Justification For Use Research Articles

The geometric mean?

The sample geometric mean (SGM) introduced by Cauchy in 1821, is a measure of central tendency with many applications in the natural and social sciences including environmental monitoring, scientometrics, nuclear medicine, infometrics, economics, finance, ecology, surface and groundwater hydrology, geoscience, geomechanics, machine learning, chemical engineering, poverty and human development, to name a few. Remarkably, it was not until 2013 that a theoretical definition of the population geometric mean (GM) was introduced. Analytic expressions for the GM are derived for many common probability distributions, including: lognormal, Gamma, exponential, uniform, Chi-square, F, Beta, Weibull, Power law, Pareto, generalized Pareto and Rayleigh. Many previous applications of SGM assumed lognormal data, though investigators were unaware that for that case, the GM is the median and SGM is a maximum likelihood estimator of the median. Unlike other measures of central tendency such as the mean, median, and mode, the GM lacks a clear physical interpretation and its estimator SGM exhibits considerable bias and mean square error, which depends significantly on sample size, pd, and skewness. A review of the literature reveals that there is little justification for use of the GM in many applications. Recommendations for future research and application of the GM are provided.

Toward a Typology of Normative Drug Users Based on Levels of Functioning, Justifications and Types of Use

The study explores 29 individuals who described themselves as functioning normatively while using drugs on a regular basis. They defined their use as intensive, constant, and playing a significant part in their normative lives. The content analysis revealed a typology consisting of four different types of normative users: the socially connected users, the better coping users, the ambivalent users, and the recovering users. This typology was created on the basis of three axes: level of functioning, justification of use, style of use. Our typology highlights the differences between normative users with varying patterns of drug usage and levels of functioning, ranging from users who claim that drug use causes them no harm to those who acknowledge that drug use has significantly damaged their functioning. This typology places particular emphasis on normative users who are experiencing a range of difficulties and need specific forms of therapy to preserve their normative lives.

Avelumab flat dose regimen: Justification for use in advanced renal cell carcinoma (aRCC).

32 Background: Avelumab, an anti–PD-L1 monoclonal antibody, was recently approved for the treatment of aRCC in combination with axitinib and was previously indicated for the treatment of metastatic Merkel cell carcinoma (MCC) and platinum-treated advanced/metastatic urothelial carcinoma (UC). Although avelumab was approved with weight-based dosing (10 mg/kg intravenously [IV] every 2 weeks [Q2W]), it was subsequently approved for flat dosing (800 mg IV Q2W) based on population pharmacokinetic (popPK), exposure-efficacy and exposure-safety modeling and simulations in MCC and UC (Novakovic AM, et al. Clin Pharmacol Ther. 2019). The justification for the recommended flat-dose regimen for avelumab as combination therapy with axitinib in aRCC is presented. Methods: Simulated exposure metrics (eg, area under the curve) from the previous popPK model (data from 1,827 patients with solid tumors across 3 clinical trials) for both weight-based and flat-dose regimens were compared with the exposure metrics obtained from treatment-naive patients with aRCC enrolled in 2 clinical studies (N = 488 from NCT02493751 and NCT02684006) who received avelumab (10 mg/kg Q2W) + axitinib (5 mg orally twice daily). Avelumab exposure-response relationships for safety and efficacy were also analyzed. Endpoints included grade ≥3 treatment-emergent adverse events (TEAEs), any-grade infusion-related reactions (IRRs) and immune-related (ir)AEs, and progression-free survival (PFS) by independent review. Results: The administration of weight-based dosing of avelumab in the aRCC population yielded similar PK exposures to simulated reference exposures of the flat-dose regimen in the solid tumor population. Avelumab exposure was not associated with increased probabilities of grade ≥3 TEAEs or IRRs, although there was a weak association with an increased probability of any-grade irAEs. Conclusions: The similar exposures observed for both avelumab dosing regimens in aRCC, and in prior studies in the MCC and UC populations, suggest that the 800 mg Q2W flat-dose regimen will maintain the benefit-risk ratio for avelumab + axitinib for treatment-naive patients with aRCC. Clinical trial information: NCT02493751 . Clinical trial information: NCT02684006.

