Design and development of poly-L/D-lactide copolymer and barium titanate nanoparticle 3D composite scaffolds using breath figure method for tissue engineering applications.

In tissue engineering, the scaffold topography influences the adhesion, proliferation, and function of cells. Specifically, the interconnected porosity is crucial for cell migration and nutrient delivery in 3D scaffolds. The objective of this study was to develop a 3D porous composite scaffold for musculoskeletal tissue engineering applications by incorporating barium titanate nanoparticles (BTNPs) into a poly-L/D-lactide copolymer (PLDLA) scaffold using the breath figure method. The porous scaffold fabrication utilised 96/04 PLDLA, dioleoyl phosphatidylethanolamine (DOPE), and different types of BTNPs, including uncoated BTNPs, Al2O3-coated BTNPs, and SiO2-coated BTNPs. The BTNPs were incorporated into the polymer scaffold, which was subsequently analysed using field emission scanning electron microscopy (FE-SEM). The biocompatibility of each scaffold was tested using ovine bone marrow stromal stem cells. The cell morphology, viability, and proliferation were evaluated using FE-SEM, LIVE/DEAD staining, and Prestoblue assay. Porous 3D composite scaffolds were successfully produced, and it was observed that the incorporation of uncoated BTNPs increased the average pore size from 1.6 µm (PLDLA) to 16.2 µm (PLDLA/BTNP). The increased pore size in the PLDLA/BTNP scaffolds provided a suitable porosity for the cells to migrate inside the scaffold, while in the pure PLDLA scaffolds with their much smaller pore size, cells elongated on the surface. To conclude, the breath figure method was successfully used to develop a PLDLA/BTNP scaffold. The use of uncoated BTNPs resulted in a composite scaffold with an optimal pore size while maintaining the honeycomb-like structure. The composite scaffolds were biocompatible and yielded promising structures for future tissue engineering applications.

Pregnancy, puerperium and perinatal constipation - an observational hybrid survey on pregnant and postpartum women and their age-matched non-pregnant controls.

OBJECTIVE: To evaluate the prevalence of constipation during pregnancy and early puerperium. DESIGN: Observational survey. SETTING: Secondary and tertiary hospital in Finland. POPULATION: Pregnant (n = 474) and postpartum (n = 403) women and a control group of 200 non-pregnant women who did not give birth in the past year. METHODS: Women reported bowel function and other gastrointestinal symptoms on a structured questionnaire using an 11-point numerical rating scale (0 = no symptom, 10 = most severe symptom) and binominal yes/no questions during the second and third trimesters and few days and 1 month after childbirth. MAIN OUTCOME MEASURE: Prevalence of constipation based on the Rome IV criteria. RESULTS: The data consist of five cohorts of women: second trimester (n = 264), third trimester (n = 210), after vaginal delivery (n = 200) or caesarean section (n = 203), and a control group (n = 200). The prevalence of constipation was 40% in pregnant women and 52% (P < 0.001) in postpartum women, which was a higher prevalence than that in the control group, where 21% had constipation (P < 0.001). A few days after delivery, the prevalence of constipation was lower after vaginal delivery (47%) than caesarean section (57%, P < 0.039). One month postpartum, the prevalence of constipation was low: 9% after vaginal delivery (P = 0.002 compared with the control group) and 15% after caesarean section. Other gastrointestinal symptoms were common; pregnant women had the highest prevalence (34%) of nausea/vomiting. CONCLUSION: The prevalence of constipation was two- to three-fold higher in pregnant women and a few days after delivery than in non-pregnant women. During puerperium, bowel function returned to or below that reported in non-pregnant women. TWEETABLE ABSTRACT: Constipation is common in pregnancy and after delivery, but bowel function returns early in puerperium.

Implementation of a 23-h surgery model in a tertiary care hospital: a safe and feasible model with high patient satisfaction.

