Showing papers by "Danube University Krems published in 2015"

Socioeconomic inequalities in non-communicable diseases and their risk factors: an overview of systematic reviews.

Abstract: Non-communicable diseases (NCDs) are the largest cause of premature death worldwide. Socioeconomic inequalities contribute to a disparity in the burden of NCDs among disadvantaged and advantaged populations in low (LIC), middle (MIC), and high income countries (HIC). We conducted an overview of systematic reviews to systematically and objectively assess the available evidence on socioeconomic inequalities in relation to morbidity and mortality of NCDs and their risk factors. We searched PubMed, The Cochrane Library, EMBASE, SCOPUS, Global Health, and Business Source Complete for relevant systematic reviews published between 2003 and December 2013. Two authors independently screened abstracts and full-text publications and determined the risk of bias of the included systematic reviews. We screened 3302 abstracts, 173 full-text publications and ultimately included 22 systematic reviews. Most reviews had major methodological shortcomings; however, our synthesis showed that having low socioeconomic status (SES) and/or living in low and middle income countries (LMIC) increased the risk of developing cardiovascular diseases (CVD), lung and gastric cancer, type 2 diabetes, and chronic obstructive pulmonary disease (COPD). Furthermore, low SES increased the risk of mortality from lung cancer, COPD, and reduced breast cancer survival in HIC. Reviews included here indicated that lower SES is a risk factor for obesity in HIC, but this association varied by SES measure. Early case fatalities of stroke were lower and survival of retinoblastoma was higher in MIC compared to LIC. The current evidence supports an association between socioeconomic inequalities and NCDs and risk factors for NCDs. However, this evidence is incomplete and limited by the fairly low methodological quality of the systematic reviews, including shortcomings in the study selection and quality assessment process.

The real type and ideal type of transdisciplinary processes: part I—theoretical foundations

Abstract: Transdisciplinarity integrates or relates different epistemics from science and practice (Mode 2 transdisciplinarity) or from branches of disciplines if interdisciplinary integration is impossible (Mode 1 transdisciplinarity). The paper explains, based on an analysis of the historical development of the Mode 2 transdisciplinarity concept, how transdisciplinary processes link interdisciplinary applied research and multi-stakeholder discourses by facilitating methods. We elaborate on what type of problems may be managed using what knowledge, how this might be accomplished, what types of objectives are desired, and by what organizational means. Thus the paper presents ontology, epistemology, methodology, functionality, and organization of an ideal type of transdisciplinary process. Socially robust orientations are the expected outcomes of this process. These orientations provide science-based, state-of-the-art, socially accepted options of solutions which acknowledge uncertainties and the incompleteness of different forms of epistemics (i.e., of knowing or thought), in particular within the sustainable transitioning of complex real-world problems.

Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1.

Abstract: Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype.

Post-stroke Cognitive Decline: An Update and Perspectives for Clinical Research

Abstract: The close relationship between stroke and dementia is an important health issue. Ischaemic stroke can facilitate the onset of vascular dementia as well as aggravate pre-existing cognitive decline. The onset of cognitive decline may become manifest immediately following the onset of ischaemic stroke, but often there is a delay in the development of cognitive decline after a stroke. This delay can be seen as a therapeutic time window allowing interventions to be applied to preserve cognition following stroke. Both neurodegenerative and vascular mechanisms are activated and probably result in overlapping processes within the neurovascular unit. This review focuses on the incidence and prevalence of cognitive decline following stroke, predisposing stroke aetiologies, pre-stroke decline, imaging factors and biomarkers. Outcomes are discussed in relation to timing of assessment and neuropsychological tests used for evaluation of cognitive decline in ischaemic stroke patients. Including such tests in routine evaluations of stroke patients after some weeks or months is recommended. Finally, an outlook on ongoing and planned intervention trials is added and some recommendations for future research are proposed.

Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis

Abstract: Study question What are the benefits and harms of second generation antidepressants and cognitive behavioral therapies (CBTs) in the initial treatment of a current episode of major depressive disorder in adults? Methods This was a systematic review including qualitative assessment and meta-analyses using random and fixed effects models. Medline, Embase, the Cochrane Library, the Allied and Complementary Medicine Database, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature were searched from January1990 through January 2015. The 11 randomized controlled trials included compared a second generation antidepressant CBT. Ten trials compared antidepressant monotherapy with CBT alone; three compared antidepressant monotherapy with antidepressant plus CBT. Summary answer and limitations Meta-analyses found no statistically significant difference in effectiveness between second generation antidepressants and CBT for response (risk ratio 0.91, 0.77 to 1.07), remission (0.98, 0.73 to 1.32), or change in 17 item Hamilton Rating Scale for Depression score (weighted mean difference, −0.38, −2.87 to 2.10). Similarly, no significant differences were found in rates of overall study discontinuation (risk ratio 0.90, 0.49 to 1.65) or discontinuation attributable to lack of efficacy (0.40, 0.05 to 2.91). Although more patients treated with a second generation antidepressant than receiving CBT withdrew from studies because of adverse events, the difference was not statistically significant (risk ratio 3.29, 0.42 to 25.72). No conclusions could be drawn about other outcomes because of lack of evidence. Results should be interpreted cautiously given the low strength of evidence for most outcomes. The scope of this review was limited to trials that enrolled adult patients with major depressive disorder and compared a second generation antidepressant with CBT, and many of the included trials had methodological shortcomings that may limit confidence in some of the findings. What this study adds Second generation antidepressants and CBT have evidence bases of benefits and harms in major depressive disorder. Available evidence suggests no difference in treatment effects of second generation antidepressants and CBT, either alone or in combination, although small numbers may preclude detection of small but clinically meaningful differences. Funding, competing interests, data sharing This project was funded under contract from the Agency for Healthcare Research and Quality by the RTI-UNC Evidence-based Practice Center. Detailed methods and additional information are available in the full report, available at http://effectivehealthcare.ahrq.gov/.

Body Composition and Survival in Dialysis Patients: Results from an International Cohort Study

Abstract: Background and objectives High body mass index appears protective in hemodialysis patients, but uncertainty prevails regarding which components of body composition, fat or lean body mass, are primarily associated with survival. Design, setting, participants, & measurements Data between April 2006 and December 2012 were extracted from the Fresenius Medical Care Europe subset of the international MONitoring Dialysis Outcomes initiative. Fresenius Medical Care Europe archives a unique repository of predialysis body composition measurements determined by multifrequency bioimpedance (BCM Body Composition Monitor). The BCM Body Composition Monitor reports lean tissue indices (LTIs) and fat tissue indices (FTIs), which are the respective tissue masses normalized to height squared, relative to an age- and sex-matched healthy population. The relationship between LTI and FTI and all-cause mortality was studied by Kaplan–Meier analysis, multivariate Cox regression, and smoothing spline ANOVA logistic regression. Results In 37,345 hemodialysis patients, median (25th–75th percentile) LTI and FTI were 12.2 (10.3–14.5) and 9.8 (6.6–12.4)kg/m2,respectively.Median(25th–75thpercentile)follow-uptimewas266(132–379)days;3458(9.2%) patients diedduringfollow-up.MortalitywaslowestwithbothLTIandFTIinthe10th–90thpercentile(reference group)andsignificantlyhigheratthelowerLTIandFTIextreme(hazardratio[HR],3.37;95%confidenceinterval [95% CI], 2.94 to 3.87; P,0.001). Survival was best with LTI between 15 and 20 kg/m2 and FTI between 4 and 15 kg/m 2 (probability of death during follow-up: ,5%). When taking the relation between both compartments into account, the interaction was significant (P=0.01). Higher FTI appeared protective in patients with low LTI (HR, 3.37; 95% CI, 2.94 to 3.87; P,0.001 at low LTI–low FTI, decreasing to HR, 1.79; 95% CI, 1.47 to 2.17; P,0.001 at low LTI–high FTI). Conclusions This large international study indicates best survival in patients with both LTI and FTI in the 10th–90th percentiles of a healthy population. In analyses of body composition, both lean tissue and fat tissue compartments and also their relationship should be considered. Clin J Am Soc Nephrol 10: ccc–ccc, 2015. doi: 10.2215/CJN.08550814

The real type and ideal type of transdisciplinary processes: part II—what constraints and obstacles do we meet in practice?

