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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Sanghamitra Pati; Subhashisa Swain; Mohammad Akhtar Hussain; Marjan van den Akker; +3 Authors

    OBJECTIVE: To systematically review the studies of prevalence, patterns and consequences of multimorbidity reported from South Asia.DESIGN: Systematic review.SETTING: South Asia.DATA SOURCES: Articles were retrieved from two electronic databases (PubMed and Embase) and from the relevant references lists. Methodical data extraction according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines was followed. English-language studies published between 2000 and March 2015 were included.ELIGIBILITY CRITERIA: Studies addressing prevalence, consequences and patterns of multimorbidity in South Asia. Articles documenting presence of two or more chronic conditions were included in the review. The quality and risk of bias were assessed using STROBE criteria.DATA SELECTION: Two reviewers independently assessed studies for eligibility, extracted data and assessed study quality. Due to heterogeneity in methodologies among reported studies, only narrative synthesis of the results was carried out.RESULTS: Of 11 132, 61 abstracts were selected and 13 were included for final data synthesis. The number of health conditions analysed per study varied from 7 to 22, with prevalence of multimorbidity from 4.5% to 83%. The leading chronic conditions were hypertension, arthritis, diabetes, cardiac problems and skin diseases. The most frequently reported outcomes were increased healthcare utilisation, lowered physical functioning and quality of life, and psychological distress.CONCLUSIONS: Our study, a comprehensive mapping of multimorbidity research in South Asia, reveals the insufficient volume of work carried out in this domain. The published studies are inadequate to provide an indication of the magnitude of multimorbidity in these countries. Research into clinical and epidemiological aspects of multimorbidity is warranted to build up scientific evidence in this geographic region. The wide heterogeneity observed in the present review calls for greater methodological rigour while conducting these epidemiological studies.TRIAL REGISTRATION NUMBER: CRD42013005456.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Article . 2015 . Peer-reviewed
    Data sources: PubMed Central
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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    BMJ Open
    Article
    License: CC BY
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    BMJ Open
    Article . 2015 . Peer-reviewed
    Data sources: Crossref
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      Europe PubMed Central
      Article . 2015 . Peer-reviewed
      Data sources: PubMed Central
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      BMJ Open
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      License: CC BY
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      BMJ Open
      Article . 2015 . Peer-reviewed
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  • Authors: Rowe, Will;

    This dissertation documents the development of an environmental framework for monitoring antimicrobial resistance gene (ARG) dissemination in the aquatic environment. The work opens with a review of the relevant literature and outlines the importance of an environmental framework for monitoring ARG dissemination as part of antimicrobial resistance risk assessments. The ability to interrogate sequencing data quickly and easily for the presence of ARGs is crucial in order to facilitate their monitoring in the environment. As current laboratory methods for the detection and surveillance of antimicrobial resistant bacteria in the environment were limited in their effectiveness and scope, the dissertation begins by describing the design and implementation of a Search Engine for Antimicrobial Resistance (SEAR), a pipeline and web interface for detection of horizontally-acquired ARGs in raw sequencing data. The suitability of metagenomic methods for monitoring the ARG content of effluents from faecal sources was then assessed via a pilot study of a river catchment. Novel metagenomes generated from effluents entering the catchment were interrogated for ARGs. The relative abundance of ARGs in effluents were determined to be higher relative to the background environment, as were sequences relating to human and animal pathogens and mobile genetic elements. Thus, effluents were implicated in the dissemination of ARGs throughout the aquatic environment. To determine if ARGs were potentially in use in the environment, the expression of ARGs within effluents was then evaluated across a series of longitudinal samples through the use of metatranscriptomics, and the presence of potential environmental antimicrobial selection pressures was examined. This demonstrated that the abundance of ARGs, as well as antimicrobial usage at the effluent source, was correlated with the transcription of ARGs in aquatic environments. The work described in this dissertation has also found that horizontally transmitted ARGs were present in pathogenic endospore-forming bacteria commonly found across the aquatic environment, potentially providing a mechanism for ARG persistence in the environment. Finally, these findings were integrated into a universal framework for monitoring ARG dissemination in aquatic environments and used to highlight the developments required to incorporate this framework into future environmental ARG research and to facilitate antimicrobial resistance risk assessments. The work described in this dissertation has been carried out as part of a BBSRC Industrial CASE PhD studentship, sponsored by GlaxoSmithKline and the Centre for Environment, Fisheries and Aquaculture Science.

