Early Pharmacological Intervention Research Articles

Biomarkers of hippocampal gene expression in a mouse restraint chronic stress model.

Acute stress provides many beneficial effects whereas chronic stress contributes to a variety of human health issues including anxiety, depression, gastrointestinal problems, cardiac disease, sleep disorders and obesity. The goal of this work was to identify, using a rodent model, hippocampal gene signatures associated with prolonged chronic stress representing candidate biomarkers and therapeutic targets for early diagnosis and pharmacological intervention for stress induced disease. Mice underwent 'restraint stress' over 7 consecutive days and hippocampal gene-expression changes were analyzed at 3, 12 and 24 h following the final restraint treatment. Data indicated that mice exposed to chronic restraint stress exhibit a differential gene-expression profile compared with non-stressed controls. The greatest differences were observed 12 and 24 h following the final stress test. Our study indicated that Gpr88, Ttr, Gh and Tac1 mRNAs were modulated in mice exposed to chronic restraint stress. These transcripts represent a panel of biomarkers and druggable targets for further analysis in the context of chronic stress associated disease in humans.

Resposta hipertensiva ao esforço: um problema silencioso

Introduction: Physically active people are usually considered healthy and protected from cardiovascular disease and hypertension due to their good physical condition. The prevalence of hypertension in these groups is estimated to be about 50% lower than in the general population. Exercise is a well-known non-pharmacological measure for diminishing cardiovascular risk. The purpose of this article is to make health professionals aware of the hypertensive response to exercise and of the need for early diagnosis in order to assess and control cardiovascular risk in these patients. Description of Case: The case of a 33 year-old asymptomatic Caucasian male is presented. He was a former high-level competitive swimmer between the ages of 10 and 22. He currently performs regular physical activity with moderate to high intensity. His personal history includes current smoking, a BMI of 28.9kg/m2 and a family history of obesity and high blood pressure. As part of his routine assessment, we detected borderline elevated blood pressure values (high normal), overweight, hypercholesterolemia (with a total cholesterol/HDL cholesterol index of 4.7), and left ventricular hypertrophy by electrocardiographic and echocardiographic criteria. The 24-hour ambulatory blood pressure measurement was negative for hypertension. A stress test was performed. It was interrupted prematurely due to a hypertensive response to exercise. This explained not only the cardiac anomalies found but also allowed early pharmacological intervention with control of blood pressure during exercise. Comments: In asymptomatic and normotensive individuals, an exaggerated blood pressure response during exercise is associated with an increased risk of future hypertension and negative cardiovascular outcomes. The treadmill test can be used to identify individuals with abnormal responses, probably preceding hypertension, allowing early intervention in the natural history of the disease. This case emphasizes the importance of knowing the patient’s lifestyle for optimal clinical evaluation.

INHERIT (INHibition of the renin angiotensin system in hypertrophic cardiomyopathy and the Effect on hypertrophy-a Randomised Intervention Trial with losartan).

Early pharmacological interventions on transgenic models of hypertrophic cardiomyopathy (HCM) using angiotensin receptor blockers (ARBs) may be effective in preventing development of clinical phenotype or causing phenotype regression in early stages of disease. In the clinical setting, however, the effects of ARBs on HCM phenotype have been less consistent. INHERIT (INHibition of the renin angiotensin system in hypertrophic cardiomyopathy and the Effect on hypertrophy—a Randomised Intervention Trial with losartan) was designed to assess the effect of 100 mg of losartan in promoting the regression of LV hypertrophy in HCM. The primary end-point of the study was the reduction in LV mass assessed by MRI or computed tomography. After 12 months, no reduction in LV mass was observed in the losartan arm, and there was no difference in LV mass change with the placebo arm. The same was true for all secondary endpoints. The implications of these findings are discussed in the light of further, ongoing study targeting the HCM phenotype.

Pharmacological interventions for preventing or delaying onset of type 2 diabetes mellitus.