Abstract: This paper builds on the theoretical foundation outlined in Part I (‘The real type and ideal type of transdisciplinary processes: part I—theoretical foundations’) which is included in the same special feature. Mode 2 transdisciplinarity processes are characterized as processes that relate or integrate problem-oriented interdisciplinary research with knowledge generated in a multi-stakeholder approach with the objective to develop socially robust orientations, for instance, on sustainable transitioning. In practice, transdisciplinary processes may have different functions (i.e., societal capacity building, consensus building, analytic mediation, and legitimization). Practitioners and scientists may follow different interests. And we may distinguish between different types of knowledge integration (including different perspectives, modes of thoughts or cultures). Thus, the reality of transdisciplinarity processes may become a very complex and ambitious venture whose multiple objectives are difficult to realize in practice. This paper reviews the existing challenges, obstacles, and constraints of transdisciplinary processes. This review refers to 41 mid- and large-scale transdisciplinary studies run by members of the ITdNet at seven universities on sustainable transitions of urban and regional systems, organizations, and policy processes. A comprehensive table can be used as a checklist for identifying and coping with constraints and obstacles of transdisciplinary processes in practice. The discussion identifies the main challenges for the future development of transdisciplinarity’s theory and practice, including linking Mode 1 transdisciplinarity (i.e., the relating of disciplinary causation for which no interdisciplinarity is possible by merging concepts and methods) and Mode 2 transdisciplinarity, which targets sustainable knowledge and action for system transitioning.

Cardiovascular and all-cause mortality in relation to various anthropometric measures of obesity in Europeans

Abstract: Background and aims: Cardiovascular and all-cause mortality in relation to various anthropometric measures of obesity is still controversial. Methods and results: Body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), A Body Shape Index (ABSI) and waist-to-hip-to-height ratio (WHHR) were measured at baseline in a cohort of 46,651 European men and women aged 24 e99 years. The relationship between anthropometric measures of obesity and mortality was evaluated by the Cox proportional hazards model with age as a time-scale and with threshold detected by a piecewise regression model. Over a median follow-up of 7.9 years, 2381 men and 1055 women died, 1071 men (45.0%) and 339 women (32.1%) from cardiovascular disease (CVD). BMI had a J-shaped relationship with CVD mortality, whereas anthropometric measures of abdominal obesity had positive linear relationships. BMI, WC and WHtR showed J-shaped as- sociations with all-cause mortality, whereas WHR, ABSI and WHHR demonstrated positive linear relationships. Accordingly, a threshold value was detected at 29.29 and 30.98 kg/m 2 for BMI, 96.4 and 93.3 cm for WC, 0.57 and 0.60 for WHtR, 0.0848 and 0.0813 m 11/6 kg � 2/3 for ABSI with CVD mortality in men and women, respectively; 29.88 and 29.50 kg/m 2 for BMI, 104.3 and 105.6 for WC, 0.61 and 0.67 for WHtR, 0.95 and 0.86 for WHR, 0.0807 and 0.0765 for ABSI in men and women, respectively, and 0.52 for WHHR in women with all-cause mortality. Conclusion: All anthropometric measures of abdominal obesity had positive linear associations with CVD mortality, whereas some showed linear and the others J-shaped relationships with

One and two equals three? The third mission of higher education institutions

Abstract: In modern, knowledge-based societies, universities play an increasingly important role in achieving economic growth and social progress. Their traditional roles and missions are being broadened as to accommodate activities that facilitate engagement with various stakeholder groups. Universities do not want to be regarded as isolated and separated islands from their surrounding communities and have therefore developed internal mechanisms to bridge their activities with the needs and expectations of external actors. In this paper, we take stock of recent scholarly work and ongoing debates surrounding universities’ third mission (TM). Broadly speaking, TM refers to the changing roles and functions of universities which, despite recent developments, have always been a matter of debate amongst academics and society at large.