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    Apollo
    Thesis . 2016
    License: CC BY SA
    Data sources: Datacite
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      Apollo
      Thesis . 2016
      License: CC BY SA
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: VASANTHAKRISHNAN RADHAKRISHNAN BALASUBRAMANIAM; Sam Brown; Vanika Gupta; Pedro Vale;

    Bacterial symbionts are widespread among metazoans and provide a range of beneficial functions. Wolbachia -mediated protection against viral infection has been extensively demonstrated in Drosophila. In mosquitoes that are artificially transinfected with Drosophila melanogaster Wolbachia (wMel), protection from both viral and bacterial infections has been demonstrated. However, no evidence for Wolbachia -mediated antibacterial protection has been demonstrated in Drosophila to date. Here, we show that the route of infection is key for Wolbachia -mediated antibacterial protection. Drosophila melanogaster carrying Wolbachia showed reduced mortality during enteric—but not systemic—infection with the opportunist pathogen Pseudomonas aeruginosa . Wolbachia -mediated protection was more pronounced in male flies and is associated with increased early expression of the antimicrobial peptide Attacin A , and also increased expression of a reactive oxygen species detoxification gene ( Gst D8 ). These results highlight that the route of infection is important for symbiont-mediated protection from infection, that Wolbachia can protect hosts by eliciting a combination of resistance and disease tolerance mechanisms, and that these effects are sexually dimorphic. We discuss the importance of using ecologically relevant routes of infection to gain a better understanding of symbiont-mediated protection.

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    Proceedings of the Royal Society B Biological Sciences; OpenAPC Global Initiative
    Article . Conference object . 2017 . Peer-reviewed
    License: Royal Society Data Sharing and Accessibility
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      Proceedings of the Royal Society B Biological Sciences; OpenAPC Global Initiative
      Article . Conference object . 2017 . Peer-reviewed
      License: Royal Society Data Sharing and Accessibility
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Anna M. Alessi; K. R. Redeker; James P. J. Chong;

    AbstractIn the context of antimicrobial resistance as one of the most serious issues faced globally by health providers, we explored a practical introduction to molecular microbial ecology. We designed field work and practical experiments for third year members of a 4 year undergraduate Masters Program, in which the students employed traditional and novel isolation techniques to identify antimicrobial activities from soil dwelling microorganisms. Students gained experience in isolating DNA from complex microbial communities, amplifying 16S rRNA genes and applied richness/diversity indices as well as principal coordinate analyses to the interpretation of the data they obtained from high throughput sequencing. Our results confirmed that isolation chips facilitate the growth of a greater diversity and different species subset from the complex soil microorganism community than traditional plate spreading techniques. However, rarefaction of 16S rRNA amplicon sequencing data showed that the majority of observed species in soil remain unculturable by current methods. Based on the written reports produced by the students carrying out the work, we concluded that the described protocols are robust and informative, that these activities provide a good practical introduction to the theories and practice of molecular ecology and can be easily deployed to groups of six or more students in a cost‐effective manner.

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    Ecology and Evolution
    Article
    License: CC BY
    Data sources: UnpayWall
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    Ecology and Evolution
    Article . 2018 . Peer-reviewed
    License: CC BY
    Data sources: Crossref
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      Ecology and Evolution
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      Ecology and Evolution
      Article . 2018 . Peer-reviewed
      License: CC BY
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Andrew Jackson; Thomas Hall; Damar Susilaradeya; Ferran Galán;

