Postoperative Adverse Events are Associated with Oncologic Recurrence Following Curative-intent Resection for Lung Cancer.

BACKGROUND: Up to 50% of patients suffer short-term postoperative adverse events (AEs) and metastatic recurrence in the long-term following curative-intent lung cancer resection. The association between AEs, particularly infectious in nature, and disease recurrence is controversial. We sought to evaluate the association of postoperative AEs on risk of developing recurrence and recurrence-free survival (RFS) following curative-intent lung resection surgery. METHODS: All lung cancer resections at a single institution (January 2008-July 2015) were included, with prospective collection of AEs using the Thoracic Morbidity & Mortality System. Cox proportional hazards models were used to estimate the effect of AEs on recurrence, with results presented as hazard ratio (HR) with 95% confidence interval (CI). An a priori, clinically driven approach to predictor variable selection was used. Kaplan-Meier curves were used examine the relationship between AE and RFS. p < 0.05 was considered statistically significant. RESULTS: 892 patients underwent curative-intent resection. 342 (38.3%) patients experienced an AE; 69 (7.7%) patients developed infectious AEs. 17.6% (n = 157) of patients had disease recurrence after mean follow-up of 26.5 months. Severe (Grade IV) AEs were associated with increased risk of recurrence (3.40; 95% CI 1.56-7.41) and a trend to decreased RFS. Major infectious AEs were associated with increased risk of recurrence (HR 1.71; CI 1.05-2.8) and earlier time to recurrence (no infectious AE 66 months, minor infectious 41 months, major infectious 54 months; p = 0.02). CONCLUSION: For patients undergoing curative-intent lung cancer resection, postoperative AEs associated with critical illness or major infection were associated with increased risk of oncologic recurrence.

Correction to: Postoperative Adverse Events are Associated with Oncologic Recurrence Following Curative­intent Resection for Lung Cancer.

The original version of this article unfortunately contained a mistake in author names. The given and family names of all the authors was transposed. The author names are corrected with this correction. The original article has been corrected.

Raltegravir in HIV-1-Infected Pregnant Women: Pharmacokinetics, Safety, and Efficacy.

BACKGROUND: The use of raltegravir in human immunodeficiency virus (HIV)-infected pregnant women is important in the prevention of mother-to-child HIV transmission, especially in circumstances when a rapid decline of HIV RNA load is warranted or when preferred antiretroviral agents cannot be used. Physiological changes during pregnancy can reduce antiretroviral drug exposure. We studied the effect of pregnancy on the pharmacokinetics of raltegravir and its safety and efficacy in HIV-infected pregnant women. METHODS: An open-label, multicenter, phase 4 study in HIV-infected pregnant women receiving raltegravir 400 mg twice daily was performed (Pharmacokinetics of Newly Developed Antiretroviral Agents in HIV-Infected Pregnant Women Network). Steady-state pharmacokinetic profiles were obtained in the third trimester and postpartum along with cord and maternal delivery concentrations. Safety and virologic efficacy were evaluated. RESULTS: Twenty-two patients were included, of which 68% started raltegravir during pregnancy. Approaching delivery, 86% of the patients had an undetectable viral load (<50 copies/mL). None of the children were HIV-infected. Exposure to raltegravir was highly variable. Overall area under the plasma concentration-time curve (AUC) and plasma concentration at 12 hours after intake (C12h) plasma concentrations in the third trimester were on average 29% and 36% lower, respectively, compared with postpartum: Geometric mean ratios (90% confidence interval) were 0.71 (.53-.96) for AUC0-12h and 0.64 (.34-1.22) for C12h. The median ratio of raltegravir cord to maternal blood was 1.21 (interquartile range, 1.02-2.17; n = 9). CONCLUSIONS: Raltegravir was well tolerated during pregnancy. The pharmacokinetics of raltegravir showed extensive variability. The observed mean decrease in exposure to raltegravir during third trimester compared to postpartum is not considered to be of clinical importance. Raltegravir can be used in standard dosages in HIV-infected pregnant women. CLINICAL TRIALS REGISTRATION: NCT00825929.

Pharmacokinetics of total and unbound darunavir in HIV-1-infected pregnant women.

