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1.
  • Lind, Lars, et al. (author)
  • Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
  • 2021
  • In: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
  • Journal article (peer-reviewed)abstract
    • From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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  • Ikuta, K. S., et al. (author)
  • Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019
  • 2022
  • In: Lancet. - : Elsevier BV. - 0140-6736. ; 400:10369, s. 2221-2248
  • Journal article (peer-reviewed)abstract
    • Background Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. Methods We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2.5th and 97.5th percentiles across 1000 posterior draws for each quantity of interest. Findings From an estimated 13.7 million (95% UI 10.9-17.1) infection-related deaths in 2019, there were 7.7 million deaths (5.7-10.2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13.6% (10.2-18.1) of all global deaths and 56.2% (52.1-60.1) of all sepsis-related deaths in 2019. Five leading pathogens-Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa-were responsible for 54.9% (52.9-56.9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185-285) per 100 000 population, and lowest in the high-income super-region, with 52.2 deaths (37.4-71.5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. Interpretation The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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  • Mishra, A, et al. (author)
  • Diminishing benefits of urban living for children and adolescents' growth and development
  • 2023
  • In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
  • Journal article (peer-reviewed)abstract
    • Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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  • Taddei, C, et al. (author)
  • Repositioning of the global epicentre of non-optimal cholesterol
  • 2020
  • In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
  • Journal article (peer-reviewed)abstract
    • High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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  • Tobias, Deirdre K, et al. (author)
  • Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
  • 2023
  • In: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
  • Research review (peer-reviewed)abstract
    • Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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  • Mainas, G, et al. (author)
  • Associations between Periodontitis, COVID-19, and Cardiometabolic Complications: Molecular Mechanisms and Clinical Evidence
  • 2023
  • In: Metabolites. - : MDPI AG. - 2218-1989. ; 13:1
  • Journal article (peer-reviewed)abstract
    • Periodontitis is a microbially driven, host-mediated disease that leads to loss of periodontal attachment and resorption of bone. It is associated with the elevation of systemic inflammatory markers and with the presence of systemic comorbidities. Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the majority of patients have mild symptoms, others experience important complications that can lead to death. After the spread of the COVID-19 pandemic, several investigations demonstrating the possible relationship between periodontitis and COVID-19 have been reported. In addition, both periodontal disease and COVID-19 seem to provoke and/or impair several cardiometabolic complications such as cardiovascular disease, type 2 diabetes, metabolic syndrome, dyslipidemia, insulin resistance, obesity, non-alcoholic fatty liver disease, and neurological and neuropsychiatric complications. Therefore, due to the increasing number of investigations focusing on the periodontitis-COVID-19 relationship and considering the severe complications that such an association might cause, this review aims to summarize all existing emerging evidence regarding the link between the periodontitis-COVID-19 axis and consequent cardiometabolic impairments.
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  • Ahuja, Vasudha, et al. (author)
  • Accuracy of 1-Hour Plasma Glucose During the Oral Glucose Tolerance Test in Diagnosis of Type 2 Diabetes in Adults : A Meta-analysis
  • 2021
  • In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 44:4, s. 1062-1069
  • Research review (peer-reviewed)abstract
    • OBJECTIVE: One-hour plasma glucose (1-h PG) during the oral glucose tolerance test (OGTT) is an accurate predictor of type 2 diabetes. We performed a meta-analysis to determine the optimum cutoff of 1-h PG for detection of type 2 diabetes using 2-h PG as the gold standard. RESEARCH DESIGN AND METHODS: We included 15 studies with 35,551 participants from multiple ethnic groups (53.8% Caucasian) and 2,705 newly detected cases of diabetes based on 2-h PG during OGTT. We excluded cases identified only by elevated fasting plasma glucose and/or HbA1c. We determined the optimal 1-h PG threshold and its accuracy at this cutoff for detection of diabetes (2-h PG ≥11.1 mmol/L) using a mixed linear effects regression model with different weights to sensitivity/specificity (2/3, 1/2, and 1/3). RESULTS: Three cutoffs of 1-h PG, at 10.6 mmol/L, 11.6 mmol/L, and 12.5 mmol/L, had sensitivities of 0.95, 0.92, and 0.87 and specificities of 0.86, 0.91, and 0.94 at weights 2/3, 1/2, and 1/3, respectively. The cutoff of 11.6 mmol/L (95% CI 10.6, 12.6) had a sensitivity of 0.92 (0.87, 0.95), specificity of 0.91 (0.88, 0.93), area under the curve 0.939 (95% confidence region for sensitivity at a given specificity: 0.904, 0.946), and a positive predictive value of 45%. CONCLUSIONS: The 1-h PG of ≥11.6 mmol/L during OGTT has a good sensitivity and specificity for detecting type 2 diabetes. Prescreening with a diabetes-specific risk calculator to identify high-risk individuals is suggested to decrease the proportion of false-positive cases. Studies including other ethnic groups and assessing complication risk are warranted.
