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Laparoscopic cholecystectomy is the «gold» standard for the surgical treatment of patients with calculous cholecystitis. It is believed that laparoscopic cholecystectomy is not only safe, but also is painless in the postoperative period. At the same time the pain syndrome after laparoscopic cholecystectomy may be very serious. The article discusses the formation and localization of the pain syndrome, diagnostics and pharmacotherapy of the pain syndrome after laparoscopic cholecystectomy.

s / Osteoarthritis and Cartilage 20 (2012) S54–S296 S178 JSN scores, medially or laterally. Progression was compartment specific for the various clusters. Medial progression occurred only in clusters 1, 2 and 4, most dramatically so in cluster 4 (48%). Cluster 3 again only showed lateral progression (61%). Conclusions: We found clear differences between the various clusters. Cluster 1 could be described as amild type of OA,with nodenuded bone and limited OA progression. Cluster 3 and 4weremore severe and erosive types of OA, showing strong increases in area of denudedbonewith increasingOA severity, and a high prevalence of progression. Interestingly, cluster 3 was purely a lateral type of OA, while cluster 4was purelymedial in all respects. The causes that led to differences between the clusters remain speculative. The higher prevalence of reported trauma in cluster 3 and 4, the more aggressive OA types might suggest a difference in OA initiation. Wekept the complexityof themodels lowtoreduce the riskofoverfittingand increase the likelihood that our findings are generalizable to other cohorts. The fact that clusters also differed on data not included in cluster finding (trauma and progression) indicates that the found clusters are meaningful. In conclusion, latent class cluster analysis confirmed the suspected existence of distinct subtypes of knee OA.

Objective: To compare the efficacy of etoricoxib, lumiracoxib, celecoxib, non-selective (ns) NSAIDs and acetaminophen in the treatment of osteoarthritis (OA) Methods: Randomized placebo controlled trials investigating the effects of acetaminophen 4000mg, diclofenac 150mg, naproxen 1000mg, ibuprofen 2400mg, celecoxib 100-400mg, lumiracoxib 100-400mg, and etoricoxib 30-60mg with treatment duration of at least two weeks were identified with a systematic literature search. The endpoints of interest were pain, physical function and patient global assessment of disease status (PGADS). Pain and physical function reported on different scales (VAS or LIKERT) were translated into effect sizes (ES). An ES 0.2 - 0.5 was defined as a “small” treatment effect, whereas ES of 0.5 – 0.8 and > 0.8 were defined as “moderate” and “large”, respectively. A negative effect indicated superior effects of the treatment group compared to the control group. Results of all trials were analyzed simultaneously with a Bayesian mixed treatment comparison. Results: There is a >95% probability that etoricoxib (30 or 60mg) shows the greatest improvement in pain and physical function of all interventions compared. ESs of etoricoxib 30mg relative to placebo, celecoxib 200mg, ibuprofen 2400mg, and diclofenac 150mg were -0.66 (95% Credible Interval -0.83; -0.49), -0.32 (-0.50; -0.14), -0.25 (-0.53; 0.03), and -0.17 (-0.41; 0.08), respectively. Regarding physical functioning, ESs of etoricoxib 30mg relative to placebo, celecoxib 200mg, ibuprofen 2400mg, and diclofenac 150mg were -0.61 (-0.76; -0.46), -0.27 (-0.43; -0.10), -0.20 (-0.47; 0.07), and -0.09 (- 0.33; 0.14) respectively. The greatest improvements in PGADS were expected with either etoricoxib or diclofenac. Conclusion: The current study estimated the efficacy of acetaminophen, nsNSAIDs, and COX-2 selective NSAIDs in OA and found that etoricoxib 30 mg is likely to result in the greatest improvements in pain and physical function. Differences in PGADS between interventions were smaller.

Hepatic encephalopathy is a serious and potentially fatal complication of both acute and chronic liver disease, arising as a result of hepatocellular failure, cirrhosis and/or portal-systemic shunting (Ferenci et al, 2002). It reflects a broad spectrum of neuropsychiatric abnormalities, encompassing a range of defects in psychomotor, locomotive, cognitive, emotional and behavioural functions (Prakash and Mullen, 2010). Hepatic encephalopathy is either overt or minimal. While overt hepatic encephalopathy can be diagnosed using bedside clinical tests, minimal hepatic encephalopathy is clinically invisible and requires psychometric testing to diagnose. The rising prevalence of end-stage viral hepatitis-related liver disease, coupled with the growing problem of alcoholic and non-alcoholic fatty liver disease, has significantly increased the burden of disease from cirrhosis (Mooney et al, 2007; Fleming et al, 2008), so recognition and appropriate management of the manifestations of decompensating cirrhosis (including hepatic encephalopathy) is essential. Hepatic encephalopathy has a substantial societal burden because of its impact on survival, quality of life and daily functioning, including an impaired ability to drive, leaving patients especially vulnerable to road traffic accidents (Ferenci et al, 2002; Prakash and Mullen, 2010).