BACKGROUND: The 23-h surgery model consists of elective operative care with an overnight hospital stay for patients unsuitable for day case surgery. The aim of this study was to assess the success of the 23-h surgery model. METHODS: This was a prospective follow-up study of patients undergoing surgery with the planned 23-h model in a tertiary-care university hospital during a 12-month period 2 years after the model was implemented. Patients were interviewed 2 weeks after surgery, and the hospital operative database and patient records were searched. The primary outcome was the success of the process, defined as discharge before 10.00 hours on the first morning after surgery. Secondary outcomes were 30-day readmission and reoperation rates, adverse events, and patient satisfaction with the process. RESULTS: Between May 2017 and May 2018, 993 adult patients underwent surgery with the 23-h model, of whom 937 adhered to the model as planned (success rate 94·4 per cent). Gynaecological, gastrointestinal and orthopaedic surgery were the three most common surgical specialties. The surgical process was changed to an in-hospital model for 45 patients (4·5 per cent), and 11 (1·1 per cent) were discharged on the day of surgery. The readmission rate was 1·9 per cent (19 of 993), and five patients (0·5 per cent) had a reoperation within 30 days of surgery. Fifty-nine adverse events were noted in 53 patients (5·3 per cent), most commonly infection. Patient satisfaction was a median of 6-7 (maximum 7) points for various aspects of the model. CONCLUSION: The success rate and patient satisfaction for the 23-h surgery model was high.

ANTECEDENTES: El modelo de cirugía de 23 horas consiste en un procedimiento quirúrgico electivo con estancia en el hospital durante una noche en aquellos pacientes que no son adecuados para cirugía ambulatoria. MÉTODOS: Se puso en marcha un estudio prospectivo de seguimiento de pacientes sometidos a cirugía con un modelo planificado de 23 horas en un hospital universitario de tercer nivel durante un periodo de 12 meses a los dos años de la implementación del modelo. Los pacientes fueron entrevistados a las dos semanas tras la cirugía, y se realizaron búsquedas en las bases de datos operativas y en los informes de los pacientes. El resultado primario fue el éxito del proceso definido como el alta antes de las 10 horas en la primera mañana postoperatoria. Los resultados secundarios fueron el reingreso a los 30 días y la tasa de reoperaciones, eventos adversos, y satisfacción del paciente con el proceso. RESULTADOS: Entre mayo de 2017 y mayo de 2018, 993 pacientes adultos fueron sometidos a cirugía con un modelo planificado de 23 horas, de los cuales 937 pacientes siguieron el modelo tal como se planificó (tasa de éxito 94,4%). Las tres especialidades quirúrgicas más frecuentes fueron ginecología, aparato digestivo y ortopedia. El proceso quirúrgico se cambió a un modelo de hospitalización en 45 (4,5%) pacientes, y 11 (1,1%) pacientes fueron dados de alta en el día de la cirugía. La tasa de reingreso fue del 1,9% (n = 19) y 5 pacientes (0,5%) precisaron de una reoperación en los primeros 30 días tras la cirugía. Se observaron eventos adversos en 53 pacientes (5,3%), siendo una infección el más frecuente. La satisfacción del paciente tuvo una mediana de 6-7 (de un total de 7) puntos para varios aspectos del modelo. CONCLUSIÓN: La tasa de éxito y la satisfacción del paciente del modelo de cirugía de 23 horas son elevadas.

Population pharmacokinetics of oxycodone in plasma and cerebrospinal fluid after epidural and intravenous administration.

Objectives: To establish the first plasma and cerebrospinal fluid (CSF) oxycodone population pharmacokinetic (PopPK) model after epidural (EPI) and intravenous (IV) oxycodone administration. Methods: The study was conducted with 30 female subjects undergoing elective gynecological surgery with epidural analgesia. A parallel single dose of EPI oxycodone with IV placebo (EPI group; n = 18) or IV oxycodone with EPI placebo (IV group; n = 12) was administered. An epidural catheter for drug administration was placed at T12/L1 and a spinal catheter for CSF sampling at L3/4. Plasma and CSF for oxycodone analysis were frequently collected. A PopPK model was built using the NONMEM software package. Results: Plasma and CSF oxycodone concentrations were evaluated using separate central plasma and CSF compartments and separate peripheral plasma and CSF compartments. Epidural space served as a depot compartment with transfer to both the plasma and CSF central compartments. The population parameters for plasma clearance and apparent distribution volumes for central and peripheral compartments for plasma and CSF were 37.4 L/h, 90.2 L, 68.9 L, 0.035 L (fixed based on literature), and 0.039 L, respectively. Conclusion: A PopPK model was developed and found to precisely and accurately describe oxycodone time-concentration data in plasma and CSF.

The usage of procalcitonin in Finland.

