Clinical use of HIV integrase inhibitors : a systematic review and meta-analysis

Background: Optimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings. Methods: MEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted. Results: 48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59-0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11-0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89-2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir. Conclusion: In first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment

Acceptability and feasibility of two interventions in the MooDFOOD Trial: A food-related depression prevention randomised controlled trial in overweight adults with subsyndromal symptoms of depression

Objectives We report on the acceptability, feasibility, dose-response relationship and adherence of two nutritional strategies to improve mood (multinutrient supplements; food-related behavioural activation (F-BA)) studied in a randomised controlled depression prevention trial (the Multi-country cOllaborative project on the rOle of Diet, Food-related behaviour, and Obesity in the prevention of Depression (MooDFOOD) Trial). We also assessed baseline determinants of adherence and assessed whether better adherence resulted in lower depressive symptoms. Design Randomised controlled trial with a 2×2 factorial design conducted between 2015 and 2017. Setting Germany, the Netherlands, UK and Spain. Participants Community sample of 1025 overweight adults with elevated depressive symptoms without a current episode of major depressive disorder. Main eligibility criteria included age (18-75 years), being overweight or obese, and having at least mild depressive symptoms, shown by a Patient Health Questionnaire Score of ≥5. A total of 76% of the sample was retained at the 12-month follow-up. Interventions Daily nutritional supplements versus pill placebo or an F-BA therapy, delivered in individual and group sessions versus no behavioural intervention over a 1-year period. Primary and secondary outcome measures Primary outcome: self-reported acceptability of the interventions. Secondary outcomes: adherence and self-reported depressive symptoms. Results Most participants reported that the F-BA was acceptable (83.61%), feasible to do (65.91%) and would recommend it to a friend (84.57%). Individual F-BA sessions (88.10%) were significantly more often rated as positive than group F-BA sessions (70.17%) and supplements (28.59%). There were statistically significant reductions in depressive symptoms for those who both adhered to the F-BA intervention and had a history of depression (B=-0.08, SE=0.03, p=0.012) versus those who had no history of depression. Supplement intake had no effect on depressive symptoms irrespective of adherence. Conclusions F-BA may have scope for development as a depression prevention intervention and public health strategy but further refinement and testing are needed

Associations of non-alcoholic beverages with major depressive disorder history and depressive symptoms clusters in a sample of overweight adults

Background: Meta-analysis of observational studies concluded that soft drinks may increase the risk of depression, while high consumption of coffee and tea may reduce the risk. Objectives were to explore the associations between the consumption of soft drinks, coffee or tea and: (1) a history of major depressive disorder (MDD) and (2) the severity of depressive symptoms clusters (mood, cognitive and somatic/vegetative symptoms). Methods: Cross-sectional and longitudinal analysis based on baseline and 12-month-follow-up data collected from four countries participating in the European MooDFOOD prevention trial. In total, 941 overweight adults with subsyndromal depressive symptoms aged 18 to 75 years were analyzed. History of MDD, depressive symptoms and beverages intake were assessed. Results: Sugar-sweetened soft drinks were positively related to MDD history rates whereas soft drinks with non-nutritive sweeteners were inversely related for the high vs. low categories of intake. Longitudinal analysis showed no significant associations between beverages and mood, cognitive and somatic/vegetative clusters. Conclusion: Our findings point toward a relationship between soft drinks and past MDD diagnoses depending on how they are sweetened while we found no association with coffee and tea. No significant effects were found between any studied beverages and the depressive symptoms clusters in a sample of overweight adults

Acceptability and feasibility of two interventions in the MooDFOOD Trial: a food-related depression prevention randomised controlled trial in overweight adults with subsyndromal symptoms of depression

Objectives We report on the acceptability, feasibility, dose-response relationship and adherence of two nutritional strategies to improve mood (multinutrient supplements; food-related behavioural activation (F-BA)) studied in a randomised controlled depression prevention trial (the Multi‐country cOllaborative project on the rOle of Diet, Food‐related behaviour, and Obesity in the prevention of Depression (MooDFOOD) Trial). We also assessed baseline determinants of adherence and assessed whether better adherence resulted in lower depressive symptoms.Design Randomised controlled trial with a 2×2 factorial design conducted between 2015 and 2017.Setting Germany, the Netherlands, UK and Spain.Participants Community sample of 1025 overweight adults with elevated depressive symptoms without a current episode of major depressive disorder. Main eligibility criteria included age (18–75 years), being overweight or obese, and having at least mild depressive symptoms, shown by a Patient Health Questionnaire Score of ≥5. A total of 76% of the sample was retained at the 12-month follow-up.Interventions Daily nutritional supplements versus pill placebo or an F-BA therapy, delivered in individual and group sessions versus no behavioural intervention over a 1-year period.Primary and secondary outcome measures Primary outcome: self-reported acceptability of the interventions. Secondary outcomes: adherence and self-reported depressive symptoms.Results Most participants reported that the F-BA was acceptable (83.61%), feasible to do (65.91%) and would recommend it to a friend (84.57%). Individual F-BA sessions (88.10%) were significantly more often rated as positive than group F-BA sessions (70.17%) and supplements (28.59%). There were statistically significant reductions in depressive symptoms for those who both adhered to the F-BA intervention and had a history of depression (B=−0.08, SE=0.03, p=0.012) versus those who had no history of depression. Supplement intake had no effect on depressive symptoms irrespective of adherence.Conclusions F-BA may have scope for development as a depression prevention intervention and public health strategy but further refinement and testing are needed.Trial registration number NCT02529423

Glia as the "bad guys": Implications for improving clinical pain control and the clinical utility of opioids

Within the past decade, there has been increasing recognition that glia are far more than simply “housekeepers” for neurons. This review explores two recently recognized roles of glia (microglia and astrocytes) in: (a) creating and maintaining enhanced pain states such as neuropathic pain, and (b) compromising the efficacy of morphine and other opioids for pain control. While glia have little-to-no role in pain under basal conditions, pain is amplified when glia become activated, inducing the release of proinflammatory products, especially proinflammatory cytokines. How glia are triggered to become activated is a key issue, and appears to involve a number of neuron-to-glia signals including neuronal chemokines, neurotransmitters, and substances released by damaged, dying and dead neurons. In addition, glia become increasingly activated in response to repeated administration of opioids. Products of activated glia increase neuronal excitability via numerous mechanisms, including direct receptor-mediated actions, upregulation of excitatory amino acid receptor function, downregulation of GABA receptor function, and so on. These downstream effects of glial activation amplify pain, suppress acute opioid analgesia, contribute to the apparent loss of opioid analgesia upon repeated opioid administration (tolerance), and contribute to the development of opioid dependence. The potential implications of such glial regulation of pain and opioid actions are vast, suggestive that targeting glia and their proinflammatory products may provide a novel and effective therapy for controlling clinical pain syndromes and increasing the clinical utility of analgesic drugs.http://www.elsevier.com/wps/find/journaldescription.cws_home/622800/description#descriptio