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  • A, Lavanya, et al. (author)
  • Smart energy monitoring and power quality performance based evaluation of 100-kW grid tied PV system
  • 2023
  • In: Heliyon. - 2405-8440. ; 9:6
  • Journal article (peer-reviewed)abstract
    • Globally, the demand for energy from renewable sources is growing due to the increasing electricity consumption and the pollution of fossil fuels. The government has framed various policies to facilitate green energy generation, encouraging renewable energy source usage through PV installations in multiple sectors, including educational institutions. The primary objective of this paper is to propose a methodological approach for analysing the performance of the installed PV system on the rooftop of a university building in Tamil Nadu, India. The site selected is favourable for electricity generation from PV systems with an average global solar radiation of 5.82 kWh/m2day. Solar energy changes periodically with annual and daily variations and is not steady due to seasonal changes. The step-by-step performance assessment and the annual performance of the 100-kW solar PV system, which was instituted in 2019, with the forecasted parameters, are presented in this paper. Therefore, the assessment analysis is carried out in four phases: feasibility assessment, Energy yield assessment, Life cycle assessment, and Power quality assessment. To improve the solar PV output and efficiency, considering the solar irradiation, temperature, wind velocity, etc., PV yield is measured to evaluate the PV system's energy metrics. This paper also considers the carbon credits earned, solar power generated in the location, and the payback period. The power quality assessment is carried out in this paper to test the PV plant's compliance with effective grid integration.
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  • Bus, Sicco A., et al. (author)
  • Guidelines on offloading foot ulcers in persons with diabetes (IWGDF 2019 update)
  • 2020
  • In: Diabetes/Metabolism Research Reviews. - : John Wiley & Sons. - 1520-7552 .- 1520-7560. ; 36:Suppl 1
  • Journal article (peer-reviewed)abstract
    • The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the prevention and management of diabetic foot disease since 1999. This guideline is on the use of offloading interventions to promote the healing of foot ulcers in people with diabetes and updates the previous IWGDF guideline. We followed the GRADE methodology to devise clinical questions and critically important outcomes in the PICO format, to conduct a systematic review of the medical-scientific literature, and to write recommendations and their rationale. The recommendations are based on the quality of evidence found in the systematic review, expert opinion where evidence was not available, and a weighing of the benefits and harms, patient preferences, feasibility and applicability, and costs related to the intervention. For healing a neuropathic plantar forefoot or midfoot ulcer in a person with diabetes, we recommend that a nonremovable knee-high offloading device is the first choice of offloading treatment. A removable knee-high and removable ankle-high offloading device are to be considered as the second- and third-choice offloading treatment, respectively, if contraindications or patient intolerance to nonremovable offloading exist. Appropriately, fitting footwear combined with felted foam can be considered as the fourth-choice offloading treatment. If non-surgical offloading fails, we recommend to consider surgical offloading interventions for healing metatarsal head and digital ulcers. We have added new recommendations for the use of offloading treatment for healing ulcers that are complicated with infection or ischaemia and for healing plantar heel ulcers. Offloading is arguably the most important of multiple interventions needed to heal a neuropathic plantar foot ulcer in a person with diabetes. Following these recommendations will help health care professionals and teams provide better care for diabetic patients who have a foot ulcer and are at risk for infection, hospitalization, and amputation.
