the first 2 postnatal weeks did not affect the risk of neonatal sepsis in preterm infants, although it changed the bacterial flora on the skin compare to the routine care group.

Pertussis serosurveillance study in Izmir, Turkey.

Pertussis is a life-threatening, vaccine-preventable infection. Adults who can be asymptomatic may infect infants. The aim of this study is to determine the IgG antibody levels against pertussis toxin (PT) and filamentous hemagglutinin from 6 months to ≥60 years in Izmir, Turkey. A cluster sample design developed by Expanded Programme on Immunization of the World Health Organization was carried out for the selection of the study population, which consisted of 399 healthy subjects. In-house ELISA was studied in Turkish Public Health Institution. Antibody levels of <10 EU/ml, ≥10 EU/ml and ≥100 EU/ml were accepted as non-immune, immune and possible acute/recent infection, respectively. Anti-PT antibody levels were 8.5% <10 EU/ml, 68.2% 10-100 EU/ml and 23.3% ≥100 EU/ml; the latter was correlated with possible acute/recent infection. Results showed that pertussis is endemic, particularly among adolescents and adults, which is a threat for infants who have not completed their primary immunization.

Effects of synchronized intermittent mandatory ventilation versus pressure support plus volume guarantee ventilation in the weaning phase of preterm infants*.

OBJECTIVE: To compare the effects and short-term outcomes of pressure support ventilation with volume guarantee versus synchronized intermittent mandatory ventilation in the weaning phase of very low-birth weight infants with respiratory distress syndrome. DESIGN: Randomized controlled prospective study. SETTING: Tertiary care neonatal unit. PATIENTS: A total of 60 premature infants who were less than 33 weeks' gestation and/or less than 1,500 g birth weight and received mechanical ventilation because of respiratory distress syndrome were studied. INTERVENTIONS: All infants were ventilated from the time of admission with synchronized intermittent positive pressure ventilation mode after surfactant treatment for respiratory distress syndrome and then switched to pressure support ventilation with volume guarantee or synchronized intermittent mandatory ventilation mode in the weaning phase. The ventilatory variables and neonatal outcomes were recorded in each group. MEASUREMENTS AND MAIN RESULTS: The mean peak inflation pressure was higher in synchronized intermittent mandatory ventilation group (p < 0.001) and the mean airway pressure was higher in pressure support ventilation with volume guarantee group (p = 0.03), whereas mean tidal volume and respiratory rates were similar in both groups. The prevalence of postextubation atelectasis was higher in synchronized intermittent mandatory ventilation group, but the difference was not statistically significant (p = 0.08). No differences were found in the prevalence of reintubation, patent ductus arteriosus, intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and pneumothorax between the groups. CONCLUSIONS: Pressure support ventilation with volume guarantee mode may be a safe and feasible mode during the weaning phase of very low-birth weight infants on mechanical ventilation support for respiratory distress syndrome with respect to reducing the frequency of postextubation atelectasis and using less peak inflation pressure.

Comparison of oral and intravenous fluid therapy in newborns with hypernatremic dehydration.

OBJECTIVE: To evaluate the efficacy and complications of oral and intravenous fluid therapy in newborns with hypernatremic dehydration. METHODS: A total of 75 term and near-term (>35 weeks) neonates with hypernatremic dehydration (Na ≥ 150 mmol/L) were included in this retrospective study. The patients were divided into two groups according to therapy approach for rehydration (breast milk-oral formula and intravenous fluid). The decline in sodium concentration (<0.5 mmol/L/h was regarded as safe drop) and complications were analyzed. RESULTS: The mean gestational age, birth weight and age at admission were 38.9 ± 1.4(36-42) weeks, 3341 ± 504 (2500-4500) gram and 4.3 ± 2.6 (1-17) day, respectively. Fever (61.8%) and jaundice (39.4%) were the most common presenting signs. Forty-four (58.6%) of the infants were treated with breast milk and/or oral formula (group 1) and 31 (41.4%) of the infants were treated with IV fluid (group 2). In group 1 and group 2, respectively, mean % weight loss, 5 and 7.5; median serum sodium at admission, 153 and 152 mmol/L; median change in sodium at 12 hours, 7 and 11 mmol/L; and median change in sodium at 24 hours, 10 and 15 mmol/L. The decline in sodium concentration was more safely in group 1 than group 2 at both 12 and 24 hours of rehydration. One patient had convulsion associated with cerebral edema in group 2. Otherwise no complication was observed in both groups. CONCLUSION: Enteral route for fluid replacement may be safe and effective and may be an alternative to intravenous fluid therapy in newborns with hypernatremic dehydration when clinical situation is stable.

Unsynchronized nasal intermittent positive pressure versus nasal continuous positive airway pressure in preterm infants after extubation.

