Ropivacaine pharmacokinetics in the arterial and venous pools after ultrasound-guided continuous thoracic paravertebral nerve block.

Background and Aims: Although thoracic paravertebral blockade (TPVB) is employed in thoracic surgery to ensure satisfactory postoperative analgesia, large doses of anesthetics are required and manifestations of local anesthetic systemic toxicity (LAST) may appear. Currently, there are limited data on the pharmacokinetics of ropivacaine after continuous TPVB. The aim of this prospective study was to investigate ropivacaine kinetics, in the arterial and venous pools, after continuous TPVB and assess the risk of LAST. Material and Methods: Immediately after induction of general anesthesia, an ultrasound-guided continuous TPVB at T5 or T6 or T7 thoracic level was performed in 18 adult patients subjected to open thoracotomy. A 25-ml single bolus injection of ropivacaine 0.5% was administered through thoracic paravertebral catheter, followed by a 14 ml/h continuous infusion of ropivacaine 0.2% starting at the end of surgery. Quantification of total ropivacaine concentrations was performed using a validated high-performance liquid chromatography method. Population pharmacokinetic models were developed separately for arterial and venous ropivacaine data. Results: The best model was one-compartment disposition with an additional pre-absorption compartment corresponding to thoracic paravertebral space. Gender had a significant effect on clearance, with females displaying lower elimination than males. Some patients had ropivacaine concentrations above the toxic threshold, but none displayed evidence of LAST. Continuous thoracic paravertebral nerve blocks provided adequate postoperative analgesia. Conclusion: Ropivacaine doses at the upper end of clinical use (800 mg/d) did not inflict the manifestations of LAST and provided adequate postoperative pain control. Pharmacokinetic models were developed, and the effect of gender was identified.

Pharmacokinetic and pharmacodynamic modeling of levetiracetam: investigation of factors affecting the clinical outcome.

This study aimed to evaluate the pharmacokinetics and pharmacodynamics of oral levetiracetam therapy in drug refractory adult epileptic outpatients, as well as factors affecting them. Concentration-time data were collected at steady state, while seizure recurrence was monitored for 13 months. Non-linear mixed effects modeling was applied, and covariates assessed included weight, height, age, daily dose and creatinine clearance.Plasma concentrations of levetiracetam were best described by a one-compartment pharmacokinetic model (V/F = 34.7 L) with first-order absorption (ka = 0.616 h-1) and clearance (CL/F = 3.26 L/h). Patient's CrCL was found to significantly affect levetiracetam clearance (beta = 0.795). Time to seizure occurrence followed an exponential distribution and the mean time to seizure occurrence was estimated Te = 22.08 days. Seizure rate per month followed a Poisson distribution, while mean seizure rate per month was estimated λ = 1.33. Daily dose significantly affected the mean estimated time to seizure (beta = -2.2) and the mean monthly seizure rate (beta = 2.27) in a reverse way. Using discrete time Markov chains, it was shown that the transition probability from focal seizures to focal to bilateral tonic-clonic is significantly altered in relation to patient's CrCL.Simulations showed that dose should be adjusted in relation to CrCL, while low doses of levetiracetam are more effective for seizure control. Modeling and simulation in every-day clinical practice may provide significant information for the optimization of seizure control using well-known agents.

Ropivacaine, Interleukin-6 and Tumor Necrosis Factor Alpha Plasma Levels during Intermittent Epidural and Continuous Wound Infusion of Ropivacaine for Analgesia after Hysterectomy or Myomectomy: An Observational Study.

BACKGROUND/AIMS: The concentration-time profile of the long-acting local anesthetic ropivacaine after epidural (EP) administration at fixed time intervals or continuous subcutaneous (SC) infusion has not been fully evaluated. The objective of this work was to determine total plasma concentrations of ropivacaine and changes in cytokine interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels during EP and SC. METHODS: In this prospective randomized controlled trial, 18 patients undergoing abdominal hysterectomy or myomectomy were randomly selected to receive ropivacaine either every 6 h via an EP catheter or by continuous wound infusion along the skin incision, after a bolus dose, for 48 h. Total plasma ropivacaine concentrations were measured before the bolus and 2, 4, 8, 24, 48, and 50 h after the bolus using high-performance liquid chromatography-UV and IL-6 and TNF-α levels were measured at 0, 8 and 24 h with ELISA and analyzed statistically. RESULTS: During EP, mean ± SD ropivacaine concentrations were relatively stable up to 50 h postoperatively, that is, 239 ± 89 ng/ml, while during SC, initial concentrations between 2 and 8 h were comparatively lower (101.5 ± 42.9 ng/ml) than 24-50 h concentrations (437.1 ± 206 ng/ml). An increase in IL-6 levels was noted between 0 and 24 h during EP and SC, but TNF-α levels increased slightly, between 0 and 24 h, only during EP. CONCLUSION: Ropivacaine plasma concentrations with both EP and SC were found to be safe throughout the administration time interval. IL-6 levels increased during the same time interval, while TNF levels varied only slightly.

