Anti-depressive effectiveness of olanzapine, quetiapine, risperidone and ziprasidone: a pragmatic, randomized trial

<p>Abstract</p> <p>Background</p> <p>Efficacy studies indicate anti-depressive effects of at least some second generation antipsychotics (SGAs). The Bergen Psychosis Project (BPP) is a 24-month, pragmatic, industry-independent, randomized, head-to-head comparison of olanzapine, quetiapine, risperidone and ziprasidone in patients acutely admitted with psychosis. The aim of the study is to investigate whether differential anti-depressive effectiveness exists among SGAs in a clinically relevant sample of patients acutely admitted with psychosis.</p> <p>Methods</p> <p>Adult patients acutely admitted to an emergency ward for psychosis were randomized to olanzapine, quetiapine, risperidone or ziprasidone and followed for up to 2 years. Participants were assessed repeatedly using the Positive and Negative Syndrome Scale - Depression factor (PANSS-D) and the Calgary Depression Scale for Schizophrenia (CDSS).</p> <p>Results</p> <p>A total of 226 patients were included. A significant time-effect showing a steady decline in depressive symptoms in all medication groups was demonstrated. There were no substantial differences among the SGAs in reducing the PANSS-D score or the CDSS sum score. Separate analyses of groups with CDSS sum scores > 6 or ≤6, respectively, reflecting degree of depressive morbidity, revealed essentially identical results to the primary analyses. There was a high correlation between the PANSS-D and the CDSS sum score (r = 0.77; p < 0.01).</p> <p>Conclusions</p> <p>There was no substantial difference in anti-depressive effectiveness among olanzapine, quetiapine, risperidone or ziprasidone in this clinically relevant sample of patients acutely admitted to hospital for symptoms of psychosis. Based on our findings we can make no recommendations concerning choice of any particular SGA for targeting symptoms of depression in a patient acutely admitted with psychosis.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID; URL: <url>http://www.clinicaltrials.gov/</url>: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00932529">NCT00932529</a></p

The SNAPSHOT study protocol : SNAcking, Physical activity, Self-regulation, and Heart rate Over Time

Peer reviewedPublisher PD

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury

Effectiveness of second-generation antipsychotics: a naturalistic, randomized comparison of olanzapine, quetiapine, risperidone, and ziprasidone

<p>Abstract</p> <p>Background</p> <p>No clear recommendations exist regarding which antipsychotic drug should be prescribed first for a patient suffering from psychosis. The primary aims of this naturalistic study were to assess the head-to-head effectiveness of first-line second-generation antipsychotics with regards to time until drug discontinuation, duration of index admission, time until readmission, change of psychopathology scores and tolerability outcomes.</p> <p>Methods</p> <p>Patients ≥ 18 years of age admitted to the emergency ward for symptoms of psychosis were consecutively randomized to risperidone (n = 53), olanzapine (n = 52), quetiapine (n = 50), or ziprasidone (n = 58), and followed for up to 2 years.</p> <p>Results</p> <p>A total of 213 patients were included, of which 68% were males. The sample represented a diverse population suffering from psychosis. At admittance the mean Positive and Negative Syndrome Scale (PANSS) total score was 74 points and 44% were antipsychotic drug naïve. The primary intention-to-treat analyses revealed no substantial differences between the drugs regarding the times until discontinuation of initial drug, until discharge from index admission, or until readmission. Quetiapine was superior to risperidone and olanzapine in reducing the PANSS total score and the positive subscore. Quetiapine was superior to the other drugs in decreasing the PANSS general psychopathology subscore; in decreasing the Clinical Global Impression - Severity of Illness scale score (CGI-S); and in increasing the Global Assessment of Functioning - Split version, Functions scale score (GAF-F). Ziprasidone was superior to risperidone in decreasing the PANSS positive symptoms subscore and the CGI-S score, and in increasing the GAF-F score. The drugs performed equally with regards to most tolerability outcomes except a higher increase of hip-circumference per day for olanzapine compared to risperidone, and more galactorrhoea for risperidone compared to the other groups.</p> <p>Conclusions</p> <p>Quetiapine appears to be a good starting drug candidate in this sample of patients admitted to hospital for symptoms of psychosis.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID; URL: <url>http://www.clinicaltrials.gov/</url>: NCT00932529</p

Effectiveness of second generation antipsychotics: A systematic review of randomized trials

