Resilience and health-related quality of life in patients with pulmonary diseases receiving ambulatory oxygen therapy

Background: Pulmonary diseases affect health-related quality of life (HRQoL), but there are few data on patients' adaptation to a serious illness. This study assessed resilience and its associations with HRQoL, life satisfaction, anxiety and depression in patients with pulmonary diseases receiving ambulatory oxygen therapy. Methods: In this prospective cohort study, we enrolled 42 patients with pulmonary diseases receiving ambulatory oxygen therapy. The patients completed the following questionnaires at baseline and after one and three months; the Resilience Scale-25, the Life Satisfaction Scale-4, the 15D instrument of HRQoL, the Hospital Anxiety and Depression Scale (HADS) and the Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST 2.0). To compare HRQoL, we recruited age- and gender-matched controls from the general population (n = 3574). The primary outcome was the proportion of patients with low resilience. Results: Half (42-48%) of the patients had low resilience, which was correlated with low HRQoL, low levels of life satisfaction and higher levels of anxiety and depression. Patients had very low HRQoL compared to controls. Dissatisfaction with life increased during the 3-months follow-up, but only a few patients had anxiety or depression. Patient satisfaction with assistive technology was high; the median QUEST 2.0 score (scale 1-5) was 4.00 at baseline, 3.92 at one month and 3.88 at three months. Conclusions: Resilience was low in half of the patients with pulmonary diseases receiving ambulatory oxygen therapy. Higher resilience was positively correlated with HRQoL and life satisfaction and negatively correlated with anxiety and depression.Peer reviewe

Maturation of Oxycodone Pharmacokinetics in Neonates and Infants : a Population Pharmacokinetic Model of Three Clinical Trials

Purpose The aim of the current population pharmacokinetic study was to quantify oxycodone pharmacokinetics in children ranging from preterm neonates to children up to 7 years of age. Methods Data on intravenous or intramuscular oxycodone administration were obtained from three previously published studies (n = 119). The median [range] postmenstrual age of the subjects was 299 days [170 days-7.8 years]. A population pharmacokinetic model was built using 781 measurements of oxycodone plasma concentration. The model was used to simulate repeated intravenous oxycodone administration in four representative infants covering the age range from an extremely preterm neonate to 1-year old infant. Results The rapid maturation of oxycodone clearance was best described with combined allometric scaling and maturation function. Central and peripheral volumes of distribution were nonlinearly related to bodyweight. The simulations on repeated intravenous administration in virtual patients indicated that oxycodone plasma concentration can be kept between 10 and 50 ng/ml with a high probability when the maintenance dose is calculated using the typical clearance and the dose interval is 4 h. Conclustions Oxycodone clearance matures rapidly after birth, and between-subject variability is pronounced in neonates. The pharmacokinetic model developed may be used to evaluate different multiple dosing regimens, but the safety of repeated doses should be ensured.Peer reviewe

Resilience, pain, and health-related quality of life in gynecological patients undergoing surgery for benign and malignant conditions : a 12-month follow-up study

Background Gynecological surgery has many impacts on women's physical and mental health, and efforts to improve recovery from surgery are constantly under evaluation. Resilience is an ability to overcome stressors and adversities, such as traumas and surgeries. This study aimed to explore patients' resilience and psychological symptoms in relation to recovery, health-related quality of life (HRQoL), and pain one year after gynecological surgery. Methods In a prospective cohort study, we enrolled consecutive elective gynecologic surgery patients who completed questionnaires before and at one year after surgery: the Resilience Scale-25, the 15D instrument of HRQoL (15D), the Life Satisfaction Scale-4, and the Hospital Anxiety and Depression Scale. Their mean 15D scores were compared to those of an age-matched sample of women from the general Finnish population (n = 2743). Results We enrolled 271 women who underwent gynecological surgery due to benign (n = 190) and malignant (n = 81) diagnoses. Resilience was equally high in women with benign and malignant diagnoses at both time points. Higher resilience associated with less pain, analgesic use, and better pain relief from the use of pain medication at 12 months after surgery. Pain intensity was similar in the two groups, but patients with benign diseases had less pain at 12 months than before surgery. Before surgery, patients' HRQoL was worse than that of the general population, but at 12 months the mean HRQoL of patients with benign diseases had improved to the same level as that in the general population but had decreased further in patients with malignant diseases. Anxiety was higher and life satisfaction was lower in patients with malignant diseases before surgery. At 12 months, anxiety had decreased in both groups, and life satisfaction had increased in patients with malignant diseases. Depression was similarly low in both groups and time points. Conclusions Resilience correlated with less pain one year after surgery. After surgery, HRQoL improved in patients with benign diseases but deteriorated in patients with malignant diseases. Patients with low resilience should be identified during preoperative evaluation, and health care professionals should give these patients psychological support to enhance their resilience. Trial Registration ClinicalTrials.gov; registered October 29, 2019; identifier: NCT04142203; retrospectively registered.Peer reviewe

