The association between psychosocial work environment,attitudes towards older workers (ageism) and planned retirement

Purpose  

The aim of this study was to examine the association between psychosocial factors (in particular ageism) at the workplace and older workers’ retirement plans, while taking health and workability of the employee into account.     

Patients with type 2 diabetes benefit from primary care-based disease management: a propensity score matched survival time analysis

This study aimed to assess the impact of a nationwide German diabetes mellitus disease management program (DMP) on survival time and costs in comparison to routine care. The authors conducted a retrospective observational cohort study using routine administration data from Germany's largest sickness fund to identify insured suffering from diabetes in 2002. A total of 95,443 insured with type 2 diabetes mellitus who were born before January 1, 1962 met the defined inclusion criteria, resulting in 19,888 pairs of DMP participants and nonparticipants matched for socioeconomic and health status using propensity score matching methods. This is the first time propensity score matching has been used to evaluate a survival benefit of DMPs. In the time frame analyzed (3 years), mean survival time for the DMP group was 1045 days vs. 985 days for the routine care group (P<0.001). Mean daily hospital and total costs (including DMP administration and medical costs) were lower for the DMP group in the case of deceased insureds (92€ vs. 139€ and 122€ vs. 169€, respectively) as well as for censored observations (6€ vs. 7€ and 12.9€ vs. 13.4€, respectively). Mean daily drug costs were slightly lower for deceased insured in the DMP group (difference 0.6€), while no identifiable difference was found for censored observations. In this study, insured who were enrolled in a DMP for diabetes mellitus in the German Statutory Health Insurance showed a significant benefit in survival time. They also incurred lower costs compared to propensity score matched insured in routine care.     

Regulation of thrombomodulin expression in human vascular smooth muscle cells by COX-2-derived prostaglandins

There is concern that cyclooxygenase (COX)-2 inhibitors may promote atherothrombosis by inhibiting vascular formation of prostacyclin (PGI2) and an increased thrombotic risk of COX-2 inhibitors has been reported. It is widely accepted that the prothrombotic effects of COX-2 inhibitors can be explained by the removal of platelet-inhibitory PGI2. Using microarray chip technology, we have previously demonstrated that thrombomodulin (TM) mRNA is upregulated in cultured human coronary artery smooth muscle cells by the stable prostacyclin mimetic iloprost. This study is the first to demonstrate a stimulation of the expression of functionally active thrombomodulin in human smooth muscle cells by prostaglandins, endogenously formed via the COX-2 pathway. Because TM is an important inhibitor of blood coagulation, these findings provide a novel platelet-independent mechanism to explain the prothrombotic effects of COX-2 inhibitors. The full text of this article is available online at http://circres.ahajournals.org.     

Truncating mutations in Peutz-Jeghers syndrome are associated with more polyps, surgical interventions and cancers

Background and Goals

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant polyposis syndrome caused by STK11 germline mutations. PJS is associated with an increased risk of cancer. In our cohort, clinical and phenotypic parameters were correlated with genotypic findings and patients were prospectively followed by surveillance.

Study

Thirty-one patients treated between 2000 and 2006, were evaluated. STK11 genotyping was performed and phenotypes of patients with truncating (TM) and nontruncating mutations (NTM) were compared.

Results

Median age at first symptoms was 11 years and complications occurred before the age of ten in 42% of patients. STK11 mutations were detected in 16 of 22 families (12 TM; four NTM). Patients with TM had more surgical gastrointestinal (GI) interventions (p = 0.021), and female patients in the TM group had an increased risk of undergoing gynecological surgery (p = 0.016). Also, there was a trend towards a higher polyp count (p = 0.11) and earlier age at first polypectomy (p = 0.13) in the TM group. Ten carcinomas were detected in six patients resulting in a cancer risk of 65% up to the age of 65 years. Patients with TM tended to develop more cancers (p = 0.10). Importantly, our surveillance strategy used detected 50% of cancers (n = 5) at an early potentially curable stage.

Conclusions

Our study shows that almost half of PJ patients have complications early in life independent of mutational status. Patients with TM require more surgical GI interventions and tend to develop more polyps and cancers. Furthermore, close surveillance detects early stage cancers in patients. We propose that surveillance should be started as early as 8 years in all patients to avoid complications. Moreover, patients with TM may benefit from surveillance at shorter intervals.     

Metabolite ratios as potential biomarkers for type 2 diabetes: a DIRECT study

Aims/hypothesis

Circulating metabolites have been shown to reflect metabolic changes during the development of type 2 diabetes. In this study we examined the association of metabolite levels and pairwise metabolite ratios with insulin responses after glucose, glucagon-like peptide-1 (GLP-1) and arginine stimulation. We then investigated if the identified metabolite ratios were associated with measures of OGTT-derived beta cell function and with prevalent and incident type 2 diabetes.

Methods

We measured the levels of 188 metabolites in plasma samples from 130 healthy members of twin families (from the Netherlands Twin Register) at five time points during a modified 3 h hyperglycaemic clamp with glucose, GLP-1 and arginine stimulation. We validated our results in cohorts with OGTT data (n = 340) and epidemiological case–control studies of prevalent (n = 4925) and incident (n = 4277) diabetes. The data were analysed using regression models with adjustment for potential confounders.

Results

There were dynamic changes in metabolite levels in response to the different secretagogues. Furthermore, several fasting pairwise metabolite ratios were associated with one or multiple clamp-derived measures of insulin secretion (all p < 9.2 × 10^?7). These associations were significantly stronger compared with the individual metabolite components. One of the ratios, valine to phosphatidylcholine acyl-alkyl C32:2 (PC ae C32:2), in addition showed a directionally consistent positive association with OGTT-derived measures of insulin secretion and resistance (p ≤ 5.4 × 10^?3) and prevalent type 2 diabetes (OR_{Val_PC ae C32:2} 2.64 [β 0.97 ± 0.09], p = 1.0 × 10^?27). Furthermore, Val_PC ae C32:2 predicted incident diabetes independent of established risk factors in two epidemiological cohort studies (HR_{Val_PC ae C32:2} 1.57 [β 0.45 ± 0.06]; p = 1.3 × 10^?15), leading to modest improvements in the receiver operating characteristics when added to a model containing a set of established risk factors in both cohorts (increases from 0.780 to 0.801 and from 0.862 to 0.865 respectively, when added to the model containing traditional risk factors + glucose).

Conclusions/interpretation

In this study we have shown that the Val_PC ae C32:2 metabolite ratio is associated with an increased risk of type 2 diabetes and measures of insulin secretion and resistance. The observed effects were stronger than that of the individual metabolites and independent of known risk factors.