In 2003 the English labour government placed a mandatory responsibility on local authorities to offer direct payments to all eligible people and are continuing to actively promote this service option. This paper explores some of the key reasons why the take-up of direct payments for mental health service users has been particularly slow compared to other user groups. The main themes of this article have been drawn from a large, detailed review of literature and research published between 2000 and 2006 and will provide practitioners and students with an overview of the key current implementation issues concerning direct payments in mental health services. Several major obstacles and dilemmas have contributed to low uptake including the legislation itself as well as local authority guidance. This paper discusses the documented confusion surrounding eligibility for mental health service users as well as the detrimental impact of fluctuating needs set in the context of a dual service provision of health and s...

Montelukast, a potent leukotriene receptor antagonist, is approved for treatment of both asthma and allergic rhinitis (AR). No studies to date have examined whether montelukast can improve asthma control over a long period of time in patients with seasonal AR and asthma.To evaluate asthma control and use of asthma-related medical resources by patients with inadequately controlled mild to moderate persistent asthma and seasonal AR who required addition of montelukast as part of routine care.This multicenter, 24-month, pre-post retrospective observational study included patients receiving current inhaled corticosteroid (ICS) therapy (alone or in combination with long-acting beta-agonist [LABA]), who received add-on treatment with montelukast for 12 consecutive months. The incidence of asthma attacks, defined as emergency department visit, hospitalization, or oral corticosteroid use for asthma, was compared for the year before and the year after addition of montelukast to therapy.For the 696 patients from Italy, Poland, and Spain who were included in the analyses, the proportion of patients experiencing an asthma attack declined from 31.5% in the year before to 10.1% (p0.001) the year after addition of montelukast to therapy. Proportions of patients with an asthma-related emergency room visit, hospitalization, and oral corticosteroid use declined from 18.7% to 3.9%, from 5.2% to 1.4%, and from 17.5% to 5.9% (all p0.01), respectively. The incidence of these outcomes declined in all three countries, regardless of baseline asthma severity or asthma therapy (ICS alone or ICS + LABA). Important study limitations include the possibility of selection bias or missing medical chart data in this retrospective study design. Also noteworthy is the inclusion of only those patients who remained persistent with montelukast therapy. Therefore, the results of the study are relevant for patients who remain persistent with montelukast therapy.Addition of montelukast to current ICS therapy improved long-term asthma control and resulted in substantial reductions in asthma-related resource use by patients with mild or moderate persistent asthma and concomitant seasonal AR who were persistent with montelukast therapy in this retrospective observational study.

Background Although bivariate relationships between depressive symptoms, health beliefs, and medication adherence have been identified, the complex relationship among these 3 constructs has not been explicated. Objective This study examines the mediating role of patients' beliefs about diabetes and diabetes medications in relation to depressive symptoms and diabetes medication adherence. Methods A survey was sent to 1700 persons with type 2 diabetes who were enrolled in a managed care organization in the United States. The bivariate relationships between depressive symptoms, diabetes-related health beliefs, and diabetes medication adherence were assessed. A structural equation model was developed to determine if health beliefs mediated the relationship between depressive symptoms and medication adherence. Results Usable responses were received from 445 subjects. Greater depressive symptoms were associated with lower adherence to diabetes medications. The structural equation model indicated that the effect of depressive symptoms on medication adherence was mediated through perceived side effect barriers, perceived general barriers, and self-efficacy. Patients with severe depressive symptoms perceived more barriers to treatment adherence and were less confident in their ability to adhere to medication. In turn, reduced self-efficacy and heightened perceived barriers had a negative association with patients' adherence to diabetes medication regimens. Conclusions Decreased adherence to diabetes medications in patients with both diabetes and depressive symptoms may be partly explained by the association of depression with patients' beliefs about diabetes medications and their self-efficacy for medication use.

Antibody fragments have been shown to penetrate into the anterior chamber when applied to the cornea. The aim of this study was to investigate whether such fragments could penetrate into the vitreous cavity after topical administration to the ocular surface of rabbits.An engineered single-chain variable-domain antibody fragment with specificity for an irrelevant rat determinant was applied as a 50 microl eye drop to the eyes of live rabbits at 20-min intervals over 12 h. Eye drops contained 0.8-1.1 mg/ml protein in a buffered salt solution supplemented with penetration and viscosity enhancers. Samples were collected by paracentesis from the vitreous cavity immediately postmortem. Antibody fragments in these samples were quantified by measuring the binding activity to specific antigen, using flow cytometry.Topically applied antibody fragments were detectable in the vitreous of rabbit eyes after 4-12 h but had cleared at 12 h following the final eye drop. Concentrations of the antibody fragment in the vitreous samples were estimated to be 50-150 ng/ml at 12 h. Penetration of the parental whole antibody into the vitreous was not observed.Antibody fragments penetrate into the vitreous chamber of the rabbit eye after topical administration to the ocular surface. Such fragments may have therapeutic potential for diseases affecting the posterior segment.