OBJECTIVES: To describe the pharmacokinetics of darunavir in pregnant HIV-infected women in the third trimester and post-partum. PATIENTS AND METHODS: This was a non-randomized, open-label, multicentre, Phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe. HIV-infected pregnant women treated with darunavir (800/100 mg once daily or 600/100 mg twice daily) as part of their combination ART were included. Pharmacokinetic curves were recorded in the third trimester and post-partum. A cord blood sample and maternal sample were collected. The study is registered at ClinicalTrials.gov under number NCT00825929. RESULTS: Twenty-four women were included in the analysis [darunavir/ritonavir: 600/100 mg twice daily (n=6); 800/100 mg once daily (n=17); and 600/100 mg once daily (n=1)]. Geometric mean ratios of third trimester versus post-partum (90% CI) were 0.78 (0.60-1.00) for total darunavir AUC0-tau after 600/100 mg twice-daily dosing and 0.67 (0.56-0.82) for total darunavir AUC0-tau after 800/100 mg once-daily dosing. The unbound fraction of darunavir was not different during pregnancy (12%) compared with post-partum (10%). The median (range) ratio of darunavir cord blood/maternal blood was 0.13 (0.08-0.35). Viral load close to delivery was <300 copies/mL in all but two patients. All children were tested HIV-negative and no congenital abnormalities were reported. CONCLUSIONS: Darunavir AUC and Cmax were substantially decreased in pregnancy for both darunavir/ritonavir regimens. This decrease in exposure did not result in mother-to-child transmission. For antiretroviral-naive patients, who are adherent, take darunavir with food and are not using concomitant medication reducing darunavir concentrations, 800/100 mg of darunavir/ritonavir once daily is adequate in pregnancy. For all other patients 600/100 mg of darunavir/ritonavir twice daily is recommended during pregnancy.

Correlations among Stress Parameters, Meat and Carcass Quality Parameters in Pigs.

Relationships among different stress parameters (lairage time and blood level of lactate and cortisol), meat quality parameters (initial and ultimate pH value, temperature, drip loss, sensory and instrumental colour, marbling) and carcass quality parameters (degree of rigor mortis and skin damages, hot carcass weight, carcass fat thickness, meatiness) were determined in pigs (n = 100) using Pearson correlations. After longer lairage, blood lactate (p<0.05) and degree of injuries (p<0.001) increased, meat became darker (p<0.001), while drip loss decreased (p<0.05). Higher lactate was associated with lower initial pH value (p<0.01), higher temperature (p<0.001) and skin blemishes score (p<0.05) and more developed rigor mortis (p<0.05), suggesting that lactate could be a predictor of both meat quality and the level of preslaughter stress. Cortisol affected carcass quality, so higher levels of cortisol were associated with increased hot carcass weight, carcass fat thickness on the back and at the sacrum and marbling, but also with decreased meatiness. The most important meat quality parameters (pH and temperature after 60 minutes) deteriorated when blood lactate concentration was above 12 mmol/L.

Body composition and muscle strength predictors of jumping performance: differences between elite female volleyball competitors and nontrained individuals.

Studies of the role of various anthropometric, physiological, and biomechanical variables in performance of rapid movements have generally revealed inconsistent findings. Within this study, we tested the hypotheses that (a) both body composition and leg extensor strength variables would reveal significant relationship with jumping performance, whereas (b) the same relationships would be stronger in physically active nonathletes than in the elite athletes proficient in vertical jumping. Top-level female volleyball players (VP; N = 35) and physically active female nonathletes (PA; N = 21) were tested on maximum vertical jumps performed with and without arm swing, as well as on body composition (percent fat and muscle) and leg press strength (maximum force and the rate of force development). The results revealed significant relationships between the jumping performance and body composition variables that appeared to be higher in PA (r = 0.65-0.76; all p < 0.01) than in VP (r = 0.37-0.42; all p ≤ 0.05). The relationships between the jumping performance and the leg strength variables were mainly significant (r = 0.23-0.68) and similar in 2 groups. We conclude that not only the leg extensor strength but also the body composition variables could be valid predictors of jumping performance and, possibly, other rapid movements. Moreover, the body composition variables that have been mainly neglected in the literature could be particularly strong predictors of performance of jumping in nonathletes, as compared with relatively homogeneous populations of elite athletes.

Does Double Mean Trouble? Coexistence of Myeloproliferative and Lymphoproliferative Neoplasms.

