In vitro and in vivo models investigating pharmacological modulators of the metabolic syndrome

BACKGROUND: Owing to the long-term health risks associated with increased adiposity and the limited efficacy of existing anti-obesity agents, there is an urgent need for further development of alternative therapeutic options to serve as an adjunct to lifestyle measures to address global cardiometabolic risk and thus reduce the risk of developing obesity-related illnesses such as type II diabetes and cardiovascular disease. AIMS/METHODS: The studies presented in this thesis aimed to investigate the effects of novel (CBi antagonist) and existing (metformin) pharmacological agents on components of the metabolic syndrome using in vitro and in vivo models. This was undertaken with in vitro studies of the effect of CBi receptor modulation on white, brown and primary (subcutaneous and omental) pre-adipocyte proliferation, adipogenesis and adipokine production as well as a randomised, double-blind cross-over trial of the effects of metformin on vascular function and metabolic profile in young women with polycystic ovary syndrome (in vivo). RESULTS: CBi receptor antagonism inhibited white and primary pre-adipocyte proliferation and increased expression of terminal markers of adipogenesis while promoting adiponectin production. In young women with PCOS, short term metformin therapy improved arterial stiffness and endothelial function, resulted in modest weight loss and an elevation in serum adiponectin. There is increasing evidence for the key role the latter plays in metabolic processes and vascular health, and these increases in adiponectin levels may underlie some of the mechanisms mediating the changes observed. Therefore treatments targeting a switch inthe adipokine profile as the therapeutic goal represent a new approach to addressing global cardiometabolic risk

A REVIEW ON OVERVIEW OF WORLDWIDE INTEROPERABILITY FOR MICROWAVE ACCESS (WIMAX) INNOVATION AND ITS FUTURE UTILIZATIONS

This paper introduces the elements of the Worldwide Interoperability for Microwave Access (WiMAX) innovation and future utilizations of WiMAX. It is a connection oriented wireless network that assures Quality of Service (QoS) for all users in the network. By comparing WiMAX with the popular Wi-Fi, 3G and LTE in the market, it analyzes the current situation and future development trend of WiMAX in terms of the difference in technology and applications. WiMAX will become the most prominent technology for Broadband Wireless Access (BWA). The next generation WMAN networks, using the WiMAX as the core technology is evolving as a 4G technology for providing ubiquitous computing solutions. In not a similar way like wireless LANs, WiMAX networks integrate various QoS mechanism at the Media Access Control (MAC) level for secured service for voice, data and video. The unique architecture of the WiMAX MAC and PHY layer that uses OFDMA to allocate multiple channels with different modulation schemes. A few references have been incorporated towards the completion of this paper for those eager to know in brief about certain points

Activity-Based Funding of Hospitals and Its Impact on Mortality, Readmission, Discharge Destination, Severity of Illness, and Volume of Care: A Systematic Review and Meta-Analysis

Background: Activity-based funding (ABF) of hospitals is a policy intervention intended to re-shape incentives across health systems through the use of diagnosis-related groups. Many countries are adopting or actively promoting ABF. We assessed the effect of ABF on key measures potentially affecting patients and health care systems: mortality (acute and post-acute care); readmission rates; discharge rate to post-acute care following hospitalization; severity of illness; volume of care.     Methods: We undertook a systematic review and meta-analysis of the worldwide evidence produced since 1980. We included all studies reporting original quantitative data comparing the impact of ABF versus alternative funding systems in acute care settings, regardless of language. We searched 9 electronic databases (OVID MEDLINE, EMBASE, OVID Healthstar, CINAHL, Cochrane CENTRAL, Health Technology Assessment, NHS Economic Evaluation Database, Cochrane Database of Systematic Reviews, and Business Source), hand-searched reference lists, and consulted with experts. Paired reviewers independently screened for eligibility, abstracted data, and assessed study credibility according to a pre-defined scoring system, resolving conflicts by discussion or adjudication.     Results: Of 16,565 unique citations, 50 US studies and 15 studies from 9 other countries proved eligible (i.e. Australia, Austria, England, Germany, Israel, Italy, Scotland, Sweden, Switzerland). We found consistent and robust differences between ABF and no-ABF in discharge to post-acute care, showing a 24% increase with ABF (pooled relative risk = 1.24, 95% CI 1.18–1.31). Results also suggested a possible increase in readmission with ABF, and an apparent increase in severity of illness, perhaps reflecting differences in diagnostic coding. Although we found no consistent, systematic differences in mortality rates and volume of care, results varied widely across studies, some suggesting appreciable benefits from ABF, and others suggesting deleterious consequences.     Conclusions: Transitioning to ABF is associated with important policy- and clinically-relevant changes. Evidence suggests substantial increases in admissions to post-acute care following hospitalization, with implications for system capacity and equitable access to care. High variability in results of other outcomes leaves the impact in particular settings uncertain, and may not allow a jurisdiction to predict if ABF would be harmless. Decision-makers considering ABF should plan for likely increases in post-acute care admissions, and be aware of the large uncertainty around impacts on other critical outcomes

A nationwide study of adults admitted to hospital with diabetic ketoacidosis or hyperosmolar hyperglycaemic state and COVID‐19

AimsTo investigate characteristics of people hospitalized with coronavirus-disease-2019 (COVID-19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission.Materials and methodsRetrospective cohort study with anonymized data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID-19 and diabetes, from start of pandemic to November 2021. The primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age-adjusted odds ratios were calculated using logistic regression.ResultsIn total, 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalized with COVID-19. Mean (SD) age was 60 (18.2) years in DKA and 74 (11.8) years in HHS (p < .001). A higher proportion of patients with HHS than with DKA were of non-White ethnicity (71.4% vs 39.0% p = .038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared with non-users [21.4% vs. 52.2%; age-adjusted odds ratio 0.13 (95% CI 0.03-0.60)]. Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, p = .001) and in statin users versus non-users (36.4% vs. 100%; p = .035) but these were not statistically significant after age adjustment.ConclusionsHospitalization with COVID-19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes-associated DKA