s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S224 397 LONGITUDINAL ASSESSMENT OF PAIN IN PATIENTS WITH KNEE OSTEOARTHRITIS (OA): USING DATA FROM THE STUDY OF REAL WORLD THERAPIES (SORT) F. Rannou y, P.M. Peloso z, S. Rajagopalan x, P. Mavros z, S.V. Everett z, N. Arden k, P. Conaghan{, C.J. Phillips #, R.A. Moore yy, M. van de Laar zz, S.D. Taylor z. yUniv. of Paris, Paris, France; zMerck Sharp & Dohme, Inc., Whitehouse Station, NJ, USA; xMedData Analytics, Inc., East Brunswick, NJ, USA; kUniv. of Southampton, Southampton, United Kingdom; {Univ. of Leeds, Leeds, United Kingdom; # Swansea Univ., Swansea, United Kingdom; yyOxford Univ., Oxford, United Kingdom; zzUniv. of Twente, Enschede, Netherlands Pain is a key concern for patients suffering with osteoarthritis (OA) and is one of the most common reasons for seeking care from a general practitioner. In this analysis, inadequate pain relief (IPR) was defined as a score of >4 on the Brief Pain Inventory (BPI) average pain question. Characterizing the variability of knee OA pain is critical in providing clinical insight and initiating effective treatment plans. Purpose: The objective was to examine variability of average pain scores, pain severity and WOMAC pain subscale scores over 12 months in knee OA patients who reported IPR at baseline as compared to those who reported non-IPR using data from SORT Methods: OA knee patients > 50 years who required medicinal therapies were recruited from physicians’ practices at 53 centres in 6 European countries. Pain was assessed by the (BPI) using average pain score and pain severity and the WOMAC Pain subscale. Descriptive statistics were used to describe and contrast IPR and non-IPR cohorts over 12 months. Results: A total of 1284 patients were enrolled with 1187 eligible for evaluation and 53.8% met the definition of IPR at baseline. Fluctuations in average pain score, pain severity, and WOMAC pain were minimal. When contrasting IPR vs. non-IPR cohorts, the magnitude of the variability was similar overtime based on group level standard deviations. Additionally, statistically significant differences between the cohorts remained regardless of the pain measures (p < 0.0001). Conclusions: Patients with IPR appear to have stable disease and remain in IPR over time. Pain levels were relatively stable in this population suggesting the importance of initially treating OA pain with alternative therapies to avoid IPR. 398 SERVICE PROVISION FOR PATIENTS WITH CHRONIC PAIN AFTER KNEE REPLACEMENT: AN EVALUATION OF CURRENT PRACTICE IN HIGH VOLUME ORTHOPAEDIC CENTRES V. Wylde, F. MacKichan, S. Dixon, R. Gooberman-Hill. Univ. of Bristol, Bristol, United Kingdom Background: Total knee replacement is one of the most commonly performed elective surgical procedures. The operation is usually conducted to relieve pain and improve function, but recent studies indicate that up to 20% of patients experience chronic post-surgical pain (CPSP) after total knee replacement; this equates to around 16,000 new cases of CPSP in the UK each year. The wider literature on chronic pain indicates that people with chronic pain encounter patchy service provision. People with CPSP after knee replacement have already undergone major surgery for pain, and follow-up after surgery may have a role in care and pain management. However, we do not know what services are on offer to this group, nor whether there is consistency in service provision including identification of need and any associated referral processes. We therefore conducted a survey to scope current UK service provision for patients with CPSP after total knee replacement. Methods: This ongoing project is funded through a National Institute for Health Research (NIHR) Programme Development Grant on the treatment and management of chronic pain after total knee replacement (the STAR programme). The project was conducted as a service evaluation of services at high volume NHS orthopaedic centres across the UK. The 23 NHS orthopaedic centres that conduct 500 or more primary total knee replacements per year were identified from the National Joint Registry. Contact was made with a key health professional at each centre who was familiar with the processes of postoperative assessment and follow-up. A structured telephone interview was conducted to obtain information about usual patient pathways at the different centres. Questions focused on identification, triage, treatment, management, and referral of patients with CPSP after total knee replacement. Information was recorded on a standardised proforma and entered into an Access database. Information was then collated and summarised in Excel. Results: The survey has been completed by 14/23 NHS orthopaedic centres. Data collection is ongoing, with completion by February 2014. All centres routinely follow-up patients at 6 weeks after total knee replacement, although the provision and timing of subsequent appointments vary. The majority of centres do not have a specific time point at which patients are diagnosed with CPSP; in those that do, time points range from 4.5–18 months post-operative. When assessing pain levels, most centres use patient narrative, and there is some use of a standardised tool, most frequently a visual analogue scale. Four centres reported using a standardised protocol for assessment of patients with CPSP, and two centres reported use of a standardised protocol for management and treatment. Treatment and management options offered to patients vary between and within centres, and include further orthopaedic interventions, referral to pain management services, analgesia review, and referral for physiotherapy. Conclusion: This survey of current service provision for patients with CPSP after total knee replacement identified national variation in the identification, assessment and management of these patients. Although some centres have developed a care pathway for patients with CPSP, the majority of centres lack standardised protocols to guide care provision. This highlights the potential to develop and evaluate standardised referral pathways and integrated service provision for patients with CPSP after total knee replacement. 399 KNEE ARTHRITIS: A CONFIRMED BURDEN C. Taieb y, P. Bruel z, M. Auges x. y PFSA, Boulogne Billancourt, France; z PFS, Castres, France; x PFSA, Paris, France Purpose: Arthritis is a joint disease characterised by progressive degradation of the cartilage. Arthritis can cause suffering in an acute manner called “inflammatory flare-up”, or in a more chronic manner leading to sometimes severe disability, which affects the everyday life of patients. Among the different locations of arthritis, arthritis of the knee

