United Medix Laboratories (Finland)

An international team spanning 19 sites across 18 biopharmaceutical and in vitro diagnostics companies in the United States, Europe, and China, along with one regulatory agency, was formed to compare the precision and robustness of imaged CIEF (ICIEF) for the charge heterogeneity analysis of the National Institute of Standards and Technology (NIST) mAb and a rhPD-L1-Fc fusion protein on the iCE3 and the Maurice instruments. This information has been requested to help companies better understand how these instruments compare and how to transition ICIEF methods from iCE3 to the Maurice instrument. The different laboratories performed ICIEF on the NIST mAb and rhPD-L1-Fc with both the iCE3 and Maurice using analytical methods specifically developed for each of the molecules. After processing the electropherograms, statistical evaluation of the data was performed to determine consistencies within and between laboratory and outlying information. The apparent isoelectric point (pI) data generated, based on two-point calibration, for the main isoform of the NIST mAb showed high precision between laboratories, with RSD values of less than 0.3% on both instruments. The SDs for the NIST mAb and the rhPD-L1-Fc charged variants percent peak area values for both instruments are less than 1.02% across different laboratories. These results validate the appropriate use of both the iCE3 and Maurice for ICIEF in the biopharmaceutical industry in support of process development and regulatory submissions of biotherapeutic molecules. Further, the data comparability between the iCE3 and Maurice illustrates that the Maurice platform is a next-generation replacement for the iCE3 that provides comparable data.

We used real-life data from a large Finnish IBD patient cohort to determine rates of target trough level (TL) achievement, antidrug antibody (ADAb) positivity, the association between switching and ADAbs, and ADAb loss over time. Serum samples for infliximab (IFX) or adalimumab (ADL) TL and ADAb measurements from 1894 (1659 adult, 235 paediatric) IBD patients were taken on a clinical basis in daily practice in 20 Finnish university or central hospitals. TL analyses were performed at United Medix Laboratories (Helsinki, Finland) using commercial methods (Promonitor ELISA, Progenika Biopharma); ADAb analyses were performed at Sanquin laboratories (Amsterdam, The Netherlands) using radioimmunoassays. Samples were collected and analysed from January 2012 until September 2017. TLs from 2 to 10 µg/ml (IFX) or 5 to 10 µg/ml (ADL) were considered as target ranges; TL values <0.1 µg/ml were considered undetectable. ADAb values ≥12 AU/ml were considered positive; ADAb values were classified as low (12-30 AU/ml), intermediate (30–100 AU/ml) and high (≥100 AU/ml). Statistical analyses were performed by SPSS (IBM, Armonk, NY). p < 0.05 was considered statistically significant. For IFX-treated patients, 60.5% (Crohn disease [CD]) and 58.1% (ulcerative colitis [UC]) of TL samples were in the target range; the corresponding values for ADL were 38.5% (CD) and 41% (UC). Rates of ADAb positivity were similar across drugs and indications (range 18.1–23.3%). For combined IFX TL and ADAb measurements, most samples with undetectable TL (CD, 4.2%; UC, 5.1%) were ADAb positive (CD, 87.5%; UC, 81.6%). For combined ADL TL and ADAb measurements, most samples with undetectable TL (CD, 10.7%; UC, 7.8%) were also ADAb positive (CD, 91.7%; UC, 93%). A total of 165 (8.7%) switchers were identified. Of the 136 (82.4%) switchers that provided a first-drug ADAb sample, 78 (47.3%) switchers were ADAb positive; 53 (68%) had high ADAbs. We identified 56 ADAb-positive patients that provided ADAb follow-up samples. Most patients (37 patients, 66.1%) experienced ADAb loss over time; 25 patients (44.6%) experienced complete ADAb loss (ADAb <12 AU/ml). All patients with ADAb loss had initially low or intermediate ADAb values. On the basis of real-life TL data, large proportions IBD patients treated with IFX or ADL may benefit from dose or interval adjustments. Low TLs are associated with ADAbs. ADAb positivity is associated with drug switching. A significant proportion of ADAb-positive patients lose ADAbs over time.