Impact of open access on CSIR-National Institute of Science Communication and Information Resources (NISCAIR) journals

On the first International Open Access Day on 14th October 2008, CSIR-NISCAIR made two of journals available in the open access domain and today all 18 CSIR-NISCAIR journals are open access journals. This study aims to explore the impact of open access on CSIR-NISCAIR journals in terms of visibility, use, citations received and impact factor. The results point out that switching to open access has benefited the journals

Impact of open access on CSIR-National Institute of Science Communication and Information Resources (NISCAIR) journals

84-89On the first International Open Access Day on 14th October 2008, CSIR-NISCAIR made two of journals available in the open access domain and today all 18 CSIR-NISCAIR journals are open access journals. This study aims to explore the impact of open access on CSIR-NISCAIR journals in terms of visibility, use, citations received and impact factor. The results point out that switching to open access has benefited the journals

Benefits and harms of citrate locking solutions for hemodialysis catheters: a systematic review and meta-analysis

Abstract Background Citrate has theoretical advantages over heparin for locking hemodialysis central venous catheters (CVCs), but the comparative effectiveness of these agents is not clear. Objectives 1) To compare the benefits and harms of citrate versus heparin locking solutions among patients undergoing hemodialysis through CVCs; 2) to appraise methodological quality of the supporting evidence. Data sources CENTRAL, MEDLINE, EMBASE, CINAHL, ISI Web of Science, and nephrology conference abstracts. Study eligibility, participants, and interventions We included randomized, parallel arm clinical trials that enrolled adult patients (>18 years) receiving chronic hemodialysis through CVCs using a citrate locking solution. We excluded studies in which citrate was combined with other agents, such as antibiotics. Appraisal and synthesis methods We used the GRADE approach to systematic reviews and quality appraisal. Two reviewers performed data extraction independently and in duplicate. We pooled count data using generic inverse variance with random-effects models, and used fixed-effect models when only two studies were available for pooling. Subgroups included low (≤5%) vs. higher (≥30%) citrate. Results We screened 600 citations. Forty-one proceeded to full-text screen; 5 met inclusion criteria. Studies included between 19 and 291 participants (Median N = 61) followed for a total of 174.6 catheter-years; 2 were multi-centred trials. Three studies assessed all-cause mortality; the pooled relative risk for death was 0.71 (95% CI = 0.42-1.24; p = 0.21; I2 = 0%). The rate ratio for bacteremic episodes was 0.54 (95% CI = 0.23-1.29; p = 0.16; I2 = 65%) while the rate ratio for bleeding was 0.48 (95% CI = 0.3-0.75; p = 0.001;I I2 = 5%). Rates of catheter exchange/replacement, all-cause hospitalization and in-situ thrombolysis were not significantly different between groups in any of the pooled analyses. Risk of bias within pooled studies was low. Limitations Outcome definitions varied across studies. Imprecision due to small sample sizes and low event rates reduce our overall confidence in the pooled effect estimates. Implications Benefits and harms of citrate vs. heparin locking solutions remain unclear; larger studies and standardization of outcome measurement and reporting are warranted. Trial registration Protocol Registration Number: CRD4201300478

Benefits and Harms of Citrate Locking Solutions for Hemodialysis Catheters: A Systematic Review and Meta-Analysis

Background: Citrate has theoretical advantages over heparin for locking hemodialysis central venous catheters (CVCs), but the comparative effectiveness of these agents is not clear. Objectives: 1) To compare the benefits and harms of citrate versus heparin locking solutions among patients undergoing hemodialysis through CVCs; 2) to appraise methodological quality of the supporting evidence. Data sources: CENTRAL, MEDLINE, EMBASE, CINAHL, ISI Web of Science, and nephrology conference abstracts. Study eligibility, participants, and interventions: We included randomized, parallel arm clinical trials that enrolled adult patients (>18 years) receiving chronic hemodialysis through CVCs using a citrate locking solution. We excluded studies in which citrate was combined with other agents, such as antibiotics. Appraisal and synthesis methods: We used the GRADE approach to systematic reviews and quality appraisal. Two reviewers performed data extraction independently and in duplicate. We pooled count data using generic inverse variance with random-effects models, and used fixed-effect models when only two studies were available for pooling. Subgroups included low (≤5%) vs. higher (≥30%) citrate. Results: We screened 600 citations. Forty-one proceeded to full-text screen; 5 met inclusion criteria. Studies included between 19 and 291 participants (Median N = 61) followed for a total of 174.6 catheter-years; 2 were multi-centred trials. Three studies assessed all-cause mortality; the pooled relative risk for death was 0.71 (95% CI = 0.42–1.24; p = 0.21; I 2 = 0%). The rate ratio for bacteremic episodes was 0.54 (95% CI = 0.23–1.29; p = 0.16; I 2 = 65%) while the rate ratio for bleeding was 0.48 (95% CI = 0.3–0.75; p = 0.001;I I 2 = 5%). Rates of catheter exchange/replacement, all-cause hospitalization and in-situ thrombolysis were not significantly different between groups in any of the pooled analyses. Risk of bias within pooled studies was low. Limitations: Outcome definitions varied across studies. Imprecision due to small sample sizes and low event rates reduce our overall confidence in the pooled effect estimates. Implications: Benefits and harms of citrate vs. heparin locking solutions remain unclear; larger studies and standardization of outcome measurement and reporting are warranted. Trial registration: Protocol Registration Number: CRD4201300478