Prevention or delay of onset of type 2 diabetes in individuals at varying risk across the dysglycaemia continuum before overt diabetes becomes clinically manifest constitutes a leading objective of global disease prevention schemes. Pharmacological intervention has been suggested as a means to help prevent diabetes and reduce the global burden of this chronic condition. However, there is no credible evidence that early pharmacological intervention leads to long-term benefit in reducing diabetes-related complications or preventing early mortality, compared to treating people with diagnosed diabetes who have crossed the glycaemic threshold. In this review, we examine published evidence from trials using pharmacological agents to delay or prevent progression to diabetes. We also explore the benefit/risk impact of such therapies, safety issues and relevant off-target effects. Current evidence suggests none of the drugs currently available sustainably lower cumulative diabetes incidence, none provides a durable delay in diabetes diagnosis and none provides a convincing concomitant excess benefit for microvascular or macrovascular risk.

Efficacy and safety of haloperidol prophylaxis for delirium prevention in older medical and surgical at-risk patients acutely admitted to hospital through the emergency department: study protocol of a multicenter, randomised, double-blind, placebo-controlled clinical trial.

BackgroundDelirium is associated with substantial morbidity and mortality rates in elderly hospitalised patients, and a growing problem due to increase in life expectancy. Implementation of standardised non-pharmacological delirium prevention strategies is challenging and adherence remains low. Pharmacological delirium prevention with haloperidol, currently the drug of choice for delirium, seems promising. However, the generalisability of randomised controlled trial results is questionable since studies have only been performed in selected postoperative hip-surgery and intensive care unit patient populations. We therefore present the design of the multicenter, randomised, double-blind, placebo-controlled clinical trial on early pharmacological intervention to prevent delirium: haloperidol prophylaxis in older emergency department patients (The HARPOON study).Methods/DesignIn six Dutch hospitals, at-risk patients aged 70 years or older acutely admitted through the emergency department for general medicine and surgical specialties are randomised (n = 390) for treatment with prophylactic haloperidol 1 mg or placebo twice daily for a maximum of seven consecutive days. Primary outcome measure is the incidence of in-hospital delirium within seven days of start of the study intervention, diagnosed with the Confusion Assessment Method, and the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for delirium. Secondary outcome measures include delirium severity and duration assessed with the Delirium Rating Scale Revised 98; number of delirium-free days; adverse events; hospital length-of-stay; all-cause mortality; new institutionalisation; (Instrumental) Activities of Daily Living assessed with the Katz Index of ADL, and Lawton IADL scale; cognitive function assessed with the Six-item Cognitive Impairment Test, and the Dutch short form Informant Questionnaire on Cognitive Decline in the Elderly. Patients will be contacted by telephone three and six months post-discharge to collect data on cognitive- and physical function, home residency, all-cause hospital admissions, and all-cause mortality.DiscussionThe HARPOON study will provide relevant information on the efficacy and safety of prophylactic haloperidol treatment for in-hospital delirium and its effects on relevant clinical outcomes in elderly at-risk medical and surgical patients.Trial registrationEudraCT Number: 201100476215; ClinicalTrials.gov Identifier: NCT01530308; Dutch Clinical Trial Registry: NTR3207

A combined analysis of 48 type 2 diabetes genetic risk variants shows no discriminative value to predict time to first prescription of a glucose lowering drug in Danish patients with screen detected type 2 diabetes.

