49 research outputs found

    Prevalence of Therapeutic use of Opioids in Chronic non-Cancer Pain Patients and Associated Factors: A Systematic Review and Meta-Analysis

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    Objectives: To determine the prevalence and factors associated with the use of opioids among patients with chronic non-cancer pain (CNCP). Methods: A systematic review and meta-analysis. Comprehensive literature searches in Medline-PubMed, Embase and SCOPUS databases. Original studies published between 2009 and 2019 with a cross-sectional design were included. The quality of the studies was assessed with Critical Appraisal Checklist for Studies Reporting Prevalence Data from the Joanna Briggs Institute. Protocol registered in the International Prospective Register of Systematic Reviews with reference number: CRD42019137990. Results: Out of the 1,310 potential studies found, 25 studies fulfilled the inclusion criteria. Most of the studies were of high quality. High levels of heterogeneity were found in the studies included. In the general population, the prevalence of long-term opioid use was 2.3% (95% CI: 1.5-3.6%), the prevalence of short-term opioid use was 8.1% (95% CI: 5.6-11.6%), and among people with chronic low back pain it was 5.8% (95% CI: 0.5-45.5%). The prevalence of opioid use among patients from the health records or medical surveys was 41% (95% CI: 23.3-61.3%). Finally, in patients with musculoskeletal pain, the prevalence was 20.5% (95% CI: 12.9-30.9%) and in patients with fibromyalgia, 24.5% (95% CI: 22.9-26.2%). A higher prevalence of opioid use was observed among men, younger people, patients receiving prescriptions of different types of drugs, smokers and patients without insurance or with noncommercial insurance. In addition, non-white and Asian patients were less likely to receive opioids than non-Hispanic white patients. Conclusions: The prevalence of opioid use among patients with CNCP was higher in subjects with short or occasional use compared to those with long-term use. Men, younger people, more chronic pain conditions, and patients without insurance or with noncommercial insurance were most related to opioid use. However, non-white and Asian patients, and those treated by a physician trained in complementary medicine were less likely to use opioids

    Genetic polymorphisms of innate immunity-related inflammatory pathways and their association with factors related to type 2 diabetes

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    Abstract Background Type 2 diabetes mellitus (T2DM) has been linked to a state of pre-clinical chronic inflammation resulting from abnormalities in the innate immune pathway. Serum levels of pro-inflammatory cytokines and acute-phase proteins, collectively known as 'inflammatory network', are elevated in the pre-, or early, stages of T2DM and increase with disease progression. Genetic variation can affect the innate immune response to certain environmental factors, and may, therefore, determine an individual's lifetime risk of disease. Methods We conducted a cross-sectional study in 6,720 subjects from the TwinsUK Registry to evaluate the association between 18 single nucleotide polymorphisms (SNPs) in five genes (TLR4, IL1A, IL6, TNFA, and CRP) along the innate immunity-related inflammatory pathway and biomarkers of predisposition to T2DM [fasting insulin and glucose, HDL- and LDL- cholesterols, triglycerides (TGs), amyloid-A, sensitive C-reactive protein (sCRP) and vitamin D binding protein (VDBP) and body mass index (BMI)]. Results Of 18 the SNPs examined for their association with nine metabolic phenotypes of interest, six were significantly associated with five metabolic phenotypes (Bonferroni correction, P ≀ 0.0027). Fasting insulin was associated with SNPs in IL6 and TNFA, serum HDL-C with variants of TNFA and CRP and serum sCRP level with SNPs in CRP. Cross-correlation analysis among the different metabolic factors related to risk of T2DM showed several significant associations. For example, BMI was directly correlated with glucose (r = 0.11), insulin (r = 0.15), sCRP (r = 0.23), LDL-C (r = 0.067) and TGs (r = 0.18) but inversely with HDL-C (r = -0.14). sCRP was also positively correlated (P < 0.0001) with insulin (r = 0.17), amyloid-A (r = 0.39), TGs (r = 0.26), and VDBP (r = 0.36) but inversely with HDL-C (r = -0.12). Conclusion Genetic variants in the innate immunity pathway and its related inflammatory cascade is associated with some metabolic risk factors for T2DM; an observation that may provide a rationale for further studying their role as biomarkers for disease early risk prediction

    Reduced-intensity Transplantation For Lymphomas Using Haploidentical Related Donors Versus Hla-matched Sibling Donors: A Center For International Blood And Marrow Transplant Research Analysis

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    Purpose: Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. Materials and Methods: We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versus-host disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor-based GVHD prophylaxis. Results: Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). Conclusion: Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD

    Autologous transplantation versus allogeneic transplantation in patients with follicular lymphoma experiencing early treatment failure.