Background: The occurrence of myeloproliferative neoplasms (MPNs) that evolve into each other is well-described, as is this occurrence of lymphoproliferative neoplasms (LPNs). However, less is known about rare MPN/LPN coexistence, and the aim of our study was to analyze charachteristics of these patients after long term follow-up. Methods: Fourteen patients with MPN/LPN coexistence were diagnosed and treated according to guidelines at a single university center across two decades. Results: The overall median age was 53 years (22-69). MPNs patients with subsequent LPNs had a shorter period of second malignancy development and a more aggressive course of LPN, which can cause fatal outcomes. Polycythemia vera and chronic lymphocytic leukemia were most commonly associated (36%). The JAK2V617F mutation had 2/3 and cytogenetic abnormalities occurred in 1/3 of patients. MPN/LPN coexistence cases had significantly higher thrombotic potential (42.8%) and a higher third malignancy accruement frequency (21.4%) versus those without such malignancies. Conclusions: Considering the younger ages at MPN diagnosis, it is recommended to check regularly for blood lymphocytosis or lymphadenopathy occurrences and organomegaly progression faster than expected for MPN, with the aim of timely LPN diagnoses. The presence of molecular-cytogenetic abnormalities in a majority of patients indicate possible genetic instability and increased risk of development of multiple neoplasms, thus elevating thrombotic risk.

Altered resting-state connectivity in adolescent cannabis users.

BACKGROUND: Cannabis is the most commonly used illicit drug in adolescence. Heavy use is associated with deficits on a broad range of cognitive functions and heavy use during adolescence may impact development of gray and white matter. OBJECTIVES: To examine differences in intrinsic brain activity and connectivity associated with cannabis dependence in adolescence using whole-brain voxelwise approaches. METHODS: Adolescents admitted to a drug-treatment facility for cannabis dependence (n = 17) and age-matched controls (n = 18) were compared on a measure of oscillations in the low-frequency blood oxygen level-dependent signal at rest (the fractional amplitude of low-frequency fluctuations fALFF, 0.01-0.1 Hz) and interhemispheric resting-state functional connectivity (RSFC) using voxel-mirrored homotopic connectivity. RESULTS: The cannabis-dependent population showed increased fALFF activity compared to the control group in right hemisphere regions including the superior parietal gyrus, superior frontal gyrus, inferior frontal gyrus, inferior semilunar lobe of the cerebellum and the inferior temporal gyrus. Post-hoc analyses revealed stronger intra-hemispheric functional connectivity between these functionally defined regions of interest (ROIs) in the cannabis-dependent population than in the controls. Reduced interhemispheric connectivity was observed in the cannabis users compared to controls in the pyramis of the cerebellum and the superior frontal gyrus. Controls showed reduced interhemispheric connectivity compared to users in the supramarginal gyrus. CONCLUSIONS: The reduced interhemispheric RSFC in adolescent cannabis users complements previous reports of white matter deficits associated with cannabis use. The evidence of elevated connectivity within the right hemisphere may reflect a compensatory mechanism. Combined, the results suggest that altered intrinsic connectivity may be characteristic of adolescent cannabis dependence.

Easily Applicable Predictive Score for Differential Diagnosis of Prefibrotic Primary Myelofibrosis from Essential Thrombocythemia.

Essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (prePMF) initially have a similar phenotypic presentation with thrombocytosis. The aim of our study was to determine significant clinical-laboratory parameters at presentation to differentiate prePMF from ET as well as to develop and validate a predictive diagnostic prePMF model. This retrospective study included 464 patients divided into ET (289 pts) and prePMF (175 pts) groups. The model was built using data from a development cohort (229 pts; 143 ET, 86 prePMF), which was then tested in an internal validation cohort (235 pts; 146 ET, 89 prePMF). The most important prePMF predictors in the multivariate logistic model were age ≥ 60 years (RR = 2.2), splenomegaly (RR = 13.2), and increased lactat-dehidrogenase (RR = 2.8). Risk scores were assigned according to derived relative risk (RR) for age ≥ 60 years (1 point), splenomegaly (2 points), and increased lactat-dehidrogenase (1 point). Positive predictive value (PPV) for pre-PMF diagnosis with a score of ≥points was 69.8%, while for a score of ≥3 it was 88.2%. Diagnostic performance had similar values in the validation cohort. In MPN patients with thrombocytosis at presentation, the application of the new model enables differentiation of pre-PMF from ET, which is clinically relevant considering that these diseases have different prognoses and treatments.