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  • Bus, Sicco A., et al. (author)
  • Guidelines on offloading foot ulcers in persons with diabetes (IWGDF 2023 update)
  • 2024
  • In: Diabetes/Metabolism Research Reviews. - : American Physical Society. - 1520-7552 .- 1520-7560. ; 40:3
  • Journal article (peer-reviewed)abstract
    • AIMS: Offloading mechanical tissue stress is arguably the most important of multiple interventions needed to heal diabetes-related foot ulcers. This is the 2023 International Working Group on the Diabetic Foot (IWGDF) evidence-based guideline on offloading interventions to promote healing of foot ulcers in persons with diabetes. It serves as an update of the 2019 IWGDF guideline.MATERIALS AND METHODS: We followed the GRADE approach by devising clinical questions and important outcomes in the PICO (Patient-Intervention-Control-Outcome) format, undertaking a systematic review and meta-analyses, developing summary of judgement tables and writing recommendations and rationales for each question. Each recommendation is based on the evidence found in the systematic review, expert opinion where evidence was not available, and a careful weighing of GRADE summary of judgement items including desirable and undesirable effects, certainty of evidence, patient values, resources required, cost effectiveness, equity, feasibility, and acceptability.RESULTS: For healing a neuropathic plantar forefoot or midfoot ulcer in a person with diabetes, use a non-removable knee-high offloading device as the first-choice offloading intervention. If contraindications or patient intolerance to non-removable offloading exist, consider using a removable knee-high or ankle-high offloading device as the second-choice offloading intervention. If no offloading devices are available, consider using appropriately fitting footwear combined with felted foam as the third-choice offloading intervention. If such a non-surgical offloading treatment fails to heal a plantar forefoot ulcer, consider an Achilles tendon lengthening, metatarsal head resection, joint arthroplasty, or metatarsal osteotomy. For healing a neuropathic plantar or apex lesser digit ulcer secondary to flexibile toe deformity, use digital flexor tendon tenotomy. For healing rearfoot, non-plantar or ulcers complicated with infection or ischaemia, further recommendations have been outlined. All recommendations have been summarised in an offloading clinical pathway to help facilitate the implementation of this guideline into clinical practice.CONCLUSION: These offloading guideline recommendations should help healthcare professionals provide the best care and outcomes for persons with diabetes-related foot ulcers and reduce the person's risk of infection, hospitalisation and amputation.
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  • Jensterle, M, et al. (author)
  • The Relationship between COVID-19 and Hypothalamic-Pituitary-Adrenal Axis: A Large Spectrum from Glucocorticoid Insufficiency to Excess-The CAPISCO International Expert Panel
  • 2022
  • In: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 23:13
  • Journal article (peer-reviewed)abstract
    • Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic–pituitary–adrenal (HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We also address several additional mechanisms that may cause HPA axis dysfunction, including critical illness-related corticosteroid insufficiency, the direct cytopathic impacts of SARS-CoV-2 infection on the adrenals, pituitary, and hypothalamus, immune-mediated inflammations, small vessel vasculitis, microthrombotic events, the resistance of cortisol receptors, and impaired post-receptor signaling, as well as the dissociation of ACTH and cortisol regulation. We also discuss the increased risk of infection and more severe illness in COVID-19 patients with pre-existing disorders of the HPA axis, from insufficiency to excess. These insights into the complex regulation of the HPA axis reveal how well the body performs in its adaptive survival mechanism during a severe infection, such as SARS-CoV-2, and how many parameters might disbalance the outcomes of this adaptation.
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  • Lazzarini, P A, et al. (author)
  • Effectiveness of offloading interventions for people with diabetes-related foot ulcers : A systematic review and meta-analysis
  • 2023
  • In: Diabetes/Metabolism Research Reviews. - : John Wiley & Sons. - 1520-7552 .- 1520-7560. ; 40:3
  • Research review (peer-reviewed)abstract
    • BACKGROUND: Offloading treatment is crucial to heal diabetes-related foot ulcers (DFU). This systematic review aimed to assess the effectiveness of offloading interventions for people with DFU.METHODS: We searched PubMed, EMBASE, Cochrane databases, and trials registries for all studies relating to offloading interventions in people with DFU to address 14 clinical question comparisons. Outcomes included ulcers healed, plantar pressure, weight-bearing activity, adherence, new lesions, falls, infections, amputations, quality of life, costs, cost-effectiveness, balance, and sustained healing. Included controlled studies were independently assessed for risk of bias and had key data extracted. Meta-analyses were performed when outcome data from studies could be pooled. Evidence statements were developed using the GRADE approach when outcome data existed.RESULTS: From 19,923 studies screened, 194 eligible studies were identified (47 controlled, 147 non-controlled), 35 meta-analyses performed, and 128 evidence statements developed. We found non-removable offloading devices likely increase ulcers healed compared to removable offloading devices (risk ratio [RR] 1.24, 95% CI 1.09-1.41; N = 14, n = 1083), and may increase adherence, cost-effectiveness and decrease infections, but may increase new lesions. Removable knee-high offloading devices may make little difference to ulcers healed compared to removable ankle-high offloading devices (RR 1.00, 0.86-1.16; N = 6, n = 439), but may decrease plantar pressure and adherence. Any offloading device may increase ulcers healed (RR 1.39, 0.89-2.18; N = 5, n = 235) and cost-effectiveness compared to therapeutic footwear and may decrease plantar pressure and infections. Digital flexor tenotomies with offloading devices likely increase ulcers healed (RR 2.43, 1.05-5.59; N = 1, n = 16) and sustained healing compared to devices alone, and may decrease plantar pressure and infections, but may increase new transfer lesions. Achilles tendon lengthening with offloading devices likely increase ulcers healed (RR 1.10, 0.97-1.27; N = 1, n = 64) and sustained healing compared to devices alone, but likely increase new heel ulcers.CONCLUSIONS: Non-removable offloading devices are likely superior to all other offloading interventions to heal most plantar DFU. Digital flexor tenotomies and Achilles tendon lengthening in combination with offloading devices are likely superior for some specific plantar DFU locations. Otherwise, any offloading device is probably superior to therapeutic footwear and other non-surgical offloading interventions to heal most plantar DFU. However, all these interventions have low-to-moderate certainty of evidence supporting their outcomes and more high-quality trials are needed to improve our certainty for the effectiveness of most offloading interventions.