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    BACKGROUND Early treatment failure (ETF) in follicular lymphoma (FL), defined as relapse or progression within 2 years of frontline chemoimmunotherapy, is a newly recognized marker of poor survival and identifies a high-risk group of patients with an expected 5-year overall survival (OS) rate of approximately 50%. Transplantation is an established option for relapsed FL, but its efficacy in this specific ETF FL population has not been previously evaluated. METHODS This study compared autologous hematopoietic stem cell transplantation (auto-HCT) with either matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo-HCT) as the first transplantation approach for patients with ETF FL (age ≄ 18 years) undergoing auto-HCT or allo-HCT between 2002 and 2014. The primary endpoint was OS. The secondary endpoints were progression-free survival, relapse, and nonrelapse mortality (NRM). RESULTS Four hundred forty FL patients had ETF (auto-HCT, 240; MSD hematopoietic stem cell transplantation [HCT], 105; and MUD HCT, 95). With a median follow-up of 69 to 73 months, the adjusted probability of 5-year OS was significantly higher after auto-HCT (70%) or MSD HCT (73%) versus MUD HCT (49%; P = .0008). The 5-year adjusted probability of NRM was significantly lower for auto-HCT (5%) versus MSD (17%) or MUD HCT (33%; P < .0001). The 5-year adjusted probability of disease relapse was lower with MSD (31%) or MUD HCT (23%) versus auto-HCT (58%; P < .0001). CONCLUSIONS Patients with high-risk FL, as defined by ETF, undergoing auto-HCT for FL have low NRM and a promising 5-year OS rate (70%). MSD HCT has lower relapse rates than auto-HCT but similar OS. Cancer 2018;124:2541-51. © 2018 American Cancer Society

    A model for homeopathic remedy effects: low dose nanoparticles, allostatic cross-adaptation, and time-dependent sensitization in a complex adaptive system

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    BACKGROUND: This paper proposes a novel model for homeopathic remedy action on living systems. Research indicates that homeopathic remedies (a) contain measurable source and silica nanoparticles heterogeneously dispersed in colloidal solution; (b) act by modulating biological function of the allostatic stress response network (c) evoke biphasic actions on living systems via organism-dependent adaptive and endogenously amplified effects; (d) improve systemic resilience. DISCUSSION: The proposed active components of homeopathic remedies are nanoparticles of source substance in water-based colloidal solution, not bulk-form drugs. Nanoparticles have unique biological and physico-chemical properties, including increased catalytic reactivity, protein and DNA adsorption, bioavailability, dose-sparing, electromagnetic, and quantum effects different from bulk-form materials. Trituration and/or liquid succussions during classical remedy preparation create “top-down” nanostructures. Plants can biosynthesize remedy-templated silica nanostructures. Nanoparticles stimulate hormesis, a beneficial low-dose adaptive response. Homeopathic remedies prescribed in low doses spaced intermittently over time act as biological signals that stimulate the organism’s allostatic biological stress response network, evoking nonlinear modulatory, self-organizing change. Potential mechanisms include time-dependent sensitization (TDS), a type of adaptive plasticity/metaplasticity involving progressive amplification of host responses, which reverse direction and oscillate at physiological limits. To mobilize hormesis and TDS, the remedy must be appraised as a salient, but low level, novel threat, stressor, or homeostatic disruption for the whole organism. Silica nanoparticles adsorb remedy source and amplify effects. Properly-timed remedy dosing elicits disease-primed compensatory reversal in direction of maladaptive dynamics of the allostatic network, thus promoting resilience and recovery from disease. SUMMARY: Homeopathic remedies are proposed as source nanoparticles that mobilize hormesis and time-dependent sensitization via non-pharmacological effects on specific biological adaptive and amplification mechanisms. The nanoparticle nature of remedies would distinguish them from conventional bulk drugs in structure, morphology, and functional properties. Outcomes would depend upon the ability of the organism to respond to the remedy as a novel stressor or heterotypic biological threat, initiating reversals of cumulative, cross-adapted biological maladaptations underlying disease in the allostatic stress response network. Systemic resilience would improve. This model provides a foundation for theory-driven research on the role of nanomaterials in living systems, mechanisms of homeopathic remedy actions and translational uses in nanomedicine