Anomalous molecular line profile shapes are the strongest indicators of the presence of the infall of gas that is associated with star formation. Such profiles are seen for well-known tracers, such as HCO+, CS and H2CO. In certain cases, optically thick emission lines with appropriate excitation criteria may possess the asymmetric double-peaked profiles that are characteristic of infall. However, recent interpretations of the HCO+ infall profile observed towards the protostellar infall candidate B335 have revealed a significant discrepancy between the inferred overall column density of the molecule and that which is predicted by standard dark cloud chemical modelling. This paper presents a model for the source of the HCO+ emission excess. Observations have shown that, in low-mass star-forming regions, the collapse process is invariably accompanied by the presence of collimated outflows; we therefore propose the presence of an interface region around the outflow in which the chemistry is enriched by the action of jets. This hypothesis suggests that the line profiles of HCO+, as well as other molecular species, may require a more complex interpretation than can be provided by simple, chemically quiescent, spherically symmetric infall models. The enhancement of HCO+ depends primarily on the presence of a shock-generated radiation field in the interface. Plausible estimates of the radiation intensity imply molecular abundances that are consistent with those observed. Further, high-resolution observations of an infall-outflow source show HCO+ emission morphology that is consistent with that predicted by this model.

Quantitative results for the time-dependent behaviour of the fractional abundance of HC3N in dense cores are given. In addition to the standard 'early-time' HC3N maximum found for many situations in which elements other than hydrogen are initially in atomic form, a secondary maximum occurs for a variety of conditions after depletion has become significant. The secondary maximum can be sufficiently large and occur for a sufficiently wide range of physical conditions that the assertion that the presence of high fractional abundances of cyanopolyynes implies chemical and dynamical youth for the cyanopolyyne emission peak in TMC-1 and other star-forming regions may not be secure.

Stars form from dense pockets of gas that have undergone gravitational collapse, and young stars are still embedded in this molecular material. There is no lack of evidence that the outflows from these stars, manifested in the form of Herbig-Haro objects and jets, interact dynamically with the dense gas either in the form of shock excitation or the imparting of momentum; molecular outflows, H2 emission, and perhaps also CO and SiO bullets and jets, are tracers of this phenomenon. However there are a set of radio observations of molecules showing emission near HH objects that are remarkable for their apparent lack of signatures of such dynamic interaction. A likely cause of this ‘quiescent’ emission is a radiative interaction between the HH shock system emission and ambient gas.

Both CH+ and OH can be produced in warm gas via endothermic reactions, yet recent observations by Federman, Weber & Lambert indicate little correspondence between the abundances for these molecules. A non-thermal origin for CH+ production is therefore suggested. Chemical models of diffuse cloud envelopes that include the presence of Alfven waves are shown to be consistent with the new observations. In these models, CH+ is formed as a result of the streaming of C+ ions, which are influenced by the passage of Alfven waves, relative to the cold background gas. Since the background gas is cold, OH production arises solely from ion-molecule reactions initiated by cosmic ray ionization.

Increased production of PTH-related protein (PTHrP) and PTH is frequently responsible for hypercalcemia and its associated morbidity. However, it is unclear whether these peptides produce identical effects on cells in the osteoclast lineage in vivo. To examine the effects of continuous in vivo exposure to these factors on both the osteoclast precursors and mature osteoclasts, we inoculated Chinese hamster ovarian cells expressing PTH-(1-84), PTHrP-(1-141), or nontransfected Chinese hamster ovarian cells into nude mice. The effects of these tumors on blood ionized calcium, plasma PTH and PTHrP concentrations, and osteoclast formation were then determined. PTH and PTHrP tumor-bearing mice became hypercalcemic (1.90 +/- 0.04 and 1.97 +/- 0.16 mmol/liter, respectively) compared with control mice (1.29 +/- 0.015 mmol/liter). After 4 days of hypercalcemia, mice were killed, and bone marrow cells were harvested to examine cells at three discrete stages of osteoclast development: multipotent osteoclast precursors, the granulocyte/macrophage colony-forming unit; more committed marrow mononuclear osteoclast precursors; and mature osteoclasts. Neither PTH nor PTHrP had an effect on granulocyte/macrophage colony-forming unit, but similarly increased the number of more committed mononuclear osteoclast progenitors as well as mature osteoclasts in the calvaria. No differences were detected between the effects of PTH and PTHrP on cells in the osteoclast lineage in vivo. Thus, PTH and PTHrP appear to affect only more differentiated cells in the osteoclast lineage, and the differences in osteoclastic bone resorption between primary hyperparathyroidism and humoral hypercalcemia of malignancy are probably due to mechanisms other than effects on osteoclast precursor cells in vivo.

