Does pretreatment testing for serotonin transporter polymorphisms lead to earlier effects of drug treatment in patients with major depression? A decision-analytic model

BACKGROUND: An estimated 30% to 40% of patients with depression do not sufficiently respond to treatment with selective serotonin reuptake inhibitors (SSRIs) and the period in which treatment efficacy can be assessed is relatively long. Therefore, a test to identify potential nonresponders could be useful in the treatment of depression. Serotonin transporter gene (SLC6A4) variations have been reported to account for differences in the way individuals respond to SSRI treatment. OBJECTIVE: A decision-analytic model was used to assess whether pretreatment genetic testing for 5-HTTLPR, a polymorphism of the SLC6A4 genotype, could be an efficient tool in the treatment of depression. METHODS: A theoretical clinical decision-analytic model was constructed to compare the current treatment strategy in The Netherlands with an alternative strategy for the treatment of depression. Under treatment guidelines in The Netherlands, all patients with depression receive SSRI treatment (nontesting strategy). Under the alternative strategy, genetic testing would be performed to identify which class of antidepressant would be the best choice for initiation of treatment (genetic testing strategy). Probabilities (predicted results) for this model were based on data from previous studies and the opinions of experts in the field of psychopharmacology. To test the robustness of the model, 6- and 12-week remission rates for patients treated with SSRIs were varied in a sensitivity analysis using a predetermined range that was established based on expert opinion. Threshold analyses were performed on the parameters of serotonin transporter genotype frequency and response and nonresponse rates for patients receiving SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs) to determine the value for a variable at which it could be concluded that a change in treatment strategy would be preferred. RESULTS: When genetic testing was performed before an antidepressant was prescribed, 64.6% of patients were predicted to be in remission after 6 weeks of treatment compared with 60.0% of patients who did not receive genetic testing. After 12 weeks, 79.5% of patients in the testing group who received an SNRI as initial treatment and 83.2% of those who received a TCA initially were predicted to be in remission compared with 76.7% of patients in the nontesting group. Sensitivity analyses indicated that the model was robust to variation of probability estimates within their plausible ranges. However, these findings were based on a theoretic model and did not include cost assessment. Pretreatment genetic testing must be evaluated further in randomized clinical trials and costs must be assessed before implementing this strategy in routine psychiatric practice can be recommended. CONCLUSIONS: The findings of this study suggest that performing genetic testing before prescribing antidepressant treatment may lead to greater numbers of patients experiencing remission early in treatment.     

Implications of High-Dosage Bisphosphonate Treatment on Bone Tissue in the Jaw and Knee Joint

Bisphosphonates are bone antiresorptive agents traditionally used on a relatively large scale for treatment of bone metabolic diseases and on a smaller scale for bone metastasis treatment. A study on the effects of bisphosphonate treatment on healthy instead of diseased animals will give more insight into the basic mechanisms of bisphosphonates and their effects on different bone sites. We aimed to assess the effect of BP on the mouse knee and jaw joint. Three-month old female C57BL/6 mice were used (twenty-four and eighteen control and experimental group, respectively). At baseline and after treatment with zoledronic acid (ZA) for one, three or six months, we combined bone assessment via µCT and additional histology. Our results showed that, in the knee joint, ZA treatment increased TMD, bone volume, trabecular thickness but did not influence cortical thickness. In both control and ZA group, a higher trabecular TMD compared to cortical TMD was seen. Unseen in the knee joint, ZA treatment in the jaw joint resulted in bone-site specific changes in mineralization; a significant time-dependent higher TMD was evident in the subchondral bone compared to the most distal region of the condyle. MicroCT images revealed the presence of mineral in this region and histology showed that this region did not contain mature bone tissue but cartilage-like tissue. Our data indicate the possibility of site-specific negative side effects, i.e., disturbing normal mandibular development under the influence of bisphosphonate therapy.     