Central nervous system distribution of buprenorphine in pregnant sheep, fetuses and newborn lambs after continuous transdermal and single subcutaneous extended-release dosing

Buprenorphine is used during pregnancy for the treatment of opioid use disorder. Limited data exist on the central nervous system (CNS) permeation and distribution, and on the fetal exposure to buprenorphine. The aim of our study was to determine the extent of buprenorphine distribution to CNS in the pregnant sheep, and their fetus at steady-state, and their newborn lambs postdelivery, using three different dosing regimens. Twenty-eight pregnant ewes in late gestation received buprenorphine via 7-day transdermal patch releasing buprenorphine 20 mu g/h (n=9) or 40 mu g/h (n=11), or an extended-release 8 mg/week subcutaneous injection (n=8). Plasma, cerebrospinal fluid, and CNS tissue samples were collected at steady-state from ewes and fetuses, and from lambs 0.33 - 45 hours after delivery. High accumulation of buprenorphine was observed in all CNS tissues. The median CNS/plasma concentration-ratios of buprenorphine in different CNS areas ranged between 13 and 50 in the ewes, and between 26 and 198 in the fetuses. In the ewes the CNS/plasma-ratios were similar after the three dosing regimens, but higher in the fetuses in the 40 mu g/h dosing group, medians 65 - 122, than in the 20 mu g/h group, medians 26 - 54. The subcutaneous injection (theoretical release rate 47.6 mu g/h) produced higher concentrations than observed after 40 mu g/h transdermal patch dosing. The median fetal/maternal concentration-ratios in different dosing groups ranged between 0.21 and 0.54 in plasma, and between 0.38 and 1.3 in CNS tissues, respectively, with the highest ratios observed in the spinal cord. Buprenorphine concentrations in the cerebrospinal fluid were 8 - 13 % of the concurrent plasma concentration in the ewes and 28 % in the fetuses. Buprenorphine was quantifiable in the newborn lambs' plasma and CNS tissues two days postdelivery. Norbu-prenorphine was analyzed from all plasma, cerebrospinal fluid, and CNS tissue samples but was nondetectable or below the LLOQ in most. The current study demonstrates that buprenorphine accumulates into CNS tissues at much higher concentrations than in plasma in pregnant sheep, fetuses, and their newborn lambs even 45 hours after delivery.Peer reviewe

Novel renal markers for the assessment of renal integrity in patients undergoing knee arthroplasty - a pilot study