Objective.To quantify the relative importance that UK physicians attach to the benefits and risks of current drugs when making treatment decisions for patients with osteoarthritis (OA).Methods.Physicians treating at least 10 patients with OA per month completed an online discrete-choice experiment survey and answered 12 treatment-choice questions comparing medication profiles. Medication profiles were defined by 4 benefits (reduction in ambulatory pain, resting pain, stiffness, and difficulty doing daily activities) and 3 treatment-related risks [bleeding ulcer, stroke, and myocardial infarction (MI)]. Each physician made medication choices for 3 of 9 hypothetical patients (varied by age, history of MI, hypertension, and history of gastrointestinal bleeding). Importance weights were estimated using a random-parameters logit model. Treatment-related risks physicians were willing to accept in exchange for various reductions in ambulatory and resting pain also were calculated.Results.The final sample was 475. A reduction in ambulatory pain from 75 mm to 25 mm (1.6 units) was 1.1 times as important as an increase in MI risk from 0% to 1.5% (1.5 units). The greatest importance was for eliminating a 3% treatment-related risk of MI or stroke. On average, physicians were willing to accept an increase in bleeding ulcer risk of 0.7% (95% CI 0.4%–1.7%) for a reduction in ambulatory pain of 75 mm to 50 mm.Conclusion.When presented with well-known benefits and risks of OA treatments, physicians placed greater importance on the risks than on the analgesic properties of the drug. This has implications for the reporting of the results of clinical research to physicians.

Patients with chronic hepatitis C infection may exhibit neuropsychological symptoms and cognitive impairment. Post-mortem studies of hepatitis C virus HCV quasispecies and replicative intermediates indicate that the brain might act as a separate compartment for viral replication and microglia may be the locus for infection and subsequent neuroinflammatory activity. We sought to use two independent in vivo imaging techniques to determine evidence of neuroinflammation in patients with histologically mild chronic hepatitis C. Using positron emission tomography (PET) with a ligand for microglial/brain macrophage activation, (11)C-(R)-PK11195 (PK11195) and cerebral proton magnetic resonance spectroscopy, we determined whether there was evidence of neuroinflammation in a pilot study of 11 patients with biopsy-proven mild chronic hepatitis C, compared to healthy volunteers. Patients were characterized by cognitive testing and the fatigue impact scale to assess for CNS impairment. PK11195 binding potential was significantly increased in the caudate nucleus of patients, compared to normal controls (P = 0.03). The caudate and thalamic binding potential were more significantly increased in six patients with genotype 1 infection (P = 0.007) and positively correlated with viraemia (r = 0.77, P = 0.005). Basal ganglia myo-inositol/creatine and choline/creatine ratios were also significantly elevated in patients with chronic hepatitis C compared to normal controls (P = 0.0004 and P = 0.01, respectively). Using PET, we demonstrated evidence of microglial activation, which positively correlated with HCV viraemia and altered cerebral metabolism in the brains of patients with mild hepatitis C. This provides further in vivo evidence for a neurotropic role for HCV.

We compared in vivo hepatic (31) P magnetic resonance spectroscopy ((31) P MRS) and hepatic vein transit times (HVTT) using contrast-enhanced ultrasound with a microbubble agent to assess the severity of hepatitis C virus (HCV)-related liver disease. Forty-six patients with biopsy-proven HCV-related liver disease and nine healthy volunteers had (31) P MRS and HVTT performed on the same day. (31) P MR spectra were obtained at 1.5 T. Peak areas were calculated for metabolites, including phosphomonoesters (PME) and phosphodiesters (PDE). Patients also had the microbubble ultrasound contrast agent, Levovist (2 g), injected into an antecubital vein, and time-intensity Doppler ultrasound signals of the right and middle hepatic veins were measured. The HVTT was calculated as the time from injection to a sustained rise in Doppler signal 10% greater than baseline. The shortest times were used for analysis. Based on Ishak histological scoring, there were 15 patients with mild hepatitis, 20 with moderate/severe hepatitis and 11 with cirrhosis. With increasing severity of disease, the PME/PDE ratio was steadily elevated, while the HVTT showed a monotonic decrease. Both imaging modalities could separate patients with cirrhosis from the mild and moderate/severe hepatitis groups. No statistical difference was observed in the accuracy of each test to denote mild, moderate/severe hepatitis and cirrhosis (Fisher's exact test P =1.00). (31) P MRS and HVTT show much promise as noninvasive imaging tests for assessing the severity of chronic liver disease. Both are equally effective and highly sensitive in detecting cirrhosis.

Improvements in neurocognitive (NC) function have been associated with commencing antiretroviral therapy in HIV-infected subjects. However, the dynamics of such improvements are poorly understood.We assessed changes in NC function via a validated computerized battery (CogState™, Melbourne, Victoria, Australia) at baseline and after 24 and 48 weeks in a subset of therapy-naïve neuro-asymptomatic HIV-infected subjects, randomized to commence three different antiretroviral regimens.Of 28 subjects enrolled in the study, nine, eight and 11 were randomly allocated to commence tenofovir/emtricitabine with efavirenz (arm 1), atazanavir/ritonavir (arm 2) and zidovudine/abacavir (arm 3), respectively. Overall improvements in NC function were observed at week 24 and function continued to improve at week 48 (changes in z-score for overall cognitive global score of 0.16 and 0.18 at weeks 24 and 48, respectively). Within the NC speed domains, generally greater improvements were observed in arms 2 and 3, compared with arm 1 (changes in z-score for composite speed scores at weeks 24/48 of 0.16/0.16, -0.29/-0.24 and -0.15/-0.31 in arms 1, 2 and 3, respectively; P = 0.04 for change at week 48 in arm 3 versus arm 1). Finally, improvements in executive function occurred later (only observed at week 48) and were driven by improvements in arm 3 (z-score changes of 0.23, 0.06 and -0.78 in arms 1, 2 and 3, respectively; P = 0.02 for change in arm 3 versus arm 1).Improvements in NC function continue over the first year after initiating antiretroviral therapy in neuro-asymptomatic HIV-infected subjects.