Simultaneous determination of lamivudine, lopinavir, ritonavir, and zidovudine concentration in plasma of HIV-infected patients by HPLC-MS/MS.

The nucleoside reverse transcriptase inhibitors lamivudine and zidovudine and the protease inhibitors lopinavir and ritonavir are currently used in anti-human immunodeficiency virus (HIV) therapy. Here, a high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method, using a hybrid quadrupole time-of-flight mass analyzer, is reported for the simultaneous quantification of lamivudine, lopinavir, ritonavir, and zidovudine in plasma of HIV-infected patients. The volume of plasma sample was 600 µL. Plasma samples were extracted by solid-phase using 1 cc Oasis HLB Cartridge (divinylbenzene and N-vinylpyrrolidone) and evaporated in a water bath under nitrogen stream. The extracted samples were reconstituted with 100-µL methanol. Five microliters of the reconstituted samples were injected into a HPLC-MS/MS apparatus, and the analytes were eluted on a Vydac column (250 × 1.0 mm i.d.) filled with 3-µm C(18) particles. The mobile phase was delivered at 70 µL/min with a linear gradient elution, both acetonitrile and ultrapure water solvents contained 0.2% formic acid. The calibration curves were linear from 0.47 to 20 ng/mL. The absolute recovery ranged between 91 and 107%. The minimal concentration of lamivudine, lopinavir, ritonavir, and zidovudine detectable by HPLC-MS/MS is 0.47, 0.28, 0.30, and 0.66 ng/mL, respectively. The great advantage of the new HPLC-MS/MS method here reported is the possibility to achieve a very high specificity toward the selected anti-HIV drugs, despite the simple and rapid sample preparation. Moreover, this method is easily extendible to the analysis of co-administrated drugs.

Functional dimorphism and characteristics of maximal hand grip force in top level female athletes.

The aim of this work is to determine functional dimorphism (F(max)Nd/DoHG(iso)) and model characteristics at maximal isometric hand grip force (F(max)HG(iso)) in top level female athletes. 275 top level female athletes were tested from Taekwondo, Synchronised Swimming, Track and field, Table tennis, Volleyball, Karate, Skiing, Handball, well-trained students (students of the Academy for Criminalistic and Police studies - ACPS) and Control group. In order to assess the F(max)HG(iso), we used standardised equipment, i.e., a sliding device that measures isometric finger flexor force, with a tensiometric probe fixed inside the device. The average values of F(max)HG(iso) and relative force measured by allometric and classic method for dominant and non-dominant hand grip for the total sample were 381.87 +/- 60.28, 344.63 +/- 55.60 N; 24.06 +/- 3.50, 21.72 +/- 3.28 N/BM0.667; 0.62 +/- 0.10, 0.56 +/- 0.09 N/BM. The average value of F(max)Nd/DoHG(iso) was 0.9030 +/- 0.0797. General Significant difference was established between subsamples for the measurement characteristics at the level of Wilks' Lambda 0.476, F = 3.276, p = 0.000. Maximal average value F(max)HG(iso) for non-dominant and dominant hand is found in Karate (372.04 +/- 46.71, 407.04 +/- 71.31 N) and minimal in Table tennis (282.00 +/- 56.00, 304.00 +/- 58.51 N). The minimal index value of F(max)Nd/DoHG(iso) was found in Control group 0.8771 +/- 0.0877. Considering defined classification of F(max)Nd/ DoHG(iso), we classified the examinees from different sports in 4 groups: dominant symmetry of functional hand grip relations (Skiing > 0.9595); symmetry (Table tennis and Taekwondo 0.9288 to 0.9594); average (Karate, Volleyball, ACPS, Track and field 0.8980 to 0.9287); asymmetry (Control, Synchronised swimming and Handball 0.8674 to 0.8979). The results obtained can be used to determine criteria decisions from the aspect of diagnostic procedures, metric aspect, medical aspect.

Microstructure of Croatian Wild Grapevine (Vitis vinifera subsp. sylvestris Gmel Hegi) Pollen Grains Revealed by Scanning Electron Microscopy.

