Adverse Clinical Findings Research Articles

Content validation of drug problem-oriented clinical record.

Worldwide, hospitals are responsible for restoring health. However, poorly executed processes in these institutions can lead to risks and harm to patients, especially in identifying drug related problems. This fact justifies the proposal of tools to support the diagnosis, management and resolution of these problems. To develop and content validate a clinical record that is oriented towards drug-related problems. A drug-oriented clinical record was first developed, after which it underwent content validation. The study was carried out between September and December 2017.7 The first version of the drug-related clinical record was prepared by two experienced researchers, using studies and problem-oriented medical tools described in the literature. Thereafter, content validation was performed using the nominal group technique. The expert panel consisted of a physician, two nurses, and three pharmacists with clinical experience in a hospital setting or pharmaceutical care. After that, the respective instrument was assessed according to the criteria objectivity, simplicity, clarity, relevance. These criteria are intended to ensure the rigor and reliability of instrument content. Experts' suggestions included modification of the order of some items, insertion of new items, modification of item-writing procedures, expansion of specific fields, and better specification of data that is to be filled in as an item. The final version of the instrument was titled "DAM Clinical Record" (Diagnostics - Adverse Clinical Findings - Medicines) and comprised 45 items categorized into six sections: Patient Identification, Anamnesis, Clinical Diagnosis, Adverse Clinical Findings, Medicines and Pharmaceutical Evaluation. A clinical record oriented towards drug-related problems, named DAM, was developed to guide healthcare professionals in identifying and solving drug-related problems. All relevant information generated in the hospital setting was consecutively stored as drug problem-oriented clinical records after undergoing thorough content validation.

Use of a drug-related problem oriented medical record in the medication review of critically ill patients - Randomized clinical trial.

The identification and reduction of drug-related problems (DRPs) through DRP-oriented medical records during the hospitalization of critically impatients can optimize health indicators, such as length of hospital stay. To determine the effect of medical records focused on drug-related problems on the duration of stay for patients in intensive care units. A randomized controlled clinical trial was conducted with patients assigned to intervention or the usual care groups involving clinical pharmacists. This trial occurred between March 2018 and March 2019 and was completed in two intensive care units within two hospitals in Brazil. Exploratory secondary outcomes included the mortality rate and reductions in Sequential Organ Failure Assessment (SOFA) and Δ SOFA scores. A total of 150 patients participated-54.6% were women, most being white (77.3 %). Further, the main diagnosis was Acute Coronary Syndrome (22.6%), followed by Congestive Heart Failure (12.6%) and Heart Failure (10%). A significant difference was observed in the length of stay between the intervention group and the control group, respectively 7.08 days (±4.38) and 10.7 days (±6.32). Among the secondary outcomes, a significant difference was observed in the mortality rates between the two groups: (6.58%) in the intervention group and 25.68% in the control group. Regarding Δ SOFA, the intervention group exhibited a reduction of 4.63 in the SOFA score during hospitalization. The control group showed an increase of 1.88 in the score during the same period. This study demonstrated that the use of Diagnoses - Adverse Clinical Findings - Medications (DAM), a medical record model aimed at resolving drug-related problems, reduced the length of hospital stay and mortality rates among patients. Furthermore, this model proved to be more effective than the usual care provided by clinical pharmacists.

Adrenal insufficiency in pediatric kidney transplantation recipients.

Immunosuppression of pediatric kidney transplant (PKT) recipients often includes corticosteroids. Prolonged corticosteroid exposure has been associated with secondary adrenal insufficiency (AI); however, little is known about its impact on PKT recipients. This was a retrospective cohort review of PKT recipients to evaluate AI prevalence, risk factors, and adverse effects. AI risk was assessed using morning cortisol (MC) and diagnosis confirmed by an ACTH stimulation test. Potential risk factors and adverse effects were tested for associations with MC levels and AI diagnosis. Fifty-one patients (60.8% male, age 7.4 (IQR 3.8, 13.1) years; 1 patient counted twice for repeat transplant) were included. Patients at risk for AI (MC < 240 nmol/L) underwent definitive ACTH stimulation testing, confirming AI in 13/51 (25.5%) patients. Identified risk factors for AI included current prednisone dosage (p = .001), 6-month prednisone exposure (p = .02), daily prednisone administration (p = .002), and rejection episodes since transplant (p = .001). MC level (2.5 years (IQR 1.1, 5.1) post-transplant) was associated with current prednisone dosage (p < .001), 6-month prednisone exposure (p = .001), daily prednisone administration (p = .006), rejection episodes since transplant (p = .003), greater number of medications (β = -16.3, p < .001), 6-month hospitalization days (β = -3.3, p = .013), creatinine variability (β = -2.4, p = .025), and occurrence of acute kidney injury (β = -70.6, p = .01). Greater corticosteroid exposure was associated with a lower MC level and confirmatory diagnosis of AI noted with an ACTH stimulation test. Adverse clinical findings with AI included greater medical complexity and kidney function lability. These data support systematic clinical surveillance for AI in PKT recipients treated with corticosteroids.