Our objective was to develop a working definition of nonresponse to analgesic treatment of arthritis, focusing on the measurement of pain on the 0–100 mm pain visual analog scale (VAS). We reviewed the literature to assess the smallest detectable difference (SDD), the minimal detectable change (MDC), and the minimal clinically important difference (MCID). The SDD for improvement reported in three studies of rheumatoid arthritis was 18.6, 19.0, and 20.0. The median MDC was 25.4 for 7 studies of osteoarthritis and 5 studies of rheumatoid arthritis (calculated for a reliability coefficient of 0.85). The MCID increased with increasing baseline pain score. For baseline VAS tertiles defined by scores of 30–49, 50–65, and >65, the MCID for improvement was, respectively, 7–11 units, 19–27 units, and 29–37 units. Nonresponse can thus be defined in terms of the MDC for low baseline pain scores and in terms of the MCID for high baseline scores.

Objectives. To evaluate the cost-effectiveness of etoricoxib (90 mg) relative to celecoxib (200/400 mg), and the nonselective NSAIDs naproxen (1000 mg) and diclofenac (150 mg) in the initial treatment of ankylosing spondylitis in Norway.Methods. A previously developed Markov state-transition model was used to estimate costs and benefits associated with initiating treatment with the different competing NSAIDs. Efficacy, gastrointestinal and cardiovascular safety, and resource use data were obtained from the literature. Data from different studies were synthesized and translated into direct costs and quality adjusted life years by means of a Bayesian comprehensive decision modeling approach.Results. Over a 30-year time horizon, etoricoxib is associated with about 0.4 more quality adjusted life years than the other interventions. At 1 year, naproxen is the most cost-saving strategy. However, etoricoxib is cost and quality adjusted life year saving relative to celecoxib, as well as diclofenac and naproxen after 5 years of follow-up. For a willingness-to-pay ceiling ratio of 200,000 Norwegian krones per quality adjusted life year, there is a >95% probability that etoricoxib is the most-cost-effective treatment when a time horizon of 5 or more years is considered.Conclusions. Etoricoxib is the most cost-effective NSAID for initiating treatment of ankylosing spondylitis in Norway.

Observations of the CO(J = 1 → 0) line are commonly used as a tracer for molecular material in interstellar clouds. The ratio of the H 2 column density to the integrated intensity of this line is often taken to be constant, despite theoretical and observational uncertainty on this point. Cloud models are presented which attempt to identify how this ratio depends on cloud parameters, testing a simple theoretical argument that suggests its invariance with respect to density. The apparent constancy of the ratio can be understood if clouds are clumpy on a scale of A V ≤ 2 mag

Carbonaceous dust is expected to release hydrocarbons upon erosion in interstellar shocks. When released into predominantly atomic gas, the subsequent chemistry of these hydrocarbons may lead to detectable amounts of CH and CH + . We predict column densities for these molecules and show how the N(CH + )/N(CH) ratio may constrain the shock parameters

The correlations deduced by Boulanger et al. (1990) from IRAS maps of the Chamaeleon, Taurus and Ursa Major molecular cloud complexes are interpreted in terms of the evolutionary hydrogenated amorphous carbon model of interstellar dust. In particular, regions of relatively strong 12-micron emission may be regions where recently accreted carbon is being converted by ambient UV to small PAHs in situ. Regions of weak 12-micron emission are probably quiescent regions where carbon has been annealed to amorphous carbon. Observational consequences of these inferences are briefly described.

BACKGROUND: Long-term studies indicate that adherence to asthma controller therapy decreases over time, and persistence with therapy may be poor. METHODS: This primary care database study assessed persistence with therapy over one year after first prescription of inhaled corticosteroid (ICS) for children aged 2–14 years with a diagnosis of asthma. Children with intermittent asthma were excluded. Discontinuation was defined as no ICS prescription during the last three months of the follow-up year. RESULTS: 2220 of 7375 children receiving a first prescription for ICS had persistent asthma. Mean (±SD) age was 7.3 (±3.8) years; 59.5% were male. A total of 745 (33.6%) continued initial ICS, 133 (6.0%) received add-on therapy, 150 (6.8%) switched to another asthma therapy, and 1192 (53.7%) discontinued therapy. These percentages were similar for children aged 2–5 or 6–14 years. CONCLUSION: Persistence with first-time ICS monotherapy is poor among children with persistent asthma.