Resistance Mechanisms to SYK Inhibition in Acute Myeloid Leukemia.

Spleen tyrosine kinase (SYK) is a nonmutated therapeutic target in acute myeloid leukemia (AML). Attempts to exploit SYK therapeutically in AML have shown promising results in combination with chemotherapy, likely reflecting induced mechanisms of resistance to single-agent treatment in vivo. We conducted a genome-scale open reading frame (ORF) resistance screen and identified activation of the RAS-MAPK-ERK pathway as one major mechanism of resistance to SYK inhibitors. This finding was validated in AML cell lines with innate and acquired resistance to SYK inhibitors. Furthermore, patients with AML with select mutations activating these pathways displayed early resistance to SYK inhibition. To circumvent SYK inhibitor therapy resistance in AML, we demonstrate that a MEK and SYK inhibitor combination is synergistic in vitro and in vivo. Our data provide justification for use of ORF screening to identify resistance mechanisms to kinase inhibitor therapy in AML lacking distinct mutations and to direct novel combination-based strategies to abrogate these. SIGNIFICANCE: The integration of functional genomic screening with the study of mechanisms of intrinsic and acquired resistance in model systems and human patients identified resistance to SYK inhibitors through MAPK signaling in AML. The dual targeting of SYK and the MAPK pathway offers a combinatorial strategy to overcome this resistance.This article is highlighted in the In This Issue feature, p. 161.

Theoretical justifi cation for use of combined methods for hardening of surfaces of machine parts in order to control their fretting resistance

The theoretical justification for the hardening process of the surface layer of machine parts for combined methods of surface hardening with subsequent application of strengthening coatings, as well as reducing or increasing the fatigue limit due to the fretting process is presented.

Wsie zanikające – identyfikacja i analiza wybranych cech społeczno-ekonomicznych = Disappearing villages – identification and analysis of selected socioeconomic features

Contemporary rural settlement in Poland is first and foremost modified by demographic processes, of which decisive ones are a migratory influx of new inhabitants into rural areas in the immediate vicinity of large cities, as well as population outflow from most rural areas that are located traditionally and above all peripherally. These two directions to migration generate mostly opposing trends where the development of rural areas is concerned. Inflows of new inhabitants into suburbs and satellite villages close to cities ensure social, economic and infrastructural development or ”progress”, and sometimes even – paradoxically – a change of status from rural to urban. On the other hand, migratory outflows from most other rural areas give rise to a process of demographic degradation whose extreme manifestation may be the actual disappearance of a rural settlement. The fundamental unit of measurement and study here was the so-called ”statistical locality”, defined by GUS as the group of places taking on the name of the leading locality and usually comprising a village plus smaller settlements adjacent to it. The research encompassed a total of 41,466 such localities existing uninterruptedly between 1950 and 2011. The analysis further encompassed six time intervals, of which each ended in a year during which a Census was carried out (i.e. 1950, 1960, 1970, 1978, 1988, 2002 and 2011). For each inter-Censal period, attention was paid to the magnitude and direction of demographic change taking place in all of the rural localities. In this work, the key focus is on the “uniformly regressing villages”, which is to say those losing more than 5% of their inhabitants in the 1950‒2011 period, but also experiencing population declines in every one of the six inter-Censal periods. This is taken to be adequate justification for use of the more-loaded term “disappearing”. Through analysis of the statistical localities in rural areas it was found that some 25,711 of all villages reported a decline in the number of inhabitants over the 1950‒2011 period. However, the steady loss of people indicated by population declines over each of the six studied time intervals was an issue for 2956 of the villages mainly located in central and eastern parts of Poland. These are areas long regarded as only poorly-developed economically, including parts of the east that are clearly categorisable as “peripheral”. To be noted among the factors behind disappearances of villages are limited attractiveness arising out of low standards of living, natural conditions unsuited to farming, limited incomes earned from agricultural activity and poor outfitting in social and technical infrastructure. Throughout the post-War period it is small villages of fewer than 100 people that have experienced the most marked demographic regress. The smallest settlements of all – with 50 people or less – have experienced the most major loss of population, at around 28% on average. The analyses reported here thus support the notion that the scale and village, the less-serious the unfavourable population processes. However, the disappearing villages are home to a number of overlapping problems with development. Inhabitants either lack opportunities to meet their daily needs, or at best have limited chances to do so. And this starts with physiological needs, though also of course ranges through the social, emotional and economic, and ends with lack of access to public goods and services. The decline of rural areas thus features a so-called triggering factor, with this then unleashing a sequence of positive-feedback processes. A most typical trigger would be lack of job opportunities, and this exerts a selective effect in relation to who leaves the countryside. A next consequence of that is a decline in the purchasing power of rural households, a further worsening of living conditions, and inefficient use of infrastructure.

