Selective serotonin reuptake inhibitors in the treatment of generalized anxiety disorder

Selective serotonin reuptake inhibitors have proven efficacy in the treatment of panic disorder, obsessive–compulsive disorder, post-traumatic stress disorder and social anxiety disorder. Accumulating data shows that selective serotonin reuptake inhibitor treatment can also be efficacious in patients with generalized anxiety disorder. This review summarizes the findings of randomized controlled trials of selective serotonin reuptake inhibitor treatment for generalized anxiety disorder, examines the strengths and weaknesses of other therapeutic approaches and considers potential new treatments for patients with this chronic and disabling anxiety disorder

Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. The VANISH Randomized Clinical Trial

IMPORTANCE: Norepinephrine is currently recommended as the first-line vasopressor in septic shock; however, early vasopressin use has been proposed as an alternative. OBJECTIVE: To compare the effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS: A factorial (2×2), double-blind, randomized clinical trial conducted in 18 general adult intensive care units in the United Kingdom between February 2013 and May 2015, enrolling adult patients who had septic shock requiring vasopressors despite fluid resuscitation within a maximum of 6 hours after the onset of shock. INTERVENTIONS: Patients were randomly allocated to vasopressin (titrated up to 0.06 U/min) and hydrocortisone (n = 101), vasopressin and placebo (n = 104), norepinephrine and hydrocortisone (n = 101), or norepinephrine and placebo (n = 103). MAIN OUTCOMES AND MEASURES: The primary outcome was kidney failure-free days during the 28-day period after randomization, measured as (1) the proportion of patients who never developed kidney failure and (2) median number of days alive and free of kidney failure for patients who did not survive, who experienced kidney failure, or both. Rates of renal replacement therapy, mortality, and serious adverse events were secondary outcomes. RESULTS: A total of 409 patients (median age, 66 years; men, 58.2%) were included in the study, with a median time to study drug administration of 3.5 hours after diagnosis of shock. The number of survivors who never developed kidney failure was 94 of 165 patients (57.0%) in the vasopressin group and 93 of 157 patients (59.2%) in the norepinephrine group (difference, -2.3% [95% CI, -13.0% to 8.5%]). The median number of kidney failure-free days for patients who did not survive, who experienced kidney failure, or both was 9 days (interquartile range [IQR], 1 to -24) in the vasopressin group and 13 days (IQR, 1 to -25) in the norepinephrine group (difference, -4 days [95% CI, -11 to 5]). There was less use of renal replacement therapy in the vasopressin group than in the norepinephrine group (25.4% for vasopressin vs 35.3% for norepinephrine; difference, -9.9% [95% CI, -19.3% to -0.6%]). There was no significant difference in mortality rates between groups. In total, 22 of 205 patients (10.7%) had a serious adverse event in the vasopressin group vs 17 of 204 patients (8.3%) in the norepinephrine group (difference, 2.5% [95% CI, -3.3% to 8.2%]). CONCLUSIONS AND RELEVANCE: Among adults with septic shock, the early use of vasopressin compared with norepinephrine did not improve the number of kidney failure-free days. Although these findings do not support the use of vasopressin to replace norepinephrine as initial treatment in this situation, the confidence interval included a potential clinically important benefit for vasopressin, and larger trials may be warranted to assess this further. TRIAL REGISTRATION: clinicaltrials.gov Identifier: ISRCTN 20769191

Marine Biodiversity of Aotearoa New Zealand

The marine-biodiversity assessment of New Zealand (Aotearoa as known to Māori) is confined to the 200 nautical-mile boundary of the Exclusive Economic Zone, which, at 4.2 million km2, is one of the largest in the world. It spans 30° of latitude and includes a high diversity of seafloor relief, including a trench 10 km deep. Much of this region remains unexplored biologically, especially the 50% of the EEZ deeper than 2,000 m. Knowledge of the marine biota is based on more than 200 years of marine exploration in the region. The major oceanographic data repository is the National Institute of Water and Atmospheric Research (NIWA), which is involved in several Census of Marine Life field projects and is the location of the Southwestern Pacific Regional OBIS Node; NIWA is also data manager and custodian for fisheries research data owned by the Ministry of Fisheries. Related data sources cover alien species, environmental measures, and historical information. Museum collections in New Zealand hold more than 800,000 registered lots representing several million specimens. During the past decade, 220 taxonomic specialists (85 marine) from 18 countries have been engaged in a project to review New Zealand's entire biodiversity. The above-mentioned marine information sources, published literature, and reports were scrutinized to give the results summarized here for the first time (current to 2010), including data on endemism and invasive species. There are 17,135 living species in the EEZ. This diversity includes 4,315 known undescribed species in collections. Species diversity for the most intensively studied phylum-level taxa (Porifera, Cnidaria, Mollusca, Brachiopoda, Bryozoa, Kinorhyncha, Echinodermata, Chordata) is more or less equivalent to that in the ERMS (European Register of Marine Species) region, which is 5.5 times larger in area than the New Zealand EEZ. The implication is that, when all other New Zealand phyla are equally well studied, total marine diversity in the EEZ may be expected to equal that in the ERMS region. This equivalence invites testable hypotheses to explain it. There are 177 naturalized alien species in New Zealand coastal waters, mostly in ports and harbours. Marine-taxonomic expertise in New Zealand covers a broad number of taxa but is, proportionately, at or near its lowest level since the Second World War. Nevertheless, collections are well supported by funding and are continually added to. Threats and protection measures concerning New Zealand's marine biodiversity are commented on, along with potential and priorities for future research