Impact of population aging on trends in diabetes prevalence: A meta-regression analysis of 160,000 Japanese adults

Abstract: Aims/Introduction To provide age- and sex-specific trends, age-standardized trends, and projections of diabetes prevalence through the year 2030 in the Japanese adult population Materials and Methods In the present meta-regression analysis, we included 161,087 adults from six studies and nine national health surveys carried out between 1988 and 2011 in Japan We assessed the prevalence of diabetes using a recorded history of diabetes or, for the population of individuals without known diabetes, either a glycated hemoglobin level of ≥65% (48 mmol/mol) or the 1999 World Health Organization criteria (ie, a fasting plasma glucose level of ≥126 mg/dL and/or 2-h glucose level of ≥200 mg/dL in the 75-g oral glucose tolerance test) Results For both sexes, prevalence appeared to remain unchanged over the years in all age categories except for men aged 70 years or older, in whom a significant increase in prevalence with time was observed Age-standardized diabetes prevalence estimates based on the Japanese population of the corresponding year showed marked increasing trends: diabetes prevalence was 61% among women (95% confidence interval [CI] 55–67), 99% (95% CI 92–106) among men, and 79% (95% CI 75–84) among the total population in 2010, and was expected to rise by 2030 to 67% (95% CI 52–92), 131% (95% CI 109–167) and 98% (95% CI 85–120), respectively In contrast, the age-standardized diabetes prevalence using a fixed population appeared to remain unchanged Conclusions This large-scale meta-regression analysis shows that a substantial increase in diabetes prevalence is expected in Japan during the next few decades, mainly as a result of the aging of the adult population

The institutionalization of universities’ third mission: introduction to the special issue

Abstract: Globally, debates on the notion of a third set of activities aimed at linking higher education institutions more closely with surrounding society are not new. In the last decade or so, calls for a re-engagement of the university in helping to tackle the great challenges facing societies and local communities have propelled the third mission to the forefront of policy discussions – this time under the mantra of ‘relevance’ and ‘social impact’. Yet, as some of the articles in this special issue attest, there is a fundamental tension in the notion of a third mission. The chief aim of this special issue is to provide a critical assessment of the extent to which the third mission has become an integral part of universities’ core structures and primary activities – from the perspective of institutionalization. The individual contributions provide different accounts and perspectives on internal developments surrounding the third mission, but they all share the notion that major tensions and volitions surrounding...

Transdisciplinarity at the crossroads

Abstract: Twentieth century science has seen an increasingly rapid development of the differentiation of science at large by building new disciplines and specialized or interdisciplinary sub-disciplines; this has been labeled fractalization and chaos of disciplines (Abbott 2001). This increasing fragmentation of the body of sciences, with different types of qualitative and quantitative methods, forms, and norms of validation such as deductive and inductive reasoning, probabilistic and deterministic models, or even different forms of reasoning (for instance, in mathematics certain schools do not consider an indirect proof as valid or acceptable; Gonzalez 1991) call for integrating meta-levels from an inner-science perspective (Godel 1931). The construction of proper meta-levels of reflection, validation, and integration may play an important role in the future development of sciences. Science has long subscribed to a Humboldtian or Newtonian world view that has been strongly shaped by a physical rationale and was lacking an integrating, coherent system of knowledge for the investigation of human– environment interactions. Understanding of the unity of nature was perceived as the ultimate reference (von Weizsacker 1980/1971; Wilson 1999). Consilience and consistency of reasoning (Bunge 1967a, b) and a strong belief in rationality (Carnap 1991; Oppenheim and Putnam 1958) were dominant. In addition, attempts at the integration of knowledge, such as the search for a general system theory (von Bertalanffy 1951), were shaped by the thinking of natural science for a long time. The search for a unifying level or entity, or a framing of the meta-level (Godel 1931) or total transdisciplinarity, can be considered Mode 1 transdisciplinarity (Piaget 1972), which sometimes leads to the assumption of spirituality and the idea of transcendence (Nicolescu 2014). However, the challenge of integration and consistency and dealing with a complexity of systems and integrated reasoning can also be approached from a realist stance (Bunge 2003; Klein 2003; Mitchell 2003; Scholz 2011). Today, the scientific challenge has become even more complex. In the age of the Anthropocene (Crutzen 2002), instead of a ‘‘unity of nature’’ we are looking at the ‘‘resilience of inextricably coupled human–environment systems’’ (Scholz 2011) and their ontology, dynamics, and governance as a basis of sustainability science (Kates 2012). This is precisely where transdisciplinarity of the Mode 2 type (Scholz and Steiner 2015a; Gibbons et al. 1994) and the turn From a science for society to a science with society (Scholz and Stauffacher 2009; Seidl et al. 2013) serve to overcome the reductionist view of science. Transdisciplinarity requires theory and practice. Much has been written about how transdisciplinarity is conceived. However, as we discovered over the course of preparing this special feature, very few scientific papers in peer-reviewed journals document the social and scientific outcomes and benefits of transdisciplinary processes. When & Roland W. Scholz roland.scholz@igb-extern.fraunhofer.de

