Present-day challenges and future solutions in postoperative pain management: results from PainForum 2014

This paper is a summary of presentations on postoperative pain control by the authors at the 2014 PainForum meeting in People's Republic of China. Postoperative pain is often untreated or undertreated and may lead to subsequent chronic pain syndromes. As more procedures migrate to the outpatient setting, postoperative pain control will become increasingly more challenging. Evidence-based guidelines for postoperative pain control recommend pain assessment using validated tools on a consistent basis. In this regard, consistency may be more important than the specific tool selected. Many hospitals have introduced a multidisciplinary acute pain service (APS), which has been associated with improved patient satisfaction and fewer adverse events. Patient education is an important component of postoperative pain control, which may be most effective when clinicians chose a multimodal approach, such as paracetamol (acetaminophen) and opioids. Opioids are a mainstay of postoperative pain control but require careful monitoring and management of side effects, such as nausea, vomiting, dizziness, and somnolence. Opioids may be administered using patient-controlled analgesia systems. Protocols for postoperative pain control can be very helpful to establish benchmarks for pain management and assure that clinicians adhere to evidence-based standards. The future of postoperative pain control around the world will likely involve more and better established APSs and greater communication between patients and clinicians about postoperative pain. The changes necessary to implement and move forward with APSs is not a single step but rather one of continuous improvement and ongoing change

GNSS jamming resilience for close to shore navigation in the Northern Sea

avigational error accounts for half of the accidents and serious incidents in close to shore maritime transport in Norway predominantly due to the rapidly changing weather conditions and the dangerous nature of the narrow inshore waters found along the Norwegian coast. This creates a dependence on Differential Global Positioning System (DGPS) use and any disruption to this service can lead to an increased accident rate. The aim of this paper is to research the jamming vulnerability of existing maritime receivers and to understand if an upgrade to a multi-constellation or multi-frequency receiver would improve system resilience. The novelty of this work is a comparison of jamming resilience between different combinations of multiple constellations (GPS and Globalnaya Navigatsionnaya Sputnikovaya Sistema (GLONASS)) and multi-frequency Global Navigation Satellite System (GNSS) signals. This paper presents results from GNSS jamming trials conducted in the northern part of Norway, confirming previous research and indicating that typical maritime GPS receivers are easy to jam and may produce erroneous positional information. Results demonstrate that the single frequency multi-constellation receivers offer better jamming resilience than multi-frequency (L1 + L2) GPS receivers. Further, the GLONASS constellation demonstrated a better resilience than GPS. Results demonstrate a known correlation between GPS L1 and L2 frequencies, as well as a probable over-dependence on GPS for signal acquisition, meaning that no signal can be received without GPS L1 present. With these limitations in mind, the authors suggest that the most economic update to the single frequency GPS receivers, currently used for maritime applications, should be multi-constellation GPS + GLONASS receivers. This solution is cheaper and it also offer better jamming resistance for close to shore navigation than dual frequency receivers

Glomerular sclerosis in kidneys with congenital nephrotic syndrome (NPHS1)

Congenital nephrotic syndrome of the Finnish type (NPHS1) is a rare genetic disease caused by mutations in the NPHS1 gene encoding a major podocyte slit-diaphragm protein, nephrin. Patients with NPHS1 have severe nephrotic syndrome from birth and develop renal fibrosis in early childhood. In this work, we studied the development of glomerular sclerosis in kidneys removed from 4- to 44-month-old NPHS1 patients. The pathological lesions and expression of glomerular cell markers were studied in nephrectomized NPHS1 and control kidneys using light and electron microscopy and immunohistochemistry. An analysis of 1528 glomeruli from 20 patients revealed progressive mesangial sclerosis and capillary obliteration. Although few inflammatory cells were detected in the mesangial area, paraglomerular inflammation and fibrosis was common. The podocytes showed severe ultrastructural changes and hypertrophy with the upregulation of cyclins A and D1. Podocyte proliferation, however, was rare. Apoptosis was hardly detected and the expression of antiapoptotic B-cell lymphoma-2 and proapoptotic p53 were comparable to controls. Moderate amounts of podocytes were secreted into the urine of NPHS1 patients. Shrinkage of the glomerular tuft was common, whereas occlusion of tubular opening or protrusion of the glomerular tuft into subepithelial space or through the Bowman's capsule were not detected. The results indicate that, in NPHS1 kidneys, the damaged podocytes induce progressive mesangial expansion and capillary obliteration. Podocyte depletion, glomerular tuft adhesion, and misdirected filtration, however, seem to play a minor role in the nephron destruction