    Genetic polymorphisms of innate immunity-related inflammatory pathways and their association with factors related to type 2 diabetes

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    BACKGROUND: Type 2 diabetes mellitus (T2DM) has been linked to a state of pre-clinical chronic inflammation resulting from abnormalities in the innate immune pathway. Serum levels of pro-inflammatory cytokines and acute-phase proteins, collectively known as 'inflammatory network', are elevated in the pre-, or early, stages of T2DM and increase with disease progression. Genetic variation can affect the innate immune response to certain environmental factors, and may, therefore, determine an individual's lifetime risk of disease. METHODS: We conducted a cross-sectional study in 6,720 subjects from the TwinsUK Registry to evaluate the association between 18 single nucleotide polymorphisms (SNPs) in five genes (TLR4, IL1A, IL6, TNFA, and CRP) along the innate immunity-related inflammatory pathway and biomarkers of predisposition to T2DM [fasting insulin and glucose, HDL- and LDL- cholesterols, triglycerides (TGs), amyloid-A, sensitive C-reactive protein (sCRP) and vitamin D binding protein (VDBP) and body mass index (BMI)]. RESULTS: Of 18 the SNPs examined for their association with nine metabolic phenotypes of interest, six were significantly associated with five metabolic phenotypes (Bonferroni correction, P ≀ 0.0027). Fasting insulin was associated with SNPs in IL6 and TNFA, serum HDL-C with variants of TNFA and CRP and serum sCRP level with SNPs in CRP. Cross-correlation analysis among the different metabolic factors related to risk of T2DM showed several significant associations. For example, BMI was directly correlated with glucose (r = 0.11), insulin (r = 0.15), sCRP (r = 0.23), LDL-C (r = 0.067) and TGs (r = 0.18) but inversely with HDL-C (r = -0.14). sCRP was also positively correlated (P < 0.0001) with insulin (r = 0.17), amyloid-A (r = 0.39), TGs (r = 0.26), and VDBP (r = 0.36) but inversely with HDL-C (r = -0.12). CONCLUSION: Genetic variants in the innate immunity pathway and its related inflammatory cascade is associated with some metabolic risk factors for T2DM; an observation that may provide a rationale for further studying their role as biomarkers for disease early risk prediction

    Serological Response of Shiga Toxin-Producing Escherichia coli Type III Secreted Proteins in Sera from Vaccinated Rabbits, Naturally Infected Cattle, and Humans ▿ †

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    Escherichia coli O157:H7 is an important zoonotic pathogen, causing hemolytic uremic syndrome (HUS). The colonization of cattle and human hosts is mediated through the action of effectors secreted via a type III secretion system (T3SS). The structural genes for the T3SS and many of the secreted effectors are located on a pathogenicity island called the locus of enterocyte effacement (LEE). We cloned and expressed the genes coding for 66 effectors and purified each to measure the cross-reactivity of type III secreted proteins from Shiga toxin-producing Escherichia coli (STEC) serotypes. These included 37 LEE-encoded proteins and 29 non-LEE effectors. The serological response against each protein was measured by Western blot analysis and enzyme-linked immunosorbent assay (ELISA) using sera from rabbits immunized with type III secreted proteins (T3SPs) from four STEC serotypes, experimentally infected cattle, and human sera from six HUS patients. Twenty proteins were recognized by at least one of the STEC T3SP-vaccinated rabbits by Western blotting. Several structural proteins (EspA, EspB, and EspD) and a number of effectors (Tir, NleA, and TccP) were recognized by O26-, O103-, O111-, and O157-specific sera. Sera from experimentally infected cattle and HUS patients were tested using an ELISA against each of the proteins. Tir, EspB, EspD, EspA, and NleA were recognized by the majority of the samples tested. A number of other proteins also were recognized by individual serum samples. Overall, proteins such as Tir, EspB, EspD, NleA, and EspA were highly immunogenic in vaccinated and naturally infected subjects and could be candidates for a cross-protective STEC vaccine