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Abstract: Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

M2 Polarization of Human Macrophages Favors Survival of the Intracellular Pathogen Chlamydia pneumoniae

Abstract: Intracellular pathogens have developed various strategies to escape immunity to enable their survival in host cells, and many bacterial pathogens preferentially reside inside macrophages, using diverse mechanisms to penetrate their defenses and to exploit their high degree of metabolic diversity and plasticity. Here, we characterized the interactions of the intracellular pathogen Chlamydia pneumoniae with polarized human macrophages. Primary human monocytes were pre-differentiated with granulocyte macrophage colony-stimulating factor or macrophage colony-stimulating factor for 7 days to yield M1-like and M2-like macrophages, which were further treated with interferon-γ and lipopolysaccharide or with interleukin-4 for 48 h to obtain fully polarized M1 and M2 macrophages. M1 and M2 cells exhibited distinct morphology with round or spindle-shaped appearance for M1 and M2, respectively, distinct surface marker profiles, as well as different cytokine and chemokine secretion. Macrophage polarization did not influence uptake of C. pneumoniae, since comparable copy numbers of chlamydial DNA were detected in M1 and M2 at 6 h post infection, but an increase in chlamydial DNA over time indicating proliferation was only observed in M2. Accordingly, 72±5% of M2 vs. 48±7% of M1 stained positive for chlamydial lipopolysaccharide, with large perinuclear inclusions in M2 and less clearly bordered inclusions for M1. Viable C. pneumoniae was present in lysates from M2, but not from M1 macrophages. The ability of M1 to restrict chlamydial replication was not observed in M1-like macrophages, since chlamydial load showed an equal increase over time for M1-like and M2-like macrophages. Our findings support the importance of macrophage polarization for the control of intracellular infection, and show that M2 are the preferred survival niche for C. pneumoniae. M1 did not allow for chlamydial proliferation, but failed to completely eliminate chlamydial infection, giving further evidence for the ability of C. pneumoniae to evade cellular defense and to persist in human macrophages.