Justification for use of selenium-modified mineral water in medical rehabilitation of patients who underwent colon surgery due to malignant tumor (overview)

The article presents the justification for the use of selenium-modified low-mineralized mineral water of Chapaevsk deposit (the Karachay-Cherkess Republic), modified by selenium. It describes its effect on the state of hormonal and immune status, antioxidant system in malignant diseases of digestive organs, prevention of complications, reduction of dose of used medicines, improvement of quality of life of this category of patients.
 Conclusion. It is noted that the use of selenium-modified low-mineralized mineral water expands and complements the possibilities of rehabilitation and rehabilitation assistance to patients who have undergone operations on the large intestine in case of malignant neoplasms.

Muscle and bone dose in paediatric limb digital radiography: a Monte Carlo evaluation.

The proliferation of digital radiography (DR) has led to a re-evaluation of exposure parameters and image quality. Currently, there is a move towards reducing X-ray tube voltage (kVp) in paediatric exposures down to 40 kVp to achieve better images. However, the effect on patient dose of these modifications is uncertain. The main aims of this phantom study were to evaluate the effect of reducing the kVp in paediatric limb DR exposures on contrast-to-noise ratio (CNR) and patient dose. For this purpose, Monte Carlo simulations of radiographic exposures on a paediatric limb phantom were performed. The phantom included muscle tissue and bone segments of five different densities in the range of 1.12 to 1.48g/cm3. The overall thickness of the phantom varied between 1 and 12cm. Dependence of the CNR at constant limb phantom muscle and bone doses and dependence of the CNR per unit of muscle and bone dose at constant detector dose on radiographic exposure factors and limb thickness were calculated. X-ray tube current-time product (mAs) values required to achieve equal detector dose versus limb thickness for different kVp were calculated, as well as muscle and bone doses for the limb phantom of varying thickness. Present work has shown that reducing the kVp in paediatric radiography of the extremities can result in a significant increase in radiation dose, particularly for thicker limbs. Low kVp radiography requires justification for use on the extremities.

Use of Force in Self-Defence for Global Peace: A Conceptual Framework

This paper attempts to link legal and theoretical perspectives of the use of force in self-defence and, thereafter, formulates a conceptual framework based on these two key concepts: use of force as a legitimate right for self-defence and pre-emptive self-defence as an unlawful security doctrine in existing legal structure (UN Charter). The focus is on identifying: i) the primary factors which, in combination as well separately, present a broader view of legal justification for use of force in self-defence and ii) the factors facilitating an unlawful unilateral military action in self-defence. The primary objective is to link both theoretical and legal aspects to formulate a conceptual model. In fact, this study presents an overall picture capable of explaining the key linkage of the use of force in self-defence and breach of international peace, whereby a state launches a pre-emptive attack against another state. 

