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.

Protein tyrosine phosphatase receptor type Q in cerebrospinal fluid reflects ependymal cell dysfunction and is a potential biomarker for adult chronic hydrocephalus.

BACKGROUND AND PURPOSE: Protein tyrosine phosphatase receptor type Q (PTPRQ) was extracted from the cerebrospinal fluid (CSF) of patients with probable idiopathic normal-pressure hydrocephalus (iNPH) by proteome analysis. We aimed to assess the feasibility of using CSF PTPRQ concentrations for the additional diagnostic criterion of iNPH in Japanese and Finnish populations. METHODS: We compared PTPRQ concentrations among patients with probable iNPH and neurologically healthy individuals (normal control [NC] group), patients with normal-pressure hydrocephalus (NPH) of acquired and congenital/developmental aetiologies, patients with Alzheimer's disease and patients with Parkinson's disease in a Japanese analysis cohort. A corresponding iNPH group and NC group in a Finnish cohort was used for validation. Patients in the Finnish cohort who underwent biopsy were classified into two groups based on amyloid and/or tau deposition. We measured PTPRQ expression levels in autopsied brain specimens of iNPH patients and the NC group. RESULTS: Cerebrospinal fluid PTPRQ concentrations in the patients with NPH of idiopathic, acquired and congenital/developmental aetiologies were significantly higher than those in the NC group and those with Parkinson's disease, but iNPH showed no significant differences when compared with those in the Alzheimer's disease group. For the patients with iNPH, the area under the receiver-operating characteristic curve was 0.860 in the Japanese iNPH and 0.849 in the Finnish iNPH cohorts. Immunostaining and in situ hybridization revealed PTPRQ expression in the ependymal cells and choroid plexus. It is highly possible that the elevated PTPRQ levels in the CSF are related to ependymal dysfunction from ventricular expansion. CONCLUSIONS: Cerebrospinal fluid PTPRQ levels indicated the validity of this assay for auxiliary diagnosis of adult chronic hydrocephalus.

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.

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.

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.

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.

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.

High sensitivity for tuberculosis in a national integrated surveillance system in Finland.

Little is known about the sensitivity of surveillance for tuberculosis after integration of formerly dedicated tuberculosis surveillance and control into the general health care system, an integration which took place in Finland in 1987. We compared routine laboratory notifications to the National Infectious Disease Register (NIDR) for Mycobacterium tuberculosis from January 1, 1995, to December 31, 1996, with data collected independently from all laboratories offering M. tuberculosis culture, and with data from patient records. 1059 culture-positive cases were found. The overall sensitivity of the NIDR was 93 % (984/1059). The positive predictive value of a culture-positive case in the NIDR to be a true culture-confirmed case was 99%. For the culture-confirmed cases in the NIDR, one or more physician notification forms had been submitted for 89%. A highly sensitive notification system for culture-positive tuberculosis can be achieved in an integrated national infectious disease surveillance system based on laboratory notification.

High sensitivity for tuberculosis in a national integrated surveillance system in Finland.

Little is known about the sensitivity of surveillance for tuberculosis after integration of formerly dedicated tuberculosis surveillance and control into the general health care system, an integration which took place in Finland in 1987. We compared routine laboratory notifications to the National Infectious Disease Register (NIDR) for Mycobacterium tuberculosis from January 1, 1995, to December 31, 1996, with data collected independently from all laboratories offering M. tuberculosis culture, and with data from patient records. 1059 culture-positive cases were found. The overall sensitivity of the NIDR was 93 % (984/1059). The positive predictive value of a culture-positive case in the NIDR to be a true culture-confirmed case was 99%. For the culture-confirmed cases in the NIDR, one or more physician notification forms had been submitted for 89%. A highly sensitive notification system for culture-positive tuberculosis can be achieved in an integrated national infectious disease surveillance system based on laboratory notification.

Sampling of Aspergillus spores in air.