    What determines how we move in the world? Motor neuroscience often focusses either on intrinsic rhythmical properties of motor circuits or extrinsic sensorimotor feedback loops. Here we show that the interplay of both intrinsic and extrinsic dynamics is required to explain the intermittency observed in continuous tracking movements. Using spatiotemporal perturbations in humans, we demonstrate that apparently discrete submovements made 2–3 times per second reflect constructive interference between motor errors and continuous feedback corrections that are filtered by intrinsic circuitry in the motor system. Local field potentials in monkey motor cortex revealed characteristic signatures of a Kalman filter, giving rise to both low-frequency cortical cycles during movement, and delta oscillations during sleep. We interpret these results within the framework of optimal feedback control, and suggest that the intrinsic rhythmicity of motor cortical networks reflects an internal model of external dynamics, which is used for state estimation during feedback-guided movement.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

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    eLife; OpenAPC Global Initiative
    Article . Conference object . 2019 . Peer-reviewed
    License: CC BY
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      eLife; OpenAPC Global Initiative
      Article . Conference object . 2019 . Peer-reviewed
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    Authors: M, Fernanda Amary; Hongtao, Ye; Fitim, Berisha; Bhavisha, Khatri; +11 Authors

    Osteosarcoma, the most common primary bone sarcoma, is a genetically complex disease with no widely accepted biomarker to allow stratification of patients for treatment. After a recent report of one osteosarcoma cell line and one tumor exhibiting fibroblastic growth factor receptor 1 (FGFR1) gene amplification, the aim of this work was to assess the frequency of FGFR1 amplification in a larger cohort of osteosarcoma and to determine if this biomarker could be used for stratification of patients for treatment. About 352 osteosarcoma samples from 288 patients were analyzed for FGFR1 amplification by interphase fluorescence in situ hybridization. FGFR1 amplification was detected in 18.5% of patients whose tumors revealed a poor response to chemotherapy, and no patients whose tumors responded well to therapy harbored this genetic alteration. FGFR1 amplification is present disproportionately in the rarer histological variants of osteosarcoma. This study provides a rationale for inclusion of patients with osteosarcoma in clinical trials using FGFR kinase inhibitors.

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    Authors: Victoria C. Barclay; Derek G. Sim; Brian H. K. Chan; Lucas A. Nell; +4 Authors

    Malaria vaccine developers are concerned that antigenic escape will erode vaccine efficacy. Evolutionary theorists have raised the possibility that some types of vaccine could also create conditions favoring the evolution of more virulent pathogens. Such evolution would put unvaccinated people at greater risk of severe disease. Here we test the impact of vaccination with a single highly purified antigen on the malaria parasite Plasmodium chabaudi evolving in laboratory mice. The antigen we used, AMA-1, is a component of several candidate malaria vaccines currently in various stages of trials in humans. We first found that a more virulent clone was less readily controlled by AMA-1-induced immunity than its less virulent progenitor. Replicated parasites were then serially passaged through control or AMA-1 vaccinated mice and evaluated after 10 and 21 rounds of selection. We found no evidence of evolution at the ama-1 locus. Instead, virulence evolved; AMA-1-selected parasites induced greater anemia in naïve mice than both control and ancestral parasites. Our data suggest that recombinant blood stage malaria vaccines can drive the evolution of more virulent malaria parasites. Author Summary Vaccination can drive the evolution of pathogens. Most obviously, molecules targeted by vaccine-induced immunity can change. Such evolution makes vaccines less effective. A different possibility is that more virulent pathogens are favored in vaccinated hosts. In that case, vaccination would create pathogens that cause more harm to unvaccinated individuals. To test this idea, we studied a rodent malaria parasite in laboratory mice immunized with a component of malaria vaccines currently in human trials. We found that a more virulent parasite clone was less well controlled by vaccine-induced immunity than was its less virulent ancestor. We then passaged parasites through sham- or vaccinated mice to study how the parasites might evolve after multiple rounds of infection of mouse hosts. The parasite molecule targeted by the vaccine did not change during this process. Instead, the parasites became more virulent if they evolved in vaccinated hosts. Our data suggest that some vaccines can drive the evolution of more virulent parasites. A candidate malaria vaccine promoted the evolution of more virulent malaria parasites in mice.

