Meta-analysis and Meta-regression of Cognitive Behavioral Therapy for Psychosis (CBTp) Across Time: The Effectiveness of CBTp has Improved for Delusions

Published research shows small-to-medium effects of Cognitive Behavioral Therapy for Psychosis (CBTp) on reducing psychotic symptoms. Given the on-going development of CBTp interventions, the aim of this systematic review is to examine whether the effectiveness of CBTp has changed across time. MEDLINE, EMBASE, PsycINFO, and CENTRAL were searched for randomized controlled trials examining CBTp interventions targeting positive and/or negative symptoms vs treatment as usual. Four meta-analyses were carried out to examine the effectiveness of CBTp for: positive symptoms; delusions; hallucinations; and negative symptoms. Four meta-regressions examined whether the effectiveness of CBTp changed across time for these groups of symptoms. A total of 28 studies (n = 2698) yielded a pooled g of −0.24 (95% confidence interval [CI] −0.32, −0.16, P < .001) favoring CBTp for positive symptoms, with nonsignificant heterogeneity (Q = 26.87, P = .47; I2 =0%); 13 studies (n = 890) yielded a pooled g of −0.36 (95% CI −0.59, −0.13, P = .002) for delusions, with substantial heterogeneity (Q = 31.99, P = .001; I2 =62%); 16 studies (n = 849) yielded a pooled g of −0.26 (95% CI −0.42, −0.11, P < .001) for hallucinations, with nonsignificant heterogeneity (Q = 18.10, P = .26; I2 =17%); 19 studies (n = 1761) yielded a pooled g of −0.22 (95% CI −0.33, −0.12, P < .001) for negative symptoms, with nonsignificant heterogeneity (Q = 20.32, P = .32, I2 =11%). Meta-regressions indicated a significant effect of year on the effectiveness of CBTp only for delusions (F[1, 11] = 5.99, P = .032; R2 = 0.594); methodological quality did not effect this finding. Findings indicate small-to-medium effects of CBTp for psychotic symptoms, with increasing effectiveness across time for delusions

Debris cover and surface melt at a temperate maritime alpine glacier: Franz Josef Glacier, New Zealand

Melt rates on glaciers are strongly influenced by the presence of supraglacial debris, which can either enhance or reduce ablation relative to bare ice. Most recently, Franz Josef Glacier has entered into a phase of strong retreat and downwasting, with the increasing emergence of debris on the surface in the ablation zone. Previously at Franz Josef Glacier, melt has only been measured on bare ice. During February 2012, a network of 11 ablation stakes was drilled into locations of varying supraglacial debris thickness on the lower glacier. Mean ablation rates over 9 days varied over the range 1.2–10.1 cm d−1, and were closely related to debris thickness. Concomitant observations of air temperature allowed the application of a degree-day approach to the calculation of melt rates, with air temperature providing a strong indicator of melt. Degree-day factors (d f) varied over the range 1.1–8.1 mm d−1 °C−1 (mean of 4.4 mm d−1 °C−1), comparable with rates reported in other studies. Mapping of the current debris cover revealed 0.7 km2 of the 4.9 km2 ablation zone surface was debris-covered, with thicknesses ranging 1–50 cm. Based on measured debris thicknesses and d f, ablation on debris-covered areas of the glacier is reduced by a total of 41% which equates to a 6% reduction in melt overall across the entire ablation zone. This study highlights the usefulness of a short-term survey to gather representative ablation data, consistent with numerous overseas ablation studies on debris-covered glaciers

An overview of harms associated with β-lactam antimicrobials: where do the carbapenems fit in?

The US Institute of Medicine's focus on patient safety has motivated hospital administrators to facilitate a culture of safety. As a result, subcommittees of the pharmacy and therapeutics committee have emerged in many hospitals to focus on adverse events and patient safety. Antimicrobial harms have gained the attention of practicing clinicians and hospital formulary committees, because they top the list of drugs that are associated with adverse events and because of certain serious harms that have ultimately led to the withdrawal of some antimicrobial agents. In the near future, several antimicrobials in the late phase of development will become available for clinical use (ceftobiprole, ceftaroline, and telavancin), and others (doripenem and dalbavancin) have recently joined the armamentarium. Because new antimicrobials will become part of the treatment armamentarium, it is important to discuss our current understanding of antimicrobial harms in general. Although not thought of as traditional adverse events, Clostridium difficile infection and development of resistance during therapy are adverse events that occur as a result of antimicrobial exposure and therefore are discussed. In addition, a distillation of our current understanding of β-lactam specific adverse events will be provided. Finally, new methods of administration are being evaluated that may influence peak concentration-related antimicrobial adverse events

Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al

Comparative effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors and human glucagon-like peptide-1 (GLP-1) analogue as add-on therapies to sulphonylurea among diabetes patients in the Asia-Pacific region: a systematic review