Drug Utilization Patterns and Costs of Erythropoiesis-Stimulating Agents in an Outpatient Setting in Greece.

UNLABELLED: Anemia in the elderly is often related to a higher prevalence of chronic diseases such as chronic kidney failure, arthritis, and malignancy. Erythropoiesis-stimulating agents (ESAs) have been used for years to effectively treat anemia and when used appropriately can substantially improve the health status and quality of life of older adults. Following the 2008 recession in Greece, the government introduced ESA price control restrictions, but no prescribing restrictions, in an effort to reduce drug expenditure. OBJECTIVE: ESA prescribing patterns and treatment costs were analyzed to determine inappropriate or appropriate use of these agents and related health care resources in Greece. METHOD: A retrospective register-based drug utilization study was carried out using data from prescriptions dispensed at the public pharmacy of the largest social insurance fund (IKA-ETAM), for patients receiving ESAs over a six-month period. For each patient, demographic data, ESA dosage regimen, treatment indication and cost, prescriber specialty, and prescription origin were recorded. RESULTS: A total of 14,387 prescriptions from 6,074 patients (median age 74 years) were reviewed. A substantial number of patients (13.5%) were treated for off-label indications, for which the average cost per patient per indication was higher. ESA dosage/frequency of administration varied but was in accordance with recommendations. The percentage of patients who received innovator and biosimilar erythropoietin (EPO) was 88% and 12%, respectively. CONCLUSION: For the optimization of ESA utilization and the reduction of treatment costs, strict ESA prescription monitoring, development of registries, and criteria for off-label indications and biosimilar use in naive patients under the umbrella of risk-sharing agreements should be proposed.

Combined intravenous and intraventricular administration of colistin methanesulfonate in critically ill patients with central nervous system infection.

Colistin pharmacokinetics were prospectively studied after intravenous administration of colistin methanesulphonate in critically ill patients without central nervous system infection (controls, n = 5) and in patients with external ventricular drain-associated ventriculitis after intravenous administration (EVDViv, n = 3) or combined intravenous/intraventricular administration (EVDVcomb, n = 4). Cerebrospinal fluid (CSF)/serum colistin concentration ratios were higher in EVDViv than in control patients (11% versus 7%, P ≤ 0.05) and in EVDVcomb compared to all other patients (P < 0.0001). CSF colistin concentrations above the MIC of 0.5 µg/ml were achieved only in EVDVcomb patients.

Hepatokine Profile in Adolescents with Polycystic Ovary Syndrome: A Case-Control Study.

The current guidelines suggest routine screening for non-alcoholic fatty liver disease (NAFLD) in patients with polycystic ovary syndrome (PCOS). Hepatokines seem to be promising surrogate endpoints for the diagnosis and severity of NAFLD. PCOS has its onset in adolescence and its metabolic sequalae begin during the same period. There are scarce data on the hepatokine profile of adolescent PCOS patients. This case-control study examined the serum profile of the hepatokines sex hormone-binding globulin (SHBG), selenoprotein P, fibroblast growth factor 21 (FGF21), and fetuin A in a sample of adolescent PCOS patients, and their association to metabolic and hormonal parameters. The selenoprotein P and SHBG serum concentrations were significantly decreased in PCOS patients vs. the controls (median (IQR), 2.47 (0.40) vs. 2.66 (0.36) µg/mL, p = 0.025; mean ± SD, 41.71 ± 19.41 vs. 54.94 ± 22.12 nmol/L, p = 0.011, respectively), whereas selenoprotein P was significantly and positively associated with testosterone (r = 0.325, p = 0.007) and the free androgen index (r = 0.361, p = 0.002). The SHBG demonstrated multiple significant negative correlations with adverse metabolic parameters. Among the PCOS patients, the FGF21 concentrations were significantly higher in those with NAFLD, whereas a 1 pg/mL increase in the FGF21 concentration increased the odds of NAFLD diagnosis by liver ultrasound by 1%, suggesting FGF21 as a potential biomarker for hepatic disease in females with PCOS in adolescence. Fetuin A was the least differentiated hepatokine between the PCOS patients and controls with the least associations with metabolic and hormonal parameters.