<p>Abstract</p> <p>Background</p> <p>Systematic reviews based on efficacy trials are inconclusive about which second generation antipsychotic drug (SGA) should be preferred in normal clinical practice, and studies with longer duration and more pragmatic designs are called for. Effectiveness studies, also known as naturalistic, pragmatic, practical or real life studies, adhere to these principles as they aim to mimic daily clinical practice and have longer follow-up.</p> <p>Objective</p> <p>To review the head-to-head effectiveness of SGAs in the domains of global outcomes, symptoms of disease, and tolerability.</p> <p>Methods</p> <p>Searches were made in Embase, PubMED, and the Cochrane central register of controlled trials for effectiveness studies published from 1980 to 2008, week 1. Different combinations of the keywords <it>antipsychotic*, neuroleptic* AND open, pragmatic, practical, naturalistic, real life, effectiveness, side effect*, unwanted effect*, tolera* AND compar* AND random* </it>were used.</p> <p>Results</p> <p>Sixteen different reports of randomized head-to-head comparisons of SGA effectiveness were located. There were differences regarding sample sizes, inclusion criteria and follow-up periods, as well as sources of financial sponsorship. In acute-phase and first-episode patients no differences between the SGAs were disclosed regarding alleviating symptoms of disease. Olanzapine was associated with more weight gain and adverse effects on serum lipids. In the chronic phase patients olanzapine groups had longer time to discontinuation of treatment and better treatment adherence compared to other SGAs. The majority of studies found no differences between the SGAs in alleviating symptoms of psychosis in chronically ill patients. Olanzapine was associated with more metabolic adverse effects compared to the others SGAs. There were surprisingly few between-drug differences regarding side effects. First generation antipsychotics were associated with lower total mental health care costs in 2 of 3 studies on chronically ill patients, but were also associated with more extrapyramidal side effects compared to the SGAs in several studies.</p> <p>Conclusion</p> <p>In chronically ill patients olanzapine may have an advantage over other SGAs regarding longer time to treatment discontinuation and better drug adherence, but the drug is also associated with more metabolic side effects. More effectiveness studies on first-episode psychosis are needed.</p

Intermediate care at a community hospital as an alternative to prolonged general hospital care for elderly patients: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Demographic changes together with an increasing demand among older people for hospital beds and other health services make allocation of resources to the most efficient care level a vital issue. The aim of this trial was to study the efficacy of intermediate care at a community hospital compared to standard prolonged care at a general hospital.</p> <p>Methods</p> <p>In a randomised controlled trial 142 patients aged 60 or more admitted to a general hospital due to acute illness or exacerbation of a chronic disease 72 (intervention group) were randomised to intermediate care at a community hospital and 70 (general hospital group) to further general hospital care.</p> <p>Results</p> <p>In the intervention group 14 patients (19.4%) were readmitted for the same disease compared to 25 patients (35.7%) in the general hospital group (p = 0.03). After 26 weeks 18 (25.0%) patients in the intervention group were independent of community care compared to seven (10.0%) in the general hospital group (p = 0.02). There were an insignificant reduction in the number of deaths and an insignificant increase in the number of days with inward care in the intervention group. The number of patients admitted to long-term nursing homes from the intervention group was insignificantly higher than from the general hospital group.</p> <p>Conclusion</p> <p>Intermediate care at a community hospital significantly decreased the number of readmissions for the same disease to general hospital, and a significantly higher number of patients were independent of community care after 26 weeks of follow-up, without any increase in mortality and number of days in institutions.</p

Statistical analysis of arthroplasty data: II. Guidelines

It is envisaged that guidelines for statistical analysis and presentation of results will improve the quality and value of research. The Nordic Arthroplasty Register Association (NARA) has therefore developed guidelines for the statistical analysis of arthroplasty register data. The guidelines are divided into two parts, one with an introduction and a discussion of the background to the guidelines (Ranstam et al. 2011a, see pages x-y in this issue), and this one with a more technical statistical discussion on how specific problems can be handled. This second part contains (1) recommendations for the interpretation of methods used to calculate survival, (2) recommendations on howto deal with bilateral observations, and (3) a discussion of problems and pitfalls associated with analysis of factors that influence survival or comparisons between outcomes extracted from different hospitals

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

New semiquantitative ultrasonographic score for peripheral arterial disease assessment and its association with cardiovascular risk factors

The data concerning the distribution, extent and progression of peripheral arterial disease (PAD), as well as its association with traditional cardiovascular (CV) risk factors, have generally been obtained from studies of patients in advanced stages of the disease undergoing surgical or endovascular treatment. In this study, we have introduced a new semiquantitative ultrasonographic score (ultrasonographic lower limb atherosclerosis (ULLA) score) that is able to categorize lower limb atherosclerotic lesions at all stages of PAD. We then associated these ultrasonographic categories with a CV risk profile. We enrolled 320 consecutive subjects with symptoms suggestive of PAD or with known CV risk factors referring to our angiology unit between 1 July 2014 and 30 June 2015 for ultrasonographic evaluation of the lower limb arteries. Femoropopliteal and run-off segments were categorized together and separately based on their ultrasonographic characteristics. In univariate and multivariate analyses, the ULLA scores were significantly associated with the main CV risk factors, that is, age, male gender, cigarette smoking, arterial hypertension, diabetes, dyslipidemia, sedentary lifestyle, previous CV events and family history of CV disease, and also confirming the specific association of single risk factors with different segments of lower limb arteries. The proposed ULLA score enables a complete evaluation of the entire lower limb atherosclerotic burden, extending the results concerning the association of PAD with CV risk factors to all stages of the disease, including the early stages. It can be feasible that this new score will facilitate better evaluation of the progression of PAD and its prospective role in CV risk stratification