The feasibility of novel kidney injury biomarkers in consecutive patients having total knee arthroplasty with local infiltration analgesia was evaluated.\nWe enrolled 30 patients scheduled for elective unilateral total knee arthroplasty. Paired plasma and urine samples were taken before surgery and at 4 h, 24 h and 48 h after surgery to measure creatinine, cystatin C, neutrophil gelatinase associated lipocalin, kidney injury molecule-1, interleukin-18 and liver-type fatty acid-binding protein.\nAt baseline, 13 subjects had normal kidney function, 15 had mild and two had moderate kidney failure evaluated by calculated glomerular filtration rate. None of the subjects had all measured novel renal markers below proposed cut-off concentrations. Altogether 28/30 subjects had one (n = 3), two (n = 7) or three (n = 18) plasma neutrophil gelatinase associated lipocalin values above normal. In seven of these 28 subjects plasma creatinine, calculated glomerular filtration rate and plasma cystatin C were within the reference values. Five subjects had a low urine output, < 0.5 mL/h, indicating transient acute kidney injury, four of these had high plasma neutrophil gelatinase associated lipocalin and one high plasma cystatin C.\nIn the present study plasma neutrophil gelatinase associated lipocalin was elevated in most subjects with total knee arthroplasty and local infiltration analgesia as a marker of possible renal proximal tubular injury. Five subjects had transient low urine output, but none developed renal deterioration requiring treatment.\nBACKGROUND\nMETHODS\nRESULTS\nCONCLUSION

Nifedipine disturbs fetal cardiac function during hypoxemia in a chronic sheep model at near term gestation

BACKGROUND: Nifedipine is a widely used drug in pregnancies complicated by maternal hypertensive disorders that can be associated with placental insufficiency and fetal hypoxemia. The evidence regarding fetal myocardial responses to nifedipine in hypoxemia is limited. OBJECTIVE: We hypothesized that nifedipine would not impair fetal sheep cardiac function under hypoxemic environment. In particular, we investigated the effects of nifedipine on fetal ventricular functional parameters and cardiac output. STUDY DESIGN: A total of 21 chronically instrumented fetal sheep at 122 to 134 gestational days (term, 145 days) were included in this study. Fetal cardiac function was evaluated by measuring global longitudinal strain, indices describing ventricular systolic and diastolic function, and cardiac outputs using two-dimensional speckle tracking and tissue and spectral pulsed-wave Doppler echocardiography. Fetal carotid artery blood pressure and blood gas values were invasively monitored. After baseline data collection, fetal hypoxemia was induced by maternal hyperoxygenation. After hypoxemia phase data collection, 9 fetuses received nifedipine infusion, and 12 fetuses received saline infusion. Data were collected 30 and 120 minutes after the infusion was started. After 120 minutes of data collection, maternal and fetal oxygenation were normalized, and normoxemia phase data were collected, while infusion was continued. RESULTS: Hypoxemia decreased fetal carotid artery mean arterial pressure from 40 (8) mm Hg to 35 (8) mm Hg (P CONCLUSION: In hypoxemic fetus, nifedipine impaired right ventricular function and reduced its cardiac output. The detrimental effects of nifedipine on fetal right ventricular function were abolished, when normoxemia was restored. Our findings suggest that in a hypoxemic environment nifedipine triggers detrimental effects on fetal right ventricular function.Peer reviewe

Effects of nifedipine and sildenafil on placental hemodynamics and gas exchange during fetal hypoxemia in a chronic sheep model

Introduction We hypothesized that nifedipine and sildenafil would have no detrimental effects on placental hemodynamics and gas exchange under fetal hypoxemia. Methods In 33 chronically instrumented fetal sheep, placental volume blood flow (QPlac) and umbilical artery (UA) vascular impedance were measured by Doppler ultrasonography. Fetal carotid artery blood pressure and blood gas values were monitored. After baseline data collection, maternal and fetal hypoxemia were induced. Following hypoxemia phase data collection, 12 fetuses received sildenafil and 9 fetuses nifedipine infusion, and 12 fetuses served as controls receiving saline infusion. Data were collected 30 and 120 min after infusion was started. Then maternal oxygenation was normalized and normoxemia phase data were collected, while infusion was continued. Results Hypoxemia significantly decreased fetal pO2 and blood pressure. In the sildenafil group at 30- and 120-min hypoxemia + infusion phases, fetal blood pressure and QPlac were significantly lower and pCO2 higher than at baseline without returning to baseline level at normoxemia + infusion phase. In hypoxemia, nifedipine did not affect fetal blood pressure or placental hemodynamics. Both in the sildenafil and nifedipine groups, fetal pO2 remained significantly lower at normoxemia + infusion phase than in the control group. Umbilical artery vascular impedance did not change during the experiment. Discussion In fetal hypoxemia, sildenafil had detrimental effects on placental hemodynamics that disturbed placental gas exchange. Nifedipine did not alter placental hemodynamics in hypoxemia but disturbed placental gas exchange upon returning to normoxemia. Umbilical artery vascular impedance did not reflect alterations in placental hemodynamics.Peer reviewe