ObjectiveTo investigate the genetic influence of 48 type 2 diabetes susceptibility variants on disease progression measured as risk of early prescription redemption of glucose lowering drugs in screen-detected patients with type 2 diabetes.MethodsWe studied type 2 diabetes progression in 1,480 patients with screen-detected type 2 diabetes from the ADDITION-Denmark study using information of redeemed prescriptions from the Register of Medicinal Products Statistics from 2001–2009 in Denmark. Patients were cluster randomized by general practitioners, who were randomized to treat type 2 diabetes according to either a conventional or a multifactorial intensive treatment algorithm. We investigated the genetic influence on diabetes progression by constructing a genetic risk score (GRS) of all 48 validated type 2 diabetes susceptibility variants, a GRS of 11 variants linked to β-cell function and a GRS of 3 variants linked to insulin sensitivity and assessed the association between number of risk alleles and time from diagnosis until first redeemed prescription of either any glucose lowering drug or an insulin drug.ResultsThe GRS linked to insulin sensitivity only nominally increased the risk of an early prescription redemption with an insulin drug by 39% (HR [95% C.I.] = 1.39 [1.09–1.77], p = 0.009] in patients randomized to the intensive treatment group. Furthermore, the strongest univariate predictors of diabetes progression for the intensive treatment group (measured as time to first insulin) were younger age (HR [95% C.I.] = 0.96 [0.93–0.99]), increased BMI (1.05 [1.01–1.09]), increased HbA1c (1.50 [1.36–.66]), increased TG (1.24 [1.11–1.39]) and reduced fasting serum HDL (0.37 [0.17–0.80]) at baseline. Similar results were obtained for the conventional treatment group.ConclusionHigher levels of HbA1c, fasting circulating levels of triglyceride, lower HDL, larger BMI and younger age are significant determinants of early pharmacological intervention in type 2 diabetes. However, known common type 2 diabetes-associated gene variants do not appear to significantly affect disease progression.

Are metabolically healthy obese individuals really healthy?

Obesity has become one of the major public health concerns of the past decades, because it is a key risk factor for type 2 diabetes, cardiovascular diseases, dyslipidemia, hypertension, and certain types of cancer, which may lead to increased mortality. Both treatment of obesity and prevention of obesity-related diseases are frequently not successful. Moreover, a subgroup of individuals with obesity does not seem to be at an increased risk for metabolic complications of obesity. In this literature, this obesity subphenotype is therefore referred to as metabolically healthy obesity (MHO). Importantly, individuals with MHO do not significantly improve their cardio-metabolic risk upon weight loss interventions and may therefore not benefit to the same extent as obese patients with metabolic comorbidities from early lifestyle, bariatric surgery, or pharmacological interventions. However, it can be debated whether MHO individuals are really healthy, especially since there is no general agreement on accepted criteria to define MHO. In addition, overall health of MHO individuals may be significantly impaired by several psycho-social factors, psychosomatic comorbidities, low fitness level, osteoarthritis, chronic pain, diseases of the respiratory system, the skin, and others. There are still open questions about predictors, biological determinants, and the mechanisms underlying MHO and whether MHO represents a transient phenotype changing with aging and behavioral and environmental factors. In this review, the prevalence, potential biological mechanisms, and the clinical relevance of MHO are discussed.

Risk factors and early pharmacological interventions to prevent chronic postsurgical pain following cardiac surgery.

Chronic postsurgical pain (CPSP) after cardiac surgery represents a significant clinical problem. The prevalence of CPSP varies widely between studies, but severe CPSP is present in less than 10% of the patients. Important differential diagnoses for CPSP after cardiac surgery are myocardial ischemia, sternal instability and mediastinitis. CPSP after cardiac surgery may be thoracic pain present at the site of the sternotomy or leg pain due to vein-graft harvesting. The CPSP can be neuropathic pain, visceral pain, somatic pain or mixed pain. Potential risk factors for CPSP are young age, female gender, overweight, psychological factors, preoperative pain, surgery-related factors and severe postoperative pain. In addition to standard postoperative analgesics, the use of N-methyl-D-aspartate (NMDA) antagonists, alpha-2 agonists, local anesthetics, gabapentinoids, and corticosteroids are all proposed to reduce the risk for CPSP after cardiac surgery. Still, no specific pharmacological therapy, cognitive therapy or physical therapy is established to protect against CPSP. The only convincing prevention of CSPS is adequate treatment of acute postoperative pain irrespective of method. Hence, interventions against acute pain, preferably in a step-wise approach titrating the interventions for each patient's individual needs, are essential concerning prevention of CPSP after cardiac surgery. It is also important that surgeons consider the risk for CPSP as a part of the basis for decision-making around performing a surgical procedure and that patients are informed of this risk.