Light therapy for preventing seasonal affective disorder

Abstract: Background Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review - one of four reviews on efficacy and safety of interventions to prevent SAD - focuses on light therapy as a preventive intervention. Light therapy is a non-pharmacological treatment that exposes people to artificial light. Mode of delivery (e.g. visors, light boxes) and form of light (e.g. bright white light) vary. Objectives To assess the efficacy and safety of light therapy (in comparison with no treatment, other types of light therapy, second-generation antidepressants, melatonin, agomelatine, psychological therapies, lifestyle interventions and negative ion generators) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. Search methods A search of the Specialised Register of the Cochrane Depression, Anxiety and Neuorosis Review Group (CCDANCTR) included all years to 11 August 2015. The CCDANCTR contains reports of relevant randomised controlled trials derived from EMBASE (1974 to date), MEDLINE (1950 to date), PsycINFO (1967 to date) and the Cochrane Central Register of Controlled Trails (CENTRAL). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Knowledge, The Cochrane Library and the Allied and Complementary Medicine Database (AMED) (to 26 May 2014). We also conducted a grey literature search and handsearched the reference lists of all included studies and pertinent review articles. Selection criteria For efficacy, we included randomised controlled trials on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we also intended to include non-randomised studies. We intended to include studies that compared any type of light therapy (e.g. bright white light, administered by visors or light boxes, infrared light, dawn stimulation) versus no treatment/placebo, second-generation antidepressants (SGAs), psychological therapies, melatonin, agomelatine, lifestyle changes, negative ion generators or another of the aforementioned light therapies. We also planned to include studies that looked at light therapy in combination with any comparator intervention and compared this with the same comparator intervention as monotherapy. Data collection and analysis Two review authors screened abstracts and full-text publications against the inclusion criteria. Two review authors independently abstracted data and assessed risk of bias of included studies. Main results We identified 2986 citations after de-duplication of search results. We excluded 2895 records during title and abstract review. We assessed 91 full-text papers for inclusion in the review, but only one study providing data from 46 people met our eligibility criteria. The included randomised controlled trial (RCT) had methodological limitations. We rated it as having high risk of performance and detection bias because of lack of blinding, and as having high risk of attrition bias because study authors did not report reasons for dropouts and did not integrate data from dropouts into the analysis. The included RCT compared preventive use of bright white light (2500 lux via visors), infrared light (0.18 lux via visors) and no light treatment. Overall, both forms of preventive light therapy reduced the incidence of SAD numerically compared with no light therapy. In all, 43% (6/14) of participants in the bright light group developed SAD, as well as 33% (5/15) in the infrared light group and 67% (6/9) in the non-treatment group. Bright light therapy reduced the risk of SAD incidence by 36%; however, the 95% confidence interval (CI) was very broad and included both possible effect sizes in favour of bright light therapy and those in favour of no light therapy (risk ratio (RR) 0.64, 95% CI 0.30 to 1.38). Infrared light reduced the risk of SAD by 50% compared with no light therapy, but in this case also the CI was too broad to allow precise estimations of effect size (RR 0.50, 95% CI 0.21 to 1.17). Comparison of both forms of preventive light therapy versus each other yielded similar rates of incidence of depressive episodes in both groups (RR 1.29, 95% CI 0.50 to 3.28). The quality of evidence for all outcomes was very low. Reasons for downgrading evidence quality included high risk of bias of the included study, imprecision and other limitations, such as self rating of outcomes, lack of checking of compliance throughout the study duration and insufficient reporting of participant characteristics. Investigators provided no information on adverse events. We could find no studies that compared light therapy versus other interventions of interest such as SGA, psychological therapies, melatonin or agomelatine. Authors' conclusions Evidence on light therapy as preventive treatment for patients with a history of SAD is limited. Methodological limitations and the small sample size of the only available study have precluded review author conclusions on effects of light therapy for SAD. Given that comparative evidence for light therapy versus other preventive options is limited, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences.

How effective are common medications: a perspective based on meta-analyses of major drugs

Abstract: The vastness of clinical data and the progressing specialization of medical knowledge may lead to misinterpretation of medication efficacy. To show a realistic perspective on drug efficacy we present meta-analyses on some of the most commonly used pharmacological interventions. For each pharmacological intervention we present statistical indexes (absolute risk or response difference, percentage response ratio, mean difference, standardized mean difference) that are often used to represent efficacy. We found that some of the medications have relatively low effect sizes with only 11 out of 17 of them showing a minimal clinically important difference. Efficacy was often established based on surrogate outcomes and not the more relevant patient-oriented outcomes. As the interpretation of the efficacy of medication is complex, more training for physicians might be needed to get a more realistic view of drug efficacy. That could help prevent harmful overtreatment and reinforce an evidence-based, but personalized medicine.

ERAP2 is associated with ankylosing spondylitis in HLA-B27-positive and HLA-B27-negative patients

Abstract: The association of endoplasmic reticulum aminopeptidase 2 (ERAP2) with ankylosing spondylitis (AS) was recently described in the large International Genetics of AS Consortium Immunochip study. Variants in ERAP2 have also been associated with inflammatory bowel disease, psoriasis, acute anterior uveitis and birdshot chorioretinopathy. Subsequent investigation demonstrated an association of ERAP2 with AS which was present when one conditioned on one of the two independent haplotypes of ERAP1 associated with AS or when HLA-B27-negative patients were analysed separately. These two analyses provide analogous evidence for the association of ERAP2 with AS in HLA-B27-negative cases because of the genetic interaction between HLA-B27 and the AS-associated ERAP1 variants in AS cases. ERAP1 and ERAP2 are located on chromosome 5q15 in the opposite orientation. The locus is challenging to analyse because of the strong linkage disequilibrium (LD) across the locus and the epistasis between ERAP1 and HLA-B alleles associated with AS. We therefore sought to investigate the association of ERAP2 with AS in HLA-B27-positive patients. This is of clinical importance because functional studies have demonstrated that the strongly AS-protective variant rs2248374 causes a functional ERAP2 protein knockout, because its G allele causes a loss of ERAP2 protein expression. There is also a variant of ERAP2 which changes its enzyme catalytic activity and specificity (rs2549782, K392A). Because this is in almost complete LD with rs2248374 (1000 Genomes D′=1.00, r2=0.90), it is almost never translated in vivo. Further, the very strong LD between these markers means that analysis of rs2549782 for association would yield results almost identical to the results for rs2248374 presented below. Therefore, it is of relevance to determine whether the association of ERAP2 with HLA-B27-negative disease is also found in HLA-B27-positive cases, since ERAP inhibition may offer a novel therapeutic for AS...

