Parecoxib, propacetamol, and their combination for analgesia after total hip arthroplasty: a randomized non-inferiority trial.

BACKGROUND: This study assessed non-inferiority of parecoxib vs. combination parecoxib+propacetamol and compared the opioid-sparing effects of parecoxib, propacetamol, and parecoxib+propacetamol vs. placebo after total hip arthroplasty. METHODS: In this randomized, placebo-controlled, parallel-group, non-inferiority study, patients received one of four IV treatments after surgery: parecoxib 40 mg bid (n = 72); propacetamol 2 g qid (n = 71); parecoxib 40 mg bid plus propacetamol 2 g qid (n = 72); or placebo (n = 38) with supplemental IV patient-controlled analgesia (morphine). Patients and investigators were blinded to treatment. Pain intensity at rest and with movement was assessed regularly, together with functional recovery (modified Brief Pain Inventory-Short Form) and opioid-related side effects (Opioid-Related Symptom Distress Scale) questionnaires up to 48 h. RESULTS: After 24 h, cumulative morphine consumption was reduced by 59.8% (P < 0.001), 38.9% (P < 0.001), and 26.8% (P = 0.005) in the parecoxib+propacetamol, parecoxib, and propacetamol groups, respectively, compared with placebo. Parecoxib did not meet criteria for non-inferiority to parecoxib+propacetamol. Parecoxib+propacetamol and parecoxib significantly reduced least-squares mean pain intensity scores at rest and with movement compared with propacetamol (P < 0.05). One day after surgery, parecoxib+propacetamol significantly reduced opioid-related symptom distress and decreased pain interference with function compared with propacetamol or placebo. CONCLUSION: Parecoxib and parecoxib+propacetamol provided significant opioid-sparing efficacy compared with placebo; non-inferiority of parecoxib to parecoxib+propacetamol was not demonstrated. Opioid-sparing efficacy was accompanied by significant reductions in pain intensity on movement, improved functional outcome, and less opioid-related symptom distress. Study medications were well tolerated.

Small-world hypergraphs on a bond-disordered Bethe lattice.

We study the thermodynamic properties of spin systems with bond-disorder on small-world hypergraphs, obtained by superimposing a one-dimensional Ising chain onto a random Bethe graph with p-spin interactions. Using transfer-matrix techniques, we derive fixed-point equations describing the relevant order parameters and the free energy, both in the replica symmetric and one step replica symmetry breaking approximation. We determine the static and dynamic ferromagnetic transition and the spinglass transition within replica symmetry for all temperatures, and demonstrate corrections to these results when one step replica symmetry breaking is taken into account. The results obtained are in agreement with Monte-Carlo simulations.

Adaptive thresholds for neural networks with synaptic noise.

The inclusion of a macroscopic adaptive threshold is studied for the retrieval dynamics of both layered feedforward and fully connected neural network models with synaptic noise. These two types of architectures require a different method to be solved numerically. In both cases it is shown that, if the threshold is chosen appropriately as a function of the cross-talk noise and of the activity of the stored patterns, adapting itself automatically in the course of the recall process, an autonomous functioning of the network is guaranteed. This self-control mechanism considerably improves the quality of retrieval, in particular the storage capacity, the basins of attraction and the mutual information content.

Metastable configurations of small-world networks.

We calculate the number of metastable configurations of Ising small-world networks that are constructed upon superimposing sparse Poisson random graphs onto a one-dimensional chain. Our solution is based on replicated transfer-matrix techniques. We examine the denegeracy of the ground state and find a jump in the entropy of metastable configurations exactly at the crossover between the small-world and the Poisson random graph structures. We also examine the difference in entropy between metastable and all possible configurations, for both ferromagnetic and bond-disordered long-range couplings.

Thermodynamics of spin systems on small-world hypergraphs.