Effect of Sildenafil on Pulmonary Circulation and Cardiovascular Function in Near-Term Fetal Sheep During Hypoxemia

Sildenafil is a potential new treatment for placental insufficiency in human pregnancies as it reduces the breakdown of vasodilator nitric oxide. Pulmonary vasodilatation is observed in normoxemic fetuses following sildenafil administration. Placental insufficiency often leads to fetal hypoxemia that can cause pulmonary vasoconstriction and fetal cardiac dysfunction as evidenced by reduced isovolumic myocardial velocities. We tested the hypotheses that sildenafil, when given directly to the hypoxemic fetus, reverses reactive pulmonary vasoconstriction, increases left ventricular cardiac output by increasing pulmonary venous return, and ameliorates hypoxemic myocardial dysfunction. We used an instrumented sheep model. Fetuses were made hypoxemic over a mean (standard deviation) duration of 41.3 (9.5) minutes and then given intravenous sildenafil or saline infusion. Volume blood flow through ductus arteriosus was measured with an ultrasonic transit-time flow probe. Fetal left and right ventricular outputs and lung volume blood flow were calculated, and ventricular function was examined using echocardiography. Lung volume blood flow decreased and the ductus arteriosus volume blood flow increased with hypoxemia. There was a significant reduction in left ventricular and combined cardiac outputs during hypoxemia in both groups. Hypoxemia led to a reduction in myocardial isovolumic velocities, increased ductus venosus pulsatility, and reduced left ventricular myocardial deformation. Direct administration of sildenafil to hypoxemic fetus did not reverse the redistribution of cardiac output. Furthermore, fetal cardiac systolic and diastolic dysfunction was observed during hypoxemia, which was not improved by fetal sildenafil treatment. In conclusion, sildenafil did not improve pulmonary blood flow or cardiac function in hypoxemic sheep fetuses.Peer reviewe

How do different extracorporeal circulation systems affect metoprolol bioavailability in coronary artery bypass surgery patients

Purpose Cardiac surgery and conventional extracorporeal circulation (CECC) impair the bioavailability of drugs administered by mouth. It is not known whether miniaturized ECC (MECC) or off-pump surgery (OPCAB) affect the bioavailability in similar manner. We evaluated the metoprolol bioavailability in patients undergoing CABG surgery with CECC, MECC, or having OPCAB. Methods Thirty patients, ten in each group, aged 44-79 years, scheduled for CABG surgery were administered 50 mg metoprolol by mouth on the preoperative day at 8-10 a.m. and 8 p.m., 2 h before surgery, and thereafter daily at 8 a.m. and 8 p.m. Blood samples were collected up to 12 h after the morning dose on the preoperative day and on first and third postoperative days. Metoprolol concentration in plasma was analyzed using liquid chromatography-mass spectrometry. Results The absorption of metoprolol was markedly reduced on the first postoperative day in all three groups, but recovered to the preoperative level on the third postoperative day. The geometric means (90% confidence interval) of AUC(0-12) on the first and third postoperative days versus the preoperative day were 44 (26-74)% and 109 (86-139)% in the CECC-group, 28 (16-50)% and 79 (59-105)% in the MECC-group, and 26 (12-56)% and 96 (77-119)% in the OPCAB-group, respectively. Two patients in the CECC-group and two in the MECC-group developed atrial fibrillation (AF). The bioavailability and the drug concentrations of metoprolol in patients developing AF did not differ from those who remained in sinus rhythm. Conclusion The bioavailability of metoprolol by mouth was markedly reduced in the early phase after CABG with no difference between the CECC-, MECC-, and OPCAB-groups.Peer reviewe