BACKGROUND: We have surveyed the use of procalcitonin (PCT) in Finland with a specific emphasis on intensive care unit (ICU) patients. METHODS: The PCT use was surveyed from all 11 laboratories providing services for all 15 secondary and all five tertiary care hospitals in Finland. The laboratories reported the PCT use of each hospital in 2014 and 2015. Four hospitals were analysed for the first 100 adult ICU patients with PCT measurements in 2015. The indication for PCT measurement and whether PCT values affected antibiotic treatment were collected from patient records. RESULTS: The overall national PCT use was similar between 2014 and 2015 with around 15 000 measurements annually. The PCT use varied greatly between hospitals and specialities; one tertiary care hospital used 5600 measurements annually, while another tertiary care hospital did not use PCT at all. Over half of the requests for PCT were in the ICU. There were significant differences in PCT use for ICU patients: in the most frequent user, PCT was mainly used for follow-up of antibiotic treatment, whereas in the other three hospitals, PCT was mainly used for differential diagnosis. The most frequent user also had the highest per patient rate of PCT measurements, with a mean of six PCT tests/patient compared to two PCT tests/patient in the three other hospitals. PCT had an effect on antibiotic treatment in every 5th case. CONCLUSION: The use of PCT in Finland varies significantly between hospitals, even though the national guideline proposes its use for septic patients.

Absorption of ibuprofen orodispersible tablets in early postoperative phase - a pharmacokinetic study.

OBJECTIVE: Patient-controlled oral analgesia has gained popularity in postoperative pain management. Anesthesia and surgery delay gastrointestinal tract function and this may therefore decrease bioavailability of drugs taken by mouth. To hasten absorption, an orodispersible ibuprofen tablet has been developed. In this study, we evaluated the pharmacokinetics and feasibility of orodispersible ibuprofen tablets in spine surgery patients. METHODS: The study design was a prospective clinical trial where each patient served as her/his own control. Fifteen patients aged 19-75 years were given two orodispersible ibuprofen 200 mg tablets the day before surgery and two more tablets immediately after surgery. Blood samples for ibuprofen concentrations were taken at intervals for 6 hours following pre- and postsurgical administration of ibuprofen. RESULTS: The mean preoperative area under time-concentration curve for ibuprofen (AUC0-360) was 4806 (SD 1104) min·mg/L, and after surgery it was 2141 (583) min·mg/L (mean difference 2664, 95% CI for difference 2003 to 3325, p < .001). The mean of the maximum preoperative plasma concentration of ibuprofen was three times higher, 26.7 (7.7) mg/L, than the postoperative value of 8.6 (2.1) mg/L (mean diff. 18.1, 95% CI 13.9 to 22.4, p < .001). Times to maximum concentration were similar pre- and postoperatively at 155 (58) minutes and 169 (113) minutes (p = .67). No serious or unexpected adverse events were recorded. CONCLUSIONS: While orodispersible ibuprofen tablets were feasible, ibuprofen absorption decreased immediately after surgery compared to the day before surgery. Thus, further studies are needed to establish the adequate initial postoperative dose.

Intravenous dexketoprofen induces less injection pain than racemic ketoprofen.

WHAT IS KNOWN AND OBJECTIVE: Ketoprofen has high analgesic efficacy against inflammatory and nociceptive pain. Additionally, when ketoprofen is administered in conjunction with an opioid during pain management, it prevents the development of opioid-induced hyperalgesia. The main limitation for racemic ketoprofen IV administration is venous irritation. Dexketoprofen is the active enantiomer of racemic ketoprofen and has a similar analgesic efficacy in a dose proportion of 1 : 2, but it causes fewer adverse effects than racemic ketoprofen. It has been claimed that dexketoprofen may cause less frequent and less severe injection pain than racemic ketoprofen. In this study, we compared the injection pain of IV administered racemic ketoprofen and dexketoprofen in elective surgical patients. METHODS: The ethics committee of our institution approved this randomized, double-blinded, two-treatment, two-period, crossover clinical comparison of ketoprofen and dexketoprofen. A total of 221 ASA I-III adult patients, aged 20-75 years, were initially IV administered either 0·5 mg/kg racemic ketoprofen followed 2 h later with 0·25 mg/kg dexketoprofen (group 1) or vice versa (group 2). Both compounds were diluted in 20 mL of normal saline and were injected over 6 min. Patients reported injection pain on an 11-point numerical rating scale (NRS) (0 = no pain, 10 = most pain). RESULTS AND DISCUSSION: Significantly less injection pain was reported after dexketoprofen administration. A total of 201 of 209 patients reported pain during racemic ketoprofen injection, and 157 of 210 patients reported pain during dexketoprofen injection, respectively. Moderate or severe pain was reported by 90 (41%) patients during racemic ketoprofen administration and by 43 (20%) during dexketoprofen injection (P = 0·001). The mean of injection pain during racemic ketoprofen injection was 4·2 (SD 2·5) and was 2·5 (2·4) during dexketoprofen injection (P = 0·001). No serious or unexpected adverse events were reported. WHAT IS NEW AND CONCLUSION: Dexketoprofen causes significantly less injection pain than racemic ketoprofen; therefore, it may be a more suitable IV non-steroidal anti-inflammatory than the racemate.