We study the thermodynamic properties of spin systems on small-world hypergraphs, obtained by superimposing sparse Poisson random graphs with p -spin interactions onto a one-dimensional Ising chain with nearest-neighbor interactions. We use replica-symmetric transfer-matrix techniques to derive a set of fixed-point equations describing the relevant order parameters and free energy, and solve them employing population dynamics. In the special case where the number of connections per site is of the order of the system size, we are able to solve the model analytically. In the more general case where the number of connections is finite, we determine the static and dynamic ferromagnetic-paramagnetic transitions using population dynamics. The results are tested against Monte-Carlo simulations.

Internal and external factors affecting the development of neuropathic pain in rodents. Is it all about pain?

It is important to know the factors that will influence animal models of neuropathic pain. A good reproducibility and predictability in different strains of animals for a given test increases the clinical relevance and possible targeting. An obligatory requirement for enabling comparisons of results of different origin is a meticulous definition of the specific sensitivities of a model for neuropathic pain and a description of the test conditions. Factors influencing neuropathic pain behavior can be subdivided in external and internal factors. The most important external factors are; timing of the measurement of pain after induction of neuropathy, circadian rhythms, seasonal influences, air humidity, influence of order of testing, diet, social variables, housing and manipulation, cage density, sexual activity, external stress factors, and influences of the experimenter. The internal factors are related to the type of animal, its genetic background, gender, age, and the presence of homeostatic adaptation mechanisms to specific situations or stress. In practice, the behavioral presentations to pain depend on the combination of genetic and environmental factors such as accepted social behavior. It also depends on the use of genetic manipulation of the animals such as in transgenic animals. These make the interpretation of data even more difficult. Differences of pain behavior between in- and outbred animals will be better understood by using modern analysis techniques. Substrains of animals with a high likelihood for developing neuropathic pain make the unraveling of specific pathophysiological mechanisms possible. Concerning the effect of stress on pain, it is important to differentiate between external and internal stress such as social coping behavior. The individual dealing with this stress is species sensitive, and depends on the genotype and the social learning. In the future, histo-immunological and genetic analysis will highlight similarities of the different pathophysiological mechanisms of pain between different species and human subjects. The final objective for the study of pain is to describe the genetics of the eliciting pain mechanisms in humans and to look for correlations with the knowledge from basic research. Therefore, it is necessary to know the genetic evolution of the different mechanisms in chronic pain. In order to be able to control the clinical predictability of a putative treatment the evolutionary pharmacogenomic structure of specific transmitters and receptors must be clarified.

Intraarticular sufentanil administration facilitates recovery after day-case knee arthroscopy.

UNLABELLED: We evaluated the efficacy of intraarticular sufentanil in the prevention of postoperative pain after day-case arthroscopic procedures. Sixty patients were randomly assigned to receive either intraarticular sufentanil, 5 or 10 microg, and saline IV, or intraarticular saline and sufentanil 5 microg IV (control). All study medication was administered in a double-blinded fashion. Postoperatively and the day after surgery, pain levels at rest and during movement (i.e., active flexion of the knee), measured by a visual analog scale, were significantly lower in the Sufentanil groups compared with the Control group. Moreover, intraarticular sufentanil significantly reduced the postoperative consumption of analgesics. The time until discharge from the postanesthesia care unit (assessed by the Aldrete score) was significantly shorter in the patients receiving sufentanil intraarticularly. There were no significant differences between the two Sufentanil groups either in the intensity of postoperative pain or in discharge times from the postanesthesia care unit. We conclude that intraarticular sufentanil in arthroscopic knee procedures is a simple, effective, safe and well-tolerated analgesic technique for outpatients undergoing arthroscopic procedures. Increasing the dose sufentanil from 5 to 10 microg intraarticularly offered no additional advantage. Intraarticular sufentanil (5-10 microg) administration improves postoperative management after day-case diagnostic arthroscopic knee procedures. IMPLICATIONS: Intraarticular sufentanil (5-10 microg) administration improves postoperative management after day-case diagnostic arthroscopic knee procedures.

Influence of intravenous clonidine pretreatment on anesthetic requirements during bispectral EEG-guided sevoflurane anesthesia.

