A study of the diagnostic accuracy of the PHQ-9 in primary care elderly

<p>Abstract</p> <p>Background</p> <p>The diagnostic accuracy of the Patient Health Questionnaire-9 (PHQ-9) for assessment of depression in elderly persons in primary care settings in the United States has not been previously addressed. Thus, the purpose of this study was to evaluate the test performance of the PHQ-9 for detecting major and minor depression in elderly patients in primary care.</p> <p>Methods</p> <p>A prospective study of diagnostic accuracy was conducted in two primary care, university-based clinics in the Pacific Northwest of the United States. Seventy-one patients aged 65 years or older participated; all completed the PHQ-9 and the 15-item Geriatric Depression Scale (GDS) and underwent the Structured Clinical Interview for Depression (SCID). Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, and likelihood ratios (LRs) were calculated for the PHQ-9, the PHQ-2, and the 15-item GDS for major depression alone and the combination of major plus minor depression.</p> <p>Results</p> <p>Two thirds of participants were female, with a mean age of 78 and two chronic health conditions. Twelve percent met SCID criteria for major depression and 13% minor depression. The PHQ-9 had an area under the curve (AUC) of 0.87 (95% confidence interval [CI], 0.74-1.00) for major depression, while the PHQ-2 and the 15-item GDS each had an AUC of 0.81 (95% CI for PHQ-2, 0.64-0.98, and for 15-item GDS, 0.70-0.91; <it>P </it>= 0.551). For major and minor depression combined, the AUC for the PHQ-9 was 0.85 (95% CI, 0.73-0.96), for the PHQ-2, 0.80 (95% CI, 0.68-0.93), and for the 15-item GDS, 0.71 (95% CI, 0.55-0.87; <it>P </it>= 0.187).</p> <p>Conclusions</p> <p>Based on AUC values, the PHQ-9 performs comparably to the PHQ-2 and the 15-item GDS in identifying depression among primary care elderly.</p

Efficient Delivery of <i>FMR1</i> across the Blood Brain Barrier Using AAVphp Construct in Adult <i>FMR1</i> KO Mice Suggests the Feasibility of Gene Therapy for Fragile X Syndrome

Background Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism. Gene therapy may offer an efficient method to ameliorate the symptoms of this disorder. Methods An AAVphp.eb-hSyn-mFMR1IOS7 vector and an empty control were injected into the tail vein of adult Fmr1 knockout (KO) mice and wildtype (WT) controls. The KO mice were injected with 2 × 1013 vg/kg of the construct. The control KO and WT mice were injected with an empty vector. Four weeks following treatment, the animals underwent a battery of tests: open field, marble burying, rotarod, and fear conditioning. The mouse brains were studied for levels of the Fmr1 product FMRP. Results: No significant levels of FMRP were found outside the CNS in the treated animals. The gene delivery was highly efficient, and it exceeded the control FMRP levels in all tested brain regions. There was also improved performance in the rotarod test and partial improvements in the other tests in the treated KO animals. Conclusion: These experiments demonstrate efficient, brain-specific delivery of Fmr1 via peripheral administration in adult mice. The gene delivery led to partial alleviation of the Fmr1 KO phenotypical behaviors. FMRP oversupply may explain why not all behaviors were significantly affected. Since AAV.php vectors are less efficient in humans than in the mice used in the current experiment, studies to determine the optimal dose using human-suitable vectors will be necessary to further demonstrate feasibility

Designing a broad-spectrum integrative approach for cancer prevention and treatment.

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered.Multiple funders. See acknowledgments within article for details.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.semcancer.2015.09.00