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    PLoS Biology
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    PLoS Biology
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    PLoS Biology
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    PLoS Biology
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    PLoS Biology
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    PLoS Biology
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      PLoS Biology
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      PLoS Biology
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    Authors: Sanjeewa Abeytunge; Francesco Gianoli; A. J. Hudspeth; Andrei S. Kozlov;

    eLife digest The sense of hearing relies on specialized sensory cells in the inner ear. Each of these hair cells converts sounds into electrical signals that the brain can interpret. The hair cell takes its name from the bundle of rod-like structures that protrude from its top surface, which resemble hairs under the microscope. The hair bundle acts as an antenna that bends in response to sound waves. When a hair bundle moves in a particular direction, it opens ion channels in the hair-cell membrane. The resulting flow of ions into the cell triggers a cascade of events that ends with an electrical signal traveling to the brain. Many experiments on hearing rely on being able to manipulate the movement of a hair bundle. Researchers typically use one of two methods to achieve this. In the first, a flexible glass fiber pushes against the hair bundle, whereas the second involves a jet of fluid directed against the cell. Neither of these techniques can move hair bundles fast enough for researchers to explore the vast range of sound frequencies that human ears can detect. What is more, both methods are prone to introducing errors into experiments. Abeytunge, Gianoli et al. have developed a new method for moving hair bundles, this time with the aid of light. When light interacts with objects it exerts a photonic force. Abeytunge, Gianoli et al. show that a tapered optical fiber with a miniscule rounded lens can focus a laser beam to deliver enough photonic force to move a hair bundle. The laser beam does not damage the hair bundle, but moves it fast enough to allow researchers to study a broader range of mammalian hearing, while avoiding the errors that have bedeviled previous methods. Hair cells, the receptors of the inner ear, detect sounds by transducing mechanical vibrations into electrical signals. From the top surface of each hair cell protrudes a mechanical antenna, the hair bundle, which the cell uses to detect and amplify auditory stimuli, thus sharpening frequency selectivity and providing a broad dynamic range. Current methods for mechanically stimulating hair bundles are too slow to encompass the frequency range of mammalian hearing and are plagued by inconsistencies. To overcome these challenges, we have developed a method to move individual hair bundles with photonic force. This technique uses an optical fiber whose tip is tapered to a diameter of a few micrometers and endowed with a ball lens to minimize divergence of the light beam. Here we describe the fabrication, characterization, and application of this optical system and demonstrate the rapid application of photonic force to vestibular and cochlear hair cells.

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    DOAJ
    Article . 2021
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    https://www.biorxiv.org/conten...
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    eLife
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    Authors: Andrew P, Prayle; Matthew N, Hurley; Alan R, Smyth;

    Objective To examine compliance with mandatory reporting of summary clinical trial results (within one year of completion of trial) on ClinicalTrials.gov for studies that fall under the recent Food and Drug Administration Amendments Act (FDAAA) legislation. Design Registry based study of clinical trial summaries. Data sources ClinicalTrials.gov, searched on 19 January 2011, with cross referencing with Drugs@FDA to determine for which trials mandatory reporting was required within one year. Selection criteria Studies registered on ClinicalTrials.gov with US sites which completed between 1 January and 31 December 2009. Main outcome measure Proportion of trials for which results had been reported. Results The ClinicalTrials.gov registry contained 83 579 entries for interventional trials, of which 5642 were completed within the timescale of interest. We identified trials as falling within the mandatory reporting rules if they were covered by the FDAAA (trials of a drug, device, or biological agent, which have at least one US site, and are of phase II or later) and if they investigated a drug that already had approval from the Food and Drug Administration. Of these, 163/738 (22%) had reported results within one year of completion of the trial compared with 76/727 (10%) trials that were not subject to mandatory reporting (95% confidence interval for the difference in proportions 7.8% to 15.5%; χ2 test, P=2.6×10−9). Later phase trials were more likely to report results (P=4.4×10−11), as were industry funded trials (P=2.2×10−16). Conclusion Most trials subject to mandatory reporting did not report results within a year of completion.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ CORE (RIOXX-UK Aggre...arrow_drop_down
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    BMJ
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Gigi Y. Lau; Nicholas Barts; Richard C. Hartley; Michael Tobler; +3 Authors