Colistin pharmacokinetics in intensive care unit patients on continuous venovenous haemodiafiltration: an observational study.

OBJECTIVES: Available data on colistin pharmacokinetics in patients undergoing continuous renal replacement therapy (CRRT) are limited. Our aim was to study colistin pharmacokinetics in critically ill patients treated with colistin methane sulphonate for Gram-negative sepsis and undergoing continuous venovenous haemodiafiltration for acute renal failure. PATIENTS AND METHODS: Three patients were studied. The colistin methane sulphonate dose administered was at the discretion of the attending physician and was in all cases lower than that recommended for individuals with intact renal function. Colistin methane sulphonate was administered intravenously over 30 min, and blood samples were collected from each patient pre- and post-filter for the HPLC determination of colistin levels in serum before infusion, at 10, 60, 120, 240, 360, 480 and 600 min from the end of infusion, and immediately before the next dose. Concurrently, spot samples of effluent from the haemofilter were also collected and analysed. Both colistin total extracorporeal clearance and clearance in the effluent were calculated. RESULTS: Extracorporeal clearance resulted in substantial removal of colistin (43%-59% of total colistin clearance). Total colistin clearance was found to be reduced (varying between 3.3 and 4.5 L/h), compared with patients with normal renal function. Colistin methane sulphonate dosage resulted in clearly suboptimal colistin steady-state concentrations. CONCLUSIONS: In spite of substantial extracorporeal clearance, total colistin clearance was reduced, compared with patients with normal renal function. Colistin adsorption by the haemofilter contributed to its extracorporeal clearance to a large extent. Studies on other patients receiving colistin methane sulphonate and undergoing CRRT are required before more appropriate dosage regimens can be recommended.

Systematic Review and Meta-Analysis of the Efficacy and Safety of Metformin and GLP-1 Analogues in Children and Adolescents with Diabetes Mellitus Type 2.

Diabetes mellitus type 2 (DMT2) is one of the most frequent glucose metabolism disorders, in which serum glucose concentrations are increased. In most cases, changes in lifestyle and diet are considered as the first step in addressing its therapy. If changes in lifestyle and diet fail, drugs, such as metformin, must be added. Lately, apart from metformin or insulin, the FDA has approved the use of glucagon-like peptide-1 (GLP-1) analogues for children and adolescents. Little is known about their efficacy and safety at this young age. The main aim of this systematic review/meta-analysis was to assess the safety and efficacy of metformin and GLP-1 analogues, exenatide and liraglutide, compared with placebos or other antidiabetic drugs used for DMT2 in children and adolescents. Metformin did not seem to demonstrate pharmacologic superiority, while GLP-1 analogues were found superior to placebos. GLP-1 analogues may be considered a useful alternative for the treatment of DMT2 in children and adolescents.

Pharmacokinetic Characteristics of Nebulized Colistimethate Sodium Using Two Different Types of Nebulizers in Critically Ill Patients with Ventilator-Associated Respiratory Infections.

Background: Rising antimicrobial resistance has led to a revived interest in inhaled colistin treatment in the critically ill patient with ventilator-associated respiratory infection (VARI). Nebulization via vibrating mesh nebulizers (VMNs) is considered the current standard-of-care, yet the use of generic jet nebulizers (JNs) is more widespread. Few data exist on the intrapulmonary pharmacokinetics of colistin when administered through VMNs, while there is a complete paucity regarding the use of JNs. Methods: In this study, 18 VARI patients who received 2 million international units of inhaled colistimethate sodium (CMS) through a VMN were pharmacokinetically compared with six VARI patients who received the same drug dose through a JN, in the absence of systemic CMS administration. Results: Surprisingly, VMN and JN led to comparable formed colistin exposures in the epithelial lining fluid (ELF) (median (IQR) AUC0-24: 86.2 (46.0-185.9) mg/L∙h with VMN and 91.5 (78.1-110.3) mg/L∙h with JN). The maximum ELF concentration was 10.4 (4.7-22.6) mg/L and 7.4 (6.2-10.3) mg/L, respectively. Conclusions: Based on our results, JN might be considered a viable alternative to the theoretically superior VMN. Therapeutic drug monitoring in the ELF can be advised due to the observed low exposure, high variability, and appreciable systemic absorption.