Chronic electrical stimulation with a peripheral suprachoroidal retinal implant: a preclinical safety study of neuroprotective stimulation.

Extraocular electrical stimulation is known to provide neuroprotection for retinal cells in retinal and optic nerve diseases. Currently, the treatment approach requires patients to set up extraocular electrodes and stimulate potentially weekly due to the lack of an implantable stimulation device. Hence, a minimally-invasive implant was developed to provide chronic electrical stimulation to the retina, potentially improving patient compliance for long-term use. The aim of the present study was to determine the surgical and stimulation safety of this novel device designed for neuroprotective stimulation. Eight normally sighted adult feline subjects were monocularly implanted in the suprachoroidal space in the peripheral retina for 9-39weeks. Charge balanced, biphasic, current pulses (100μA, 500 µs pulse width and 50 pulses/s) were delivered continuously to platinum electrodes for 3-34weeks. Electrode impedances were measured hourly. Retinal structure and function were assessed at 1-, 2-, 4-, 6- and 8-month using electroretinography, optical coherence tomography and fundus photography. Retina and fibrotic thickness were measured from histological sections. Randomized, blinded histopathological assessments of stimulated and non-stimulated retina were performed. All subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. The device position was stable after a post-surgery settling period. Median electrode impedance remained within a consistent range (5-10kΩ) over time. There was no change in retinal thickness or function relative to baseline and fellow eyes. Fibrotic capsule thickness was equivalent between stimulated and non-stimulated tissue and helps to hold the device in place. There was no scarring, insertion trauma, necrosis, retinal damage or fibroblastic response in any retinal samples from implanted eyes, whilst 19% had a minimal histiocytic response, 19% had minimal to mild acute inflammation and 28% had minimal to mild chronic inflammation. Chronic suprathreshold electrical stimulation of the retina using a minimally invasive device evoked a mild tissue response and no adverse clinical findings. Peripheral suprachoroidal electrical stimulation with an implanted device could potentially be an alternative approach to transcorneal electrical stimulation for delivering neuroprotective stimulation.

Preclinical species gene expression database: Development and meta-analysis.

The evaluation of toxicity in preclinical species is important for identifying potential safety liabilities of experimental medicines. Toxicology studies provide translational insight into potential adverse clinical findings, but data interpretation may be limited due to our understanding of cross-species biological differences. With the recent technological advances in sequencing and analyzing omics data, gene expression data can be used to predict cross species biological differences and improve experimental design and toxicology data interpretation. However, interpreting the translational significance of toxicogenomics analyses can pose a challenge due to the lack of comprehensive preclinical gene expression datasets. In this work, we performed RNA-sequencing across four preclinical species/strains widely used for safety assessment (CD1 mouse, Sprague Dawley rat, Beagle dog, and Cynomolgus monkey) in ∼50 relevant tissues/organs to establish a comprehensive preclinical gene expression body atlas for both males and females. In addition, we performed a meta-analysis across the large dataset to highlight species and tissue differences that may be relevant for drug safety analyses. Further, we made these databases available to the scientific community. This multi-species, tissue-, and sex-specific transcriptomic database should serve as a valuable resource to enable informed safety decision-making not only during drug development, but also in a variety of disciplines that use these preclinical species.

E-Cigarettes and Cardiopulmonary Health: Review for Clinicians.