Wild grapevine (Vitis vinifera subsp. sylvestris Gmel Hegi) is dioecious with male and female plants, whereas domesticated grapevine is mostly hermaphrodite with self-fertile hermaphrodite flowers. The pollen morphology of wild grapevine has been poorly studied. There is no detailed palynological study of V. sylvestris in Croatia and neighboring countries. Here, scanning electron microscopy (SEM) was used to analyze the pollen of V. sylvestris from male and female individuals growing at two natural sites in Croatia. The selective APT3 marker was used to confirm the flower phenotype with the genetic background. SEM analysis showed that the pollen grains of V. sylvestris were isopolar and radially symmetrical, with foveolate perforated ornamentation, regardless of the flower type of the individuals. All male flowers were 3-colporate and prolate in shape, whereas female individuals varied from subprolate to spheroidal and had inaperturate pollen grains. Pollen shape, dimensions and exine ornamentation proved very informative, and here we address the most polymorphic traits in the analyzed V. sylvestris individuals. Principal component analysis (PCA) and clustering based on pollen morphology variables clearly differentiated individuals by their flower type, and no grouping specific to population was observed, pointing to the conserved pollen structure of V. sylvestris. The results indicate the need to continue the palynological study of V. sylvestris and serve as a good phenotypic basis for functional genetic studies on genes involved in pollen morphology and function.

Specific Physical Ability Prediction in Youth Basketball Players According to Playing Position.

This study investigated the hierarchical structure of physical characteristics in elite young (i.e., U17-U19) basketball players according to playing positions. In addition, their predictive value of physical characteristics was determined for the evaluation of players' physical preparedness. Sixty elite male basketball players performed 13 standardized specific field tests in order to assess the explosive power of lower limbs, speed, and change-of-direction speed. They were divided into three groups according to playing positions (guard [n = 28], forward [n = 22], center [n = 10]). The basic characteristics of the tested sample were: age = 17.36 ± 1.04 years, body height = 192.80 ± 4.49 cm, body mass = 79.83 ± 6.94 kg, and basketball experience = 9.38 ± 2.10 years for guards; age = 18.00 ± 1.00 years, body height = 201.48 ± 3.14 cm, body mass = 90.93 ± 9.85 kg, and basketball experience = 9.93 ± 2.28 years for forwards; and age = 17.60 ± 1.43 years; body height = 207.20 ± 3.29 cm, body mass = 104.00 ± 9.64 kg, and basketball experience = 9.20 ± 1.62 years for centers. For all playing positions factor analysis extracted three factors, which cumulatively explained 76.87, 88.12 and 87.63% of variance, respectively. The assessed performance measures were defined as significant (p < 0.001), with regression models of physical performance index (PPINDEX). PPINDEX of guards = -6.860 + (0.932 × t-test) - (1.656 × Acceleration 15 m) - (0.020 × Countermovement jump); PPINDEX of forwards = -3.436 - (0.046 × Countermovement jump with arm swing) - (1.295 × Acceleration 15 m) + (0.582 × Control of dribbling); PPINDEX of centers = -4.126 + (0.604 × Control of dribbling) - (1.315 × Acceleration 15 m) - (0.037 × Sargent jump). A model for the evaluation of physical performance of young basketball players has been defined. In addition, this model could be used as a reference model for selection procedures, as well as to monitor the efficacy of applied training programmes within the short, medium and long-term periodization.

Marked increase in etravirine and saquinavir plasma concentrations during atovaquone/proguanil prophylaxis.

The case of a 32-year-old Caucasian female with multi-drug resistant HIV-1 subtype B infection treated with a salvage regimen including maraviroc, raltegravir, etravirine and unboosted saquinavir who started atovaquone/proguanil prophylaxis, is reported. The potential interactions between atovaquone/proguanil and these anti-retroviral drugs are investigated. Pharmacokinetic analyses documented a marked increase in etravirine and saquinavir plasma concentrations (+55% and +274%, respectively), but not in raltegravir and maraviroc plasma concentrations. The evidence that atovaquone/proguanil significantly interacts with etravirine and saquinavir, but not with raltegravir and maraviroc, suggests that the mechanism of interaction is related to cytochrome P450.

