The association between antidepressant use and disturbances in glucose homeostasis: evidence from spontaneous reports

Objectives Depression is common in patients with diabetes, and the use of antidepressants may impair glycaemic control. We assessed the association between antidepressant use and hyper- and hypoglycaemia. Methods Based on spontaneous reports listed in the World Health Organization (WHO) Adverse Drug Reaction Database, a case-control study was conducted. The study base consisted of all adverse drug reactions (ADRs) ascribed to antidepressants, antipsychotics and benzodiazepines between 1969 and 2005. Cases were defined as reported ADRs classified as hyper- or hypoglycaemia and separated in different study populations. All other reports were considered as controls. Exposure to antidepressants was the primary determinant investigated. Benzodiazepines and antipsychotics were chosen as reference groups. Potential confounding factors, namely, age, gender, use of antidiabetic medication, use of hyper- or hypoglycaemia-inducing comedication and reporting year, were determined on the index date. Multivariate logistic regression was used to evaluate the strength of the association, which was expressed as reporting odds ratios (RORs) with 95% confidence intervals (95% CI). Results Overall, the use of antidepressants was associated with hyperglycaemia [ROR 1.52 (95% CI: 1.20–1.93)] and of hypoglycaemia [ROR 1.84 (95% CI: 1.40–2.42)]. The association with hyperglycaemia was most pronounced for antidepressants with affinity for the 5-HT_2c receptor, histamine-₁ receptor and norepinephrinic (NE) reuptake transporter. The association with hypoglycaemia was most pronounced for antidepressants with affinity for the serotonin reuptake transporter. Conclusion The results of this study strengthen the findings in individual case reports that the use of antidepressants is associated with disturbances in glucose homeostasis. Role of the funding source: No funding source was involved.     

Surpass Flow Diverter for Treatment of Posterior Circulation Aneurysms

BACKGROUND AND PURPOSE:Flow diverters for the treatment of posterior circulation aneurysms remain controversial. We aimed to identify factors contributing to outcome measures in patients treated with the Surpass flow diverter for aneurysms in this location.MATERIALS AND METHODS:We conducted an observational study of 53 patients who underwent flow-diverter treatment for posterior circulation aneurysms at 15 centers. Key outcome measures were mortality, complete aneurysm occlusion, and modified Rankin Scale score at follow-up.RESULTS:At follow-up (median, 11.3 months; interquartile range, 5.9–12.7 months), 9 patients had died, resulting in an all-cause mortality rate of 17.3% (95% CI, 7%–27.6%); 7 deaths (14%) were directly related to the procedure and none occurred in patients with a baseline mRS score of zero. After adjusting for covariates, a baseline mRS of 3–5 was more significantly (P = .003) associated with a higher hazard ratio for death than a baseline mRS of 0–2 (hazard ratio, 17.11; 95% CI, 2.69–109.02). After adjusting for follow-up duration, a 1-point increase in the baseline mRS was significantly (P < .001) associated with higher values of mRS at follow-up (odds ratio, 2.93; 95% CI, 1.79–4.79). Follow-up angiography in 44 patients (median, 11.3 months; interquartile range, 5.9–12.7 months) showed complete aneurysm occlusion in 29 (66%; 95% CI, 50.1%–79.5%).CONCLUSIONS:Clinical results of flow-diverter treatment of posterior circulation aneurysms depend very much on patient selection. In this study, poorer outcomes were related to the treatment of aneurysms in patients with higher baseline mRS scores. Angiographic results showed a high occlusion rate for this subset of complex aneurysms.