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  • Lazzarini, Peter A., et al. (author)
  • Effectiveness of offloading interventions to heal foot ulcers in persons with diabetes : a systematic review
  • 2020
  • In: Diabetes/Metabolism Research Reviews. - : John Wiley & Sons. - 1520-7552 .- 1520-7560. ; 36:Suppl. 1
  • Research review (peer-reviewed)abstract
    • BACKGROUND: Offloading interventions are commonly used in clinical practice to heal foot ulcers. The aim of this updated systematic review is to investigate the effectiveness of offloading interventions to heal diabetic foot ulcers.METHODS: We updated our previous systematic review search of PubMed, EMBASE, and Cochrane databases to also include original studies published between July 29, 2014 and August 13, 2018 relating to four offloading intervention categories in populations with diabetic foot ulcers: (a) offloading devices, (b) footwear, (c) other offloading techniques, and (d) surgical offloading techniques. Outcomes included ulcer healing, plantar pressure, ambulatory activity, adherence, adverse events, patient-reported measures, and cost-effectiveness. Included controlled studies were assessed for methodological quality and had key data extracted into evidence and risk of bias tables. Included non-controlled studies were summarised on a narrative basis.RESULTS: We identified 41 studies from our updated search for a total of 165 included studies. Six included studies were meta-analyses, 26 randomised controlled trials (RCTs), 13 other controlled studies, and 120 non-controlled studies. Five meta-analyses and 12 RCTs provided high-quality evidence for non-removable knee-high offloading devices being more effective than removable offloading devices and therapeutic footwear for healing plantar forefoot and midfoot ulcers. Total contact casts (TCCs) and non-removable knee-high walkers were shown to be equally effective. Moderate-quality evidence exists for removable knee-high and ankle-high offloading devices being equally effective in healing, but knee-high devices have a larger effect on reducing plantar pressure and ambulatory activity. Low-quality evidence exists for the use of felted foam and surgical offloading to promote healing of plantar forefoot and midfoot ulcers. Very limited evidence exists for the efficacy of any offloading intervention for healing plantar heel ulcers, non-plantar ulcers, and neuropathic ulcers with infection or ischemia.CONCLUSION: Strong evidence supports the use of non-removable knee-high offloading devices (either TCC or non-removable walker) as the first-choice offloading intervention for healing plantar neuropathic forefoot and midfoot ulcers. Removable offloading devices, either knee-high or ankle-high, are preferred as second choice over other offloading interventions. The evidence bases to support any other offloading intervention is still weak and more high-quality controlled studies are needed in these areas.
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24.
  • Martin, Nicolas F., et al. (author)
  • The Pristine survey - XVI. The metallicity of 26 stellar streams around the Milky Way detected with the STREAMFINDER in Gaia EDR3
  • 2022
  • In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 516:4, s. 5331-5354
  • Journal article (peer-reviewed)abstract
    • We use the photometric metallicities provided by the panoramic Pristine survey to study the veracity and derive the metallicities of the numerous stellar streams found by the application of the STREAMFINDER algorithm to the Gaia Early Data Release 3 data. All 26 streams present in Pristine show a clear metallicity distribution function, which provides an independent check of the reality of these structures, supporting the reliability of STREAMFINDER in finding streams and the power of Pristine to measure precise metallicities. We further present six candidate structures with coherent phase-space and metallicity signals that are very likely streams. The majority of studied streams are very metal-poor (14 structures with [Fe/H] < −2.0) and include three systems with [Fe/H] < −2.9 (C-11, C-19, and C-20). These streams could be the closest debris of low-luminosity dwarf galaxies or may have originated from globular clusters of significantly lower metallicity than any known current Milky Way globular cluster. Our study shows that the promise of the Gaia data for Galactic Archeology studies can be substantially strengthened by quality photometric metallicities, allowing us to peer back into the earliest epochs of the formation of our Galaxy and its stellar halo constituents.