Horizon Scanning for pharmaceuticals and effective health care programming: 2 years' experience at the Italian Medicines Agency.

The Italian Medicines Agency (AIFA) developed Horizon Scanning (HS) methodology to address programming and sustainability challenges posed by accelerating pharmaceutical innovation and increasing costs. From July 2018 to June 2020, 563 new potential treatments (new medicines and new indications of existing medicines) with an expected impact in 2020-2022 were identified. In this review, we assess and discuss these HS results, including medicine characteristics related to higher prioritization scores, such as clinical areas of major development. After exclusions because of the selection process, 213 (40.6%) new potential treatments were included in the prioritization tool; 25 (11.7%) were shown to be possibly associated with a major impact on healthcare systems (HCSs) according to overall prioritization criteria. Lessons learned from the process led to HS system improvements.

Assessments of Ground Reaction Force and Range of Motion in Terms of Fatigue during the Body Weight Squat.

The purpose of this study was to analyse in detail body weight squat (BWS)' fatigue effect on the range of motions (ROM) of the hip, knee, ankle and ground reaction forces (GRF). Twenty male recreational athletes (24.0 ± 3.1 years, 178.85 ± 7.12 cm and 78.7 ± 11.45 kg) participated in this study. BWS were performed on four load cell platforms until the participants failed to continue. Participants performed 73 ± 27 repetitions and the duration to complete of the repetitions was 140.72 ± 62.28 s during the BWS exercise. The forefoot and hindfoot of the feet were on two load cells, thus, there were two under each foot. All of the data collected was divided into three sections for analysis (24 ± 9 repetitions for each). In terms of GRF of the fore feet and hind feet, significant differences and medium to large effect size were found between each section (p = 0.006~0.040, ES = 0.693~0.492). No significant differences were found between right and left leg in all sections. Significant differences were found in the ROM of the hip between the sections of first-third (p = 0.044, ES = 0.482) and second-third (p = 0.034, ES = 0.510), the ROM of the knee first-third (p = 0.014, ES = 0.602) and second-third (p = 0.005, ES = 0.701) and for the ROM of the ankle first-second (p = 0.045, ES = 0.479). As a result, end-of-exercise fatigue caused an increase in the ROM of the hip, knee and ankle. Thus, it is observed that fatigue induced increased ROM, also increases the GRF towards the forefeet.

Real-World Observational Study on the Characteristics and Treatment Patterns of Allergic Asthma Patients Receiving Omalizumab in Canada.

BACKGROUND: Omalizumab is a treatment option for pediatric and adult patients with moderate to severe allergic asthma poorly controlled with standard inhaled therapies. Clinical trials and observational studies have demonstrated the efficacy of omalizumab. There is limited real-world evidence on the characteristics and treatment patterns of Canadian asthma patients receiving omalizumab. OBJECTIVE: We profiled Canadian omalizumab users to estimate time to omalizumab discontinuation and to assess changes in concurrent medication usage before, during, and after therapy. METHODS: This was a retrospective, observational, cohort study that analyzed data from Canadian prescription claims databases. An algorithm was used to select naïve users of omalizumab with an inferred diagnosis of GINA 5-asthma who made a claim for omalizumab from February 1, 2007, to June 2, 2015. Demographic and baseline characteristics were assessed at index. Outcomes examined over the analysis period included (i) daily omalizumab dose per patient and per claim; (ii) omalizumab discontinuation (defined as ≥100-day gap in making omalizumab claims) and its potential predictors (ie, age, sex, province of residence, drug insurer; assessed by Cox Proportional Hazards Model); and (iii) for patients who discontinued omalizumab, changes in concurrent medication usage before, during, and 6 months after omalizumab usage. RESULTS: The final study cohort consisted of 1160 patients (mean age: 45.8 ± 15.2 years; 64.7% female). During the first year of omalizumab therapy, 29.5% of patients discontinued treatment. The singular characteristic that predicted omalizumab discontinuation with statistical significance was age group (20‒34 years vs 12‒19 years; hazard ratio 1.75, 95% confidence interval 1.11-2.76; P<0.05). There were significant reductions in the use of some concurrent inhaled and oral asthma medications during and/or after omalizumab use (P<0.05). CONCLUSION: Nearly one-third of patients who initiated omalizumab in Canada for refractory, moderate to severe allergic asthma discontinued treatment during the first year.