New Strategy to Reduce the Global Burden of Stroke

Abstract: The socioeconomic and health effect of stroke and other noncommunicable disorders (NCDs) that share many of the same risk factors with stroke, such as heart attack, dementia, and diabetes mellitus, is huge and increasing.1–4 Collectively, NCDs account for 34.5 million deaths (66% of deaths from all causes)3 and 1344 million disability-adjusted life years lost worldwide in 2010.2 The burden of NCDs is likely to burgeon given the aging of the world’s population and the epidemiological transition currently observed in many low- to middle-income countries (LMICs).5,6 In addition, there is low awareness in the population about these NCDs and their risk factors,7–10 particularly in LMICs.11 These factors, coupled with underuse of strategies for primary prevention of stroke/NCDs on an individual level and the lack of accurate data on the prevalence and effect of risk factors in different countries and populations have been implicated in the ever-increasing worldwide burden of the NCDs.12–15 Of particular concern is a significant increase in the number of young adults (aged <65 years) affected by stroke,16 and the increasing epidemic of overweight/obesity17 and diabetes mellitus worldwide.18 If these trends continue, the burden of stroke and other major NCDs will increase even faster. The increasing burden of stroke and other major NCDs provide strong support for the notion that the currently used primary prevention strategies for stroke and other major NCDs (business as usual) are not sufficiently effective. The most pertinent solution to this problem is the implementation of new, effective, widely available, and cost-effective prevention and treatment strategies to reduce the incidence and severity distribution of stroke and other major NCDs. The recent INTERSTROKE case-control study, conducted in 22 countries worldwide, provided evidence that, collectively, 10 risk factors accounted …

Impact of population aging on trends in diabetes prevalence: A meta-regression analysis of 160,000 Japanese adults

Abstract: Aims/Introduction To provide age- and sex-specific trends, age-standardized trends, and projections of diabetes prevalence through the year 2030 in the Japanese adult population. Materials and Methods In the present meta-regression analysis, we included 161,087 adults from six studies and nine national health surveys carried out between 1988 and 2011 in Japan. We assessed the prevalence of diabetes using a recorded history of diabetes or, for the population of individuals without known diabetes, either a glycated hemoglobin level of ≥6.5% (48 mmol/mol) or the 1999 World Health Organization criteria (i.e., a fasting plasma glucose level of ≥126 mg/dL and/or 2-h glucose level of ≥200 mg/dL in the 75-g oral glucose tolerance test). Results For both sexes, prevalence appeared to remain unchanged over the years in all age categories except for men aged 70 years or older, in whom a significant increase in prevalence with time was observed. Age-standardized diabetes prevalence estimates based on the Japanese population of the corresponding year showed marked increasing trends: diabetes prevalence was 6.1% among women (95% confidence interval [CI] 5.5–6.7), 9.9% (95% CI 9.2–10.6) among men, and 7.9% (95% CI 7.5–8.4) among the total population in 2010, and was expected to rise by 2030 to 6.7% (95% CI 5.2–9.2), 13.1% (95% CI 10.9–16.7) and 9.8% (95% CI 8.5–12.0), respectively. In contrast, the age-standardized diabetes prevalence using a fixed population appeared to remain unchanged. Conclusions This large-scale meta-regression analysis shows that a substantial increase in diabetes prevalence is expected in Japan during the next few decades, mainly as a result of the aging of the adult population.