Role of orchiectomy in severe testicular pain after inguinal hernia surgery: audit of the Finnish Patient Insurance Centre.

PURPOSE: Testicular ischemia and necrosis are uncommon complications after inguinal hernioplasty. Our aim was to evaluate the incidence of severe urological complications related to adult inguinal hernia surgery in Finland with special reference to orchiectomy in relieving intractable chronic testicular pain. METHODS: All urological complications related to inguinal hernia surgery during 2003-2010 were analysed from the Finnish Patient Insurance Centre. The patients with intractable chronic scrotal or testicular pain that resulted in orchiectomy were re-evaluated after a median follow-up of 7 years (range 2-15 years). The operative factors related to chronic testicular pain and atrophy were analysed using multiple regression analysis. RESULTS: Altogether 62 urological complications (from 335 litigations) were recorded from 92,000 inguinal hernia operations. The distribution of claimed urological complications consisted of 34 testicular injuries, ten bladder perforations, seven massive scrotal haemorrhage or 11 miscellaneous injuries. Seventeen atrophic testes were left in situ and 17 (six early < 7 days, 11 late > 8 days) orchiectomies were performed due to necrosis or chronic testicular pain syndrome. In the conservative group of moderate scrotal or testicular pain (n = 17), all patients had late pain symptoms (>8 days), but pain was not so severe that orchiectomy was attempted. Using a multivariate analysis, postoperative infections were associated with chronic testicular or scrotal pain and atrophy, but hospital status, surgeon's training level, laparoscopic or open operation, type of hernia or use of mesh did not correlate with testicular injuries. During follow-up, 11/17 (65%) patients with orchiectomy were free of testicular pain. CONCLUSION: Urological injuries form one-fifth of the major complications after inguinal hernioplasty. Orchiectomy appears to help the majority of patients with severe testicular pain syndrome.

Validation of a symptom-score questionnaire and long- term results of endoscopic dacryocystorhinostomy.

BACKGROUND: Endoscopic dacryocystorhinostomy (EN-DCR) is a commonly used procedure in the treatment of nasolacrimal duct obstruction (NLDO). However, there is no generally accepted disease-specific questionnaire for assessing outcomes. METHODOLOGY: We conducted a prospective study to initially validate a Nasolacrimal Duct Obstruction Symptom Score questionnaire(NLDO-SS) and to evaluate the long-term success of EN-DCR procedures. Seventy-six patients (86 eyes) were evaluated in follow-up visits at 1-8 years after EN-DCR. The patients completed the NLDO-SS questionnaire twice, first, at home and, second,after receiving information from the otorhinolaryngologist, during the visit. The surgical outcome was considered successful if the irrigation succeeded and if the patient symptoms were relieved as assessed with the NLDO-SS. RESULTS: The diagnostic accuracy of the NLDO-SS was 84%, sensitivity 82%, specificity 85%, positive predictive value 58%, negative predictive value 95%, odds ratio 26, risk ratio 11 and usefulness index 0.55. Cronbach's alpha was 0.85, and the test-retest reliability coefficient was 0.87. The long-term success rate after EN-DCR was 79%. CONCLUSION: The NLDO-SS iss a feasible clinical tool in assessing the success of EN-DCR. The success rate was found to decrease EN-DCR at long-term follow-up.

Population pharmacometrics in support of analgesics studies.