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25.
  • Navamani, Divya, et al. (author)
  • Pathway to investigate and assess the performance of solar ON-Grid plant
  • 2023
  • In: International Journal of Ambient Energy. - : Informa UK Limited. - 0143-0750 .- 2162-8246. ; 44:1, s. 186-200
  • Journal article (peer-reviewed)abstract
    • This study investigates the long-term performance of a 52-kW on-grid solar PV plant in the Mechanical ‘C’ block, SRM Institute of Science and Technology (SRMIST). This article delivers a simple approach that would act as a pivot for PV system assessment. Therefore, methodologies like Energy yield analysis, Energy distribution, and Life cycle costing are implemented. This empowers the methods to facilitate pre-auditing, energy conservation, and economic analysis. The performance ratio and a capacity factor of the 52-kW PV plant in 2020 are determined as 60% and 12.8%, respectively. The study offers that the plant has a less simple payback period and energy pack time for 2020. From this study, the issues identified in the plant are highlighted with the solution. It also paves the way for the researchers to suggest the solutions for the underutilisation of the plant, especially in the situations like fault occurrence, pandemic conditions, etc.
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  • Ammanath, Aparna Viswanathan, et al. (author)
  • From an Hsp90 - binding protein to a peptide drug.
  • 2022
  • In: microLife. - : Oxford University Press (OUP). - 2633-6693. ; 4
  • Journal article (peer-reviewed)abstract
    • The Lpl proteins represent a class of lipoproteins that was first described in the opportunistic bacterial pathogen Staphylococcus aureus, where they contribute to pathogenicity by enhancing F-actin levels of host epithelial cells and thereby increasing S. aureus internalization. The model Lpl protein, Lpl1 was shown to interact with the human heat shock proteins Hsp90α and Hsp90ß, suggesting that this interaction may trigger all observed activities. Here we synthesized Lpl1-derived peptides of different lengths and identified two overlapping peptides, namely, L13 and L15, which interacted with Hsp90α. Unlike Lpl1, the two peptides not only decreased F-actin levels and S. aureus internalization in epithelial cells but they also decreased phagocytosis by human CD14+ monocytes. The well-known Hsp90 inhibitor, geldanamycin, showed a similar effect. The peptides not only interacted directly with Hsp90α, but also with the mother protein Lpl1. While L15 and L13 significantly decreased lethality of S. aureus bacteremia in an insect model, geldanamycin did not. In a mouse bacteremia model L15 was found to significantly decreased weight loss and lethality. Although the molecular bases of the L15 effect is still elusive, in vitro data indicate that simultaneous treatment of host immune cells with L15 or L13 and S. aureus significantly increase IL-6 production. L15 and L13 represent not antibiotics but they cause a significant reduction in virulence of multidrug-resistant S. aureus strains in in vivo models. In this capacity, they can be an important drug alone or additive with other agents.
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  • Anjana, Ranjit Mohan, et al. (author)
  • Contrasting Associations Between Diabetes and Cardiovascular Mortality Rates in Low-, Middle-, and High-Income Countries: Cohort Study Data From 143,567 Individuals in 21 Countries in the PURE Study.
  • 2020
  • In: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:12, s. 3094-3101
  • Journal article (peer-reviewed)abstract
    • We aimed to compare cardiovascular (CV) events, all-cause mortality, and CV mortality rates among adults with and without diabetes in countries with differing levels of income.The Prospective Urban Rural Epidemiology (PURE) study enrolled 143,567 adults aged 35-70 years from 4 high-income countries (HIC), 12 middle-income countries (MIC), and 5 low-income countries (LIC). The mean follow-up was 9.0 ± 3.0 years.Among those with diabetes, CVD rates (LIC 10.3, MIC 9.2, HIC 8.3 per 1,000 person-years, P < 0.001), all-cause mortality (LIC 13.8, MIC 7.2, HIC 4.2 per 1,000 person-years, P < 0.001), and CV mortality (LIC 5.7, MIC 2.2, HIC 1.0 per 1,000 person-years, P < 0.001) were considerably higher in LIC compared with MIC and HIC. Within LIC, mortality was higher in those in the lowest tertile of wealth index (low 14.7%, middle 10.8%, and high 6.5%). In contrast to HIC and MIC, the increased CV mortality in those with diabetes in LIC remained unchanged even after adjustment for behavioral risk factors and treatments (hazard ratio [95% CI] 1.89 [1.58-2.27] to 1.78 [1.36-2.34]).CVD rates, all-cause mortality, and CV mortality were markedly higher among those with diabetes in LIC compared with MIC and HIC with mortality risk remaining unchanged even after adjustment for risk factors and treatments. There is an urgent need to improve access to care to those with diabetes in LIC to reduce the excess mortality rates, particularly among those in the poorer strata of society.