We assessed human papillomavirus (HPV) prevalence among HPV-16/18-vaccinated and unvaccinated Finnish male adolescents participating in chlamydia screening 4 years after vaccination with AS04-adjuvanted HPV-16/18 vaccine in 2007-2009. Previously vaccinated (n = 395) or unvaccinated (n = 149) male adolescents were enrolled in 12 municipalities. First-void urine samples were tested for HPV types 6, 11, 16, 18, 31, 33, 35, 45, 51, 52, 56, 58, 59, 66, and 68, and prevalence rates for HPV-16/18, and HPV-11/16/18/31/33/45 were reduced profoundly (0% vs 2.1% [P = .02] and 0.8% vs 5.3 [P = .002], respectively). Overall HPV DNA prevalence was also significantly reduced among HPV-16/18-vaccinated (4.1%) compared with unvaccinated subjects (10.1%) (P = .01). In this post hoc study, a highly significant reduction in HPV prevalence 4 years after vaccination suggests that the bivalent HPV-16/18 vaccine has protective efficacy in men.

We investigate whether high-dose (HD, ≥60 Gy) radiotherapy in definitive concurrent chemoradiotherapy (CCRT) based on cisplatin could yield benefits compared to conventional-dose (CD) CCRT. PubMed, Embase and Google Scholar were searched and data were pooled and analyzed for response rate, survival, failure patterns and toxicity. Results showed advantages in response rate, 5-year overall survival rate, local regional recurrence and distant failure rate compared to the CD arm with no difference in Grade ≥3 acute and late esophagitis, other toxicities were rare with moderate tolerance, subgroup analysis of squamous cell carcinoma also showed advantages for HD arm. We concluded that ≥60 Gy CCRT improved clinical outcomes compared to the CD arm, especially for esophageal squamous cell carcinoma. Our findings may provide a basis for future trials.

BackgroundThere is a strong will and need to find alternative models of health care delivery driven by the ever-increasing burden of chronic diseases.ObjectiveThe purpose of this 1-year trial was to study whether a structured mobile phone-based health coaching program, which was supported by a remote monitoring system, could be used to improve the health-related quality of life (HRQL) and/or the clinical measures of type 2 diabetes and heart disease patients.MethodsA randomized controlled trial was conducted among type 2 diabetes patients and heart disease patients of the South Karelia Social and Health Care District. Patients were recruited by sending invitations to randomly selected patients using the electronic health records system. Health coaches called patients every 4 to 6 weeks and patients were encouraged to self-monitor their weight, blood pressure, blood glucose (diabetics), and steps (heart disease patients) once per week. The primary outcome was HRQL measured by the Short Form (36) Health Survey (SF-36) and glycosylated hemoglobin (HbA1c) among diabetic patients. The clinical measures assessed were blood pressure, weight, waist circumference, and lipid levels.ResultsA total of 267 heart patients and 250 diabetes patients started in the trial, of which 246 and 225 patients concluded the end-point assessments, respectively. Withdrawal from the study was associated with the patients’ unfamiliarity with mobile phones—of the 41 dropouts, 85% (11/13) of the heart disease patients and 88% (14/16) of the diabetes patients were familiar with mobile phones, whereas the corresponding percentages were 97.1% (231/238) and 98.6% (208/211), respectively, among the rest of the patients (P=.02 and P=.004). Withdrawal was also associated with heart disease patients’ comorbidities—40% (8/20) of the dropouts had at least one comorbidity, whereas the corresponding percentage was 18.9% (47/249) among the rest of the patients (P=.02). The intervention showed no statistically significant benefits over the current practice with regard to health-related quality of life—heart disease patients: beta=0.730 (P=.36) for the physical component score and beta=-0.608 (P=.62) for the mental component score; diabetes patients: beta=0.875 (P=.85) for the physical component score and beta=-0.770 (P=.52) for the mental component score. There was a significant difference in waist circumference in the type 2 diabetes group (beta=-1.711, P=.01). There were no differences in any other outcome variables.ConclusionsA health coaching program supported with telemonitoring did not improve heart disease patients' or diabetes patients' quality of life or their clinical condition. There were indications that the intervention had a differential effect on heart patients and diabetes patients. Diabetes patients may be more prone to benefit from this kind of intervention. This should not be neglected when developing new ways for self-management of chronic diseases.Trial RegistrationClinicalTrials.gov NCT01310491; http://clinicaltrials.gov/ct2/show/NCT01310491 (Archived by WebCite at http://www.webcitation.org/6Z8l5FwAM).