Butyrlycholine esterase inhibitory activity and effects of extracts (fruit, bark and leaf) from Zanthoxylum armatum DC in gut, airways and vascular smooth muscles

BackgroundFruit, bark and leaves of Zanthoxylum armatum DC are popular remedies for gastrointestinal, cardiovascular and respiratory disorders in the subcontinent traditional practices. The aim of the study was to individually probe the profile of methanol extracts from three different parts of Zanthoxylum armatum.MethodsThe ex-vivo muscle relaxant effects of extracts were assessed in the isolated intestine, trachea and thoracic aortic rings and were compared with the positive controls and CRC were constructed. The anti-diarrheal effect of extracts was evaluated in mice by inducing diarrhea with castor oil. The extracts were also studied for acute toxicity and butyrylcholine esterase inhibition.ResultsThe extracts from fruit, bark and leaves of Z. armatum showed inhibitory effect against the butyrylcholine esterase enzyme with percent inhibition of 50.75 ± 1.23, 82.57 ± 1.33, and 37.52 ± 1.11respectively, compared to standard serine (IC50: 0.04 ± 0.001 μmol/L). The fruit and bark extracts provided 75, and 52% diarrheal protection, compared to verapamil (96%). In isolated rabbit jejunum strips, increasing addition of the extracts inhibited the spontaneous and high K+ precontractions with EC50 values of 0.71 and 3 mg/mL for fruit, EC50 values of 0.61 and 0.5 mg/mL for bark, EC50 0.81 and 3.1 mg/mL for leaves, like verapamil. The extracts induced a concentration-dependent relaxation of the carbachol (1 μM) and high K+ (80 mM) precontractions with EC50 values of 2.4 and 0.9 mg/mL for fruit, EC50 values of 1.2 and 3 for leaves. The bark extract was equipotent against both contractions with EC50 3.1 and 0.7 mg/mL, respectively. In the aortic rings, the fruit extract completely relaxed the phenylephrine (1 μM)-induced contractions with (EC50 value = 0.8 mg/ml) and a partial inhibition of high K+ induced contractions. The leaves extract completely relaxed the aortic contractions with (EC50 values = 1.0 and 8.5 mg/ml). The extracts caused no acute toxicity up to 3 g/kg dose.ConclusionsThe experiments revealed that the extracts of aerial parts of Z. armatum have antidiarrheal properties in vivo and showed spasmolytic effect in intestinal and tracheal preparations with possible mechanism involving the blockage of Ca++ channels. These experiments provide enough justification for use of this plant in ethnomedicine in diarrhea, gut and bronchial spasms.

Antimicrobial use practices, attitudes and responsibilities in UK farm animal veterinary surgeons

Increasing levels of antimicrobial resistance in human and veterinary medicine have raised concerns around the issue of overprescribing and the indiscriminate use of antimicrobials. Their use in food producing animals is under scrutiny due to the perceived risk from the zoonotic transfer of resistant pathogens from animals to humans. This study aimed to explore UK veterinary surgeons antimicrobial prescribing behaviours, their attitudes to antimicrobial resistance and their perceptions of responsibility of antimicrobial use in pigs through a questionnaire study on a census sample of 261 veterinary surgeons in England, Wales and Scotland who had a clinical caseload which included commercial pigs. The questionnaire had a useable response rate of 34.1% (n = 61/179) in eligible veterinary surgeons.Overall, veterinary surgeons reported personal confidence that their prescribing decisions were responsible however, there was concern that the prescribing behaviours of other veterinary surgeons and physicians in human medicine may be less responsible; a sociological concept known as ‘othering’. In parallel, veterinary surgeons seldom identified that treatment failure was a consequence of antimicrobial resistance in their own clinical caseload, however they considered it an issue for other veterinary surgeons and for human prescribers. Veterinary surgeons consulted a wide spectrum of resources on antimicrobial use in pigs which, on occasion, contained conflicting guidance on what was defined as responsible prescribing. The decision over whether or not to prescribe an antimicrobial was influenced by numerous factors relating to the veterinary surgeons’ experience and the clinical situation presented, but maintaining pig welfare was a high priority. There was a shared desire to seek alternative methods to prevent disease to antimicrobial use, however the use of diagnostics to support prescribing decisions was an infrequently reported behaviour and could play a more significant role in prescriber decisions if more cost effective and rapid tests were available.Future interventions to optimise antimicrobial use in pigs needs to focus on the evolution of antimicrobial use practices in a changing political and scientific landscape whilst also considering individual motivations and justifications for use.

Phytochemical Constituents and Biological Activities of Melicope lunu-ankenda.