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28.
  • Beal, Jacob, et al. (author)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Journal article (peer-reviewed)abstract
    • Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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29.
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30.
  • Joseph, Philip G, et al. (author)
  • Global variations in the prevalence, treatment, and impact of atrial fibrillation in a multi-national cohort of 153,152 middle-aged individuals.
  • 2021
  • In: Cardiovascular research. - : Oxford University Press (OUP). - 1755-3245 .- 0008-6363. ; 117:6, s. 1523-1531
  • Journal article (peer-reviewed)abstract
    • To compare the prevalence of electrocardiogram (ECG)-documented atrial fibrillation (or flutter) (AF) across eight regions of the world, and to examine anti-thrombotic use and clinical outcomes.Baseline ECGs were collected in 153,152 middle-aged participants (ages 35 to 70 years) to document AF in two community-based studies, spanning 20 countries. Medication use and clinical outcome data (mean follow up of 7.4 years) were available in one cohort. Cross sectional analyses were performed to document the prevalence of AF and medication use, and associations between AF and clinical events were examined prospectively. Mean age of participants was 52.1 years, and 57.7% were female. Age and sex-standardized prevalence of AF varied 12-fold between regions; with the highest in North America, Europe, China and Southeast Asia (270-360 cases per 100,000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100,000 persons)(p<0.001). Compared with low-income countries (LICs), AF prevalence was 7-fold higher in middle-income countries (MICs) and 11-fold higher in high-income countries (HICs)(p<0.001). Differences in AF prevalence remained significant after adjusting for traditional AF risk factors. In LICs/MICs, 24% of participants with AF and a CHADS2 score ≥1 received anti-thrombotic therapy, compared with 85% in HICs. AF was associated with an increased risk of stroke (hazard ratio [HR: 2.29; 95% confidence interval [CI] 1.49-3.52) and death (HR: 2.97; 95% CI 2.25-3.93); with similar rates in different country income levels.Large variations in AF prevalence occur in different regions and country income settings, but this is only partially explained by traditional AF risk factors. Anti-thrombotic therapy is infrequently used in poorer countries despite the high risk of stroke associated with AF.We examined atrial fibrillation (AF) prevalence in 153,152 middle-aged participants spanning 20 countries. Age and sex-standardized prevalence of AF varied by as much as 12-fold between regions; highest in North America, Europe, China and Southeast Asia (270-360 cases per 100,000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100,000 persons)(p<0.001); and by as much as 11-fold between groups of countries at different income levels (p<0.001). Global variations were poorly explained by traditional AF risk factors. Future studies are needed to understand the predominant determinants driving the variation in AF burden across different regions of the world.
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31.
  • Miller, Victoria, et al. (author)
  • Associations of the glycaemic index and the glycaemic load with risk of type 2 diabetes in 127594 people from 20 countries (PURE): a prospective cohort study
  • 2024
  • In: The Lancet Diabetes and Endocrinology. - 2213-8587 .- 2213-8595. ; 12, s. 330-338
  • Journal article (peer-reviewed)abstract
    • Background: The association between the glycaemic index and the glycaemic load with type 2 diabetes incidence is controversial. We aimed to evaluate this association in an international cohort with diverse glycaemic index and glycaemic load diets. Methods: The PURE study is a prospective cohort study of 127 594 adults aged 35–70 years from 20 high-income, middle-income, and low-income countries. Diet was assessed at baseline using country-specific validated food frequency questionnaires. The glycaemic index and the glycaemic load were estimated on the basis of the intake of seven categories of carbohydrate-containing foods. Participants were categorised into quintiles of glycaemic index and glycaemic load. The primary outcome was incident type 2 diabetes. Multivariable Cox Frailty models with random intercepts for study centre were used to calculate hazard ratios (HRs). Findings: During a median follow-up of 11·8 years (IQR 9·0–13·0), 7326 (5·7%) incident cases of type 2 diabetes occurred. In multivariable adjusted analyses, a diet with a higher glycaemic index was significantly associated with a higher risk of diabetes (quintile 5 vs quintile 1; HR 1·15 [95% CI 1·03–1·29]). Participants in the highest quintile of the glycaemic load had a higher risk of incident type 2 diabetes compared with those in the lowest quintile (HR 1·21, 95% CI 1·06–1·37). The glycaemic index was more strongly associated with diabetes among individuals with a higher BMI (quintile 5 vs quintile 1; HR 1·23 [95% CI 1·08–1·41]) than those with a lower BMI (quintile 5 vs quintile 1; 1·10 [0·87–1·39]; p interaction=0·030). Interpretation: Diets with a high glycaemic index and a high glycaemic load were associated with a higher risk of incident type 2 diabetes in a multinational cohort spanning five continents. Our findings suggest that consuming low glycaemic index and low glycaemic load diets might prevent the development of type 2 diabetes. Funding: Full funding sources are listed at the end of the Article.