AB0333 The Risk of Osteoporotic Fractures According to the FRAX Model in Korean Patients with Rheumatoid Arthritis

BackgroundRheumatoid arthritis (RA) is a systemic inflammatory disease and is commonly associated with osteoporosis. To prevent osteoporotic fractures in patients with RA, it is important to identify the high risk...

Predisposition - obesity phenotype

Obesity belongs to the five most important health burdens in modern societies and reaches with ~20 % prevalence in Germany epidemic proportions. Obesity significantly increases the risk of developing metabolic (e. g. type 2 diabetes), cardiovascular, orthopaedic, psychologic and other disorders. Despite the well established epidemiologic relationship between obesity and these co-morbidities, there is a subgroup of metabolically healthy obese patients, which seems to be protected against metabolic and cardiovascular obesity related disorders. Compared to metabolically unhealthy or high risk obese patients, metabolically healthy obese individuals are characterized by preserved insulin sensitivity, lower liver fat content, lower visceral fat mass, as well as normal adipose tissue function. Noteworthy, metabolically healthy obese individuals do not significantly improve their obesity-associated risk for the development of type 2 diabetes and vascular diseases. Therefore, distinction between metabolically healthy from high-risk obese phenotypes will facilitate the identification of the obese person who will benefit the most from early lifestyle, pharmacological or bariatric surgery interventions. A stratified treatment approach considering these different obesity phenotypes should be introduced into clinical management of obese patients.

Early versus delayed initiation of pharmacotherapy in Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease and pathologically is characterised by a progressive loss of dopaminergic cells of the nigrostriatal pathway. Clinically, PD is mainly defined by the presence of the motor symptoms of bradykinesia, rigidity, rest tremor and postural instability, but non-motor symptoms such as depression, dementia and autonomic disturbances are recognised as integral parts of the disease. Although pharmacotherapy for PD was introduced almost 50years ago, and has improved significantly over the intervening period, the timing of initiation of treatment in newly diagnosed PD remains controversial. While some physicians favour an early start of pharmacotherapy at or soon after diagnosis, others prefer to delay pharmacological treatment until a certain degree of disability has developed. This article aims to discuss the advantages and disadvantages of both strategies by exploring their effects on symptoms, disease progression and quality of life. Although the data on putative disease-modifying effects of early pharmacological intervention in PD are still inconclusive, we believe that the most important indication for an early initiation of anti-parkinsonian treatment should be to maintain the quality of life of PD patients and to secure their socioeconomic status as long as possible.

Age-related Vascular Differences among Patients Suffering from Multiple Sclerosis

The aim of our study was to analyze morphological and functional aspects of cerebral veins by means of ecocolor-Doppler in young (i.e., ≤ 30 years old) and older (i.e., >30 years old) patients suffering from multiple sclerosis. 552 multiple sclerosis patients were evaluated by means of a dedicated Echo-Color-Doppler support (MyLab Vinco echocolor Doppler System, Esaote), in both supine and sitting positions. 458 (83%) showed alterations in their morphological and functional structures of cerebral veins and were divided in two different groups: 1) ≤ 30 (110 patients) and 2) >30 years old (348 patients). Young patients showed a statistically significant higher number of both hemodynamically (44% vs. 35%, p<0.01) and non-hemodynamically (51% vs. 45%, p<0.05) significant stenosis in the internal jugular veins as compared to older patients. A lower percentage of young patients showed blocked outflow in the cervical veins (50% vs. 65%, p<0.01) as compared to older ones. Patients >30 years old outlined a significantly higher disability degree (Expanded Disability Status Scale score: 5 vs. 3, p<0.01) as well as higher disease duration (12 vs. 5 months, p<0.01) than younger. No differences could be outlined about multiple sclerosis clinical form of the disease. It was evidenced that young and adult groups are different kind of patients, the former showing much more cerebral veins stenosis and blocked flow in internal jugular veins and vertebral veins than the latter. Duration of disease could explain such differences: the higher the diseases duration, the higher the degree of vascular alterations and, therefore, the disability degree. This could be due to the complex venous hemodynamic impairments induced by alterations in vascular walls: the blocked or difficult blood flow through stenosis could increase the hydrostatic pressure in the skull and this could induce damages to cerebral cells leading to the genesis of more advanced morphological abnormalities. Furthermore, the vessels' alterations could impair venous endothelial functions which could turn in a possible alteration of the controls of cerebral vein return which could worsen the cerebral vascular outflow. It may be possible that early clinical, pharmacological and/or invasive vascular interventions could exert a possible role in the natural history of multiple sclerosis. Nevertheless, further trials are needed in order to confirm such considerations.