Natural products, either pure compounds or standardized plant extracts, have provided opportunities for the discovery of new drugs. Nowadays, most of the world’s population still relies on traditional medicines for healthcare purposes. Plants, in particular, are always used as traditional medicine, as they contain a diverse number of phytochemicals that can be used for the treatment of diseases. The multicomponent feature in the plants is considered a positive phytotherapeutic hallmark. Hence, ethnopharmacognosy has been the focus for finding alternative treatments for diseases. Melicope lunu-ankenda, also known as Euodia lunu-ankenda, is widely distributed in tropical regions of Asia. Different parts of M. lunu-ankenda have been used for treatment of hypertension, menstrual disorder, diabetes, and fever, and as an emmenagogue and tonic. It has also been consumed as salad and as a condiment for food flavorings. The justification of use of M. lunu-ankenda in folk medicines is supported by its reported biological activities, including its cytotoxic, antibacterial, antioxidant, analgesic, antidiabetic, and anti-inflammatory activities. This review summarizes the phytochemical compounds isolated from various parts of M. lunu-ankenda, such as root and leaves, and also its biological activities, which could make the species a new therapeutic agent for some diseases, including diabetes, in the future.

Robotics and augmented reality : Current state of development and future perspectives

Digitalization in surgery is gaining attention in the surgical community, with robotics and augmented reality as key issues. The term surgical robot is basically not adequate to describe currently available telesupport and manipulation systems. These are passive tools which have to be activated by the surgeon and only provide relatively low levels of active support. Accordingly, justification of use is currently difficult with respect to the cost-benefit relationship. Areal breakthrough will be achieved by upgrading them into genuine intelligent and collaborative support systems and justify the term as the true meaning of robotics. Augmented or enriched reality improves or facilitates normal sensory perception by the integration of additional information of adifferent nature. Intuitive perception of the surgical site would have the potential to revolutionize surgery, but prior to clinical use, the matching of the real and the virtual world still has to be optimized (referencing); however, AR is now already avaluable tool for training and simulation as well as workflow support in the operating room (OR). The promising new technological development towards the future cooperative surgical OR environment, including both robotic and AR modules, will have asignificant impact on surgery, even in the mid-term. Decisive for this is that surgeons actively take part in the evaluation of this process to ensure that future "intelligent" tools will remain mere assistant or supporting systems.

Lipoprotein(a) and Cardiovascular Risk Prediction Among Women

BackgroundAlthough lipoprotein(a) [Lp(a)] is associated with incident cardiovascular disease (CVD), its contribution to prediction remains controversial. ObjectivesThis study examined the association and clinical utility of Lp(a) with incident CVD in women. MethodsA turbidimetric assay assessed Lp(a) in 3 cohorts of women (the WHS [Women’s Health Study] [N = 24,558], a case-cohort sample from the WHI [Women’s Health Initiative] Observational Study [n = 1,815 cases, subcohort n = 1,989], and the JUPITER [Justification for Use of Statins in Prevention] trial [n = 2,569]) and in men from JUPITER (n = 5,161). A WHS derivation sample (n = 16,400) determined the form of association with incident CVD. This was tested in WHS validation data (n = 8,158) and the other study samples. Models including traditional CV risk factors but with and without Lp(a) were compared using risk reclassification. ResultsIn the WHS, there was a curvilinear association, with increased CVD risk among those with Lp(a) >50 mg/dl, but only among women with total cholesterol (TC) >220 mg/dl. In the WHS test sample, there was a small but significant change in the C-statistic (0.790 to 0.797; p = 0.035) but no improvement in measures of reclassification. This pattern was replicated among women in the WHI and JUPITER trial. In contrast, there was a strong association of Lp(a) with CVD among men with low TC levels in JUPITER. ConclusionsIn 3 cohorts of women, Lp(a) was associated with CVD only among those with high TC, and improvement in prediction was minimal. These data have implications for Lp(a) in clinical practice among women and for trials of Lp(a)-lowering agents.

Trends in Results of HBIPS National Performance Measures and Association With Year of Adoption.

