The Cost-Effectiveness of Biologics for the Treatment of Rheumatoid Arthritis : A Systematic Review

Background and Objectives Economic evaluations provide information to aid the optimal utilization of limited healthcare resources. Costs of biologics for Rheumatoid arthritis (RA) are remarkably high, which makes these agents an important target for economic evaluations. This systematic review aims to identify existing studies examining the cost-effectiveness of biologics for RA, assess their quality and report their results systematically. Methods A literature search covering Medline, Scopus, Cochrane library, ACP Journal club and Web of Science was performed in March 2013. The cost-utility analyses (CUAs) of one or more available biological drugs for the treatment of RA in adults were included. Two independent investigators systematically collected information and assessed the quality of the studies. To enable the comparison of the results, all costs were converted to 2013 euro. Results Of the 4890 references found in the literature search, 41 CUAs were included in the current systematic review. While considering only direct costs, the incremental cost-effectiveness ratio (ICER) of the tumor necrosis factor inhibitors (TNFi) ranged from 39,000 to 1 273,000 (sic)/quality adjusted life year (QALY) gained in comparison to conventional disease-modifying antirheumatic drugs (cDMARDs) in cDMARD naive patients. Among patients with an insufficient response to cDMARDs, biologics were associated with ICERs ranging from 12,000 to 708,000 (sic)/QALY. Rituximab was found to be the most cost-effective alternative compared to other biologics among the patients with an insufficient response to TNFi. Conclusions When 35,000 (sic)/QALY is considered as a threshold for the ICER, TNFis do not seem to be cost-effective among cDMARD naive patients and patients with an insufficient response to cDMARDs. With thresholds of 50,000 to 100,000 (sic)/QALY biologics might be cost-effective among patients with an inadequate response to cDMARDs. Standardization of multiattribute utility instruments and a validated standard conversion method for missing utility measures would enable better comparison between CUAs.Peer reviewe

Work stress and risk of cancer: meta-analysis of 5700 incident cancer events in 116 000 European men and women

Peer reviewe

Loss of Cardioprotective Effects at the ADAMTS7 Locus as a Result of Gene-Smoking Interactions

BACKGROUND: Common diseases such as coronary heart disease (CHD) are complex in etiology. The interaction of genetic susceptibility with lifestyle factors may play a prominent role. However, gene-lifestyle interactions for CHD have been difficult to identify. Here, we investigate interaction of smoking behavior, a potent lifestyle factor, with genotypes that have been shown to associate with CHD risk. METHODS: We analyzed data on 60 919 CHD cases and 80 243 controls from 29 studies for gene-smoking interactions for genetic variants at 45 loci previously reported to be associated with CHD risk. We also studied 5 loci associated with smoking behavior. Study-specific gene-smoking interaction effects were calculated and pooled using fixed-effects meta-analyses. Interaction analyses were declared to be significant at a P value of <1.0x10(-3) (Bonferroni correction for 50 tests). RESULTS: We identified novel gene-smoking interaction for a variant upstream of the ADAMTS7 gene. Every T allele of rs7178051 was associated with lower CHD risk by 12% in never-smokers (P= 1.3x10(-16)) in comparison with 5% in ever-smokers (P= 2.5x10(-4)), translating to a 60% loss of CHD protection conferred by this allelic variation in people who smoked tobacco (interaction P value= 8.7x10(-5)). The protective T allele at rs7178051 was also associated with reduced ADAMTS7 expression in human aortic endothelial cells and lymphoblastoid cell lines. Exposure of human coronary artery smooth muscle cells to cigarette smoke extract led to induction of ADAMTS7. CONCLUSIONS: Allelic variation at rs7178051 that associates with reduced ADAMTS7 expression confers stronger CHD protection in never-smokers than in ever-smokers. Increased vascular ADAMTS7 expression may contribute to the loss of CHD protection in smokers.Peer reviewe

Job Strain and Alcohol Intake: A Collaborative Meta-Analysis of Individual-Participant Data from 140 000 Men and Women

Peer reviewe

Results of quality assessment.

<p>Results of quality assessment.</p

Flow chart of the study selection process.