Electronic cigarettes (e-cigarettes) are battery powered electronic nicotine delivery systems that use a propylene glycol/vegetable glycerin base to deliver vaporized nicotine and flavorings to the body. E-cigarettes became commercially available without evidence regarding their risks, long-term safety, or utility in smoking cessation. Recent clinical trials suggest that e-cigarette use with counseling may be effective in reducing cigarette use but not nicotine dependence. However, meta-analyses of observational studies demonstrate that e-cigarette use is not associated with smoking cessation. Cardiovascular studies reported sympathetic activation, vascular stiffening, and endothelial dysfunction, which are associated with adverse cardiovascular events. The majority of pulmonary clinical trials in e-cigarette users included standard spirometry as the primary outcome measure, reporting no change in lung function. However, studies reported increased biomarkers of pulmonary disease in e-cigarette users. These studies were conducted in adults, but >30% of high school-age adolescents reported e-cigarette use. The effects of e-cigarette use on cardiopulmonary endpoints in adolescents and young adults remain unstudied. Because of adverse clinical findings and associations between e-cigarette use and increased incidence of respiratory diseases in people who have never smoked, large longitudinal studies are needed to understand the risk profile of e-cigarettes. Consistent with the Centers for Disease Control and Prevention recommendations, clinicians should monitor the health risks of e-cigarette use, discourage nonsmokers and adolescents from using e-cigarettes, and discourage smokers from engaging in dual use without cigarette reduction or cessation.

Visceral Fat-Reducing Effect and Safety of Continuous Consumption of Beverage Containing Resistant Maltodextrin: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Clinical Trial.

Obesity is regarded as a global concern with increasing prevalence, most notably in developed countries. Metabolic syndrome is a predictor of cardiovascular disease and type 2 diabetes mellitus and is defined as the accumulation of multiple risk factors caused by abdominal visceral obesity. Resistant maltodextrin (RMD) is a soluble dietary fiber that has been shown to reduce visceral fat in long-term clinical trials when continuously administered at 10 g, three times daily. Herein, we evaluated the effects of long-term consumption of 5 g RMD three times daily. A total of 140 healthy adults were randomly assigned to two intervention groups for a 12-wk randomized, double-blind, placebo-controlled, parallel-group trial. Participants ingested a test beverage containing 5 g RMD or a placebo beverage without RMD. Interviews, anthropometric measurements, physiological examination, blood tests, and urinalyses were conducted at baseline and every 4 wk during the trial. Computed tomography scans were performed at baseline and at the end of week 8 and 12. Results showed that abdominal visceral fat area (VFA) significantly decreased in the test group from 105.33±26.83 cm2 at baseline to 101.15±24.33 cm2 at week 12. Further, a significant difference was observed in the VFA between the test and control groups (p<0.05), confirming the function of continuous RMD consumption in reducing abdominal visceral fat. Furthermore, neither serious adverse events nor adverse clinical findings were observed in the blood or urine tests following consumption of RMD, suggesting that continuous consumption of RMD containing beverages is safe.

Coinfection With Multiple Nontuberculous Mycobacteria as a Possible Exacerbating Factor in Pulmonary Nontuberculous Mycobacteriosis: Clone Library Analysis Using the 16S Ribosomal RNA Gene

Mycobacterial culture is the gold standard for the diagnosis of nontuberculous Mycobacterium (NTM) infections. However, this method is not suitable for detection of coinfection with different NTMs. The goal of this study was to determine if clone library analysis of BAL fluid (BALF) was useful for detection of NTM phylotypes, including multiple NTM phylotypes, in pulmonary NTM infections. BALF samples obtained from 120 patients with suspected pulmonary NTM infections were retrospectively evaluated by using the mycobacterial culture and clone library methods between July 2010 and August2016. In total, 55 (45.8%) patients were diagnosed as NTM positive according to results of mycobacterial culture, and 52 patients were NTM positive as determined by using the clone library method. Furthermore, 45 (86.5%) and seven (13.5%) patients exhibited a single phylotype (mono-phylotype group) and multiple phylotypes of NTM (multi-phylotype group), respectively. Compared with the mono-phylotype group, the multi-phylotype group had a significantly higher incidence of adverse chest CT findings (P= .048). In addition, 11 patients who were NTM negative according to results of BALF mycobacterial culture were determined to be NTM positive according to the clone library method. Six of these 11 patients were eventually diagnosed as NTM positive by using mycobacterial culture results within 6.2 ± 2.1months following the initial sample collection. Coinfection multiple phylotypes could be associated with adverse clinical findings. In addition, patients who test positive for NTM genes but negative for mycobacterial culture may be diagnosed with NTM lung infection within 1 year of the initial sample collection. Further follow-up of these patients may facilitate early detection of NTM species.