Multiple studies demonstrate a consistent pattern of improvement on quality measures among health care organizations after they begin collecting and reporting data. This study compared results on psychiatric performance measures among cohorts of hospitals with different characteristics that elected to begin reporting on the measures at various points in time. Quarterly reporting of Hospital-Based Inpatient Psychiatric Services (HBIPS) measures to the Joint Commission was used to examine trends in performance among four hospital cohorts that began reporting in 2009 (N=243), 2011 (N=139), 2014 (N=137), or 2015 (N=372). The HBIPS measures address admission screening, restraint and seclusion use, justification of use of multiple antipsychotic medications, and discharge planning. Comparisons were based upon initial quarters of data reported and change rates. After adjustment for covariates, the analyses showed that all cohorts significantly improved across quarters for admission screening, justification of multiple antipsychotic medications, and discharge planning. Restraint hours significantly dropped over the initial reporting periods, but only for the 2009 and 2015 cohorts. Seclusion hours significantly dropped over the six reporting periods for all cohorts except 2011. Several differences were observed across cohorts in the rate of change between baseline and final measurement for various measures. In nearly every case, however, hospitals that began reporting measurement data earlier performed better than subsequent cohorts during the later cohorts' first quarter of reporting.

Justification for use of two-component mixtures for cooking wheat bread

The object of research is wheat bread. One of the most problematic places is the need to correct the food ration of the population in order to enrich traditional food with vital nutrients. Taking into account that bread refers to the products that are in the daily diet of the majority of the population, improving its nutritional value helps to improve the diet as a whole. Improving the nutritional value of bread can be achieved by adding alternative types of flour – corn, oatmeal, spring wheat flour. In the course of research, the modeling of formulations was used by the method of tasting evaluation. 9 formulations of bread based on two-component flour mixtures with the addition of corn, oats, buckwheat and spring wheat flour were developed (7.5 % and 15 %). The obtained samples were examined for compliance with organoleptic and physicochemical parameters, as well as safety indices. According to the physicochemical indicators of quality (humidity and acidity), all the samples corresponded to the Ukrainian normative documentation, the safety indicators also did not exceed the permissible limits. The best organoleptic properties were bread, in the composition of the recipe which was added wheat flour in the amount of 7.5 % and 15 %. A high number of points received bread from a mixture of wheat and oat flour (7.5 %). Samples with the addition of corn and buckwheat flour differed in organoleptic properties. This is due to the fact that different types of flour in different ways affect the taste characteristics of the finished product. The received results of researches testify to expediency of application of two-component mixtures of flour. It is expected to improve the amino acid composition of the product, reduce energy value due to the chemical composition of flour used in new formulations. Thanks to this, it is possible to obtain bread for functional and dietary purposes. In comparison with similar known formulations, the developed samples provide the following advantages: improvement of nutritional value, improvement of organoleptic properties of the product.

Meta-analysis: explicit value of mono-component proteases in monogastric diets

A meta-analysis was conducted to investigate the effect of mono-component proteases on performance and apparent ileal amino acid digestibility (AIAAD, %) in monogastrics. A total of 67 experimental trials were included in the meta-analysis from published and internal reports, contributing 467 lines of data. Poultry and swine data accounted for 81 and 19% of the dataset, respectively. Forty-four different proteases were included in the meta-analysis, accounting for commercial and non-commercial products. Mixed Model analysis was used to assess protease effect and the influence of inherent characteristics of the control on protease response. The mean performance response to protease was a reduction in feed conversion ratio (FCR) for poultry (1%, P < 0.05) and swine (4%, P > 0.05). The mean relative effect of protease on AIAAD over the control was 1.6 ± 0.3%, ranging from 1.2% for Arg, Phe and Trp to 2.6% for Cys. For the majority of amino acids, inherent AIAAD of control diets influenced (P < 0.05) the magnitude of the protease response such that, as inherent digestibility increased, the effect of protease on amino acid digestibility decreased. The dataset was subsequently divided into 2 subgroups: diets with and without other enzymes, namely non-starch polysaccharide degrading enzymes (NSPase) and phytase. Addition of protease in diets containing no other enzymes significantly (P < 0.05) increased AIAAD for the majority of amino acids and tended (P < 0.10) to improve Met, Trp, Pro, Gly, and Tyr. However, when other enzymes were included in the experiment, the beneficial effect of protease on AIAAD was lost (P > 0.05). These findings suggest that when other enzymes are already included in the diet, addition of protease requires further justification for use in monogastric diets.