A framework for evolutionary systems biology

<p>Abstract</p> <p>Background</p> <p>Many difficult problems in evolutionary genomics are related to mutations that have weak effects on fitness, as the consequences of mutations with large effects are often simple to predict. Current systems biology has accumulated much data on mutations with large effects and can predict the properties of knockout mutants in some systems. However experimental methods are too insensitive to observe small effects.</p> <p>Results</p> <p>Here I propose a novel framework that brings together evolutionary theory and current systems biology approaches in order to quantify small effects of mutations and their epistatic interactions <it>in silico</it>. Central to this approach is the definition of fitness correlates that can be computed in some current systems biology models employing the rigorous algorithms that are at the core of much work in computational systems biology. The framework exploits synergies between the realism of such models and the need to understand real systems in evolutionary theory. This framework can address many longstanding topics in evolutionary biology by defining various 'levels' of the adaptive landscape. Addressed topics include the distribution of mutational effects on fitness, as well as the nature of advantageous mutations, epistasis and robustness. Combining corresponding parameter estimates with population genetics models raises the possibility of testing evolutionary hypotheses at a new level of realism.</p> <p>Conclusion</p> <p>EvoSysBio is expected to lead to a more detailed understanding of the fundamental principles of life by combining knowledge about well-known biological systems from several disciplines. This will benefit both evolutionary theory and current systems biology. Understanding robustness by analysing distributions of mutational effects and epistasis is pivotal for drug design, cancer research, responsible genetic engineering in synthetic biology and many other practical applications.</p

Burnout Syndrome and alcohol consumption in prison employees

Objective: The aims of this study were to estimate the association between an at-risk drinking pattern and sociodemographic variables, and to compare the mean scores of the factors associated with the Burnout Syndrome, according to the alcohol consumption pattern in staff members from two Brazilian prisons. Methods: A cross-sectional study was developed with 339 participants (response rate = 63.8%). The instruments used were a sociodemographic questionnaire, the Alcohol Use Disorders Identification Test (AUDIT), and the Maslach Burnout Inventory – General Survey (MBI-GS). Results: The participants’ average age was 40.2 (SD = 8.8) years, and 81.0% were male. Among 78.5% of participants (95%CI 74.1 – 82.8) reported consuming alcoholic beverages. The prevalence of at-risk drinking behavior in the sample was 22.4% (95%CI 18.0 – 26.9), and of the Burnout Syndrome was 14.6% (95%CI 10.8 – 18.4). We observed a significant association between at-risk drinking behavior with gender, higher risk for men (OR = 7.32, p < 0.001), smoking, increased risk for smokers (OR = 2.77, p < 0.001), and religious practice, showing lower risks for religion practitioners (OR = 0.364, p < 0.001). We noticed significantly higher mean scores (p < 0.001) of emotional exhaustion and cynicism, and lower scores of professional achievement among individuals who reported consuming alcoholic beverages. Conclusion: Men who smoke were more likely to develop an at-risk drinking pattern, while religion is presented as a protective factor. Individuals who consume alcohol were more affected by the different factors of the Burnout Syndrome

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Automated Production of Potassium-38 for the Study of Myocardial Perfusion Using Positron Emission Tomography

The 35Cl(alpha, n)38K nuclear reaction was developed for the routine cyclotron production of repeated multimillicurie batches of 38K for dynamic studies of regional tissue perfusion with positron emission tomography. The objective is to make this isotope available as an alternative to the use of [13N]NH3 and 82Rb for the investigation of flow in experimental and clinical use. A sodium chloride powder target mounted on a water-cooled nickel backing is bombarded with 26 MeV helium-4 ions at a maximum beam current of 25 microA. The target is remotely disconnected from the bombardment port, transported to a hot cell and entirely processed by a computer-controlled system within a total time of less than 4 min. The final pyrogen-free isotonic and sterile solution of 38K has a radionuclidic purity of more than 99.99%. A typical yield of 19 +/- 2 mCi of 38K is obtained at the end of a 30 min bombardment at 10 microA. The production rate at saturation can therefore be estimated to 2.05 +/- 0.2 mCi/microA