A retrospective study on the evaluation of the symptoms, medications and improvement of the quality of life of patients undergoing robotic surgery for gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder requiring lifestyle adaptations and administration of medications. Another approach is the surgical treatment of GERD through laparoscopic or robotic operations. The aim of the present study was to investigate the improvement of symptoms and quality of life of patients with GERD, before and after robotic surgical restoration using the Nissen robotic fundoplication technique. The potential effects of body weight, age and sex, as well as the response to medications and progress over time, were also assessed. A retrospective study was conducted in a tertiary hospital between October 2019 and March 2020. Data were collected and recorded from 144 patients who underwent robotic surgery, using the Nissen fundoplication technique, during the period 2009-2019. All patients involved in this analysis pre-operatively exhibited severe symptoms of heartburn and reflux, as well as poor quality of life. All of these symptoms were re-examined after surgery, and a marked decrease was observed with respect to their frequency and intensity. Improvement was not affected by body mass index, whereas older patients exhibited greater improvement. Women initially experienced more severe symptoms before the surgery, but they appeared to respond as well as the male patients. The long-term beneficial effects of surgery for up to the 10-year period studied were validated. After the robotic surgical rehabilitation, the vast majority of patients overcame the unpleasant symptoms of GERD and stayed off their medications. More than 4/5 of the patients were satisfied after surgery. In conclusion, restoration of GERD, using Nissen robotic fundoplication, led to the minimization of symptoms and to a marked improvement in the quality of life of patients.

Oxidized LDL in human carotid plaques is related to symptomatic carotid disease and lesion instability.

BACKGROUND: Oxidative stress is an important determinant in atherosclerosis development. Various markers of oxidative stress, such as oxidation of low-density lipoprotein (LDL), nitrosative stress, lipid peroxidation, and protein oxidation, have been implicated in the initiation and/or progression of atherosclerosis, but their association with plaque erosion and symptomatic carotid disease has not been fully defined. In addition, certain oxidative markers have been shown in various models to promote plaque remodeling through matrix metalloproteinase (MMP) activation. OBJECTIVE: To perform a global investigation of various oxidative stress markers and assess for potential relationships with destabilization and symptomatic development in human carotid plaques. METHODS: Thirty-six patients undergoing endarterectomy were evaluated and compared with 20 control specimens obtained at the time of autopsy. Differences between stable and unstable plaques, symptomatic and asymptomatic patients, and >or=90% and <90% stenosis were evaluated. Oxidized LDL (ox-LDL), nitrotyrosine (NT), malondialdehyde (MDA), and protein carbonyls (PCs) levels were determined in atheromatic plaques homogenates by corresponding biochemical assays. Immunohistochemical (IHC) analysis was also employed to determine the percentage and topological distribution of cells expressing NT and metalloproteinase-9 (MMP-9) in serial sections from corresponding atheromatic plaques. MMP-9 expression was further verified using Western blot analysis. RESULTS: Ox-LDL was increased in symptomatic patients (P < .05). Also, ox-LDL and NT levels were significantly higher in unstable versus stable carotid plaques (P < .05, respectively). Furthermore, IHC serial section analysis, corroborated by statistical analysis, showed a topological and expressional correlation between NT and MMP-9 (P < .05). MDA and PCs levels, although increased in carotid plaques, did not distinguish stable from unstable carotid plaques as well as symptomatic from asymptomatic patients with various degrees of stenosis. CONCLUSION: All types of investigated oxidative stress markers were significantly increased in human carotid plaques, but only ox-LDL levels were associated with clinical symptoms, while peroxynitrite products and MMP-9 were specifically related to plaque instability.

Do we need to adopt antifungal stewardship programmes?