OBJECTIVE: To determine the effect of unsynchronized nasal intermittent positive pressure ventilation compared to continuous positive airway pressure in preterm infants after extubation. METHODS: A total of 67 premature infants who were <35 weeks gestation and/or <2000 g birth weight and received mechanical ventilation because of respiratory distress syndrome (RDS) were studied. Infants were randomized to receive either unsynchronized nasal intermittent positive pressure ventilation (NIPPV) with shortened endotracheal tube (Group 1) or nasal continuous positive airway pressure (NCPAP) with binasal prongs (Group 2) after extubation. Extubation failure and neonatal outcomes were recorded in each group. RESULTS: There were no significant differences in clinical characteristics between the two groups. The prevalence of re-intubation and post-extubation atelectasis were higher in CPAP group (p = 0.03 and p = 0.01). No differences were observed in the prevalence of IVH, ROP, PDA, NEC, sepsis, pneumothorax, BPD and BPD/death between the groups while the mortality was higher in NCPAP group (p < 0.01). Neither procedure had any serious side effects such as intestinal perforation. CONCLUSION: NIPPV (although non-synchronized and delivered by single nasal prong) had a better effect than NCPAP after extubation of preterm infants on mechanical ventilation in respect to reducing the prevalence of post-extubation atelectasis, re-intubation and also death.

Papaverine intoxication in a newborn: an unusual case report.

Herbal agents are increasingly used for medicinal purposes, but there is a lack of knowledge about the content of these agents. Indiscriminate use of herbal agents may cause severe side effects and also death. We report a newborn who developed convulsions and respiratory arrest after oral intake of an opium poppy preparation containing papaverine for its antitussive effect. The infant experienced a good outcome with supportive treatment. To the best of our knowledge, this is the first time a newborn with papaverine intoxication has been described. Parents should avoid self-medication of their children, and the possibility of exposure to foreign products should be kept in mind in any seizure of a newborn with unexplained origin.

Reference ranges for sonographic renal dimensions in preterm infants.

BACKGROUND: Ultrasonographic measurement of kidney dimensions is important in evaluation of renal disease in preterm infants who have multiple comorbidities that affect renal function. OBJECTIVE: The purpose of this study was to determine the reference ranges of kidney dimensions in preterm newborns and to provide a chart to use easily in daily practice. MATERIALS AND METHODS: We evaluated renal dimensions in 498 preterm infants with a gestational age of <37 weeks using sonography within the first week of life. We statistically analyzed the relationships between all dimensions and gender, gestational age (based on the last menstrual period), height and weight. Minimum and maximum values of dimensions were defined. RESULTS: All dimensions of the kidneys were statistically different in boys and girls (P < 0.05). Both longitudinal and anteroposterior dimensions of the right and left kidneys showed high correlation with gestational age, weight and height in girls and boys. Weight correlated best with dimensions. CONCLUSION: Nomograms from these data can be used to determine an abnormality in kidneys of preterm newborns.

Reference ranges for sonographic dimensions of the liver and spleen in preterm infants.

BACKGROUND: Preterm infants usually have multiple comorbidities that affect spleen and liver. Ultrasonographic measurement of organ sizes is an important and reliable parameter in evaluation of spleen and liver pathology in preterm newborns. OBJECTIVE: The purpose of this study was to determine reference values of ultrasonographic measurements of the liver and spleen in preterm newborns. MATERIALS AND METHODS: We prospectively performed sonography on 498 preterm newborns in the first week of life. We measured spleen and liver dimensions and statistically analyzed relationships between the dimensions and gender, gestational age (based on mother's last menstrual period), height and weight. Reference ranges of dimensions were defined. RESULTS: Longitudinal and anteroposterior dimensions of the liver and spleen were statistically significantly different between the boys and girls (P < 0.05) and showed high correlation with the gestational age, weight and height. Weight was the parameter best correlated with the dimensions. CONCLUSION: Nomograms from these data are useful for sonographic evaluation of the liver and spleen in preterm newborns.

Escherichia coli brain abscess in a twin pair associated with TLR4 gene mutation.

Brain abscesses are uncommon complications of bacterial meningitis or sepsis in neonates and infants. The causative pathogens of brain abscess in newborns are various. Of those, Escherichia coli is rarely seen as a pathogen in brain abscess at this age. Herein we reported brain abscesses in twin infants caused by E. coli sepsis. Interestingly, genetic analysis identified heterozygous Toll-like receptor 4 (TLR4) gene mutation in the twins. Because TLR plays an important role in the natural response to bacterial products and initiates specific immune response against these pathogens, this may explain the development of brain abscess in the present case.

Homocysteine levels and its association with intraventricular hemorrhage in preterm infants born to preeclamptic mothers.

OBJECTIVE: To investigate the relation between serum homocysteine levels and intraventricular hemorrhage (IVH) in preterm infants born to preeclamptic mothers. METHOD: This study included 84 preterm infants (42 born to preeclamptic mothers and 42 born to normotensive healthy mothers) who were admitted to Izmir Tepecik Training and Research Hospital Neonatology Clinic on the postnatal first day. The measurement of homocysteine levels in all samples were performed with an Immulite 2000 analyzer, using the chemiluminescence method. Cranial ultrasounds were performed on the fourth day and in the 1 month of age. RESULTS: The mean plasma levels of homocysteine in infants born to preeclamptic mothers and in the control group were 8.2 ± 5.9 µmol/L and 5.3 ± 2.7 µmol/L, respectively. The plasma levels of homocysteine were significantly higher in the study group (p = 0.006). There was no association between the plasma homocysteine levels and IVH or other neonatal complications including necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia and mortality. CONCLUSION: Our data suggest that plasma levels of homocysteine are higher among infants born to preeclamptic mothers, but these high levels are not associated with IVH and other neonatal complications in preterm infants.