A pilot study of inhaled nitric oxide in preterm infants treated with nasal continuous positive airway pressure for respiratory distress syndrome

Objective To explore the acute effects of inhaled nitric oxide (iNO) on oxygenation, respiratory rate, and CO₂ levels in spontaneously breathing preterm infants treated with nasal continuous positive airway pressure (nCPAP) for moderate respiratory distress syndrome (RDS).Design and setting Randomized, prospective, double-blind, cross-over study in the neonatal intensive care units of a university hospital.Patients 15 infants treated for RDS, with a median gestational age of 32 weeks (27–36), birth weight 1940 g (1100–4125), and postnatal age at the beginning of study 23 h (3–91). nCPAP pressure was kept constant at 4.3 cmH₂O (3.4–5.1).Interventions We examined effects on gas exchange and vital signs during a 30-min exposure to 10 ppm iNO or placebo gas (nitrogen).Results Before administering test gases the baseline arterial to alveolar oxygen tension ratio (aAPO₂) was 0.19±0.06. aAPO₂ remained unchanged during placebo but increased to 0.22±0.05 (+20%) during iNO exposure. Respiratory rate and arterial carbon dioxide tension remained unchanged, as did heart rate, blood pressure, and methemoglobin. Follow-up at 30 days of age showed no deaths, delayed morbidity, or need for supplemental oxygen.Conclusions Adding 10 ppm nitric oxide to nasal CPAP treatment in preterm infants suffering from RDS results in a moderate but statistically significant improvement in oxygenation, with no effect on respiratory drive or systemic circulatory parameters.     

Life-Time Adversities,Reported Thirteen Years After a Suicide Attempt: Relationship to Recovery, 5HTTLPR Genotype,and Past and Present Morbidity

In this study, we investigated how adversities related to past and present morbidity, and genotype. Forty-two, suicide attempters and 22 matched control patients were followed-up after 13 years. Life-time adversities were explored in an interview, and the patients were reassessed psychiatrically. The serotonin-transporter-linked promotor region (5-HTTLPR) was typed. More adversities were reported by suicide attempters than controls, and by still-ill than recovered suicide attempters. Adversities reported at follow-up were related to psychiatric morbidity at follow-up, but not to morbidity 13 years earlier. The 5-HTTLPR, genotype was associated with reported adversities, but not chances of recovery. Adversities potentially affected chronic morbidity. 5-HTTLPR genotype did not affect long-term recovery.     

A new application of pre-normalized principal component analysis for improvement of image quality and clinical diagnosis in human brain PET studies--clinical brain studies using [11C]-GR205171, [11C]-L-deuterium-deprenyl, [11C]-5-Hydroxy-L-Tryptophan, [11C]-L-DOPA and Pittsburgh Compound-B

Principal component analysis (PCA) is one of the most applied multivariate image analysis tool on dynamic Positron Emission Tomography (PET). Independent of used reconstruction methodologies, PET images contain correlation in-between pixels, correlations in-between frame and errors caused by the reconstruction algorithm including different corrections, which can affect the performance of the PCA. In this study, we have investigated a new approach of application of PCA on pre-normalized, dynamic human PET images. A range of different tracers have been used for this purpose to explore the performance of the new method as a way to improve detection and visualization of significant changes in tracer kinetics and to enhance the discrimination between pathological and healthy regions in the brain. We compare the new results with the results obtained using other methods. Images generated using the new approach contain more detailed anatomical information with higher quality, precision and visualization, compared with images generated using other methods.     

Feasibility of spinal cord stimulation in angina pectoris in patients with chronic pacemaker treatment for cardiac arrhythmias