Fgf2 improves functional recovery—decreasing gliosis and increasing radial glia and neural progenitor cells after spinal cord injury

ObjectivesA major impediment for recovery after mammalian spinal cord injury (SCI) is the glial scar formed by proliferating reactive astrocytes. Finding factors that may reduce glial scarring, increase neuronal survival, and promote neurite outgrowth are of major importance for improving the outcome after SCI. Exogenous fibroblast growth factor (Fgf) has been shown to decrease injury volume and improve functional outcome; however, the mechanisms by which this is mediated are still largely unknown.MethodsIn this study, Fgf2 was administered for 2 weeks in mice subcutaneously, starting 30 min after spinal cord hemisection.ResultsFgf2 treatment decreased the expression of TNF-a at the lesion site, decreased monocyte/macrophage infiltration, and decreased gliosis. Fgf2 induced astrocytes to adopt a polarized morphology and increased expression of radial markers such as Pax6 and nestin. In addition, the levels of chondroitin sulfate proteoglycans (CSPGs), expressed by glia, were markedly decreased. Furthermore, Fgf2 treatment promotes the formation of parallel glial processes, “bridges,” at the lesion site that enable regenerating axons through the injury site. Additionally, Fgf2 treatment increased Sox2-expressing cells in the gray matter and neurogenesis around and at the lesion site. Importantly, these effects were correlated with enhanced functional recovery of the left paretic hind limb.ConclusionsThus, early pharmacological intervention with Fgf2 following SCI is neuroprotective and creates a proregenerative environment by the modulation of the glia response.

Delayed BDNF alterations in the prefrontal cortex of rats exposed to prenatal stress: Preventive effect of lurasidone treatment during adolescence

Psychiatric diseases may often represent the consequence of exposure to adverse events early in life. Accordingly, exposure to stress during gestation in rats has a strong impact on development and can cause long-term abnormalities in adult behavior. Considering that neuronal plasticity has emerged as a major vulnerability element in psychiatric disorders, we investigated the postnatal developmental profile of Brain-Derived Neurotrophic Factor expression (BDNF), an important mediator for long-term functional deterioration associated to mental illness, in male and female rats following exposure to prenatal stress (PNS). Since we found that the majority of alterations became fully manifest at early adulthood, we tried to prevent these abnormalities with an early pharmacological intervention. To address this point, we treated rats during adolescence with the multi-receptor antipsychotic lurasidone, which was proven to be effective in animal models of schizophrenia. Interestingly, we show that lurasidone treatment was able to prevent the reduction of BDNF expression in adult rats that were exposed to PNS.Collectively, our results provide further support to the notion that exposure to early life stress has a negative impact on neuronal plasticity and that pharmacological intervention during critical time windows may prove effective in preventing neuroplastic dysfunction, leading to long-term beneficial effects on brain function.