Echocardiographic assessment of right heart size and function in dogs with pulmonary valve stenosis

Introduction/ObjectivesWe sought to determine the prevalence and clinical significance of right heart remodeling and right ventricular (RV) dysfunction in dogs with pulmonary valve stenosis (PS). We also sought to evaluate repeatability of several measurements of severity of PS, right heart size, and RV function in dogs with PS. Animals, materials and methodsSeveral indices of right atrial (RA) size and RV size and function were prospectively evaluated in 48 dogs with PS. Regression analysis was used to determine if indices of right heart size and function were independently associated with maximum transpulmonary pressure gradient (max PG) and adverse clinical findings (exercise intolerance, syncope, or right heart failure). Eight dogs underwent a second echocardiogram performed by the same operator to assess repeatability of the echocardiographic indices, which was quantified by coefficient of variation (CV) and repeatability coefficient. ResultsIncreased RA size (81%), increased RV wall thickness (83%), and decreased tricuspid annular plane systolic excursion (TAPSE [81%]) were common. Right atrial size, end-diastolic RV area, and RV wall thickness were independently associated with max PG. Decreased TAPSE was independently associated with adverse clinical findings. All indices except RA area (18.6%) and RV systolic velocity (20.7%) had CVs <15%. Repeatability coefficients are available to help distinguish a true change versus measurement variability during serially obtained exams. ConclusionsRight heart remodeling and RV dysfunction are common in dogs with PS and are associated with echocardiographic and clinical severity. Results support the quantitative assessment of right heart size and function in dogs with PS.

Clinical significance and determinants of prompt recruitment collaterals during primary percutaneous coronary intervention

Due to ischaemic time delays from the chest pain occurrence in acute ST elevation myocardial infarction (STEMI), prompt recruitment collaterals (PRCCs) to infarct-related artery (IRA) are the major protective structures during this period. We aimed to investigate the clinical significance and determinants of PRCCs in acute STEMI patients. A total of 1375 consecutive acute STEMI patients were prospectively enrolled in the study. The patients were divided into two groups, according to PRCCs to IRA; Rentrop ≤ 1 were defined as inadequate collateral development (ICD) group and Rentrop ≥ 2 defined as adequate collateral development (ACD) group. Patients in the ICD group had higher incidence of baseline risk characteristics, including older age, hypertension, and diabetes mellitus; however, pre-infarct angina incidence was lower than in the ACD group (p < 0.05 for all). In addition, the ICD group had worse haemodynamic status on admission and 30-day mortality. Compared to the ACD group, the non-IRA chronic total occlusion (CTO), peak troponin-T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high sensitivity C-reactive protein (hs-CRP) levels were higher in the ICD group. On multivariate logistic regression analysis, non-IRA CTO (b = 3.114, 95% CI 1.382-7.017, p < 0.006) with pre-infarction angina together with higher values of peak troponin-T, NT-proBNP, and hs-CRP were associated with PRCCs in acute STEMI. Taking into account that the main message of the study is that if patients have higher cardiac biomarkers and adverse clinical findings (which, of note, may show the extent of myocardial infarction) and have non-IRA CTO, there is a higher chance that they will have inadequate collateralisation.

Success Rate of MTA Pulpotomy on Vital Pulp of Primary Molars: A 3-Year Observational Study

