Characteristics of effective collaborative care for treatment of depression: a systematic review and meta-regression of 74 randomised controlled trials

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.BACKGROUND: Collaborative care is a complex intervention based on chronic disease management models and is effective in the management of depression. However, there is still uncertainty about which components of collaborative care are effective. We used meta-regression to identify factors in collaborative care associated with improvement in patient outcomes (depressive symptoms) and the process of care (use of anti-depressant medication). METHODS AND FINDINGS: Systematic review with meta-regression. The Cochrane Collaboration Depression, Anxiety and Neurosis Group trials registers were searched from inception to 9th February 2012. An update was run in the CENTRAL trials database on 29th December 2013. Inclusion criteria were: randomised controlled trials of collaborative care for adults ≥18 years with a primary diagnosis of depression or mixed anxiety and depressive disorder. Random effects meta-regression was used to estimate regression coefficients with 95% confidence intervals (CIs) between study level covariates and depressive symptoms and relative risk (95% CI) and anti-depressant use. The association between anti-depressant use and improvement in depression was also explored. Seventy four trials were identified (85 comparisons, across 21,345 participants). Collaborative care that included psychological interventions predicted improvement in depression (β coefficient -0.11, 95% CI -0.20 to -0.01, p = 0.03). Systematic identification of patients (relative risk 1.43, 95% CI 1.12 to 1.81, p = 0.004) and the presence of a chronic physical condition (relative risk 1.32, 95% CI 1.05 to 1.65, p = 0.02) predicted use of anti-depressant medication. CONCLUSION: Trials of collaborative care that included psychological treatment, with or without anti-depressant medication, appeared to improve depression more than those without psychological treatment. Trials that used systematic methods to identify patients with depression and also trials that included patients with a chronic physical condition reported improved use of anti-depressant medication. However, these findings are limited by the observational nature of meta-regression, incomplete data reporting, and the use of study aggregates.NIH

A Simple Method for Analyzing Exome Sequencing Data Shows Distinct Levels of Nonsynonymous Variation for Human Immune and Nervous System Genes

To measure the strength of natural selection that acts upon single nucleotide variants (SNVs) in a set of human genes, we calculate the ratio between nonsynonymous SNVs (nsSNVs) per nonsynonymous site and synonymous SNVs (sSNVs) per synonymous site. We transform this ratio with a respective factor f that corrects for the bias of synonymous sites towards transitions in the genetic code and different mutation rates for transitions and transversions. This method approximates the relative density of nsSNVs (rdnsv) in comparison with the neutral expectation as inferred from the density of sSNVs. Using SNVs from a diploid genome and 200 exomes, we apply our method to immune system genes (ISGs), nervous system genes (NSGs), randomly sampled genes (RSGs), and gene ontology annotated genes. The estimate of rdnsv in an individual exome is around 20% for NSGs and 30–40% for ISGs and RSGs. This smaller rdnsv of NSGs indicates overall stronger purifying selection. To quantify the relative shift of nsSNVs towards rare variants, we next fit a linear regression model to the estimates of rdnsv over different SNV allele frequency bins. The obtained regression models show a negative slope for NSGs, ISGs and RSGs, supporting an influence of purifying selection on the frequency spectrum of segregating nsSNVs. The y-intercept of the model predicts rdnsv for an allele frequency close to 0. This parameter can be interpreted as the proportion of nonsynonymous sites where mutations are tolerated to segregate with an allele frequency notably greater than 0 in the population, given the performed normalization of the observed nsSNV to sSNV ratio. A smaller y-intercept is displayed by NSGs, indicating more nonsynonymous sites under strong negative selection. This predicts more monogenically inherited or de-novo mutation diseases that affect the nervous system

Diversity in Defining End of Life Care: An Obstacle or the Way Forward?