Background: Although antimicrobial stewardship programmes are one of the highest priorities in healthcare systems and many articles have been published, few refer to the implementation of antifungal stewardship and highlight specific points on which efforts should be focused. Objective: To assess the percentage of patients with confirmed candidaemia in whom de-escalation was conducted, and the economic impact of step-down or step-up antifungal therapy. Additionally, we attempted to estimate the potential increase in drug minimum inhibitory concentrations or to detect resistant strains of Candida species. Methods: We selected, retrospectively, patients who had received systemic antifungal therapy between 2011 and 2016 for documented candidaemia. Statistical analysis and diagrams were used to assess the results. Results: Of 157 patients with confirmed candidaemia, 58 received azoles, 74 echinocandinsand 18 liposomal amphotericin B for empirical therapy. 51 patients were eligible to step-down to fluconazole but only 23 patients did so. Furthermore, in nine patients unjustified step-up from fluconazole to echinocandins or liposomal amphotericin B was carried out. The additional cost incurred bythe healthcare system due to high prices of echinocandins and liposomal amphotericin B in comparison with fluconazole was€211 837. Interestingly, it was found that one strain of C. albicans and two strains of C. glabrata were resistant to echinocandins. Conclusion: The presence of a multidisciplinary team, including an infection control specialist and a clinical pharmacist, would limit the prescription of advanced antifungal agents as empirical therapy. Moreover, this team would control the de-escalation process-where applicable-leading to a reduction in costs and, probably, a decrease in the emergence of resistant Candida species. These facts contribute to the broader discussion on the adoption of antifungal stewardship programmes.

Caffeine versus theophylline for apnea of prematurity: a randomised controlled trial.

AIM: To compare standard doses of theophylline and caffeine for apnea of prematurity in terms of apnea frequency and assess the need for therapeutic drug monitoring. METHODS: Seventy neonates less than 33 weeks gestation, breathing spontaneously, were randomly assigned (open-label) to receive either theophylline or caffeine for treatment or prevention of apnea. The primary outcome measure was the difference in apnea frequency between theophylline and caffeine patient groups. Methylxanthine serum levels were measured on the 1st, 3rd and 7th days of therapy and every 7 days thereafter. RESULTS: Thirty-seven neonates received theophylline (T) and 33 caffeine (C) for treatment (8 T/10 C) or prevention of apnea (29 T/23 C). Treatment with either methylxanthine significantly decreased apnea events (T, P= 0.012; C, P= 0.005) while only C prophylaxis appeared to control apnea in infants at risk. Analysis of combined (treatment plus prophylaxis) data showed a significant decrease in apnea frequency only in those infants receiving caffeine (P= 0.001). However, there was no sustained benefit of C over T beyond the first week of therapy. T and C concentrations (2.2-13.9 mg/L; 5.5-23.7 mg/L, respectively) in the majority of cases fell within the recommended therapeutic ranges and were not significantly associated with apnea events. CONCLUSIONS: This study shows an advantage of C over T for premature infants <33 weeks gestation during the first week of therapy. Standard regimens of both methylxanthines do not seem to require routine concentration monitoring in the first 3 weeks of treatment unless indicated by clinical effect.

Netilmicin in the neonate: pharmacokinetic analysis and influence of parenteral nutrition.

OBJECTIVE: The aim of this study was to investigate the impact of parenteral nutrition on netilmicin pharmacokinetics in critically ill neonates during the first week of life. METHOD: A total of 200 neonates (gestational ages 26.4-41 weeks) treated with netilmicin (4-5 mg/kg in extended dosing intervals) for postnatal sepsis in the first week of life received either fluid therapy or parenteral nutrition. Netilmicin peak and trough serum concentrations were monitored and netilmicin pharmacokinetic parameters were compared with and without parenteral nutrition. RESULTS: There were no statistically significant differences between the pharmacokinetic parameters of netilmicin (volume of distribution, elimination half-life, clearance) in critically ill neonates >32 weeks during the first week of life that received either fluid therapy or parenteral nutrition. For neonates <32 weeks this comparison was not feasible as the majority were parenterally fed. CONCLUSION: Provision of parenteral nutrition (versus fluid therapy) in critically ill neonates >32 weeks did not significantly affect netilmicin pharmacokinetics and therefore does not require modification of recommended netilmicin dosage regimens.

Exploring knowledge and perceptions on generic drugs of final year pharmacy school students in Greece.