Voriconazole more likely than posaconazole increases plasma exposure to sublingual buprenorphine causing a risk of a clinically important interaction

This study aimed to determine possible effects of voriconazole and posaconazole on the pharmacokinetics and pharmacological effects of sublingual buprenorphine.We used a randomized, placebo-controlled crossover study design with 12 healthy male volunteers. Subjects were given a dose of 0.4 mg (0.6 mg during placebo phase) sublingual buprenorphine after a 5-day oral pretreatment with either (i) placebo, (ii) voriconazole 400 mg twice daily on the first day and 200 mg twice daily thereafter or (iii) posaconazole 400 mg twice daily. Plasma and urine concentrations of buprenorphine and its primary active metabolite norbuprenorphine were monitored over 18 h and pharmacological effects were measured.Compared to placebo, voriconazole increased the mean area under the plasma concentration-time curve (AUC(0-a)) of buprenorphine 1.80-fold (90 % confidence interval 1.45-2.24; P < 0.001), its peak concentration (C-max) 1.37-fold (P < 0.013) and half-life (t (A1/2) ) 1.37-fold (P < 0.001). Posaconazole increased the AUC0(0-a) of buprenorphine 1.25-fold (P < 0.001). Most of the plasma norbuprenorphine concentrations were below the limit of quantification (0.05 ng/ml). Voriconazole, unlike posaconazole, increased the urinary excretion of norbuprenorphine 1.58-fold (90 % confidence interval 1.18-2.12; P < 0.001) but there was no quantifiable parent buprenorphine in urine. Plasma buprenorphine concentrations correlated with the pharmacological effects, but the effects did not differ significantly between the phases.Voriconazole, and to a minor extent posaconazole, increase plasma exposure to sublingual buprenorphine, probably via inhibition of cytochrome P450 3 A and/or P-glycoprotein. Care should be exercised in the combined use of buprenorphine with triazole antimycotics, particularly with voriconazole, because their interaction can be of clinical importance

Congenital nephrotic syndrome

Congenital nephrotic syndrome (CNS) is a rare kidney disorder characterized by heavy proteinuria, hypoproteinemia, and edema starting soon after birth. The majority of cases are caused by genetic defects in the components of the glomerular filtration barrier, especially nephrin and podocin. CNS may also be a part of a more generalized syndrome or caused by a perinatal infection. Immunosuppressive medication is not helpful in the genetic forms of CNS, and kidney transplantation is the only curative therapy. Before the operation, management of these infants largely depends on the magnitude of proteinuria. In severe cases, daily albumin infusions are required to prevent life-threatening edema. The therapy also includes hypercaloric diet, thyroxin and mineral substitution, prevention of thrombotic episodes, and prompt management of infectious complications. The outcome of CNS patients without major extrarenal manifestations is comparable with other patient groups after kidney transplantation

