969 research outputs found

    Modelling environmental factors correlated with podoconiosis: a geospatial study of non-filarial elephantiasis

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    Introduction The precise trigger of podoconiosis — endemic non-filarial elephantiasis of the lower legs — is unknown. Epidemiological and ecological studies have linked the disease with barefoot exposure to red clay soils of volcanic origin. Histopathology investigations have demonstrated that silicon, aluminium, magnesium and iron are present in the lower limb lymph node macrophages of both patients and non-patients living barefoot on these clays. We studied the spatial variation (variations across an area) in podoconiosis prevalence and the associated environmental factors with a goal to better understanding the pathogenesis of podoconiosis. Methods Fieldwork was conducted from June 2011 to February 2013 in 12 kebeles (administrative units) in northern Ethiopia. Geo-located prevalence data and soil samples were collected and analysed along with secondary geological, topographic, meteorological and elevation data. Soil data were analysed for chemical composition, mineralogy and particle size, and were interpolated to provide spatially continuous information. Exploratory, spatial, univariate and multivariate regression analyses of podoconiosis prevalence were conducted in relation to primary (soil) and secondary (elevation, precipitation, and geology) covariates. Results Podoconiosis distribution showed spatial correlation with variation in elevation and precipitation. Exploratory analysis identified that phyllosilicate minerals, particularly clay (smectite and kaolinite) and mica groups, quartz (crystalline silica), iron oxide, and zirconium were associated with podoconiosis prevalence. The final multivariate model showed that the quantities of smectite (RR = 2.76, 95% CI: 1.35, 5.73; p = 0.007), quartz (RR = 1.16, 95% CI: 1.06, 1.26; p = 0.001) and mica (RR = 1.09, 95% CI: 1.05, 1.13; p < 0.001) in the soil had positive associations with podoconiosis prevalence. Conclusions More quantities of smectite, mica and quartz within the soil were associated with podoconiosis prevalence. Together with previous work indicating that these minerals may influence water absorption, potentiate infection and be toxic to human cells, the present findings suggest that these particles may play a role in the pathogenesis of podoconiosis and acute adenolymphangitis, a common cause of morbidity in podoconiosis patients

    Screening and Health Behaviors among Persons Diagnosed with Familial Adenomatous Polyposis and Their Relatives

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    Familial Adenomatous Polyposis (FAP) is a rare autosomal dominantly inherited colorectal cancer syndrome. Individuals with FAP often undergo colectomy and are recommended to follow several surveillance protocols. Biological relatives of persons with FAP may also be at risk and thus should undergo genetic counseling. Screening adherence, genetic testing, and other health behaviors among individuals with FAP and their relatives are not well characterized. We conducted a cross-sectional self-report survey with individuals who have FAP (n=35) and their biological relatives (n=15). Respondents were recruited through a cancer center registry for inherited colon cancers. Most relatives had undergone colon cancer screening; 40% had undergone genetic testing. One fifth of respondents with FAP had not undergone an upper endoscopy, contrary to usual recommendations. Cigarette smoking rates were above average and were higher among FAP respondents. Use of vitamin supplements was fairly common, more so among those with FAP. Although most people had been screened, there are areas for improvement, notably for upper endoscopy among individuals with FAP and genetic testing among family members. Several other health-risk behaviors and health concerns other than FAP were identified. Further research into factors contributing to screening rates and other health behaviors in this high-risk population is warranted

    Relationship separation and length of time in receipt of income support payments: a longitudinal analysis of Australian Government administrative data

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    In recent years, the Australian government has encouraged open access to administrative data, providing new opportunities to examine life course pathways and evaluate social policies, particularly those aimed at supporting minority populations such as single parent families. Expenditure on government income support in Australia is expected to rise, largely due to increasing costs associated with an ageing population and the introduction of a national disability insurance scheme, raising concerns about the long-term fiscal viability of government spending on welfare. This paper investigates the association between income support receipt and relationship breakdown using two potential sources of national data: administrative data on income support payments and the Households, Income and Labour Dynamics in Australia panel survey. A comparative approach showed that the administrative data provided much greater statistical power for detecting associations for minority groups than was possible with panel data highlighting the importance of administrative data for understanding the outcomes of such groups