Population pharmacometric modeling is used to explain both population trends as well as the sources and magnitude of variability in pharmacokinetic and pharmacodynamics data; the later, in part, by taking into account patient characteristics such as weight, age, renal function and genetics. The approach is best known for its ability to analyze sparse data, i.e. when only a few measurements have been collected from each subject, but other benefits include its flexibility and the potential to construct more detailed models than those used in the traditional individual curve fitting approach. This review presents the basic concepts of population pharmacokinetic and pharmacodynamic modeling and includes several analgesic drug examples. In addition, the use of these models to design and optimize future studies is discussed. In this context, finding the best design factors, such as the sampling times or the dose, for future studies within pre-defined criteria using a previously constructed population pharmacokinetic model can help researchers acquire clinically meaningful data without wasting resources and unnecessarily exposing vulnerable patient groups to study drugs and additional blood sampling.

Prescribing for off-label use and unauthorized medicines in three paediatric wards in Finland, the status before and after the European Union Paediatric Regulation.

WHAT IS KNOWN AND OBJECTIVE: The European Paediatric Regulation aims to reduce off-label use of medicines in paediatric pharmacotherapy. Prescribing for off-label use and unauthorized medicines was common in the paediatric wards of the Kuopio University Hospital in 2001. To evaluate the possible impact of the Regulation on the prevalence and the frequency on such prescribing, we repeated the study in 2011 as it was conducted 10 years earlier. METHODS: In this prospective study, the prescriptions for patients below 18 years of age were reviewed during a 2-week period in each of the three wards; neonatal intensive care unit, general paediatric ward and paediatric surgical ward in April and May 2011. The medicine's authorizing status of all prescriptions was determined according to the approved summary of product characteristics valid during the study in Finland. Data concerning unauthorized medicines were also recorded and classified. RESULTS: Out of the entire study population of 123 patients, 119 received a total of 1054 prescriptions in 2011. The proportion of patients with at least one prescription for off-label use or for an unauthorized medicine was significantly higher, 79% (n = 97) in 2011, compared to 58% in 2001 (P < 0·001). For newborns, significantly more prescriptions were for off-label use in 2011 than in 2001 (51% vs. 22%; P < 0·001). The proportion of prescriptions for unauthorized medicines was significantly higher in children below 2 years of age than in older children in both years (21% vs. 5% in 2011 and 24% vs. 3% in 2001, P < 0·001). WHAT IS NEW AND CONCLUSION: The prescribing for off-label use and unauthorized medicines was more prevalent in 2011 than in 2001. This indicates that the recent legislation has had only minor or no impact on the authorizing status of medicines commonly used in paediatric inpatients in specialized care.

Central nervous system penetration of oxycodone after intravenous and epidural administration.

BACKGROUND: Despite being increasingly used for pain management, only two studies, with controversial results, have evaluated the epidural use of oxycodone. METHODS: Twenty-four women, aged 26-64 yr, undergoing elective gynaecological surgery were enrolled in this randomized, double-blinded, parallel group study. The subjects were administered either i.v. oxycodone and epidural placebo (IV group; n=12) or epidural oxycodone and i.v. placebo (EPI group; n=12) after operation. Oxycodone was administered as a single dose of 0.1 mg kg(-1). An epidural catheter for drug administration was placed at T12/L1 and a spinal catheter for cerebrospinal fluid (CSF) sampling at L3/4. Plasma and CSF were frequently collected for the analysis of oxycodone and its major metabolites. The primary outcomes were the peak concentration (C(max)), time to peak concentration (T(max)), and the exposure (AUC(last)) of oxycodone in CSF and plasma. The secondary outcome was the analgesic efficacy, measured as the total dose of rescue fentanyl during the first four postoperative hours. RESULTS: In the EPI group, the median oxycodone Cmax and AUC(last) in the CSF were 320- and 120-fold higher, respectively, compared with the IV group. The total dose of rescue fentanyl was significantly lower in the EPI group (seven subjects needed 16 doses) than in the IV group [12 subjects needed 71 doses (P=0.001)]. No serious or unexpected adverse events were reported. CONCLUSIONS: Epidural oxycodone provides much higher CSF concentrations and possibly better analgesic efficacy than does i.v. oxycodone. CLINICAL TRIAL REGISTRATION: EudraCT reference number: 2011-000125-76.

The influence of timing on the effectiveness of epidural blood patches in parturients.