Nosocomially acquired aspergillosis typically occurs in the setting of treatment for leukaemia or other haematological malignancy. As Aspergillus species can be readily found in the environment, it has been widely believed that aspergillosis occurs as a consequence of exogenous acquisition of the fungus. Stringent environmental controls in transplant units have included high-efficiency air filtration, positive-pressure ventilation and frequent room air changes. Although there have been several well-documented examples of aspergillosis outbreaks as a result of hospital demolition and reconstruction, it has not always been possible to demonstrate elevated spore counts in clinical areas during building work. The sampling of air for Aspergillus is very problematic. Careful attention must be given to the design of air sampler, sampling protocols and an understanding of air sampling data. This review outlines many of the physical and environmental parameters that influence meaningful air sampling and recommends a simple procedure that has been tried and tested in many aspergillosis outbreaks.

New perspectives in the diagnosis of systemic fungal infections.

Profound and prolonged neutropenia following chemotherapy is a major risk factor for systemic fungal infections. Mortality associated with disseminated fungal infection is high, and treatment with conventional amphotericin B is complicated by renal toxicity. Candida and Aspergillus are among the major pathogens in these patients. Many patients remaining neutropenic over a prolonged period of time will receive empirical antifungal therapy. The clinical and laboratory diagnoses of these infections are neither sensitive nor specific and are generally limited in the early detection of invasive fungal infection. However, several new approaches to diagnosis are being developed, which should be translated into routine practice, based on a greater understanding of the pathogenesis of systemic fungal infection and virulence determinants of fungal pathogens. These include antigen detection and polymerase chain reaction. Patients with presumed fungal infection require more intense and accurate monitoring for signs of disseminated infection. Early diagnosis may guide appropriate treatment and prevent mortality. Continued development of commercial tests should help achieve the objective of definitive diagnostic tests for systemic fungal infections.

Swimming-associated outbreak of Escherichia coli O157:H7.

In 1997 the first outbreak of Escherichia coli O157:H7 infections involving 14 cases occurred in Finland. A case was defined as a resident of Alavus with an episode of diarrhoea between 5 and 17 July 1997, and from whom E. coli O157:H7 was isolated from stool. The investigation included case searching and a population-based case control study. Five primary and eight symptomatic secondary cases of E. coli O157:H7 illness were detected. In the 10 days before the outbreak, all 5 primary patients (aged 3-8 years), but only 6 of 32 population controls from the same age range (Fisher's test, P < 0.001) and 4 of 10 sibling controls (P < 0.05) had visited (but had not necessarily bathed in) a shallow beach popular among young children. Four out of 5 primary cases had remained within 5 m of the beach while swimming and had swallowed lake water compared to 1 of 5 population controls. These analytical epidemiologic findings incriminated fresh lake water as the vehicle of E. coli O157:H7 transmission.

Diagnosis and prevention of fungal infection in the immunocompromized patient.

Profound and prolonged neutropenia following chemotherapy is a major risk factor for systemic fungal infections. Mortality associated with disseminated fungal infection is high and treatment with conventional amphotericin B is complicated by renal toxicity. Candida and Aspergillus are among the major pathogens in this patient population. Many patients remaining neutropenic over a prolonged period of time will receive empirical antifungal therapy. The clinical and laboratory diagnosis of these infections are neither sensitive nor specific and are generally limited in the early detection of invasive fungal infection. However, several new approaches to diagnosis are being developed which should be translated into routine practice. These include antigen detection and PCR. It is still unclear how effective the various measures that are currently being used are in preventing serious fungal infection. Refinements in the prophylactic use of fluconazole, itraconazole and aerosolized amphoteric in B, and the introduction of new formulations of existing antifungals may reduce the incidence of systemic fungal infections in some patient groups. Patients with presumed fungal infection require more intense and accurate monitoring for signs of disseminated infection. Early diagnosis may guide appropriate treatment and prevent mortality.