AIM: The terms used to describe care at the end of life (EoL), and its definitions, have evolved over time and reflect the changes in meaning the concept has undergone as the field develops. We explore the remit of EoL care as defined by experts in EoL care, from across Europe and beyond, to understand its current usage and meanings. METHOD: A qualitative survey attached to a call for expertise on cultural issues in EoL care was sent to experts in the field identified through the literature, European EoL care associations, and conferences targeted at EoL care professionals. Respondents were asked to identify further contacts for snowball recruitment.The responses were analysed using content and discourse analysis. RESULTS: Responses were received from 167 individuals (33% response rate), mainly from academics (39%) and clinical practitioners working in an academic context (23%) from 19 countries in Europe and beyond. 29% of respondents said explicitly that there was no agreed definition of EoL care in practice and only 14% offered a standard definition (WHO, or local institution). 2% said that the concept of EoL care was not used in their country, and 5% said that there was opposition to the concept for religious or cultural reasons. Two approaches were identified to arrive at an understanding of EoL care: exclusively by drawing boundaries through setting time frames, and inclusively by approaching its scope in an integrative way. This led to reflections about terminology and whether defining EoL care is desirable. CONCLUSION: The global expansion of EoL care contributes to the variety of interpretations of what it means. This complicates the endeavour of defining the field. However, when diversity is taken seriously it can open up new perspectives to underpin the ethical framework of EoL care

Role of high tibial osteotomy in chronic injuries of posterior cruciate ligament and posterolateral corner

High tibial osteotomy (HTO) is a surgical procedure used to change the mechanical weight-bearing axis and alter the loads carried through the knee. Conventional indications for HTO are medial compartment osteoarthritis and varus malalignment of the knee causing pain and dysfunction. Traditionally, knee instability associated with varus thrust has been considered a contraindication. However, today the indications include patients with chronic ligament deficiencies and malalignment, because an HTO procedure can change not only the coronal but also the sagittal plane of the knee. The sagittal plane has generally been ignored in HTO literature, but its modification has a significant impact on biomechanics and joint stability. Indeed, decreased posterior tibial slope causes posterior tibia translation and helps the anterior cruciate ligament (ACL)-deficient knee. Vice versa, increased tibial slope causes anterior tibia translation and helps the posterior cruciate ligament (PCL)-deficient knee. A review of literature shows that soft tissue procedures alone are often unsatisfactory for chronic posterior instability if alignment is not corrected. Since limb alignment is the most important factor to consider in lower limb reconstructive surgery, diagnosis and treatment of limb malalignment should not be ignored in management of chronic ligamentous instabilities. This paper reviews the effects of chronic posterior instability and tibial slope alteration on knee and soft tissues, in addition to planning and surgical technique for chronic posterior and posterolateral instability with HTO

Current strategies for treatment of intervertebral disc degeneration: substitution and regeneration possibilities

Background: Intervertebral disc degeneration has an annual worldwide socioeconomic impact masked as low back pain of over 70 billion euros. This disease has a high prevalence over the working age class, which raises the socioeconomic impact over the years. Acute physical trauma or prolonged intervertebral disc mistreatment triggers a biochemical negative tendency of catabolic-anabolic balance that progress to a chronic degeneration disease. Current biomedical treatments are not only ineffective in the long-run, but can also cause degeneration to spread to adjacent intervertebral discs. Regenerative strategies are desperately needed in the clinics, such as: minimal invasive nucleus pulposus or annulus fibrosus treatments, total disc replacement, and cartilaginous endplates decalcification. Main Body: Herein, it is reviewed the state-of-the-art of intervertebral disc regeneration strategies from the perspective of cells, scaffolds, or constructs, including both popular and unique tissue engineering approaches. The premises for cell type and origin selection or even absence of cells is being explored. Choice of several raw materials and scaffold fabrication methods are evaluated. Extensive studies have been developed for fully regeneration of the annulus fibrosus and nucleus pulposus, together or separately, with a long set of different rationales already reported. Recent works show promising biomaterials and processing methods applied to intervertebral disc substitutive or regenerative strategies. Facing the abundance of studies presented in the literature aiming intervertebral disc regeneration it is interesting to observe how cartilaginous endplates have been extensively neglected, being this a major source of nutrients and water supply for the whole disc. Conclusion: Severalinnovative avenues for tackling intervertebral disc degeneration are being reported â from acellular to cellular approaches, but the cartilaginous endplates regeneration strategies remain unaddressed. Interestingly, patient-specific approaches show great promise in respecting patient anatomy and thus allow quicker translation to the clinics in the near future.The authors would like to acknowledge the support provided by the Portuguese Foundation for Science and Technology (FCT) through the project EPIDisc (UTAP-EXPL/BBBECT/0050/2014), funded in the Framework of the “International Collaboratory for Emerging Technologies, CoLab”, UT Austin|Portugal Program. The FCT distinctions attributed to J. Miguel Oliveira (IF/00423/2012 and IF/01285/ 2015) and J. Silva-Correia (IF/00115/2015) under the Investigator FCT program are also greatly acknowledged.info:eu-repo/semantics/publishedVersio