The prevalence of diabetes mellitus is rising globally, and it induces a substantial public health burden to the healthcare systems. Its optimal control is one of the most significant challenges faced by physicians and policy-makers. Whereas some of the established oral hypoglycaemic drug classes like biguanide, sulphonylureas, thiazolidinediones have been extensively used, the newer agents like dipeptidyl peptidase-4 (DPP-4) inhibitors and the human glucagon-like peptide-1 (GLP-1) analogues have recently emerged as suitable options due to their similar efficacy and favorable side effect profiles. These agents are widely recognized alternatives to the traditional oral hypoglycaemic agents or insulin, especially in conditions where they are contraindicated or unacceptable to patients. Many studies which evaluated their clinical effects, either alone or as add-on agents, were conducted in Western countries. There exist few reviews on their effectiveness in the Asia-Pacific region. The purpose of this systematic review is to address the comparative effectiveness of these new classes of medications as add-on therapies to sulphonylurea drugs among diabetic patients in the Asia-Pacific countries. We conducted a thorough literature search of the MEDLINE and EMBASE from the inception of these databases to August 2013, supplemented by an additional manual search using reference lists from research studies, meta-analyses and review articles as retrieved by the electronic databases. A total of nine randomized controlled trials were identified and described in this article. It was found that DPP-4 inhibitors and GLP-1 analogues were in general effective as add-on therapies to existing sulphonylurea therapies, achieving HbA1c reductions by a magnitude of 0.59–0.90% and 0.77–1.62%, respectively. Few adverse events including hypoglycaemic attacks were reported. Therefore, these two new drug classes represent novel therapies with great potential to be major therapeutic options. Future larger-scale research should be conducted among other Asia-Pacific region to evaluate their efficacy in other ethnic groups

Effect of predictive sign of acceleration on heart rate variability in passive translation situation: preliminary evidence using visual and vestibular stimuli in VR environment

<p>Abstract</p> <p>Objective</p> <p>We studied the effects of the presentation of a visual sign that warned subjects of acceleration around the yaw and pitch axes in virtual reality (VR) on their heart rate variability.</p> <p>Methods</p> <p>Synchronization of the immersive virtual reality equipment (CAVE) and motion base system generated a driving scene and provided subjects with dynamic and wide-ranging depth information and vestibular input. The heart rate variability of 21 subjects was measured while the subjects observed a simulated driving scene for 16 minutes under three different conditions.</p> <p>Results</p> <p>When the predictive sign of the acceleration appeared 3500 ms before the acceleration, the index of the activity of the autonomic nervous system (low/high frequency ratio; LF/HF ratio) of subjects did not change much, whereas when no sign appeared the LF/HF ratio increased over the observation time. When the predictive sign of the acceleration appeared 750 ms before the acceleration, no systematic change occurred.</p> <p>Conclusion</p> <p>The visual sign which informed subjects of the acceleration affected the activity of the autonomic nervous system when it appeared long enough before the acceleration. Also, our results showed the importance of the interval between the sign and the event and the relationship between the gradual representation of events and their quantity.</p

Sexual dimorphism in relation to adipose tissue and intrahepatocellular lipid deposition in early infancy

Sexual dimorphism in adiposity is well described in adults, but the age at which differences first manifest is uncertain. Using a prospective cohort, we describe longitudinal changes in directly measured adiposity and intrahepatocellular lipid (IHCL) in relation to sex in healthy term infants. At median ages of 13 and 63 days, infants underwent quantification of adipose tissue depots by whole-body magnetic resonance imaging and measurement of IHCL by in vivo proton magnetic resonance spectroscopy. Longitudinal data were obtained from 70 infants (40 boys and 30 girls). In the neonatal period girls are more adipose in relation to body size than boys. At follow-up (median age 63 days), girls remained significantly more adipose. The greater relative adiposity that characterises girls is explained by more subcutaneous adipose tissue and this becomes increasingly apparent by follow-up. No significant sex differences were seen in IHCL. Sex-specific differences in infant adipose tissue distribution are in keeping with those described in later life, and suggest that sexual dimorphism in adiposity is established in early infancy

Cost-Effectiveness of Strategies to Improve HIV Testing and Receipt of Results: Economic Analysis of a Randomized Controlled Trial

The CDC recommends routine voluntary HIV testing of all patients 13-64 years of age. Despite this recommendation, HIV testing rates are low even among those at identifiable risk, and many patients do not return to receive their results. To examine the costs and benefits of strategies to improve HIV testing and receipt of results. Cost-effectiveness analysis based on a Markov model. Acceptance of testing, return rates, and related costs were derived from a randomized trial of 251 patients; long-term costs and health outcomes were derived from the literature. Primary-care patients with unknown HIV status. Comparison of three intervention models for HIV counseling and testing: Model A = traditional HIV counseling and testing; Model B = nurse-initiated routine screening with traditional HIV testing and counseling; Model C = nurse-initiated routine screening with rapid HIV testing and streamlined counseling. Life-years, quality-adjusted life-years (QALYs), costs and incremental cost-effectiveness. Without consideration of the benefit from reduced HIV transmission, Model A resulted in per-patient lifetime discounted costs of $48,650 and benefits of 16.271 QALYs. Model B increased lifetime costs by$53 and benefits by 0.0013 QALYs (corresponding to 0.48 quality-adjusted life days). Model C cost $66 more than Model A with an increase of 0.0018 QALYs (0.66 quality-adjusted life days) and an incremental cost-effectiveness of$36,390/QALY. When we included the benefit from reduced HIV transmission, Model C cost $10,660/QALY relative to Model A. The cost-effectiveness of Model C was robust in sensitivity analyses. In a primary-care population, nurse-initiated routine screening with rapid HIV testing and streamlined counseling increased rates of testing and receipt of test results and was cost-effective compared with traditional HIV testing strategies

Purification of Nanoparticles by Size and Shape

Producing monodisperse nanoparticles is essential to ensure consistency in biological experiments and to enable a smooth translation into the clinic. Purification of samples into discrete sizes and shapes may not only improve sample quality, but also provide us with the tools to understand which physical properties of nanoparticles are beneficial for a drug delivery vector. In this study, using polymersomes as a model system, we explore four techniques for purifying pre-formed nanoparticles into discrete fractions based on their size, shape or density. We show that these techniques can successfully separate polymersomes into monodisperse fractions