Erratum to: Should Mild COPD Be Treated? Evidence for Early Pharmacological Intervention

Erratum to: Should Mild COPD Be Treated? Evidence for Early Pharmacological Intervention

Early Pharmacological Treatment of Delirium May Reduce Physical Restraint Use

Evidence surrounding pharmacological treatment of delirium is limited. The negative impact of physical restraints on patient outcomes in the intensive care unit (ICU), however, is well published. The objective of this study was to evaluate whether initiating pharmacologic delirium treatment within 24 hours of a positive screen reduces the number of days in physical restraints and improves patient outcomes compared with delayed or no treatment. Patients from a mixed ICU with a documented positive delirium score using the Intensive Care Delirium Screening Checklist were retrospectively grouped based on having received pharmacologic treatment within 24 hours of the first positive screen or not. Primary end points were number of days spent in physical restraints and time to extubation after delirium onset. Secondary end points included hospital and ICU length of stay (LOS) and survival to discharge. Two hundred intubated patients were either pharmacologically treated (n = 98) or not treated (n = 102) within 24 hours of the first positive delirium score. Patients receiving treatment spent a shorter median time in restraints compared with patients who were not treated (3 vs 6 days; P < .001), and had a shorter median time to extubation (3 vs 6.5 days; P < .001). The treatment group also experienced a shorter ICU LOS (9.5 vs 16 days; P < .001) and hospital LOS (14.5 vs 22 days; P < .001) compared with the no-treatment group. Delirious patients who received pharmacological treatment within 24 hours of the first positive screen spent fewer days in physical restraints and less time receiving mechanical ventilation compared with those who did not. Although delirium management is multifactorial, early pharmacological therapy may benefit patients diagnosed with delirium.

Should Mild COPD Be Treated? Evidence for Early Pharmacological Intervention

Chronic obstructive pulmonary disease (COPD) is a common and often progressive inflammatory disease of the airways that is both preventable and treatable. It is well established that those with mild-to-moderate disease severity represent the majority of patients with COPD, yet this subpopulation is relatively under-studied. Because of an insidious pre-clinical phase, COPD is both under-diagnosed and under-treated. Recent studies have confirmed that even patients with mild, grade 1 COPD [i.e. those with a reduced forced expiratory volume in one second (FEV1)/forced vital capacity ratio but normal FEV1], have measurable physiological impairment with increased morbidity and a higher risk of mortality compared with non-smoking healthy controls. Beyond the imperative of smoking cessation-the pivotal intervention in all COPD stages-the role of pharmacotherapy for prevention of disease progression has yet to be established. The main objective of this review is to provide a concise overview of the heterogeneous pathophysiology of COPD with only mild airway obstruction on spirometry and obstacles for early diagnosis. We emphasize that the absence of sufficiently powered trials involving a large number of patients precludes definitive recommendations in support of (or against) long-term pharmacological treatment in mild COPD. Despite these limitations, we present a rationale for earlier pharmacological intervention derived from recent physiological studies performed in symptomatic patients with mild COPD.

Treatment strategy of patent ductus arteriosus in preterm infants

Objective – This study was to assess the efficacy and safety of oral ibuprofen and intravenous ibuprofen for the early pharmacological treatment of patent ductus arteriosus (PDA) in preterm infants. Methods – A randomized, single-blinded, controlled study was performed on premature neonates at the neonatal unit tertiary care hospital, from January 2010 to December 2012. The study enrolled 80 preterm infants with gestational age between 28-32 weeks, birth weight ≤ 2000 g, postnatal age 48-96 h, and with echocardiographically confirmed significant PDA (a duct size >1.5 mm). The preterm infants received either intravenous or oral ibuprofen randomly as an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 h after the first dose (the first treatment course). Serum creatinine (sCr), blood urea nitrogen (BUN) and urine output (UO) were recorded prior to treatment, before each dose and after the first treatment course. Results – Forty patients were treated with oral ibuprofen and 40 with intravenous ibuprofen in this period. There was no difference between treatment groups in demographics or baseline renal function. After the first course of the treatment, the PDA closed in 28 (70%) of the patients assigned to the oral ibuprofen group, versus 23 (57.5%) of those enrolled in the intravenous ibuprofen group (p=0.35). In the evaluation of renal tolerance, none of the patients had oliguria. Moreover, in patients who underwent a second course of intravenous therapy, the urinary output significantly decreased, but the sCr levels after the first and after the second treatment course did not differ significantly from the baseline for each group. 7.5% of the intravenous group underwent surgery, versus 0% of the oral group. (p=0.23) Conclusions – Successful pharmacological closure of PDA can be achieved by the use of ibuprofen orally or intravenously, without statistically significant difference in efficacy and safety between the two treatments. Patients treated with ibuprofen intravenously probably have a much higher risk of undergoing surgery.