STUDY OBJECTIVE: To assess the anesthetic effects of clonidine during sevoflurane anesthesia guided by the bispectral index (BIS), which is a processed EEG variable correlated with anesthetic-hypnotic depth. DESIGN: Placebo-controlled, double-blind clinical trial. SETTINGS: Elective laparoscopic surgery. PATIENTS: 60 ASA physical status I patients scheduled for laparoscopic surgery. INTERVENTIONS: Patients received either clonidine (3 micrograms/kg, 15 min before induction) or placebo premedication for a sevoflurane-induced and sevoflurane-maintained anesthesia. Sevoflurane was titrated against a BIS held between 40 and 50. Analgesia was provided by local infiltration with bupivacaine. Need for postoperative analgesia was recorded. RESULTS AND CONCLUSION: Mean sevoflurane requirements were not lower with clonidine pretreatment. There was statistically better perioperative hemodynamic stability (i.e., fewer episodes of hypertension and tachycardia) without clinical relevance. A decreased need for postoperative analgesia was observed.

The fetomaternal dependency of cord blood interleukin-6.

Interleukin-6 (IL-6) plays a major role in hematopoiesis, immune functioning, and the acute phase response. In umbilical cord blood, this cytokine was thought to be a marker of neonatal defense to stress and infection, however, neonatal IL-6 production is immature. We speculated that a maternal influence exists on neonatal IL-6, at least during uncomplicated deliveries. Of the 81 healthy parturients included in this study, 51 delivered vaginally, 20 with and 31 without epidural analgesia, and 30 underwent elective cesarean section, 20 with epidural and 10 with general anesthesia. Maternal blood was sampled on hospital admission and just after delivery. Neonatal blood was collected from the umbilical cord. A significant positive correlation was found between neonatal cord blood interleukin-6 levels and maternal serum IL-6 levels on admission (r = 0.57, p <0.001) and just after delivery (r = 0.79, p <0.001). This was not influenced by the type of delivery or anesthesia. Neonatal IL-6 levels were weakly negatively correlated with the duration of gestation and with the Apgar score 1 min after birth. A feto-maternal dependency of neonatal IL-6 on maternal serum IL-6 levels implies a priming or modulatory role of the maternal immune system on that of the neonate.

[Early enteral feeding in cranial trauma]. / L'alimentation entérale précoce du traumatisé crânien.

Until some years ago, patients suffering from head injury were poorly fed and nutrition was not a primary concern in the medical treatment of these patients. To date, six studies on head-injury patients have examined the effect of nutritional support on their outcome. All showed that lack of adequate nutrition contributed to increased mortality and morbidity. Head-injured patients on conventional enteral nutrition receive significantly less calories and proteins, resulting in an increased morbidity and mortality rate. Most of the severely head injured patients receiving enteral nutrition do not tolerate enteral feedings because of abnormal gastric emptying. The mechanisms of altered gastric function remain obscure. Increased intracranial pressure, cytokines, corticotropin-releasing factor, opiates, and other agents may all play a role. Impaired gastric motility has led to increasing use of small bowel feeding in head-injured patients. Jejunal feeding enables a higher caloric input and a better nitrogen balance. Moreover, it enables early enteral administration of nutrients in a safe and efficient way. Early administration of nutrients may be extremely important as it seems to decrease the hypermetabolic response to traumatic injury. Therefore, early jejunal enteral feeding may become an important cornerstone in the medical management of head-injured patients.

Anti-retroviral drugs--implications for dental prescribing.

Many patients with HIV/AIDS are now being treated with two or more drugs to reduce HIV viraemia and boost CD4 T-cell counts. Patients are using these drugs earlier in the course of their disease and so GDPs are likely to encounter them in practice. The drugs have dramatically altered short term prognosis but are potent and have potentially serious drug interactions. Some of these drugs have interactions with drugs used in the dental care setting and this paper sets out to summarise those that are relevant in this area.

