Single nucleotide polymorphisms and breast cancer: not yet a success story

Numerous studies have examined low penetrance susceptibility polymorphisms in candidate genes, with some reporting significant findings. However, for the most part these associations could not be replicated in subsequent studies, suggesting that the original observations were due to chance. The failure to identify meaningful common genetic variation in relation to breast cancer should give us pause for thought and make us reconsider our current research strategies. The most recent directions of pooling samples to increase statistical power and pursuing whole genome screens may overcome some obstacles while also creating new challenges. Future studies should perhaps also consider alternative designs such as using surrogate (preferably continuous) markers of breast cancer, focusing on high-risk populations, and defining pathologically distinct outcomes

Single nucleotide polymorphisms and breast cancer: not yet a success story

Numerous studies have examined low penetrance susceptibility polymorphisms in candidate genes, with some reporting significant findings. However, for the most part these associations could not be replicated in subsequent studies, suggesting that the original observations were due to chance. The failure to identify meaningful common genetic variation in relation to breast cancer should give us pause for thought and make us reconsider our current research strategies. The most recent directions of pooling samples to increase statistical power and pursuing whole genome screens may overcome some obstacles while also creating new challenges. Future studies should perhaps also consider alternative designs such as using surrogate (preferably continuous) markers of breast cancer, focusing on high-risk populations, and defining pathologically distinct outcomes

Definition of treatment goals for moderate to severe psoriasis: a European consensus

Patients with moderate to severe psoriasis are undertreated. To solve this persistent problem, the consensus programme was performed to define goals for treatment of plaque psoriasis with systemic therapy and to improve patient care. An expert consensus meeting and a collaborative Delphi procedure were carried out. Nineteen dermatologists from different European countries met for a face-to-face discussion and defined items through a four-round Delphi process. Severity of plaque psoriasis was graded into mild and moderate to severe disease. Mild disease was defined as body surface area (BSA) ≤10 and psoriasis area and severity index (PASI) ≤10 and dermatology life quality index (DLQI) ≤10 and moderate to severe psoriasis as (BSA > 10 or PASI > 10) and DLQI > 10. Special clinical situations may change mild psoriasis to moderate to severe including involvement of visible areas or severe nail involvement. For systemic therapy of plaque psoriasis two treatment phases were defined: (1) induction phase as the treatment period until week 16; however, depending on the type of drug and dose regimen used, this phase may be extended until week 24 and (2) maintenance phase for all drugs was defined as the treatment period after the induction phase. For the definition of treatment goals in plaque psoriasis, the change of PASI from baseline until the time of evaluation (ΔPASI) and the absolute DLQI were used. After induction and during maintenance therapy, treatment can be continued if reduction in PASI is ≥75%. The treatment regimen should be modified if improvement of PASI is <50%. In a situation where the therapeutic response improved ≥50% but <75%, as assessed by PASI, therapy should be modified if the DLQI is >5 but can be continued if the DLQI is ≤5. This programme defines the severity of plaque psoriasis for the first time using a formal consensus of 19 European experts. In addition, treatment goals for moderate to severe disease were established. Implementation of treatment goals in the daily management of psoriasis will improve patient care and mitigate the problem of undertreatment. It is planned to evaluate the implementation of these treatment goals in a subsequent programme involving patients and physicians

Estimating Dengue Transmission Intensity from Case-Notification Data from Multiple Countries

Despite being the most widely distributed mosquito-borne viral infection, estimates of dengue transmission intensity and associated burden remain ambiguous. With advances in the development of novel control measures, obtaining robust estimates of average dengue transmission intensity is key for assessing the burden of disease and the likely impact of interventions.We estimated the force of infection (λ) and corresponding basic reproduction numbers (R0) by fitting catalytic models to age-stratified incidence data identified from the literature. We compared estimates derived from incidence and seroprevalence data and assessed the level of under-reporting of dengue disease. In addition, we estimated the relative contribution of primary to quaternary infections to the observed burden of dengue disease incidence. The majority of R0 estimates ranged from one to five and the force of infection estimates from incidence data were consistent with those previously estimated from seroprevalence data. The baseline reporting rate (or the probability of detecting a secondary infection) was generally low (<25%) and varied within and between countries.As expected, estimates varied widely across and within countries, highlighting the spatio-temporally heterogeneous nature of dengue transmission. Although seroprevalence data provide the maximum information, the incidence models presented in this paper provide a method for estimating dengue transmission intensity from age-stratified incidence data, which will be an important consideration in areas where seroprevalence data are not available

Integration of decision support systems to improve decision support performance

Decision support system (DSS) is a well-established research and development area. Traditional isolated, stand-alone DSS has been recently facing new challenges. In order to improve the performance of DSS to meet the challenges, research has been actively carried out to develop integrated decision support systems (IDSS). This paper reviews the current research efforts with regard to the development of IDSS. The focus of the paper is on the integration aspect for IDSS through multiple perspectives, and the technologies that support this integration. More than 100 papers and software systems are discussed. Current research efforts and the development status of IDSS are explained, compared and classified. In addition, future trends and challenges in integration are outlined. The paper concludes that by addressing integration, better support will be provided to decision makers, with the expectation of both better decisions and improved decision making processes