Биорегуляционная медицина: научное обоснование использования в лечебных программах у детей

Биорегуляционная медицина: научное обоснование использования в лечебных программах у детей

\u201cNot pathogenic until proven otherwise\u201d: perspectives of UK clinical genomics professionals toward secondary findings in context of a Genomic Medicine Multidisciplinary Team and the 100,000 Genomes Project

PurposeApproaches to secondary findings in genome sequencing (GS) are unresolved. In the United Kingdom, GS is now routinely available through the 100,000 Genomes Project, which offers participants feedback of limited secondary findings.MethodsIn Oxford, a Genomic Medicine Multidisciplinary Team (GM-MDT) governs local access to GS, and reviews findings. Semistructured interviews were conducted with 19 GM-MDT members to explore perspectives on secondary findings.ResultsWhile enthusiastic about GS for diagnosing rare disease, members question the rationale for genome screening largely because of lack of evidence for clinical utility and limited justification for use of resources. Members’ views are drawn from diverse experiences; they feel a strong sense of responsibility to act in participants’ best interests. The capacity to return limited secondary findings should be enabled, but members favor a cautious approach that is responsive to accumulating evidence. Informed participant choice is considered critical, yet challenging. Discrimination of variants is considered essential, and requiring of specialist input and consensus. Multiple areas requiring enhanced engagement and education are identified, i.e., for patients, the public, and health-care professionals; at present, mainstreaming of genomics may be premature.ConclusionUK experts believe that evidence to inform policy toward secondary findings is lacking, arguing for caution.

Pharmacoeconomic Analysis of Different Biologic Therapies in Inflammatory Bowel Disease Patients in 1 Tertiary Center in Croatia

Table: Table. Results of pharmacoeconomic analysis of different biologic therapiesIntroduction: Biologics are used in patients with inflammatory bowel disease (IBD) usually after failure of conventional therapy, or, sometimes, instead of it early in the disease course. In Croatia, in the treatment of IBD, anti-tumor necrosis factor alpha (anti-TNF) agents infliximab, adalimumab and golimumab, and anti-integrin antibody vedolizumab are available. In patients achieving remission with anti-TNFs, loss of response should be treated firstly by dose optimization (dose increase or interval shortening). Our aim was to compare costs of different biologic therapies considering the costs of dose optimization. Methods: During March of 2017, we collected data of 91 patients with Crohn's disease and ulcerative colitis currently receiving biologic therapy at the Department of Gastroenterology and Hepatology of Clinical Hospital Center Osijek, Croatia. Data of our interest were: diagnosis, drug used, date of first and last drug application, projected date of next application, drug dosage of last application, and data of whether patient is receiving induction or maintenance therapy. We calculated the projected yearly cost of maintenance therapy with each biologic drug including costs of dose optimization. Projected yearly costs of maintenance therapy with different biologics were then compared. Drug prices were obtained from currently active list of medications of Croatian Health Insurance Fund. Results: 19% of our patients on infliximab and 26% of our patients on adalimumab had dose optimization due to loss of response. Projected average yearly dose per patient for infliximab considering dose optimization is 3053 mg/y compared to yearly dose recommended in summary of product characteristics (SmPC), which is 2600 mg/y. For adalimumab, projected average yearly dose per patient considering dose optimization is 1337 mg/y compared to 1040 mg/y recommended in SmPC. Projected cost of maintenance therapy per year after dose optimization is 1.2 times higher (13937 vs. 11868 USD) for infliximab and 1.3 times higher (17449 vs. 13571 USD) for adalimumab when comparing to costs of maintenance therapy in doses recommended in SmPC. Results are presented in table 1. Conclusion: As our results show, costs of maintenance therapy for certain biologics are higher when considering dose optimization. Inclusion of costs of dose optimization would give more accurate calculation of different biologic therapy costs and would help in understanding of pharmacoeconomic justification of use of different biologic therapies.