    ABSTRACT In this paper, we outline the use of a mitochondria-targeted ratiometric mass spectrometry probe, MitoA, to detect in vivo changes in mitochondrial hydrogen sulfide (H2S) in Poecilia mexicana (family Poeciliidae). MitoA is introduced via intraperitoneal injection into the animal and is taken up by mitochondria, where it reacts with H2S to form the product MitoN. The MitoN/MitoA ratio can be used to assess relative changes in the amounts of mitochondrial H2S produced over time. We describe the use of MitoA in the fish species P. mexicana to illustrate the steps for adopting the use of MitoA in a new organism, including extraction and purification of MitoA and MitoN from tissues followed by tandem mass spectrometry. In this proof-of-concept study we exposed H2S tolerant P. mexicana to 59 µM free H2S for 5 h, which resulted in increased MitoN/MitoA in brain and gills, but not in liver or muscle, demonstrating increased mitochondrial H2S levels in select tissues following whole-animal H2S exposure. This is the first time that accumulation of H2S has been observed in vivo during whole-animal exposure to free H2S using MitoA. This article has an associated First Person interview with the first author of the paper. Summary: We established the mitochondria-targeted mass spectrometry probe MitoA for H2S detection in vivo in the animal model Poecilia mexicana for the first time.

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    Biology Open
    Article . 2019
    Data sources: DOAJ-Articles
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    DOAJ
    Article . 2019
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    Biology Open
    Article . 2019 . Peer-reviewed
    License: CC BY
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    Apollo
    Article . 2019
    License: CC BY
    Data sources: Datacite
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    Apollo
    Article . 2019
    License: CC BY
    Data sources: Apollo
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      Biology Open
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      Biology Open
      Article . 2019 . Peer-reviewed
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      Apollo
      Article . 2019
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      Article . 2019
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Sanghamitra Pati; Subhashisa Swain; Mohammad Akhtar Hussain; Marjan van den Akker; +3 Authors

    OBJECTIVE: To systematically review the studies of prevalence, patterns and consequences of multimorbidity reported from South Asia.DESIGN: Systematic review.SETTING: South Asia.DATA SOURCES: Articles were retrieved from two electronic databases (PubMed and Embase) and from the relevant references lists. Methodical data extraction according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines was followed. English-language studies published between 2000 and March 2015 were included.ELIGIBILITY CRITERIA: Studies addressing prevalence, consequences and patterns of multimorbidity in South Asia. Articles documenting presence of two or more chronic conditions were included in the review. The quality and risk of bias were assessed using STROBE criteria.DATA SELECTION: Two reviewers independently assessed studies for eligibility, extracted data and assessed study quality. Due to heterogeneity in methodologies among reported studies, only narrative synthesis of the results was carried out.RESULTS: Of 11 132, 61 abstracts were selected and 13 were included for final data synthesis. The number of health conditions analysed per study varied from 7 to 22, with prevalence of multimorbidity from 4.5% to 83%. The leading chronic conditions were hypertension, arthritis, diabetes, cardiac problems and skin diseases. The most frequently reported outcomes were increased healthcare utilisation, lowered physical functioning and quality of life, and psychological distress.CONCLUSIONS: Our study, a comprehensive mapping of multimorbidity research in South Asia, reveals the insufficient volume of work carried out in this domain. The published studies are inadequate to provide an indication of the magnitude of multimorbidity in these countries. Research into clinical and epidemiological aspects of multimorbidity is warranted to build up scientific evidence in this geographic region. The wide heterogeneity observed in the present review calls for greater methodological rigour while conducting these epidemiological studies.TRIAL REGISTRATION NUMBER: CRD42013005456.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Article . 2015 . Peer-reviewed
    Data sources: PubMed Central
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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    BMJ Open
    Article
    License: CC BY
    Data sources: UnpayWall
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    BMJ Open
    Article . 2015 . Peer-reviewed
    Data sources: Crossref
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      Europe PubMed Central
      Article . 2015 . Peer-reviewed
      Data sources: PubMed Central
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      BMJ Open
      Article
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      BMJ Open
      Article . 2015 . Peer-reviewed
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  • Authors: Rowe, Will;
    <