IntroductionVital pulp therapy is a major contributor in the preservation of primary dentition after caries affliction. Introduction of mineral trioxide aggregate (MTA) has revolutionized such treatment.AimThe aim of our study was to evaluate and correlate the effects of MTA clinically and radiographically on pulpotomized primary molars till their exfoliation or extraction followed by histological evaluation.Study designThis is an observational study.Materials and methodsA total of 25 teeth were selected from 5- to 8-year-old children requiring pulp therapy on the basis of inclusion and exclusion criterion. The teeth were treated by conventional pulpotomy technique under aseptic conditions using MTA and were immediately restored with stainless steel crown. The teeth were assessed postoperatively till 36 months. The exfoliated or extracted teeth were examined histologically.ResultsThe pulpotomized teeth were vital with no adverse clinical findings during the observation period. After 3 months, one tooth showed internal resorption, but the same was not observed after 12 months. Pulp canal obliteration was seen in three cases. At the end of the study, five teeth were exfoliated and one tooth was extracted for maintaining arch symmetry. The histological examination of extracted tooth revealed the presence of healthy pulp and the area of true calcification. Remaining exfoliated teeth presented dentin bridge formation.StatisticsFrequencies and percentages were used for descriptive statistics. Fisher’s exact tests were used to see the difference between clinical and radiological findings. The probability value was fixed at 5% level of significance.ConclusionThe response of pulp in primary teeth to MTA was favorable in all cases from clinical and radiographic perspective, and histological evaluation confirmed the observation.How to cite this articleGodhi B, Tyagi R. Success Rate of MTA Pulpotomy on Vital Pulp of Primary Molars: A 3-Year Observational Study. Int J Clin Pediatr Dent 2016;9(3):222-227.

Practicality of intermittent fasting in humans and its effect on oxidative stress and genes related to aging and metabolism.

Caloric restriction has consistently been shown to extend life span and ameliorate aging-related diseases. These effects may be due to diet-induced reactive oxygen species acting to up-regulate sirtuins and related protective pathways, which research suggests may be partially inhibited by dietary anti-oxidant supplementation. Because caloric restriction is not sustainable long term for most humans, we investigated an alternative dietary approach, intermittent fasting (IF), which is proposed to act on similar biological pathways. We hypothesized that a modified IF diet, where participants maintain overall energy balance by alternating between days of fasting (25% of normal caloric intake) and feasting (175% of normal), would increase expression of genes associated with aging and reduce oxidative stress and that these effects would be suppressed by anti-oxidant supplementation. To assess the tolerability of the diet and to explore effects on biological mechanisms related to aging and metabolism, we recruited a cohort of 24 healthy individuals in a double-crossover, double-blinded, randomized clinical trial. Study participants underwent two 3-week treatment periods-IF and IF with anti-oxidant (vitamins C and E) supplementation. We found strict adherence to study-provided diets and that participants found the diet tolerable, with no adverse clinical findings or weight change. We detected a marginal increase (2.7%) in SIRT3 expression due to the IF diet, but no change in expression of other genes or oxidative stress markers analyzed. We also found that IF decreased plasma insulin levels (1.01 μU/mL). Although our study suggests that the IF dieting paradigm is acceptable in healthy individuals, additional research is needed to further assess the potential benefits and risks.

Abstract A08: Race and aggressive prostate cancer: Resolving bias introduced by treatment selection.