Objectives: The economic crisis in Greece has triggered an extensive public debate about the use of generic drugs (generics). Despite their cost-saving potential, generic market penetration remains very low. This raises questions on awareness of, perception on and preference for generics by health-care professionals and patients. This is a descriptive study on the level of knowledge and attitudes towards generics of final year pharmacy school students in Greece. Methods: An electronic questionnaire was distributed to 173 senior pharmacy school students in three Universities in Greece. Responses were submitted electronically. Results: The majority of students knew that generics contain the same active ingredient as the originator products and are cheaper. Students were somehow concerned with safety and efficacy of generics. The majority of students agreed that pharmacists should probably recommend the use of generics, and indicated that prescribing and dispensing practices would largely depend on the profit margin. Despite more than half of the students expressing a positive attitude towards generics, they were inadequately educated on their features. Conclusion: It is critical to improve knowledge of and preference for generics amongst health-care professionals from early on if to build the trust required to increase generic market penetration and achieve measurable savings in pharmaceutical expenditure.

Systematic review and network meta-analysis of approved medicines for the treatment of idiopathic pulmonary fibrosis.

Background: Clinical practice guidelines for the treatment of idiopathic pulmonary fibrosis (IPF) currently recommend pirfenidone and nintedanib. However, there is a lack of evidence from head-to-head comparisons. Objectives: To perform a systematic review and network meta-analysis (NMA) to access the efficacy and tolerability of two new treatments for IPF, pirfenidone and nintedanib. Methods: Randomized controlled trials (RCTs) selection (CENTRAL, MEDLINE, Embase), data extraction, risk of bias analysis, and GRADE assessment were carried out by two authors separately. Direct estimates were calculated using standard pairwise meta-analysis. A Bayesian mixed treatment comparison approach for NMA estimates, with 95% confidence intervals (CI), was used to compare the treatments, calculating odds ratios (OR) and number needed to treat (NNTB) or harm (NNTH). Results: The NMA on 10 randomized controlled trials showed that each drug had a positive effect on percentage of forced vital capacity (FVC) decline ≥ 10% (pirfenidone OR = 0.54 [95% CI = 0.37-0.80], NNTB = 9 [95% CI = 7-22]; nintedanib OR = 0.59 [95% CI = 0.41-0.84], NNTB = 9 [95% CI = 6-23]), but no significant differences were noted when comparing pirfenidone and nintedanib with respect to acute exacerbations, mortality, and serious adverse events (FVC decline OR = 0.91 [95% CI = 0.45-2.03]) or dropouts (OR = 0.75 [95% CI = 0.33-1.27]). Nintedanib showed an effect on dropouts, OR = 1.61 (1.13-2.28) and NNTH = 14 (8-61). Conclusions: Based on RCTs of 12 month duration in patients with IPF, a positive effect on FVC decline was noted for both treatments and on dropouts for nintedanib, but no significant differences were noted between treatments.

End-of-Life Health-Care Cost of Patients With Lung Cancer: A Retrospective Study.

INTRODUCTION: Lung cancer exerts a significant societal and health-care-related economic burden and chemotherapy drugs constitute a major factor of total direct cost. The aim of the present study was to assess the direct health-care cost of lung cancer in Greece by conducting a retrospective analysis on the last 6 months of life. METHODS: The present study was based on both the medical data and costs of treatment of deceased adult patients who suffered from terminal stage IIIB/IV lung cancer (non-small cell lung cancer and small cell lung cancer) during the last 6 months of their life. The study's protocol was approved by the Hospital's Research Ethics Committee. Costs included outpatient (outpatient services) and inpatient (inpatient services) costs. Descriptive statistics were mainly used for statistical analysis. RESULTS: The files of 144 patients were analyzed. The total cost of health-care services for the study population during the last 6 months of life was attributed by 57% to inpatient services, whereas chemotherapy costs (74%) comprised the largest proportion of the total inpatient cost. The highest expenditure for outpatient services was attributed to concomitant medication (59%), followed by the cost of tests (21%) and radiotherapy (20%). CONCLUSIONS: The results of our study indicate that both inpatient and outpatient costs were substantial. The main inpatient and outpatient cost drivers were chemotherapy and concomitant medication, respectively. A more comprehensive nationwide study would be useful to validate our results and to include also indirect costs of cancer care in Greece.