Combinations of noninvasive markers may improve discrimination of chronic liver disease severity. The aims of this study were to compare four validated serum and ultrasound-based markers of hepatic disease severity head-to-head with liver biopsy and to assess optimal combinations with consideration of cost. A total of 67 patients with biopsy-proven chronic hepatitis C underwent all four techniques on the same visit [aspartate aminotransferase (AST) to platelet ratio index (APRI); Enhanced Liver Fibrosis (ELF) panel; transient elastography (TE) and ultrasound microbubble hepatic transit times (HTT)]. Markers were combined according to increasing financial cost and ordinal regression used to determine contributions. APRI, ELF, TE and HTT predicted cirrhosis with diagnostic accuracy of 86%, 91%, 90% and 83% respectively. ELF and TE were the most reliable tests with an intra-class correlation of 0.94 each. Either ELF or TE significantly enhanced the prediction of fibrosis stage when combined with APRI, but when combined together, did not improve the model further. Addition of third or fourth markers did not significantly improve prediction of fibrosis. Combination of APRI with either ELF or TE effectively predicts fibrosis stage, but combinations of three or more tests lead to redundancy of information and increased cost.

Central nervous system (CNS) manifestations of chronic hepatitis C virus (HCV) and chronic human immune deficiency virus-1 (HIV-1) infections have been reported, but the impact of acute HCV infection on the CNS is unknown. A total of 10 individuals with chronic stable HIV-1 with documented acute HCV (HCV-RNA polymerase chain reaction positive and HCV antibody negative, group 1) underwent cerebral proton magnetic resonance spectroscopy (MRS) using acquisition parameters to quantify myo-inositol/creatine (mI/Cr) ratio in the right basal ganglia (RBG). Two matched control groups also underwent MRS; group 2: ten with chronic HIV-1 and no evidence of HCV, and group 3: ten with no evidence of HIV or HCV. Subjects also underwent computerized neurocognitive assessments (CogState). RBG mI/Cr ratio in group 1 (acute HCV in a background of HIV) was significantly lower than that in groups 2 and 3 [2.90 (+/-0.7) vs 3.34 (+/-0.4) and 3.43 (+/-0.4), mean (SD) for group 1 vs 2 and 3 respectively, P = 0.049], with 50% of subjects in group 1 having a mI/Cr ratio below the lowest observed ratio in either of the other groups. On neurocognitive testing, significant defects in the monitoring domain were observed in group-1, compared with matched controls (P = 0.021). Acute HCV in HIV-1 infected subjects is associated with CNS involvement. Clinicians should be vigilant of early CNS involvement when assessing subjects with acute HCV.

Concomitant allergic rhinitis (AR) adds to the symptomatic burden of asthma.To determine the proportion of adults with concomitant asthma and AR whose AR is diagnosed and/or treated, data were derived from a cross-sectional, stratified, random sample of 26,468 adults from France, Germany and the UK, participants in the 2004 web-based National Health and Wellness Survey. Patients were drawn from the database if they reported (1) experiencing asthma in the prior 12 months, (2) a physician diagnosis of asthma, and (3) ever experiencing 'nasal allergies/hay fever' (physician diagnosed or self-reported symptoms).Of 1139 patients with asthma who reported AR, 203 (18%) did not have a diagnosis of AR. Of these, 86 (42%) pursued over-the-counter self-treatment for AR, and 117 (58%) remained untreated. Of 936 patients who reported diagnosed AR, 471 (50%) received AR prescriptions, 200 (21%) pursued over-the-counter self-treatment, and 265 (28%) remained untreated. Overall, 34% of patients with asthma and diagnosed or self-reported AR were not treated for AR. There were no significant differences in QoL over the prior 4 weeks, nor healthcare resource use over the prior 6 months between patients treated and those not treated for AR.Based on self-reported data, despite global treatment guidelines recommending evaluation and treatment of AR among patients with asthma, AR was not diagnosed for 1 in 5 patients, and AR was not treated for 1 in 3 patients with asthma.

Background Differences could exist in the likelihood of asthma attacks in patients treated with inhaled corticosteroid (ICS), long-acting beta-agonist (LABA), and montelukast (MON) (ICS/LABA/MON) and patients treated with an inhaled corticosteroid (ICS) and montelukast (MON) (ICS/MON). Methods This was a post-hoc analysis of a pretest-posttest retrospective cohort study. Patients with mild persistent asthma and allergic rhinitis, who were taking an ICS either alone or in combination with a LABA, started concomitant MON treatment as part of their routine care. Rates of asthma- and allergic rhinitis-related medical resource use in the 12-months after the initial (index) MON prescription were compared in the ICS/MON and ICS/LABA/MON groups. An asthma attack was defined as an asthma-related hospitalization, ER visit, or use of an oral corticosteroid. Results Of the total of 344 patients, 181 (53%) received ICS/MON and 163 (47%) received ICS/LABA/MON in the post-index period for means of 10.5 and 11.4 months, respectively, (P < 0.05). Short-acting beta-agonists were used by 74.6% in the ICS/MON and 71.8% in the ICS/LABA/MON groups (P > 0.05). An asthma attack occurred in 4.4% of the ICS/MON group and 6.8% of the ICS/LABA/MON group (P > 0.05). The adjusted odds of an asthma attack in the post-index period in the ICS/LABA/MON group relative to the ICS/MON group was 1.24, 95% confidence interval 0.35–4.44. Conclusion In this observational study of combination drug treatment of mild persistent asthma and allergic rhinitis, no difference was observed between LABA/ICS/MON combination therapy and the ICS/MON combination without LABA use, for the rate of asthma attacks over one year.