A previous study involving a proteomic screen of induced sputum from smokers and patients with chronic obstructive pulmonary disease (COPD) demonstrated elevated levels of bactericidal/permeability-increasing fold-containing protein B1 (BPIFB1). The aim of the present study was to further evaluate the association of sputum BPIFB1 levels with smoking and longitudinal changes in lung function in smokers with COPD. Sputum BPIFB1 was characterized by two-dimensional gel electrophoresis and mass spectrometry. The expression of BPIFB1 in COPD was investigated by immunoblotting and immunohistochemistry using sputum and lung tissue samples. BPIFB1 levels were also assessed in induced sputum from nonsmokers (n = 31), smokers (n = 169), and patients with COPD (n = 52) via an ELISA-based method. The longitudinal changes in lung function during the 4-year follow-up period were compared with the baseline sputum BPIFB1 levels. In lung tissue samples, BPIFB1 was localized to regions of goblet cell metaplasia. Secreted and glycosylated BPIFB1 was significantly elevated in the sputum of patients with COPD compared with that of smokers and nonsmokers. Sputum BPIFB1 levels correlated with pack-years and lung function as measured by forced expiratory volume in 1 s (FEV1) % predicted and FEV1/FVC (forced vital capacity) at baseline and after the 4-year follow-up in all participants. The changes in lung function over 4 years were significantly associated with BPIFB1 levels in current smokers with COPD. In conclusion, higher sputum concentrations of BPIFB1 were associated with changes of lung function over time, especially in current smokers with COPD. BPIFB1 may be involved in the pathogenesis of smoking-related lung diseases.

The synthesis and method of analysis of hydroxylated mesocarb metabolites are described. Six potential hydroxylated mesocarb metabolites were prepared, characterized, and compared with the mesocarb metabolites synthesized enzymatically in vitro using human liver proteins and also compared with metabolites extracted from human urine after oral administration of mesocarb. p-Hydroxymesocarb was the most prevalent metabolite (conjugated and non-conjugated) observed. With respect to doping analysis, synthesis of p-hydroxymesocarb, the main urinary metabolite of mesocarb, and its availability as a reference material is important.

The list of prohibited substances and methods of doping issued by the World Anti-Doping Agency is updated and modified annually based on most recent developments and scientific data. Compounds and methods are maintained, added, or removed from the list, or they are placed in so-called monitoring programmes that have been established to obtain reliable data on the prevalence of particular substances and methods in- and/or out-of-competition. Consequently, doping control laboratories continuously update, modify and optimize existing screening and confirmation assays to ensure utmost comprehensiveness in detecting the prohibited and monitored substances as well as chemically and pharmacologically related analogs. The annual banned-substance review for human sports drug testing critically summarizes recent innovations in analytical approaches supporting the detection of established and newly outlawed substances and methods of doping. Literature from January 2007 through September 2008 as indexed in Medline and Web of Science was screened and articles on detection methods for substances and methods of doping in humans were compiled according to the 2008 Prohibited List of the World Anti-Doping Agency. Few new approaches were presented for individual doping agents and the majority of reports demonstrated new options for increasing the comprehensiveness of existing doping control assays. In addition, new techniques in separation and/or ionization of analytes complementary to commonly used procedures were described, which, so far, did not meet all requirements of sports drug testing.