Greater late lumen loss after successful coronary balloon angioplasty in the proximal left anterior descending coronary artery is not explained by extent of vessel wall damage or plaque burden

OBJECTIVES: We investigated whether the greater late lumen loss after coronary balloon angioplasty in the proximal left anterior descending artery (P-LAD) compared with that in other segments might be related to differences in vascular dimensions or morphology as determined by angiography and intravascular ultrasound imaging. BACKGROUND: The greater late lumen loss after angioplasty in the P-LAD that has been observed in several studies has not been explained. METHODS: We studied 178 patients and 194 coronary artery lesions by quantitative angiography and 30 MHz intravascular ultrasound imaging after successful balloon angioplasty. Vessel wall morphology was compared among three proximal and three nonproximal segments. Follow-up quantitative angiography for late lumen loss calculation was performed in 168 lesions. Multivariate analysis was used to determine predictors of late lumen loss. RESULTS: Absolute and relative late loss were significantly greater at the P-LAD compared with the pooled group of other segments (0.42 +/- 0.60 mm vs. 0.10 +/- 0.48 mm, p = 0.0008 and 0.14 +/- 0.24 vs. 0.03 +/- 0.17, p < 0.001). Also, a greater percentage of calcific lesions (65% vs. 44%, p = 0.034), a lower incidence of rupture (51% vs. 74%, p = 0.009) and a larger reference segment plaque area (5.4 +/- 2.2 mm2 vs. 4.7 +/- 1.9 mm2, p = 0.05) were found in the P-LAD. In multivariate analysis however, these variables were not predictive of late loss. CONCLUSIONS: Greater late lumen loss after coronary balloon angioplasty of the P-LAD is not explained by differences in atherosclerotic plaque burden or in vessel wall damage.     

Immunotherapy and immunotherapy biomarkers for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is increasing in prevalence and has the potential to be a highly lethal malignancy. Patients with early-stage HCC have potentiall...     

A virtual reality intervention to improve the understanding and empathy for people with dementia in informal caregivers: results of a pilot study

ABSTRACT

Objective: Informal caregivers often experience psychological distress due to the changing functioning of the person with dementia they care for. Improved understanding of the person with dementia reduces psychological distress. To enhance understanding and empathy in caregivers, an innovative technology virtual reality intervention Through the D'mentia Lens (TDL) was developed to experience dementia, consisting of a virtual reality simulation movie and e-course. A pilot study of TDL was conducted.

Methods: A pre-test–post-test design was used. Informal caregivers filled out questionnaires assessing person-centeredness, empathy, perceived pressure from informal care, perceived competence and quality of the relationship. At post-test, additional questions about TDL's feasibility were asked.

Results: Thirty-five caregivers completed the pre-test and post-test. Most participants were satisfied with TDL and stated that TDL gave more insight in the perception of the person with dementia. The simulation movie was graded 8.03 out of 10 and the e-course 7.66. Participants significantly improved in empathy, confidence in caring for the person with dementia, and positive interactions with the person with dementia.

Conclusion: TDL is feasible for informal caregivers and seems to lead to understanding of and insight in the experience of people with dementia. Therefore, TDL could support informal caregivers in their caregiving role.     

The Effects of Carbohydrate versus Fat Restriction on Lipid Profiles in Highly Trained,Recreational Distance Runners: A Randomized,Cross-Over Trial

A growing number of endurance athletes have considered switching from a traditional high-carbohydrate/low-fat (HCLF) to a low-carbohydrate/high-fat (LCHF) eating pattern for health and performance reasons. However, few studies have examined how LCHF diets affect blood lipid profiles in highly-trained runners. In a randomized and counterbalanced, cross-over design, athletes (n = 7 men; VO_2max: 61.9 ± 6.1 mL/kg/min) completed six weeks of two, ad libitum, LCHF (6/69/25% en carbohydrate/fat/protein) and HCLF (57/28/15% en carbohydrate/fat/protein) diets, separated by a two-week washout. Plasma was collected on days 4, 14, 28, and 42 during each condition and analyzed for: triglycerides (TG), LDL-C, HDL-C, total cholesterol (TC), VLDL, fasting glucose, and glycated hemoglobin (HbA1c). Capillary blood beta-hydroxybutyrate (BHB) was monitored during LCHF as a measure of ketosis. LCHF lowered plasma TG, VLDL, and TG/HDL-C (all p < 0.01). LCHF increased plasma TC, LDL-C, HDL-C, and TC/HDL-C (all p < 0.05). Plasma glucose and HbA1c were unaffected. Capillary BHB was modestly elevated throughout the LCHF condition (0.5 ± 0.05 mmol/L). Healthy, well-trained, normocholesterolemic runners consuming a LCHF diet demonstrated elevated circulating LDL-C and HDL-C concentrations, while concomitantly decreasing TG, VLDL, and TG/HDL-C ratio. The underlying mechanisms and implications of these adaptive responses in cholesterol should be explored.