Abstract Purpose: According to population-based studies, prostate cancer (PC) is a more common, more aggressive, and more often fatal disease in African American (AA) men compared to American men of European decent (W). Factors hypothesized to contribute to these disparities include differences in cancer screening and treatment, risk factors such as obesity, and PC risk gene variants. Radical prostatectomy (RP) datasets have been used to examine whether racial disparities in PC outcomes might stem from differences in the biology of the tumors themselves. We sought to test whether selection bias (stemming from imbalances among factors determining who receives RP vs. other non-surgical treatment) could alter the associations between patient race and adverse pathological findings in RP specimens. We present an application of marginal structural modeling using inverse probability weights (IPW) as a means of identifying and counteracting potential treatment selection biases in PC. Materials and Methods: Among 259 AA and 343 W men with prostate cancer recruited at Henry Ford Health System from July 2001 to January 2005, we tested associations between clinical and demographic characteristics with race and receipt of RP. We used logistic regression to estimate the odds of adverse clinical findings (diagnostic PSA&amp;gt;10ng/ml, biopsy Gleason score≥7, or intermediate/high clinical risk) in AA vs. W cases at the time of biopsy (n=602), and compared these estimates to those obtained from cases treated with RP (n=395). We modeled patient factors associated with receipt of RP, and computed an IPW for each case. We report weighted and un-weighted, multivariable-adjusted generalized estimating equation (GEE) models examining the associations between race and adverse pathological findings in RP specimens. Results: At the time of biopsy, compared to W, AA men were 1.66(95%CI 1.09-2.52) times more likely to have intermediate/high clinical risk disease (diagnostic PSA&amp;gt;10ng/ml, biopsy Gleason score ≥7, or clinical stage ≥T2b). AA patients were younger at diagnosis (61.9 vs. 62.9 years), had a greater degree of co-morbidity (p&amp;lt;0.001), lower educational attainment (p&amp;lt;0.001), and lower median household income level (p&amp;lt;0.001), compared to W. When modeling potential treatment selection factors among 602 biopsy confirmed cases, AA men with low clinical risk (biopsy Gleason≤6, PSA&amp;lt;10 and clinical stage ≤T2a) were 2.73(95%CI 1.23-6.08) times as likely to receive RP as W, adjusting for age, family history, co-morbidities, educational attainment, and census tract income level, whereas no such difference existed between AA and W with higher clinical risk (OR=0.918, 95%CI 0.48-1.76)(p&amp;lt;0.05 for interaction term). When testing for racial disparities in tumor characteristics among the 395 cases who received RP, in conventional multivariate models (without IPW), there were no statistically significant differences by race for any adverse clinical or pathological features. However, after weighting each of the 395 cases by their inverse probability of receiving RP, AA men had greater odds of intermediate/high clinical risk (OR=1.62, 95%CI 1.06-2.50), and pathologic Gleason grade (OR=1.86, 95%CI 1.16-2.99). Conclusions: In the current dataset, treatment selection bias nullified the associations between race and adverse clinical and pathological characteristics, in multivariate adjusted models. After applying IPW, our data support an association between AA race and adverse clinical and pathological findings among men treated with RP. Our results suggest that, if unaddressed, treatment selection bias may obscure estimated disparities between AA and W PCa patients, and that the use of marginal structural modeling may benefit cancer risk factor analyses utilizing treatment series datasets. Citation Format: Russell B. McBride, Carlos Cordon-Cardo, Benjamin A. Rybicki. Race and aggressive prostate cancer: Resolving bias introduced by treatment selection. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A08.

Effects of dietary supplementation with probiotic CS-A on performance in broiler chickens

As alternatives to antibiotics, probiotics, enzymes, organic acids, oligosaccharides, antioxidants, and other functional materials are actively being explored. Probiotics include live beneficial microorganisms that colonize the intestinal tract and competitively inhibit the attachment and growth of harmful microbes. Probiotics also increase feed efficiency by assisting in nutrient absorption and digestion. The present study was carried out to evaluate the effect of a new probiotic, CS-A, as a dietary supplement of a fermented product on growth performance, feed intake, and feed conversion efficiency in broiler chickens, and to evaluate its value as an alternative for antibiotics used as a feed additive. Antibacterial and anti-inflammatory effects of CS-A were investigated in vitro and in vivo the effects of a constant concentration of supplemented CS-A on growth rate and feed efficiency were evaluated. As well, the safety of CS-A was assessed by the examination of common symptoms and mortality. Determination of minimal inhibitory concentration revealed an excellent antibacterial effect of CS-A. Cytotoxicity was low and the effective concentration of CS-A produced anti-inflammatory effects. Supplementation with 0.1% CS-A produced a feed efficiency score of 1.84 in broilers, compared to 2.00 in the control group. There were no adverse clinical findings, necropsy findings, hematology, and altered serum biochemistry parameters, and no mortality. Thus CS-A is concluded to be safe and effective as a feed additive.