The magnitude and sign of the electric charge on large and small interstellar grains are calculated, in a range of environments. Physical properties appropriate for realistic grain materials are assumed. The grain charge calculation is linked to a reliable model of the chemistry of an interstellar cloud in hydrostatic equilibrium, and results are presented as a function of depth into the cloud. Grains of high and low band-gap energy have distinctly different behaviours with respect to charging, and, for a wide variety of interstellar conditions, zones in clouds occur where grains of opposite charge coexist. The consequences of such a situation are briefly described.

Smoking habits of asthmatics are similar to those of the general population. However, little attention has been paid to the associations between smoking and asthma-related outcomes.To evaluate relationships between cigarette smoking, asthma symptoms, and asthma-related resource utilization in subjects with persistent asthma.A stratified, random sample of adults from France, Germany, and the UK with persistent asthma were surveyed in 2001 through 2004. Statistical analyses compared asthma symptoms and healthcare resource utilization for cigarette smokers compared with those for non-smokers.Analyses included 1109 subjects with persistent asthma symptoms in 2001-2003 and 852 subjects with persistent asthma symptoms in 2004. Using multivariate analysis of data from eligible subjects in 2004 that did not have concomitant chronic obstructive pulmonary disease and adjusting for subjects' baseline and demographic characteristics, cigarette smokers were more likely to experience nighttime symptoms (OR 1.46, 95% CI 1.07, 1.97 P = 0.015) and were more likely to use healthcare resources than were non-smokers (Por = 0.004). Findings were similar in a secondary analysis of subjectsor =55 years of age.Cigarette smoking appears to be associated with more asthma symptoms and more ED visits and hospitalizations in adults with persistent asthma.

Intestinal neoplasia of horses is inadequately described.Intestinal neoplasia of horses has characteristic clinicopathologic features.Thirty-four horses with intestinal neoplasia.Retrospective study.Anamnesis, clinical signs, clinicopathologic and pathologic findings in 34 adult horses diagnosed histologically with intestinal neoplasia were reviewed. The horses ranged in age from 2 to 30 years (mean 16.6 years at presentation). The Arabian breed was most represented and there was no sex predisposition. The most common presenting complaints were weight loss, colic, anorexia, and fever. The most consistent clinical signs were poor body condition, tachycardia, tachypnea, fever, and diarrhea. Useful diagnostic tools included rectal examination, routine blood analyses, abdominocentesis, ultrasonographic examination, rectal biopsy, and exploratory laparotomy. Alimentary lymphoma was the most common intestinal neoplasia identified, followed by adenocarcinoma and smooth muscle tumors. The small intestine was the most common segment of intestine affected for all neoplasms. Intestinal neoplasia was diagnosed antemortem in 13 of 34 (38%) horses. The median time from onset of clinical signs to death or euthanasia was 1.9 months. The discharge rate was 15%. Although the longest survival was observed in horses with jejunal adenocarcinoma, all horses were eventually euthanized because of intestinal neoplasia.Arabian horses were 4.5 times more likely to have intestinal neoplasia diagnosed than were other breeds.

To examine the association between medication expectations and subsequent experience on treatment satisfaction and intention to continue using the medication. A longitudinal study with two surveys administered to each patient. Patients prescribed a new medication were recruited in pharmacies within Michigan. Medication-related expectations were evaluated at baseline. Experiences, satisfaction and intent to continue were evaluated a month later. Analyses used included factorial ANOVA models, multiple linear regressions and structural equation modeling (SEM). Impact of satisfaction on intention to continue was evaluated using correlation analysis and SEM. A total of 344 usable responses were obtained. SEM showed that expectation scores were not associated with both experience (path coefficient = 0.10) and satisfaction (path coefficient = 0.02, NS). On the other hand, experience was strongly associated with satisfaction (path coefficient = 0.89) and satisfaction was strongly associated with intent to continue using the new medication (path coefficient = 0.81). This study empirically supports the value of the patient’s experience and its contribution to satisfaction, which in turn is associated with intended continued use mainly due to greater effectiveness of the newly prescribed medication. Satisfied consumers should be more adherent, thus enhancing the probability of positive therapeutic outcomes.

Chronic hypoxia due to chronic obstructive pulmonary disease (COPD) constitutes a stress to cerebral metabolic homeostasis. Previous studies using phosphorus-31 magnetic resonance spectroscopy (31P MRS) have suggested that the brains of such patients utilize anaerobic glycolysis, which in neonatal, animal, and in vitro studies is associated with a protective intracellular alkalosis. To identify such a compensatory intracellular alkalosis in hypoxic COPD patients, in vivo cerebral 31P MRS was performed in eight patients and eight controls. The mean intracellular pH (pHi) in patients with COPD was similar to that of age-matched controls, but decreased in the patients with COPD by a mean pHi of 0.02 (p = 0.04), following supplemental oxygen. There was no change in cerebral pHi in normal subjects following oxygen administration. The broadband component of the MR spectrum increased in all the patients with COPD (p = 0.01), suggesting altered phospholipid membrane fluidity in the brain associated with the change in pHi following oxygen administration. The change in the broadband resonance was strongly correlated with the change in pHi (r = -0.68, p = 0.014). This study suggests that patients with COPD exhibit a compensatory change in pHi and abnormalities in cerebral membrane phospholipid conformation in the face of chronic hypoxia.