Pregnancy-related pelvic girdle pain: an update

A large number of scientists from a wide range of medical and surgical disciplines have reported on the existence and characteristics of the clinical syndrome of pelvic girdle pain during or after pregnancy. This syndrome refers to a musculoskeletal type of persistent pain localised at the anterior and/or posterior aspect of the pelvic ring. The pain may radiate across the hip joint and the thigh bones. The symptoms may begin either during the first trimester of pregnancy, at labour or even during the postpartum period. The physiological processes characterising this clinical entity remain obscure. In this review, the definition and epidemiology, as well as a proposed diagnostic algorithm and treatment options, are presented. Ongoing research is desirable to establish clear management strategies that are based on the pathophysiologic mechanisms responsible for the escalation of the syndrome's symptoms to a fraction of the population of pregnant women

Strategies to Target Tumor Immunosuppression

The tumor microenvironment is currently in the spotlight of cancer immunology research as a key factor impacting tumor development and progression. While antigen-specific immune responses play a crucial role in tumor rejection, the tumor hampers these immune responses by creating an immunosuppressive microenvironment. Recently, major progress has been achieved in the field of cancer immunotherapy, and several groundbreaking clinical trials demonstrated the potency of such therapeutic interventions in patients. Yet, the responses greatly vary among individuals. This calls for the rational design of more efficacious cancer immunotherapeutic interventions that take into consideration the “immune signature” of the tumor. Multimodality treatment regimens that aim to enhance intratumoral homing and activation of antigen-specific immune effector cells, while simultaneously targeting tumor immunosuppression, are pivotal for potent antitumor immunity

Contribution of Microbe-Mediated Processes in Nitrogen Cycle to Attain Environmental Equilibrium

Nitrogen (N), the most important element, is required by all living organisms for the synthesis of complex organic molecules like amino acids, proteins, lipids etc. Nitrogen cycle is considered to be the most complex yet arguably important cycle next to carbon cycle. Nitrogen cycle includes oxic and anoxic reactions like organic N mineralization, ammonia assimilation, nitrification denitrification, anaerobic ammonium oxidation (anammox), dissimilatory nitrate reduction to ammonium (DNRA), comammox, codenitrification etc. Nitrogen cycling is one of the most crucial processes required for the recycling of essential chemical requirements on the planet. Soil microorganisms not only improve N-cycle balance but also pave the way for sustainable agricultural practices, leading to improved soil properties and crop productivity as most plants are opportunistic in the uptake of soluble or available forms of N from soil. Microbial N transformations are influenced by plants to improve their nutrition and vice versa. Diverse microorganisms, versatile metabolic activities, and varied biotic and abiotic conditions may result in the shift in the equilibrium state of different N-cycling processes. This chapter is an overview of the mechanisms and genes involved in the diverse microorganisms associated in the operation of nitrogen cycle and the roles of such microorganisms in different agroecosystems