Flow diverters (FDs) have proved to be reliable tools for the treatment of complex aneurysms,¹ but their use for aneurysms in the posterior circulation remains controversial.^2–4 The large number of perforating and branching arteries of the posterior circulation potentially increases the risk in flow diversion, exposing patients to thromboembolic complications and brain stem stroke. FD treatment of giant, fusiform aneurysms of the vertebrobasilar (VB) junction or basilar trunk (BT) has been associated with high morbidity and mortality of up to 71%.^2–4A recent meta-analysis identified 14 studies, which reported on 225 posterior circulation aneurysms treated with FDs in 220 patients.⁵ The procedure-related good outcome rate was 79% (95% confidence interval, 72%–84%), and the procedure-related mortality rate was 15% (95% CI, 10%–21%). Most studies included only a small number of patients (median, 9.5; range, 5–55), and most of these patients (155/220) were treated with the Pipeline Embolization Device (Covidien, Irvine, California).The Surpass FD (Stryker Neurovascular, Fremont, California) has various features that seem to predetermine its use in the posterior circulation: 1) The maximum length of 50 mm allows aneurysm treatment with a single device, thus avoiding telescoping; 2) due to the rhomboid shape of the FD cells, the flow-diverting effect remains constant in tapered vessels. The rhomboid shape allows a consistent cell shape across a wide range of vessel diameters. Specifically, this feature enables consistent porosity and pore density along the length of the implant in a tapering vessel. These are known variables that contribute to flow diversion and thrombosis of the aneurysm.On the other hand, the Surpass FD has a particularly high mesh density compared with the Pipeline Embolization Device, potentially increasing the risk of perforator strokes.⁶ The purpose of this study was to identify factors contributing to outcome measures in patients treated with the Surpass FD for aneurysms located in the posterior circulation.     

Comparison of a basic and an advanced pharmacotherapy-related clinical decision support system in a hospital care setting in the Netherlands

Objective

To compare the clinical relevance of medication alerts in a basic and in an advanced clinical decision support system (CDSS).

Design

A prospective observational study.

Materials and methods

We collected 4023 medication orders in a hospital for independent evaluation in two pharmacotherapy-related decision support systems. Only the more advanced system considered patient characteristics and laboratory test results in its algorithms. Two pharmacists assessed the clinical relevance of the medication alerts produced. The alert was considered relevant if the pharmacist would undertake action (eg, contact the physician or the nurse). The primary analysis concerned the positive predictive value (PPV) for clinically relevant medication alerts in both systems.

Results

The PPV was significantly higher in the advanced system (5.8% vs 17.0%; p<0.05). Significant differences were found in the alert categories: drug–(drug) interaction (9.9% vs 14.8%; p<0.05), drug–age interaction (2.9% vs 73.3%; p<0.05), and dosing guidance (5.6% vs 16.9%; p<0.05). Including laboratory values and other patient characteristics resulted in a significantly higher PPV for the advanced CDSS compared to the basic medication alerts (12.2% vs 23.3%; p<0.05).

Conclusion

The advanced CDSS produced a higher proportion of clinically relevant medication alerts, but the number of irrelevant alerts remained high. To improve the PPV of the advanced CDSS, the algorithms should be optimized by identifying additional risk modifiers and more data should be made electronically available to improve the performance of the algorithms. Our study illustrates and corroborates the need for cyclic testing of technical improvements in information technology in circumstances representative of daily clinical practice.     

Cord blood-hematopoietic stem cell expansion in 3D fibrin scaffolds with stromal support

Expansion of multipotent, undifferentiated and proliferating cord blood (CB)-hematopoietic stem cells (HSC) in?vitro is limited and insufficient. Bone marrow (BM) engineering in?vitro allows mimicking the main components of the hematopoietic niche compared to conventional expansion strategies. In this study, four different 3D biomaterial scaffolds (PCL, PLGA, fibrin and collagen) were tested for freshly isolated cord blood (CB)-CD34(+) cell expansion in presence of (i) efficient exogenous cytokine supplementation and (ii) umbilical cord (UC)-mesenchymal stem cells (MSC). Cell morphology, growth and proliferation were analyzed in?vitro as well as multi-organ engraftment and multilineage differentiation in a murine transplantation model. All scaffolds, except 3D PLGA meshes, supported CB-CD34(+) cell expansion, which was additionally stimulated by UC-MSC support. CB-CD34(+) cells cultured on human-derived 3D fibrin scaffolds with UC-MSC support i) reached the highest overall growth (5?×?10(8)-fold expansion of total nuclear cells after fourteen days and 3?×?10(7)-fold expansion of CD34(+) cells after seven days, p?相似文献