Should we consider Dupuytren's contracture as work-related? A review and meta-analysis of an old debate

International audienceABSTRACT: BACKGROUND: In view of the conflicting opinions published, a meta-analysis was undertaken on epidemiological studies in order to assess any association between Dupuytren's contracture and work exposure. METHODS: Using the key words: "occupational disease", "work" and "Dupuytren contracture" without limitation on language or year of publication, epidemiological studies were selected from four databases (Pub-Med, Embase, Web of science, BDSP) after two rounds (valid control group, valid work exposure). A quality assessment list was constructed and used to isolate papers with high quality methodological criteria (scores of 13 or above, HQMC). Relevant associations between manual work, vibration exposure (at work) and Dupuytren's contracture were extracted from the articles and a metarisk calculated using the generic variance approach (meta-odds ratios, meta-OR). RESULTS: From 1951 to 2007, 14 epidemiological studies (including 2 cohort studies, 3 case-control studies, and 9 cross-sectional studies/ population surveys) were included. Two different results could be extracted from five studies (based on different types of exposure), leading to 19 results, 12 for manual work (9 studies), and 7 for vibration exposure (5 studies). Six studies met the HQMC, yielding 9 results, 5 for manual work and 4 for vibration exposure. Five studies found a dose-response relationship. The meta-OR for manual work was 2.02[1.57;2.60] (HQMC studies only: 2.01[1.51;2.66]), and the meta-OR for vibration exposure was 2.88 [1.36;6.07] (HQMC studies only: 2.14[1.59;2.88]). CONCLUSION: These results support the hypothesis of an association between high levels of work exposure (manual work and vibration exposure) and Dupuytren's contracture in certain cases

Preventing mental health problems in children : the families in mind population-based cluster randomised controlled trial.

BackgroundExternalising and internalising problems affect one in seven school-aged children and are the single strongest predictor of mental health problems into early adolescence. As the burden of mental health problems persists globally, childhood prevention of mental health problems is paramount. Prevention can be offered to all children (universal) or to children at risk of developing mental health problems (targeted). The relative effectiveness and costs of a targeted only versus combined universal and targeted approach are unknown. This study aims to the effectiveness, costs and uptake of two approaches to early childhood prevention of mental health problems ie: a Combined universal-targeted approach, versus a Targeted only approach, in comparison to current primary care services (Usual care).DesignThree armed, population-level cluster randomised trial (2010-2014) within the universal, well child Maternal Child Health system, attended by more than 80% of families in Victoria, Australia at infant age eight months. Participants: Families of eight month old children from nine participating local government areas. Randomised to one of three groups: Combined, Targeted or Usual care. Intervention: (a) the Combined universal and targeted program where all families are offered the universal Toddlers Without Tears group parenting program followed by the targeted Family Check-Up one-on-one program or (b) the Targeted Family Check-Up program. The Family Check-Up program is only offered to children at risk of behavioural problems. Analysis: Participants will be analysed according to the trial arm to which they were randomised, using logistic and linear regression models to compare primary and secondary outcomes. An economic evaluation (cost consequences analysis) will compare incremental costs to all incremental outcomes from a societal perspective.DiscussionThis trial will inform public health policy by making recommendations about the effectiveness and cost-effectiveness of these early prevention programs. If effective prevention programs can be implemented at the population level, the growing burden of mental health problems could be curbed.<br /

Meta-Analysis of Genome-Wide Association Studies and Network Analysis-Based Integration with Gene Expression Data Identify New Suggestive Loci and Unravel a Wnt-Centric Network Associated with Dupuytren’s Disease

Dupuytren´s disease, a fibromatosis of the connective tissue in the palm, is a common complex disease with a strong genetic component. Up to date nine genetic loci have been found to be associated with the disease. Six of these loci contain genes that code for Wnt signalling proteins. In spite of this striking first insight into the genetic factors in Dupuytren´s disease, much of the inherited risk in Dupuytren´s disease still needs to be discovered. The already identified loci jointly explain ~1% of the heritability in this disease. To further elucidate the genetic basis of Dupuytren´s disease, we performed a genome-wide meta-analysis combining three genome-wide association study (GWAS) data sets, comprising 1,580 cases and 4,480 controls. We corroborated all nine previously identified loci, six of these with genome-wide significance (p-value < 5x10-8). In addition, we identified 14 new suggestive loci (p-value < 10−5). Intriguingly, several of these new loci contain genes associated with Wnt signalling and therefore represent excellent candidates for replication. Next, we compared whole-transcriptome data between patient- and control-derived tissue samples and found the Wnt/β-catenin pathway to be the top deregulated pathway in patient samples. We then conducted network and pathway analyses in order to identify protein networks that are enriched for genes highlighted in the GWAS meta-analysis and expression data sets. We found further evidence that the Wnt signalling pathways in conjunction with other pathways may play a critical role in Dupuytren´s disease

Safety of aromatase inhibitors in the adjuvant setting

The third-generation aromatase inhibitors (AIs) letrozole, anastrozole, and exemestane are replacing tamoxifen as adjuvant therapy in most postmenopausal women with early breast cancer. Although AIs have demonstrated superior efficacy and better overall safety compared with tamoxifen in randomized controlled trials, they may not provide the cardioprotective effects of tamoxifen, and bone loss may be a concern with their long-term adjuvant use. Patients require regular bone mineral density monitoring, and prophylactic bisphosphonates are being evaluated to determine whether they may protect long-term bone health. AIs decrease the risks of thromboembolic and cerebrovascular events compared with tamoxifen, and the overall rate of cardiovascular events in patients treated with AIs is within the range seen in age-matched, non-breast-cancer populations. AIs are also associated with a lower incidence of endometrial cancer and fewer vaginal bleeding/discharge events than tamoxifen. Compared with tamoxifen, the incidence of hot flashes is lower with anastrozole and letrozole but may be higher with exemestane. Generally, adverse events with AIs are predictable and manageable, whereas tamoxifen may be associated with life-threatening events in a minority of patients. Overall, the benefits of AIs over tamoxifen are achieved without compromising overall quality of life

Great War Shakespeare: Somewhere in France, 1914-1919

This paper explores the various ways in which the entente cordiale and the political alliance between France and England in 1914-1918 created a unique climate in which the reception of Shakespeare thrived on either side of the Channel. Studying a number of manifestations during the period, we learn that Shakespeare could be a national hero for the English, but at the same time also a supranational hero shared by the two nations. Tracing the ways in which England and France cherished their Shakespeare during the period, this paper also makes a case for exploring the long-neglected presence of Shakespeare in French popular culture. - Cet article explore les différentes façons dont l’entente cordiale et l’alliance politique entre la France et l’Angleterre pendant la Première Guerre Mondiale ont créé un climat favorable à la réception de Shakespeare des deux côtés de la Manche. L’étude de plusieurs manifestations culturelles pendant cette période nous apprend que si Shakespeare était un héros national pour les Anglais, il a aussi pu incarner un héros supra-national commun aux deux nations. Il s’agit donc d’étudier la présence de Shakespeare dans la culture populaire non seulement en Angleterre mais aussi en France, domaine longtemps négligé