BACKGROUND: Postdural puncture headache is common in parturients following lumbar puncture. If headache is severe and persistent, an epidural blood patch is recommended. In this paper we reviewed the efficacy of epidural blood patches over a 13-year period at two hospitals in Finland with a particular emphasis on its timing. METHODS: The hospitals' databases were searched to identify parturients who underwent an epidural blood patch from March 1998 to June 2011. Parturients' records were reviewed to establish the characteristics and associated symptoms of headache and the effectiveness of the epidural blood patch. RESULTS: A total of 129 parturients received 151 epidural blood patches. These followed spinal (n = 49), epidural (n = 47) or combined spinal-epidural blocks (n = 33). The success rate of the first procedure was 89%, with permanent relief in 76%. The first procedure provided permanent relief of postdural puncture headache for 86% of 78 patients having the procedure after 48 h, compared to 65% of 37 patients when it was performed between 24 and 48 h, and 50% of 14 patients with the procedure within the first 24 h after dural puncture (P = 0.003). A second procedure was performed for 22 parturients due to incomplete relief (n = 5) or recurrent symptoms (n = 17); all had complete resolution of symptoms. CONCLUSIONS: Epidural blood patch performed later than 48 h following lumbar puncture or accidental dural puncture is effective in parturients with postdural puncture symptoms. The recurrence rate of symptoms after an initially successful epidural blood patch is high, and therefore patients should be provided with counselling and contact information.

Stability of an epidural analgesic admixture of levobupivacaine, fentanyl and epinephrine.

WHAT IS KNOWN AND OBJECTIVE: Admixtures of levobupivacaine, fentanyl and epinephrine are increasingly used in epidural pain management. Neither the compatibility nor the stability of levobupivacaine with fentanyl and epinephrine is known and therefore we examined the chemical, physical and microbiological stability of levobupivacaine-fentanyl-epinephrine and levobupivacaine-fentanyl admixtures prepared in the hospital pharmacy. METHODS: Fentanyl and epinephrine were added into commercial levobupivacaine infusion bags. The components were analysed by HPLC and assays were performed up to 60 days of storage of the bags both protected and exposed to light at room temperature and stored in the refrigerator. In addition, sterility, bacterial endotoxins, organoleptic properties, pH and mass of the admixture were determined. RESULTS AND DISCUSSION: Levobupivacaine, fentanyl and epinephrine concentrations remained within the ± 10% specification limit during 60 days storage in the refrigerator in tightly closed secondary packing material and protected from light and for at least 40 days at room temperature. The degradation of epinephrine exceeded 10% within 60 hours when exposed to light. The solutions were microbiologically and physically stable. WHAT IS NEW AND CONCLUSION: Epidural analgesic admixtures of levobupivacaine and fentanyl with or without epinephrine have to be stored in a tightly closed secondary package protected from light. The extended stability, up to 60 days, in a refrigerator enables the centralized preparation in the hospital pharmacy.

Parental reporting of adverse drug events and other drug-related problems in children in Finland.

PURPOSE: Drug-related problems (DRPs) are common in paediatric pharmacotherapy, but few studies describe them from the parents' perspective. In the present survey, we have investigated the lifetime prevalence and type of DRPs in children in Finland. METHODS: This was a population-based survey of a random sample of 6,000 children below 12 years of age in 2007. A questionnaire was sent to their parents. The final response rate was 67% with a study population of 4,032. The main outcome measure was the lifetime prevalence and type of DRPs. RESULTS: The lifetime prevalence of DRPs was 21% (95% CI 20-22). The most common (82%) of the 1,346 reported DRPs were adverse drug events (ADEs). The prevalence of ADEs was 17% (95% CI 16-19), that of other DRPs 5.2% (95% CI 4.5-5.9). The prevalence of serious ADEs was 0.4% and that of unexpected ADEs was 0.8%. The most common system involved in the ADEs was the gastrointestinal tract, comprising 34% of the 1,106 ADEs. The most common of the 240 other DRPs were problems with the administration and dosing of medicine (86%). Overall, 64% of DRPs were related to anti-infectives. CONCLUSIONS: One fifth of the Finnish children below 12 years of age had experienced DRPs. Appropriate counselling, including possible adverse drug reactions and dosing directions, is important for parents and children at both the prescribing and dispensing of medicines for paediatric patients. Reporting of any suspected serious or unexpected ADEs is an essential part of efficient pharmacovigilance in paediatrics.

Prolonged-release oxycodone/naloxone in postoperative pain management: from a randomized clinical trial to usual clinical practice.