Sonographic assessment of facial HIV-related lypoatrophy.

OBJECTIVE: To investigate the utility of ultrasonography (US) for assessing and grading facial lypoatrophy (FLA) in patients with HIV. DESIGN: The social effect of FLA is huge and may reduce antiretroviral therapy adherence. Strategies for the early detection of FLA are crucial, because complete correction of FLA in late stages is unlikely. METHODS: Fifty-two HIV-positive patients undergoing highly active antiretroviral therapy underwent US with nasogenian transversal scan using a high-frequency broadband transducer (5-17 MHz) to detect FLA. Intra- and interobserver variability were calculated to assess US reproducibility. Concerning FLA grading, patients were categorized in five clinical classes and four US classes. RESULTS: Our results regarding inter- and intraobserver coefficients of variation permit the validation of US as a reproducible technique (p<.001), and a high correlation between US and clinical classification was obtained, with complete concordance for more advanced FLA classes. CONCLUSIONS: The lack of a reference objective method to quantify subcutaneous fat is a major difficulty in measuring HIV-related FLA. Our results, in accordance with data from the literature, suggest that US is an ideal tool for assessing and grading FLA. Furthermore, US may be suitable for routine evaluation in HIV-infected patients for early detection of FLA and to select its optimal management.

The Horizon Scanning System at The Italian Medicines Agency.

The new era of medical innovation is a great opportunity for healthcare; but it poses new challenges for affordability of healthcare systems. To enable timely implementation of value-based clinical care and payment approaches, it is important to look beyond usual timescales to inform decision makers about forthcoming disruptive technologies early. Horizon scanning could represent an efficient tool in support of decision making and rational use of available resources. Different horizon scanning programmes exist in Europe and there is a need for further international cooperation between competent authorities. In relation to this, the present review aims to highlight the importance of early information availability and illustrates the Italian Medicines Agency Horizon Scanning System in the context of the European regulatory network.

Real-world utilization of methotrexate or prednisone co-therapy with etanercept among Canadian patients with rheumatoid arthritis: a retrospective cohort study.

Objective: To evaluate whether initiation of etanercept therapy among patients with rheumatoid arthritis (RA) impacts use of co-therapy with methotrexate or prednisone, and to describe etanercept dosing dynamics compared to product monograph in the Canadian real-world setting. Methods: A retrospective cohort study was conducted using claims-level data from IQVIA Private Drug Plan database, Ontario Public Drug Plan database and Régie de l'assurance maladie du Québec database. Bio-naïve RA patients initiating etanercept between July 2014 and June 2015 were identified and their claims for methotrexate or prednisone were analyzed. Utilization of methotrexate or prednisone was calculated as average weekly dose in milligrams, and compared in the 6 months pre-initiation versus 12 months post-initiation of etanercept. Weekly etanercept dosing of each patient was calculated and analyzed to determine whether patients had at least 20% higher or lower average dose than monograph recommended dose (50 mg/week), and were then flagged as above-monograph or below-monograph, respectively. Results: A total of 2876 patients with RA (66% female, 76% aged 18-65) were included; 62% (n = 1,140) used methotrexate and 27% used prednisone (n = 498) both pre- and post-initiation of etanercept. In methotrexate patients, the average weekly dose dispensed was 25.4 mg in the 6 months pre-etanercept, and 25.0 mg in the 12 months post-etanercept initiation (p = .5282). In prednisone patients, the average weekly dose dispensed reduced from 122.6 mg pre-etanercept to 107.1 mg post-etanercept initiation (p = .2173). Among patients who were already on methotrexate or prednisone, after initiating on etanercept 16% (n = 213) and 34% (n = 254) of patients stopped methotrexate and prednisone, respectively. When compared to the recommended dose, 12% (n = 168) of patients were below-monograph and 7.1% of patients were above-monograph during their first year of etanercept therapy. Average etanercept dosing was consistently lower than product monograph during the follow-up year. Conclusions: Patients had a modest but not statistically significant decrease in prescribed doses of co-therapy with methotrexate and prednisone when etanercept was added to patients' therapy. In addition, 12-14% of patients stopped their co-therapy with methotrexate or prednisone. Further study is needed to understand the impact on patient outcomes and safety.