New perspectives on the renal slit diaphragm protein podocin

Podocin is a critical component of the glomerular filtration barrier, its mutations causing recessive steroid-resistant nephrotic syndrome. A GenBank analysis of the human podocin (NPHS2) gene resulted in the possible existence of a new splice variant of podocin in the kidney, missing the in-frame of exon 5, encoding the prohibitin homology domain. Using RT–polymerase chain reaction and immunoblotting followed by sequence analysis, we are for the first time able to prove the expression of a novel podocin isoform (isoform 2), exclusively and constitutively expressed in human podocytes. Furthermore, we reveal singular extrarenal podocin expression in human and murine testis. Our data show the Sertoli cells of the seminiferous tubules to be the origin of testicular podocin. Confocal laser microscopy illustrates the co-localization of podocin with filamentous actin within Sertoli cells, suggesting a role of podocin in the blood/testis barrier. These results led to the rationale to examine podocin expression in testes of men with Sertoli cell-only syndrome, a disorder characterized by azoospermia. Interestingly, we observed a complete down-regulation of podocin mRNA in Sertoli cell-only syndrome, indicating a possible role of podocin in the pathogenesis of this germinal aplasia. Men with Sertoli cell-only syndrome show normal renal podocin expression, suggesting an alternate regulation of the testicular promoter. Our findings may change the perception of podocin and give new insights into the ultrastructure of glomerular slit diaphragm and the blood/testis barrier

The renal cortical interstitium: morphological and functional aspects

The renal interstitial compartment, situated between basement membranes of epithelia and vessels, contains two contiguous cellular networks. One network is formed by interstitial fibroblasts, the second one by dendritic cells. Both are in intimate contact with each other. Fibroblasts are interconnected by junctions and connected to basement membranes of vessels and tubules by focal adhesions. Fibroblasts constitute the “skeleton” of the kidney. In the renal cortex, fibroblasts produce erythropoietin and are distinguished from other interstitial cells by their prominent F-actin cytoskeleton, abundance of rough endoplasmic reticulum, and by ecto-5′-nucleotidase expression in their plasma membrane. The resident dendritic cells belong to the mononuclear phagocyte system and fulfil a sentinel function. They are characterized by their expression of MHC class II and CD11c. The central situation of fibroblasts suggests that signals from tubules, vessels, and inflammatory cells converge in fibroblasts and elicit an integrated response. Following tubular damage and inflammatory signals fibroblasts proliferate, change to the myofibroblast phenotype and increase their collagen production, potentially resulting in renal fibrosis. The acquisition of a profibrotic phenotype by fibroblasts in renal diseases is generally considered a main causal event in the progression of chronic renal failure. However, it might also be seen as a repair process

Postoperative pain management with transdermal fentanyl after forefoot surgery: a randomized, placebo-controlled study

Riika Merivirta,1 Mikko Pitk&auml;nen,2 Jouko Alanen,3 Elina Haapoja,1 Mari Koivisto,4 Kristiina Kuusniemi11Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine of Turku University Hospital and University of Turku, Turku, 2Department of Anaesthesia, Hospital Orton, Invalid Foundation, Helsinki, 3Terveystalo Clinic Hospital, Helsinki, 4Department of Biostatistics, University of Turku, Turku, FinlandBackground: Quality of life is decreased in patients with hallux valgus deformity, mainly because of pain. Significant improvement is usually achieved by surgery. However, postoperative pain can be moderate to severe for 2&ndash;3 days. The aim of the present study was to evaluate the use of transdermal fentanyl for postoperative pain management after forefoot surgery.Methods: Sixty patients undergoing hallux valgus or hallux rigidus surgery were allocated to receive a patch delivering either fentanyl 12 &micro;g/hour or placebo for postoperative pain. The consumption of rescue opioid oxycodone, the primary outcome measure, was evaluated daily until the fourth postoperative day. Total consumption of oxycodone during the study period was also assessed. Pain scores and possible adverse effects were evaluated every 6 hours during the first 24 hours and on the fourth postoperative day.Results: The use of rescue opioid was low in both groups, the median (range) consumption of oxycodone being 10 (0&ndash;50) mg on the day of surgery (no difference between the groups, P=0.31) and 0 (0&ndash;35) mg thereafter. The total combined consumption was 10 (0&ndash;105) mg in the fentanyl group and 20 (0&ndash;70) mg in the placebo group (P=0.23). There were no statistically significant differences in pain scores or adverse effects between the groups.Conclusion: As a part of multimodal analgesia with ibuprofen and acetaminophen, a patch delivering fentanyl 12 &micro;g/hour did not significantly decrease the consumption of rescue opioid or pain scores after forefoot surgery.Keywords: pain management, transdermal fentanyl, multimodal analgesia, forefoot surgery, hallux valgus, hallux rigidu