Intestinal Absorption of Lipid Emulsion in Premature Infants: A Pilot Study

Background: Adequate nutritional intake is essential in the very-low-birth-weight infant, but difficult to achieve in the first few postnatal days. Can lipids be given enterally in the first few days of life in sick preterm infants? Objective: To determine tolerance and absorption of lipid emulsion when fed enterally to very-low-birth-weight infants. Design/Methods: Infants had a birth weight <1,500 g, an appropriate weight for gestational age, and were receiving parenteral nutrition. We performed a progressive series of studies, enrolling 5 infants in each group. Group 1 infants were fed enteral lipid emulsion at 1 g/kg/day for 4 days, starting when 60 ml/kg/day of breast milk was tolerated enterally. Simultaneously, a matched control group which received no oral lipid emulsion was enrolled. We then enrolled group 2 infants who were fed 3 g/kg/day with the same protocol as group 1. Group 3 infants were fed enteral lipid emulsion starting in the first 72 h of life. The infants were fed 1, 2 and 3 g/kg/day subsequently for 48 h each. Fat absorption was measured. Results: Gestational age was 24.6–30.8 weeks and birth weight was 620–1,400 g. One infant (group 1) developed necrotizing enterocolitis 1 week after the study. There were no other adverse clinical findings. On average, enteral lipid emulsion was started on day 8 of life in groups 1 and 2, and on day 2 in group 3. The intestinal lipid absorption was 93.6% (min. = 76%). There was no difference in fat absorption between the 4 groups (p > 0.05). Conclusions: Lipid emulsions are an isotonic high-calorie source which can be given safely enterally instead of intravenously in the immediate neonatal period of very-low-birth-weight infants without clinical adverse effects and with almost complete absorption. There are potential advantages to oral administration of a lipid emulsion starting in early life which require further investigation.

The red blood cell storage lesion: a method to the madness

The red blood cell storage lesion: a method to the madness

Increased levels of cardiac troponin-T in outpatients with heart failure and preserved systolic function are related to adverse clinical findings and outcome

The implications of increased levels of cardiac troponin T in congestive heart failure with preserved systolic function have been poorly evaluated. We hypothesized that its presence might be related to disease severity and prognosis in this setting. Clinical, echocardiographic, 6-min walking test and laboratory data were prospectively obtained in 69 congestive heart failure outpatients with ejection fraction > or = 40%. Serial blood samples were assayed for cardiac troponin T with a third-generation immunoassay and values > or = 0.02 ng/ml were considered abnormal. Abnormal cardiac troponin T levels in at least one sample were found in 27 patients (39%, group 1). These patients were older (71.7 +/- 11 vs. 63 +/- 12.4 years, P = 0.002); more frequently hospitalized during the previous year (63 vs. 26.2%, P = 0.003), had lower systolic blood pressure (129.3 +/- 19.6 vs. 140.4 +/- 23.5 mmHg, P = 0.04), but had similar proportion of ischemic etiology (55.6 vs. 42.9%, P = 0.21) than those with normal cardiac troponin T (group 2). In groups 1 and 2, the functional class was 2.8 +/- 0.8 and 2.1 +/- 0.9 (P = 0.03), and the distance covered in 6 min was 339 +/- 100 and 386 +/- 103 m (P = 0.05), respectively. In groups 1 and 2, the 18-month congestive heart failure hospitalization-free survival was 22 and 87%, respectively (log-rank test P = 0.0003). In a Cox-proportional hazard model, functional class III-IV (hazard ratio = 5.21, 95% confidence interval: 1.43-18.96) and myocardial injury (hazard ratio = 5.51, confidence interval: 1.58-19.24) were independently associated with prognosis. Increased levels of cardiac troponin T were detected in one out of three congestive heart failure outpatients with preserved systolic function and correlated with clinical measures of disease severity and poor outcome. These findings suggest a link between ongoing myocardial injury and progressive impairment in congestive heart failure despite preserved systolic function.

Korrekte Voraussage eines sehr guten Outcomes nach Schädel-Hirn-Trauma durch multimodale EP bei klinisch und neuroradiologisch infaust erscheinendem Befund

Unusual positive outcome of severe skull-brain trauma with epidural bleeding and consecutive subtotal supratentorial hemiation is presented. Despite unfavourable clinical and neuroradiological findings, repeatedly measured SEPs consistently showed electric scalp potentials. Early acustically evoced potentials also always showed all 5 peaks. This enabled a prediction of positive cerebral outcome. The slow recovery of initial prolonged cortical SEPs preceeded clinical recovery. Multimodal evoked potentials enable us, inspite of, adverse clinical findings, to predict a promising outcome correctly. SEP can be used as easily implemented, quickly learned and non-invasive standard monitoring of severe trauma of the CNS.