<p>Flow chart of the study selection process.</p

Elinympäristöjen tilan edistäminen Suomessa : ELITE-työryhmän mietintö elinympäristöjen tilan edistämisen priorisointisuunnitelmaksi ja arvio suunnitelman kokonaiskustannuksista

Kestävä luonnonvarojen käyttö on perusta sekä ihmisen että luonnon hyvinvoinnille. Tähän mietintöön on koottu Elinympäristöjen tilan edistämisen (ELITE) työryhmän työn tulokset. Työ edistää osaltaan luonnonvarojen käytön kestävyyttä antamalla suuntaviivoja luonnon monimuotoisuuden turvaamiseen Suomen metsissä, soilla, perinnebiotoopeilla, maatalousalueilla, kallioilla, tuntureilla sekä rannikolla. Osin tarkastelussa mukana olivat myös kaupunkiympäristöt ja sisävedet. Varsinaisen tarkastelun ulkopuolelle jätettiin rannikkovesien ulkopuoliset meret. Elinympäristöjen tilan edistämisen toimenpiteet voivat käsittää suojelua, luonnonhoitoa tai perinteisellä tavalla ymmärrettyä ennallistamista. Toimenpiteet voivat myös olla mahdollistavia, kuten lainsäädännön muutoksia. Työn ensimmäisessä vaiheessa kullekin elinympäristölle määritettiin elinympäristön tilaa tehokkaasti ja kustannuksia minimoiden edistävistä toimenpiteistä koostuvat toimenpidepaletit. Elinympäristökohtaisten toimenpidepalettien, uhanalaisten ja silmälläpidettävien lajien ja luontotyyppien lukumäärän, elinympäristöjen pinta-alojen sekä työryhmän harkinnan pohjalta laadittiin tämän jälkeen työryhmän esitys elinympäristöjen väliseksi priorisointisuunnitelmaksi. Esitys sisältää useita priorisointivaihtoehtoja ja arviot niiden kokonaiskustannuksista. Työryhmä ei arvioinut esityksen laajempia taloudellisia, sosiaalisia ja yhteiskunnallisia vaikutuksia. Tulosten perusteella tarkastelun kohteena olleiden elinympäristöjen tila on heikentynyt keskimäärin noin 60 prosenttia verrattuna luonnontilaan. Johtopäätöksenä tästä on, että vaikka Suomi on elinympäristöjen tilan edistämisen kansainvälinen edelläkävijä, on tilaa edistäviä toimia edelleen jatkettava, laajennettava ja tehostettava. Lisäksi mietintö osoittaa, että elinympäristöjen tilaa edistävien kustannusvaikuttavien toimenpiteiden valinnalla ja elinympäristöjen yhtäaikaisella tarkastelulla voidaan säästää kustannuksia jopa 60–90 prosenttia verrattuna tilanteeseen, jossa kaikkien elinympäristöjen tilaa edistetään toisistaan riippumatta. Työryhmä esittää, että kustannusvaikuttavimpien tulosten saavuttamiseksi elinympäristökohtaisista suojelu- ja toimintaohjelmista siirrytään useiden elinympäristöjen tilaa samanaikaisesti edistäviin ohjelmiin. Jatkoselvityksissä tulee tarkentaa erityisesti tässä mietinnössä esitettyjen toimenpiteiden kustannuksia ja niiden kohdentumista, sosiaalisia ja taloudellisia vaikutuksia sekä toimenpiteiden käytännön kohdentamista ja toteutusmenetelmiä.nonPeerReviewe

Job strain as a risk factor for coronary heart disease:a collaborative meta-analysis of individual participant data

BACKGROUND: Published work assessing psychosocial stress (job strain) as a risk factor for coronary heart disease is inconsistent and subject to publication bias and reverse causation bias. We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies. METHODS: We used individual records from 13 European cohort studies (1985-2006) of men and women without coronary heart disease who were employed at time of baseline assessment. We measured job strain with questions from validated job-content and demand-control questionnaires. We extracted data in two stages such that acquisition and harmonisation of job strain measure and covariables occurred before linkage to records for coronary heart disease. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death. FINDINGS: 30,214 (15%) of 197,473 participants reported job strain. In 1·49 million person-years at risk (mean follow-up 7·5 years [SD 1·7]), we recorded 2358 events of incident coronary heart disease. After adjustment for sex and age, the hazard ratio for job strain versus no job strain was 1·23 (95% CI 1·10-1·37). This effect estimate was higher in published (1·43, 1·15-1·77) than unpublished (1·16, 1·02-1·32) studies. Hazard ratios were likewise raised in analyses addressing reverse causality by exclusion of events of coronary heart disease that occurred in the first 3 years (1·31, 1·15-1·48) and 5 years (1·30, 1·13-1·50) of follow-up. We noted an association between job strain and coronary heart disease for sex, age groups, socioeconomic strata, and region, and after adjustments for socioeconomic status, and lifestyle and conventional risk factors. The population attributable risk for job strain was 3·4%. INTERPRETATION: Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking. FUNDING: Finnish Work Environment Fund, the Academy of Finland, the Swedish Research Council for Working Life and Social Research, the German Social Accident Insurance, the Danish National Research Centre for the Working Environment, the BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical Research Council, the Wellcome Trust, and the US National Institutes of Health