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32.
  • Misra, Shivani, et al. (author)
  • The case for precision medicine in the prevention, diagnosis, and treatment of cardiometabolic diseases in low-income and middle-income countries
  • 2023
  • In: The Lancet Diabetes and Endocrinology. - 2213-8587. ; 11:11, s. 836-847
  • Research review (peer-reviewed)abstract
    • Cardiometabolic diseases are the leading preventable causes of death in most geographies. The causes, clinical presentations, and pathogenesis of cardiometabolic diseases vary greatly worldwide, as do the resources and strategies needed to prevent and treat them. Therefore, there is no single solution and health care should be optimised, if not to the individual (ie, personalised health care), then at least to population subgroups (ie, precision medicine). This optimisation should involve tailoring health care to individual disease characteristics according to ethnicity, biology, behaviour, environment, and subjective person-level characteristics. The capacity and availability of local resources and infrastructures should also be considered. Evidence needed for equitable precision medicine cannot be generated without adequate data from all target populations, and the idea that research done in high-income countries will transfer adequately to low-income and middle-income countries (LMICs) is problematic, as many migration studies and transethnic comparisons have shown. However, most data for precision medicine research are derived from people of European ancestry living in high-income countries. In this Series paper, we discuss the case for precision medicine for cardiometabolic diseases in LMICs, the barriers and enablers, and key considerations for implementation. We focus on three propositions: first, failure to explore and implement precision medicine for cardiometabolic disease in LMICs will enhance global health disparities. Second, some LMICs might already be placed to implement cardiometabolic precision medicine under appropriate circumstances, owing to progress made in treating infectious diseases. Third, improvements in population health from precision medicine are most probably asymptotic; the greatest gains are more likely to be obtained in countries where health-care systems are less developed. We outline key recommendations for implementation of precision medicine approaches in LMICs.
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33.
  • Santosa, Ailiana, et al. (author)
  • Psychosocial Risk Factors and Cardiovascular Disease and Death in a Population-Based Cohort From 21 Low-, Middle-, and High-Income Countries.
  • 2021
  • In: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 4:12
  • Journal article (peer-reviewed)abstract
    • Stress may increase the risk of cardiovascular disease (CVD). Most studies on stress and CVD have been conducted in high-income Western countries, but whether stress is associated with CVD in other settings has been less well studied.To investigate the association of a composite measure of psychosocial stress and the development of CVD events and mortality in a large prospective study involving populations from 21 high-, middle-, and low-income countries across 5 continents.This population-based cohort study used data from the Prospective Urban Rural Epidemiology study, collected between January 2003 and March 2021. Participants included individuals aged 35 to 70 years living in 21 low-, middle-, and high-income countries. Data were analyzed from April 8 to June 15, 2021.All participants were assessed on a composite measure of psychosocial stress assessed at study entry using brief questionnaires concerning stress at work and home, major life events, and financial stress.The outcomes of interest were stroke, major coronary heart disease (CHD), CVD, and all-cause mortality.A total of 118706 participants (mean [SD] age 50.4 [9.6] years; 69842 [58.8%] women and 48864 [41.2%] men) without prior CVD and with complete baseline and follow-up data were included. Of these, 8699 participants (7.3%) reported high stress, 21797 participants (18.4%) reported moderate stress, 34958 participants (29.4%) reported low stress, and 53252 participants (44.8%) reported no stress. High stress, compared with no stress, was more likely with younger age (mean [SD] age, 48.9 [8.9] years vs 51.1 [9.8] years), abdominal obesity (2981 participants [34.3%] vs 10599 participants [19.9%]), current smoking (2319 participants [26.7%] vs 10477 participants [19.7%]) and former smoking (1571 participants [18.1%] vs 3978 participants [7.5%]), alcohol use (4222 participants [48.5%] vs 13222 participants [24.8%]), and family history of CVD (5435 participants [62.5%] vs 20255 participants [38.0%]). During a median (IQR) follow-up