Cystic fibrosis gene therapy trials and tribulations

Cystic fibrosis (CF) has long been seen as a candidate for treatment by gene therapy. Reasons for this include: the genetics of CF are simple; it is an autosomal recessive disorder caused by mutations in a single gene, cystic fibrosis transmembrane conductance regulator (CFTR); only symptomatic treatments are currently available; the lung, the principal organ affected by CF, is accessible; and less than 100% gene transfer might still modulate the disease process. The cloning of the CFTR gene in 1989 led rapidly to clinical studies testing gene therapy for CF, but even the potential for a therapeutic benefit using this approach has proven somewhat harder to achieve than was perhaps initially foreseen.Over the past eight years, approximately 12 independent CF gene-therapy clinical trials have been reported, testing different delivery systems, target sites and routes of administration and assay systems. These studies have described variable degrees of gene transfer, functional correction, and adverse clinical findings. To add to this list are two new clinical studies that, although still not giving clear guidance as to an optimal approach, do continue to stimulate hope for gene transfer as a therapeutic approach for CF. They also demonstrate the problems that have beset researchers trying to move this technology from the laboratory to the clinic. Joseph et al.1xAerosol and lobar administration of a recombinant adenovirus to individuals with cystic fibrosis. I. Methods, safety, and clinical implications. Joseph, P.M. et al. Hum. Gene Ther. 2001; 12: 1369–1382Crossref | PubMed | Scopus (62)See all References1 and Perricone etal.2xAerosol and lobar administration of a recombinant adenovirus to individuals with cystic fibrosis. II. Transfection efficiency in airway epithelium. Perricone, M.A. et al. Hum. Gene Ther. 2001; 12: 1383–1394Crossref | PubMed | Scopus (54)See all References2 describe a multi-center clinical trial that assessed an adenoviral vector expressing the CFTR gene administered by bronchoscopy and/or aerosol. Rutz et al.3xA clinical inflammatory syndrome attributable to aerosolized lipid–DNA administration in cystic fibrosis. Ruiz, F.E. et al. Hum. Gene Ther. 2001; 12: 751–761Crossref | PubMed | Scopus (125)See all References3 report on a clinical trial assessing an aerosolized complex of plasmid DNA encoding the CFTR gene and a cationic lipid. Both studies report the presence of vector-derived CFTR mRNA, but only in a limited number (∼30–60%) of respiratory epithelial brushing samples available for testing. Interestingly, Perricone et al.2xAerosol and lobar administration of a recombinant adenovirus to individuals with cystic fibrosis. II. Transfection efficiency in airway epithelium. Perricone, M.A. et al. Hum. Gene Ther. 2001; 12: 1383–1394Crossref | PubMed | Scopus (54)See all References2 estimated that the maximum of percentage of cells positive for the CFTR adenovirus vector was less than or equal to 2.4%; cell culture experiments have estimated that at least 5% of an epithelial cell layer must express CFTR to obtain a functional effect.These studies also demonstrate an important clinical problem that has been noted in some, but not all, previous trials: a transient inflammatory response (characterized by muscle and joint pain and fever) against the gene delivery vehicle in a significant proportion of individuals. So, is there still hope for CF gene therapy? Overall, yes; gene transfer has been clearly demonstrated in most of the trials conducted over the past few years and in these most recent studies, but it is likely that a significant improvement in gene-transfer efficiency will be needed in pre-clinical studies before new trials will be initiated.

Sudden death and its relation to QT-interval prolongation after acute myocardial infarction: Two-year follow-up

Risk of sudden death was assessed in 533 patients who survived 10 days after acute myocardial infarction (AMI) and were followed for up to 24 months (mean 18) in the Multicenter Investigation of the Limitation of Infarct Size. Analysis of clinical and laboratory variables measured before hospital discharge revealed that the QT interval, either corrected (QTc) or uncorrected for heart rate, did not contribute significantly to prediction of subsequent sudden death or total mortality. In this population, frequent ventricular premature complexes (more than 10 per hour) on ambulatory electrocardiographic monitoring and left ventricular (LV) dysfunction (radionuclide LV ejection fraction of 0.40 or less) identify patients at high risk of sudden death. In patients with these adverse clinical findings, the QTc was 0.468 ± 0.044 second among those who died suddenly and 0.446 ± 0.032 second in survivors, and was not statistically significant as an additional predictor of sudden death. Consideration of the use of type I antiarrhythmic agents, digoxin, presence of U waves and correction for intraventricular conduction delay did not alter these findings. Although QT-interval prolongation occurs in some patients after acute myocardial infarction, reduced LV ejection fraction and frequent ventricular premature complexes are the most important factors for predicting subsequent sudden death in this patient population.