OBJECTIVE: These studies evaluated the feasibility of using oral prolonged-release oxycodone/naloxone (OXN PR) for the management of acute postoperative pain. METHODS: Three studies were undertaken: (i) the analgesic efficacy of OXN PR was compared with prolonged-release oxycodone (OXY PR) in patients with knee arthroplasty in an immediate postoperative period (IPOP) study; (ii) OXN PR treatment was compared with other opioids during rehabilitation after knee arthroplasty in a noninterventional study (NIS); and (iii) surgical patients on other opioids were switched to OXN PR postoperatively during a quality improvement programme (QIP). RESULTS: In the IPOP study, the pain intensity at rest score decreased by a similar amount in the OXN PR and OXY PR groups, indicating similar analgesic efficacies. In the NIS, patient assessments indicated enhanced efficacy and tolerability for OXN PR compared with other opioids. The QIP indicated significant improvements in bowel function and less difficulty passing urine at the end of OXN PR treatment compared with baseline. No safety concerns were raised. CONCLUSIONS: The analgesic efficacies of OXN PR and OXY PR were similar in postoperative pain settings. OXN PR reduced the degree of restriction in relation to patients carrying out physiotherapy compared with other opioids, and improved bowel and bladder function.

Serum and CSF soluble CD26 and CD30 concentrations in healthy pediatric surgical outpatients.

Activated T-helper type 1 (Th1) lymphocytes induce a cellular type immune response, and Th2 lymphocytes, a humoral or antibody-mediated type immune response. Soluble CD26 (sCD26) and soluble CD30 (sCD30) are regarded as markers of Th1 and Th2 lymphocyte activation, respectively. Serum from 112 generally healthy pediatric surgical patients and cerebrospinal fluid (CSF) from 39, aged 1-17 years were measured for sCD26 and sCD30 using an enzyme-linked immunosorbent assay method. The detection limit for sCD26 was 6.8 ng/ml and for sCD30, 1.9 IU/ml. For serum sCD26 and sCD30, 2.5% and 97.5% percentiles constituted the reference limits, and the 95% credible intervals for the percentiles were calculated using regression models with a Bayesian approach. A significant between-gender difference was observed (P = 0.015) in serum sCD26 concentration, of which the lower limits ranged between 273 and 716 ng/ml for girls and 235 and 797 ng/ml for boys. The upper limits ranged between 1456 and 1898 ng/ml for girls and between 1419 and 1981 ng/ml for boys. Moreover, the concentrations of sCD26 increased in infants and children up to 10 years in girls and 12 years in boys. After this however, the values decreased. The serum sCD30 concentration was highest among the youngest infants aged 1 year (80-193 IU/ml), after which a consistent age-related decrease was found. The lowest values were found at the age of 17 years (10-89 IU/ml). A significant between-gender difference in sCD30 concentration was observed (P = 0.019). sCD26 and sCD30 concentrations were low in the CSF samples analyzed: 13.3 ng/ml (median); range 8.3-51.5 ng/ml and 7.6 IU/ml; 2.1-18.5 IU/ml, respectively. Reference limits for serum sCD26 in children aged 1-17 years were established as being 235-1800 ng/ml in toddlers and 400-1800 ng/ml in female adolescents and 700-2000 ng/ml in male adolescents. For sCD30; reference limits of 80-190 IU/ml were established in the youngest age group and 10-90 IU/ml in adolescents.

Effects of fluoxetine treatment on striatal dopamine transporter binding and cerebrospinal fluid insulin-like growth factor-1 in children with autism.

A positive effect of fluoxetine has been shown in some children with autism. The present study was undertaken to correlate striatal dopamine transporter (DAT) binding and cerebrospinal fluid insulin-like growth factor-1 (CSF-IGF-1) with clinical response in autistic children (n=13, age 5-16 years) after a 6-month fluoxetine treatment. Good clinical responders (n=6) had a decrease (p=0.031) in DAT binding as assessed using single-photon emission computed tomography with [123I]-nor-ß-CIT, whereas poor responders had a trend to an increase. An increase in CSF-IGF-1 (p=0.003) was detected after the treatment period, but no correlation between the clinical response and CSF-IGF-1 was found. In conclusion, fluoxetine decreases DAT binding indicating alleviation of the hyperdopaminergic state and increases CSF-IGF-1 concentration, which may also have a neuroprotective effect against dopamine-induced neurotoxicity in autistic children.