    Novel APC promoter and exon 1B deletion and allelic silencing in three mutation-negative classic familial adenomatous polyposis families

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    BACKGROUND: The overwhelming majority (approximately 80%) of individuals with classic familial adenomatous polyposis (FAP) exhibit mutations in the coding sequence of the adenomatous polyposis coli (APC) tumor suppressor gene. Families without detectable APC mutations are unable to benefit from the use of genetic testing for clinical management of this autosomal dominant syndrome. METHODS: We used exome sequencing and linkage analysis, coupled with second-generation sequencing of the APC locus including non-coding regions to investigate three APC mutation-negative classical FAP families. RESULTS: We identified a novel ~11 kb deletion localized 44 kb upstream of the transcription start site of APC that encompasses the APC 1B promoter and exon. This deletion was present only in affected family members of one kindred with classical FAP. Furthermore, this same deletion with identical breakpoints was found in the probands of two additional APC mutation-negative classical FAP kindreds. Phasing analysis of single nucleotide polymorphisms (SNPs) around the deletion site in the three probands showed evidence of a shared haplotype, suggesting a common founder deletion in the three kindreds. SNP analysis within the coding sequence of APC, revealed that this ~11 kb deletion was accompanied by silencing of one of the APC alleles in blood-derived RNA of affected individuals. CONCLUSIONS: These results support the causal role of a novel promoter deletion in FAP and suggest that non-coding deletions, identifiable using second-generation sequencing methods, may account for a significant fraction of APC mutation-negative classical FAP families

    Glycaemic benefit of iGlarLixi in insulin-naive type 2 diabetes patients with high HbA1c or those with inadequate glycaemic control on two oral antihyperglycaemic drugs in the LixiLan-O randomized trial

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    In this post hoc analysis of the randomized controlled LixiLan‐O trial in insulin‐naive type 2 diabetes mellitus (T2DM) patients not controlled on metformin with or without a second oral antihyperglycaemic drug (OAD), the efficacy and safety of the fixed‐ratio combination, iGlarLixi (insulin glargine 100 U [iGlar] and lixisenatide [Lixi]), compared to its individual components was assessed in two patient subgroups: (1) a baseline HbA1c ≥9% (n = 134); (2) inadequate control (HbA1c ≥7.0% and ≤9.0%) despite administration of two OADs at screening (n = 725). Treatment with iGlarLixi resulted in a significantly greater reduction in least squares mean HbA1c compared with iGlar or Lixi alone in both subgroups (HbA1c ≥9% group: 2.9%, 2.5%, 1.7%; two OADs group: 1.5%, 1.2%, 0.7%, respectively). Target HbA1c 70% of patients on iGlarLixi in both subgroups, while mitigating the weight gain observed with iGlar alone. Rates of hypoglycaemic events were low overall. These results suggest that iGlarLixi achieves superior glycaemic control compared with iGlar or Lixi alone in T2DM patients with HbA1c ≥9% or those inadequately controlled on two OADs

    Screening and Health Behaviors among Persons Diagnosed with Familial Adenomatous Polyposis and Their Relatives

    Get PDF
    Familial Adenomatous Polyposis (FAP) is a rare autosomal dominantly inherited colorectal cancer syndrome. Individuals with FAP often undergo colectomy and are recommended to follow several surveillance protocols. Biological relatives of persons with FAP may also be at risk and thus should undergo genetic counseling. Screening adherence, genetic testing, and other health behaviors among individuals with FAP and their relatives are not well characterized. We conducted a cross-sectional self-report survey with individuals who have FAP (n = 35) and their biological relatives (n = 15). Respondents were recruited through a cancer center registry for inherited colon cancers. Most relatives had undergone colon cancer screening; 40% had undergone genetic testing. One fifth of respondents with FAP had not undergone an upper endoscopy, contrary to usual recommendations. Cigarette smoking rates were above average and were higher among FAP respondents. Use of vitamin supplements was fairly common, more so among those with FAP. Although most people had been screened, there are areas for improvement, notably for upper endoscopy among individuals with FAP and genetic testing among family members. Several other health-risk behaviors and health concerns other than FAP were identified. Further research into factors contributing to screening rates and other health behaviors in this high-risk population is warranted

    Real-life experience with ceftolozane/tazobactam in Canada: results from the CLEAR (Canadian LEadership on Antimicrobial Real-life usage) registry.