Spinal cord stimulation (SCS) has been used since 1985 as additional symptom-relieving treatment for patients with severe angina pectoris despite optimal conventional medical and invasive treatment. SCS has antiischemic effects and is safe and effective in long-term use. Several patients with coronary artery disease also suffer from disorders that necessitate the use of a cardiac permanent pacemaker (PPM). The combination of SCS and PPM has previously been considered hazardous because of possible false inhibition of the PPM. To assess if thoracic SCS and PPM can be safely combined in patients with refractory angina pectoris, 18 patients treated with both SCS and PPM were tested. The PPM settings were temporarily modified to increase the probability of interference, while the SCS intensity (used in bipolar mode) was increased to the maximum level tolerated by the patient. Any sign of inhibition of the ventricular pacing was recorded by continuous ECG monitoring. With the aid of a questionnaire, symptoms of interference during long-term treatment were evaluated. No patient had signs of inhibition during the tests. Reprogramming of the pacemaker because of the test results was not needed in any of the patients. The long-term follow-up data revealed no serious events. This study indicates that bipolar SCS and PPM can be safely combined in patients with refractory angina pectoris. However, individual testing is mandatory to ascertain safety in each patient. A testing procedure for patients in need of SCS and PPM is suggested in this article.     

Population pharmacokinetics of rifampin in pulmonary tuberculosis patients, including a semimechanistic model to describe variable absorption

This article describes the population pharmacokinetics of rifampin in South African pulmonary tuberculosis patients. Three datasets containing 2,913 rifampin plasma concentration-time data points, collected from 261 South African pulmonary tuberculosis patients aged 18 to 72 years and weighing 28.5 to 85.5 kg and receiving regular daily treatment that included administration of rifampin (450 to 600 mg) for at least 10 days, were pooled. A compartmental pharmacokinetic model was developed using nonlinear mixed-effects modeling. Variability in the shape of the absorption curve was described using a flexible transit compartment model, in which a delay in the onset of absorption and a gradually changing absorption rate were modeled as the passage of drug through a chain of hypothetical compartments, ultimately reaching the absorption compartment. A previously described implementation was extended to allow its application to multiple-dosing data. The typical population estimate of oral clearance was 19.2 liters x h(-1), while the volume of distribution was estimated to be 53.2 liters. Interindividual variability was estimated to be 52.8% for clearance and 43.4% for volume of distribution. Interoccasional variability was estimated for CL/F (22.5%) and mean transit time during absorption (67.9%). The use of single-drug formulations was found to increase both the mean transit time (by 104%) and clearance (by 23.6%) relative to fixed-dose-combination use. A strong correlation between clearance and volume of distribution suggested substantial variability in bioavailability, which could have clinical implications, given the dependence of treatment effectiveness on exposure. The final model successfully described rifampin pharmacokinetics in the population studied and is suitable for simulation in this context.     

Outcome and determinants of failure to complete primary R-CHOP treatment for reasons other than non-response among patients with diffuse large B-cell lymphoma

Patients with diffuse large B-cell lymphoma (DLBCL) who fail to complete planned treatment with R-CHOP due to toxicity are sparsely described. We investigated the extent of failure to complete treatment (six cycles or more, or three cycles + RT for patients with stage I disease) with R-CHOP for reasons unrelated to non-response, the determinants of such failure and the outcome among these patients. Three thousand one hundred and forty nine adult DLBCL patients who started primary treatment with R-CHOP were identified through the Swedish lymphoma register 2007-2014. Of these, 147 (5%) stopped prematurely after 1-3 cycles of R-CHOP for reasons unrelated to non-response, 168 (5%) after 4-5 cycles and 2639 patients (84%) completed planned treatment. Additionally, 195 (6%) patients did not complete treatment due to non-response or death before treatment end. In a multivariable logistic regression model, age > 75 years, poor performance status, extranodal disease and Charlson Comorbidity Index ≥1 were significantly associated with failure to complete planned R-CHOP treatment for other reasons than non-response. Non-completion of treatment strongly correlated with survival. Five-year overall survival for patients who received 1-3 cycles was 26% (95% CI: 19%-33%), 49% (95% CI: 41%-57%) for 4-5 cycles and 76% (74%-77%) for patients who completed treatment. Failure to complete planned R-CHOP treatment is an important clinical issue associated with inferior survival. Old age and poor performance status most strongly predict such failure. These results indicate a need for improved treatment tailoring for patients with certain baseline demographics to improve tolerability and chance for treatment completion.     

Item Response Model Adaptation for Analyzing Data from Different Versions of Parkinson’s Disease Rating Scales

Pharmaceutical Research - Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel technique delivering drugs into the abdominal cavity as an aerosol under high pressure. It is...