Clara cell protein: concentrations in cerebrospinal fluid, serum and amniotic fluid.

Clara cell protein (CC16) is an endogenous anti-inflammatory agent. It is produced mainly in the respiratory and urogenital tracts. CC16 has been quantified in serum, but not in cerebrospinal fluid (CSF). The aim of this study was to examine CSF CC16 in relation to age, gender and serum CC16, and to examine CC16 levels in parturients. If CC16 levels are increased with age and during pregnancy, it may be responsible for the attenuation of inflammatory diseases such as multiple sclerosis during these conditions. CC16 was measured in CSF and serum taken just before Caesarean section (n=33) or just before an elective surgical procedure in females (n=52) or males (n=31). Fetal serum, amniotic fluid, and maternal urine were also sampled during Caesarean section. CC16 levels in CSF did not differ between parturients and an age and gender matched non-pregnant group, but was higher in male than in female patients. There was a significant and positive relationship between age and CSF CC16 levels and between serum and CSF CC16 levels. Fetal CC16 was significantly and positively correlated with amniotic fluid CC16. The present study suggests that CC16 found in CSF originates from passive diffusion from blood, and that CC16 found in amniotic fluid is derived from the fetal lung. During pregnancy, CC16 does not appear to contribute to alterations which occur in the progression of inflammatory disorders.

The effects of anticoagulation and processing on assays of IL-6, sIL-6R, sIL-2R and soluble transferrin receptor.

Levels of plasma cytokines, their receptors or immune-related peptides, are used in experimental and clinical medicine. However, no standards are available regarding the use of anticoagulants or blood processing including the technique of blood collection or time delay between blood sampling and centrifugation. Blood was collected from 10 patients in order to assay interleukin 6, soluble interleukin 6 receptor, soluble interleukin 2 receptor and soluble transferrin receptor by enzyme-linked immunosorbent assay (ELISA). At the time of sampling, five different collecting tubes were used: allowing coagulation, in the presence of EDTA, with EDTA being administered to the serum after its separation, in citrated and in heparinized blood. Blood was centrifuged 10 min after collection and separated serum or plasma was immediately frozen at -20 degrees C. To study the effect of time delay between blood sampling and processing, blood from 11 other patients was sampled, allowing coagulation; or in EDTA tubes and stored at 4 degrees C. The blood was centrifuged 10 min, 8 h and 24 h later, and the separated serum or EDTA plasma was stored at -20 degrees C until thawed for protein determination. Plasma interleukin 6 and soluble interleukin 6 receptor concentrations did not depend on the type of anticoagulant used or the time delay between sampling and processing. Soluble interleukin 2 receptor concentrations were not influenced by time delay before centrifugation, but concentrations were increased 10-fold in EDTA plasma exclusively when EDTA had contact with blood cells. Soluble transferrin receptor concentrations rose progressively with storage time before centrifugation. Contact of EDTA to whole blood or serum resulted in the same increase of soluble transferrin receptor concentration. The results suggest that standardization of the use of anticoagulant and time delay before centrifugation and serum or plasma separation is necessary for soluble interleukin 2 receptor and soluble transferrin receptor.

An attempt to withdraw coverage by the insurance company in the event of gross negligence. Costs totalling US $ 4.5 million.

In its judgement of 11 June 1993, the Court of Appeal of Brussels upheld the personal liability of a trainee and the in solidum liability of the hospital in a case where an erroneous spinal injection caused permanent paraplegia and incontinence. Although the attempt of withdrawal coverage by the insurance company on base of the concept of gross negligence, did not succeed in this case, it is clear that under the new insurance law of 25 June 1992, several risks will not be covered by the insurance companies in the future. The exemplary list of gross negligence cases, which may be used by the insurance companies, involves predominantly anesthesiology practice. The coverage of several insurance contracts exclude e.g., damages resulting from simultaneous anesthesia, or from the absence of an anesthesiologist during the full course of the surgery and damages resulting from anesthesia in the absence of necessary monitoring and reanimation equipment.