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    Objectives Ceftolozane/tazobactam is a cephalosporin/β-lactamase inhibitor combination with activity against Gram-negative bacilli. We report the use of ceftolozane/tazobactam in Canada using a national registry. Methods The CLEAR registry uses REDCapTM (Research Electronic Data Capture) (online survey, https://is.gd/CLEAR_ceftolozanetazobactam) to capture details associated with clinical use of ceftolozane/tazobactam. Results Data from 51 patients treated in 2020 with ceftolozane/tazobactam are available. Infections treated included hospital-acquired bacterial pneumonia (37.3% of patients), ventilator-associated bacterial pneumonia (15.7%), bone/joint infection (11.8%), complicated intra-abdominal infection (7.8%) and complicated skin and skin structure infection (7.8%). 17.6% of patients had bacteremia and 47.1% were in intensive care. Ceftolozane/tazobactam was primarily used as directed therapy for Pseudomonas aeruginosa infections (92.2% of patients). Ceftolozane/tazobactam was used because of resistance to (86.3%), failure of (11.7%), or adverse effects from (2.0%) previously prescribed antimicrobials. Ceftolozane/tazobactam susceptibility testing was performed on isolates from 88.2% of patients. Ceftolozane/tazobactam was used in combination with another antimicrobial active versus Gram-negative bacilli in 39.2% of patients (aminoglycosides [15.7%], fluoroquinolones [7.8%] and colistin/polymyxin B [7.8%]). The dosage regimen was customized in all patients based on their creatinine clearance. Treatment duration was primarily >10 days (60.8% of patients) with microbiological success in 60.5% and clinical success in 64.4% of patients. 7.8% of patients had adverse effects not requiring drug discontinuation. Conclusions In Canada, ceftolozane/tazobactam is used as directed therapy to treat a variety of severe infections caused MDR P. aeruginosa. It is commonly used in combination with other antimicrobials with relatively high microbiological/clinical cure rates, and an excellent safety profile

    Individual correlates of podoconiosis in areas of varying endemicity: a case-control study

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    BACKGROUND Podoconiosis is a non-filarial form of elephantiasis resulting in lymphedema of the lower legs. Previous studies have suggested that podoconiosis arises from the interplay of individual and environmental factors. Here, our aim was to understand the individual-level correlates of podoconiosis by comparing 460 podoconiosis-affected individuals and 707 unaffected controls. METHODS/PRINCIPAL FINDINGS This was a case-control study carried out in six kebeles (the lowest governmental administrative unit) in northern Ethiopia. Each kebele was classified into one of three endemicity levels: 'low' (prevalence 5%). A total of 142 (30.7%) households had two or more cases of podoconiosis. Compared to controls, the majority of the cases, especially women, were less educated (OR = 1.7, 95% CI = 1.3 to 2.2), were unmarried (OR = 3.4, 95% CI = 2.6-4.6) and had lower income (t = -4.4, p<0.0001). On average, cases started wearing shoes ten years later than controls. Among cases, age of first wearing shoes was positively correlated with age of onset of podoconiosis (r = 0.6, t = 12.5, p<0.0001). Among all study participants average duration of shoe wearing was less than 30 years. Between both cases and controls, people in 'high' and 'medium' endemicity kebeles were less likely than people in 'low' endemicity areas to 'ever' have owned shoes (OR = 0.5, 95% CI = 0.4-0.7). CONCLUSIONS Late use of shoes, usually after the onset of podoconiosis, and inequalities in education, income and marriage were found among cases, particularly among females. There were clustering of cases within households, thus interventions against podoconiosis will benefit from household-targeted case tracing. Most importantly, we identified a secular increase in shoe-wearing over recent years, which may give opportunities to promote shoe-wearing without increasing stigma among those at high risk of podoconiosis
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