Role of electrocardiography and echocardiography in prevention and predicting outcome of subjects at increased risk of heart failure

Asymptomatic left ventricular dysfunction (ALVD) is relatively common in both community and high-risk populations. Early pharmacological intervention can improve clinical outcomes in subjects with this condition. This multicentre study consists on electrocardiographic and echocardiographic examination of stage A and B heart failure (HF) asymptomatic subjects with one or more cardiovascular risk factors, to assess the prognostic value of cardiovascular risk factors per se, clinical history, and electrocardiographic and echocardiographic parameters in prediction of progression of HF and/or in development of cardiovascular primary or secondary events. A total of 2142 asymptomatic subjects (mean age 63 years, 1162 males) performed an electrocardiographic and echocardiographic examination. Electrocardiogram (ECG) pathological signs according to Minnesota code and left ventricular dysfunction both systolic and diastolic by echocardiography were evaluated. There were 2002 subjects who were followed up for 26 ± 11 months, observing their primary and secondary end points. At follow up, the study population presented 111 primary end points (5.2%) and 441 secondary end points (20.6%). ECG criteria of LV hypertrophy and signs of ischaemia or previous myocardial infarction (p < 0.0001) were highly significantly related to primary end points. Both ECG and echocardiography (systolic function) are able at Kaplan-Meier cumulative survival curves to predict primary end points (p < 0.0001). Presence or absence of left ventricular systolic and /or diastolic dysfunction has an incremental value in comparison to cardiovascular risk factors, clinical history, and ECG findings to predict both the evolution towards a more severe HF stage (stage C) and also the occurrence of cardiovascular events.

ORAL VERSUS INTRAVENOUS IBUPROFEN FOR THE EARLY CLOSURE OF PATENT DUCTUS ARTERIOSUS IN LOW BIRTH WEIGHT PRETERM INFANTS

Background Patent ductus arteriosus (PDA) is common in very premature infants. Pharmacological closure of PDA with indomethacin, a prostaglandin inhibitor, has remained the mainstay of treatment in premature infants over the last three decades. Intravenous ibuprofen was recently shown to be as effective and to have fewer adverse reaction in preterm infants. If equally effective, then oral ibuprofen for PDA closure would have several important advantages over the intravenous route.This study was designed to assess the efficacy and safety of oral ibuprofen and intravenous ibuprofen for the early pharmacological treatment of PDA in LBW preterm infants with respiratory distress syndrome.MethodsA randomized, single-blinded, controlled study was performed on premature neonates at the neonatal care unit of the University Hospital for Obstetrics and Gynecology”Koco Gliozheni”, Tirana, Albania, from January 2010 to December 2012. The study enrolled 68 preterm infants with gestational age between 28-32 weeks, birth weight ≤ 2000 g, postnatal age 48-96 h, and had echocardiographically confirmed significant PDA. The preterm infants received either intravenous or oral ibuprofen randomly as an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 h. After the first dose of treatment in both groups, echocardiographic evaluation was performed, to determine the need for a second or third dose. The rate of ductal closure, adverse effects, complications, and the patient’s clinical course were recorded.Results All patients were born after 28 until 32 weeks’ gestation. 36 patients were treated with oral ibuprofen and 32 with intravenous ibuprofen in this period. After the first course of the treatment, the PDA closed in 30 (83.3%) of the patients assigned to the oral ibuprofen group versus 23 (71.8%) of those enrolled in the intravenous ibuprofen group (p = 0.355). There was no difference between treatment groups in demographics or baseline renal function. In the evaluation of renal tolerance, none of the patients had oliguria. There were no significant differences with respect to complications during the stay.Conclusions In low birth weight infants, the rate of early ductal closure with oral ibuprofen is at least as good as with the intravenous route. Oral ibuprofen is associated with fewer adverse effects