Laparoscopic total extraperitoneal inguinal hernia repair: Retrospective study on prosthetic materials, postoperative management, and quality of life.

Laparoscopic inguinal hernia repair is one of the most frequently performed operations. However, the search for the most appropriate prosthetic materials continues to occupy the surgical community. The purpose of this study was to evaluate the postoperative short- and mid-term effects (like duration of stay, number and type of complications, and inguinal pain) of laparoscopic inguinal hernia repair using the total extraperitoneal (TEP) approach. The evaluation encompassed different types of mesh and fixation devices, as well as medications prescribed during hospitalization.This retrospective study was conducted at the General, Laparoendoscopic, Bariatric, and Robotic Surgical Clinic of the Athens Medical Center. Clinical data from 524 patients were evaluated. The answers from an appropriately designed questionnaire completed from each individual were used to obtain information about their postoperative course. The statistical analysis was implemented in SPSS v 23.Analysis revealed that pain sensation on discharge decreased with increasing age (P < .05). No clear relationship was found between surgical clips and pain (P = .292), as well as mesh absorbability and chronic pain (P = .539). The major postoperative complications were annoyance and discomfort (15.9%). The recurrence rate was 1.7%.Postoperative complications following the TEP approach were mostly found to be minor; chronic pain, as an aspect of impaired quality of life, was not experienced in the majority (89.08%). The properties of prosthetic materials used and the type of medications prescribed were not found to exert a significant role in satisfactory postoperative outcomes.

Acupressure on the extra 1 acupoint: the effect on bispectral index, serum melatonin, plasma beta-endorphin, and stress.

BACKGROUND: Acupressure on the "extra 1" point decreases bispectral index (BIS) values and stress. METHODS: We investigated the BIS, melatonin, beta-endorphin, and verbal stress score values before, after 10 min of acupressure application on the extra 1 point, on a sham point, after no acupressure, and 1 h after completion of each intervention in 12 volunteers. RESULTS: The BIS and verbal stress score values were decreased after acupressure on the extra 1 point (P = 0.0001 and P = 0.008, respectively), but melatonin and beta-endorphin did not change. CONCLUSION: Acupressure on the extra 1 point has no effect on melatonin and beta-endorphin levels.

No change in serum melatonin, or plasma beta-endorphin levels after sevoflurane anesthesia.

STUDY OBJECTIVE: To investigate the effect of sevoflurane as single anesthetic on melatonin and beta-endorphin plasma levels during the first 24 hours postoperatively. DESIGN: Prospective, open-cohort study. SETTING: University hospital. PATIENTS: 13 ASA physical status I and II, adults, scheduled for dilatation and curettage of the uterus, and 13 healthy volunteers. INTERVENTIONS: Patients received general anesthesia with sevoflurane. MEASUREMENTS: Melatonin and beta-endorphin plasma levels were determined before anesthesia, immediately after, and two, 4, 8, and 24 hours after the end of anesthesia. Melatonin and beta-endorphin were also measured in 13 healthy subjects (controls) not undergoing anesthesia at similar times during the day. Systolic and diastolic blood pressure, heart rate, bispectral index, and oxygen saturation via pulse oximeter (SpO(2)) were recorded before and after anesthesia. Quality of sleep postoperatively was also assessed. MAIN RESULTS: Melatonin levels (pg/mL) in the patients and controls were 8.2 +/- 7.9 versus 15.2 +/- 15.0 before anesthesia and 7.7 +/- 7.9 versus 11.1 +/- 7.0, 6.5 +/- 6.1 versus 15.6 +/- 16.3, and 19.5 +/- 17.9 versus 23.7 +/- 23.3 at the end of anesthesia and 4 and 24 hours after the end of anesthesia, respectively (P = 0.057). At the same time points, beta-endorphin plasma levels (pmol/L) in patients and controls were 5.2 +/- 2.0 versus 4.0 +/- 2.3, 5.4 +/- 3.3 versus 3.9 +/- 2.5, 4.9 +/- 1.2 versus 4.4 +/- 1.7, and 3.7 +/- 2.6 versus 4.2 +/- 1.8, respectively (P= 0.285). The quality of sleep assessed clinically was not altered. CONCLUSION: Sevoflurane as a single anesthetic for minor gynecological procedures did not influence significantly melatonin or beta-endorphin plasma levels. Sleep quality assessed clinically was not influenced.