of 10.2 (8.6-11.9) years, a total of 7248 deaths occurred. During the course of follow-up, there were 5934 CVD events, 4107 CHD events, and 2880 stroke events. Compared with no stress and after adjustment for age, sex, education, marital status, location, abdominal obesity, hypertension, smoking, diabetes, and family history of CVD, as the level of stress increased, there were increases in risk of death (low stress: hazard ratio [HR], 1.09 [95% CI, 1.03-1.16]; high stress: 1.17 [95% CI, 1.06-1.29]) and CHD (low stress: HR, 1.09 [95% CI, 1.01-1.18]; high stress: HR, 1.24 [95% CI, 1.08-1.42]). High stress, but not low or moderate stress, was associated with CVD (HR, 1.22 [95% CI, 1.08-1.37]) and stroke (HR, 1.30 [95% CI, 1.09-1.56]) after adjustment.This cohort study found that higher psychosocial stress, measured as a composite score of self-perceived stress, life events, and financial stress, was significantly associated with mortality as well as with CVD, CHD, and stroke events.
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34.
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35.
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36.
  • Yusuf, Salim, et al. (author)
  • Modifiable risk factors, cardiovascular disease, and mortality in 155722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study.
  • 2020
  • In: Lancet (London, England). - 1474-547X. ; 395:10226, s. 795-808
  • Journal article (peer-reviewed)abstract
    • Global estimates of the effect of common modifiable risk factors on cardiovascular disease and mortality are largely based on data from separate studies, using different methodologies. The Prospective Urban Rural Epidemiology (PURE) study overcomes these limitations by using similar methods to prospectively measure the effect of modifiable risk factors on cardiovascular disease and mortality across 21 countries (spanning five continents) grouped by different economic levels.In this multinational, prospective cohort study, we examined associations for 14 potentially modifiable risk factors with mortality and cardiovascular disease in 155722 participants without a prior history of cardiovascular disease from 21 high-income, middle-income, or low-income countries (HICs, MICs, or LICs). The primary outcomes for this paper were composites of cardiovascular disease events (defined as cardiovascular death, myocardial infarction, stroke, and heart failure) and mortality. We describe the prevalence, hazard ratios (HRs), and population-attributable fractions (PAFs) for cardiovascular disease and mortality associated with a cluster of behavioural factors (ie, tobacco use, alcohol, diet, physical activity, and sodium intake), metabolic factors (ie, lipids, blood pressure, diabetes, obesity), socioeconomic and psychosocial factors (ie, education, symptoms of depression), grip strength, and household and ambient pollution. Associations between risk factors and the outcomes were established using multivariable Cox frailty models and using PAFs for the entire cohort, and also by countries grouped by income level. Associations are presented as HRs and PAFs with 95% CIs.Between Jan 6, 2005, and Dec 4, 2016, 155722 participants were enrolled and followed up for measurement of risk factors. 17249 (11·1%) participants were from HICs, 102680 (65·9%) were from MICs, and 35793 (23·0%) from LICs. Approximately 70% of cardiovascular disease cases and deaths in the overall study population were attributed to modifiable risk factors. Metabolic factors were the predominant risk factors for cardiovascular disease (41·2% of the PAF), with hypertension being the largest (22·3% of the PAF). As a cluster, behavioural risk factors contributed most to deaths (26·3% of the PAF), although the single largest risk factor was a low education level (12·5% of the PAF). Ambient air pollution was associated with 13·9% of the PAF for cardiovascular disease, although different statistical methods were used for this analysis. In MICs and LICs, household air pollution, poor diet, low education, and low grip strength had stronger effects on cardiovascular disease or mortality than in HICs.Most cardiovascular disease cases and deaths can be attributed to a small number of common, modifiable risk factors. While some factors have extensive global effects (eg, hypertension and education), others (eg, household air pollution and poor diet) vary by a country's economic level. Health policies should focus on risk factors that have the greatest effects on averting cardiovascular disease and death globally, with additional emphasis on risk factors of greatest importance in specific groups of countries.Full funding sources are listed at the end of the paper (see Acknowledgments).
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