    Plasma vitamin D levels and risk of metabolic syndrome in Canadians

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    Purpose: Vitamin D deficiency has been implicated in susceptibility to the development of metabolic syndrome, obesity and type 2 diabetes mellitus. The present study aimed to quantify the association between vitamin D plasma level, the number of metabolic syndrome components and insulin resistance in Canadians. Methods: Vitamin D plasma level and clinical data were determined from 1,818 subjects from the Canadian Health Measures Survey; a representative health survey of the general population of Canada conducted from 2007 to 2009. The definition of metabolic syndrome was based on the National Cholesterol Education Program, Adult Treatment Panel III criteria. Adjusted general linear models were used to estimate the association between vitamin D level and probability of having metabolic syndrome, as well as the association between plasma vitamin D and insulin resistance (homeostasis model assessment for insulin resistance, or HOMA-IR). Results: The prevalence of metabolic syndrome in the study population was 8.9%. The number of metabolic syndrome components was inversely correlated with plasma vitamin D level (ρ= -0.1, p < 0.0001). Subjects in the highest vitamin D quartile had lower odds ratio of metabolic syndrome compared with their counterparts in the lowest vitamin D quartile (0.50, 95% CI= 0.24-1.06). Increasing plasma vitamin D level (by 10 nmol/L) was inversely associated with HOMA-IR score (ÎČ= -0.08, p=0.006) in a model adjusted for physical activity, smoking status, month of interview, age, sex and ethnicity. Conclusion: Vitamin D plasma levels are associated with the occurrence of metabolic syndrome components and insulin resistance among Canadians and are linked to increased level of insulin resistance

    Quantitation of 55 Common Human Plasma Proteins in Healthy Young Adults and Correlation with Body Mass Index and Dietary Patterns

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    Plasma biomarkers are a useful tool for monitoring dietary exposures and the development of chronic disease. Measuring multiple biomarkers at once provides a more complete characterization of phenotype than measuring single markers. Certain dietary patterns have been associated with increased risk of obesity. Adhering to a &#x2018;Western&#x2019; dietary pattern, characterized by high consumption of meat products and low fruit and vegetable consumption, may put individuals at a higher risk of becoming overweight or obese than a &#x2018;Prudent&#x2019; or an &#x2018;Eastern&#x2019; dietary pattern. A novel mass spectrometry-based multiple reaction monitoring (MRM) proteomics assay was used to quantitate 55 common plasma proteins that have been linked to chronic disease. We measured the concentrations of these proteins in 1088 participants of the Toronto Nutrigenomics and Health (TNH) study, an ethnically diverse population of young adults. Our goals were: 1) to explore clustering patterns within the protein panel; 2) to investigate whether protein cluster scores differ between normal weight (BMI&#x3c;25) and overweight/obese (BMI&#x2265;25) individuals; and 3) to determine whether protein cluster scores differ between &#x2018;Prudent&#x2019;, &#x2018;Western&#x2019; and &#x2018;Eastern&#x2019; dietary patterns. Four principal components (PC) account for most of the variability in the protein profiles, with eigenvalues ranging from 22.3 (PC 1) to 2.9 (PC 4). Significant differences were observed in the average loading scores between normal weight and overweight/obese individuals for PCs 2 and 3. In particular, PC3 scores were significantly higher among those with BMI&#x2265;25. Linear regression adjusted for age, sex, ethnicity, physical activity and total caloric intake showed significant associations between dietary intake and PCs 1, 2 and 3. PCs 1 and 3 were positively associated with the &#x2018;Western&#x2019; dietary pattern, and PC1 was also inversely associated with the &#x2018;Eastern&#x2019; pattern. PC 2 was positively associated with the &#x2018;Eastern&#x2019; dietary pattern. These results suggest a relationship between the examined panel of protein biomarkers, BMI and certain dietary patterns. Future analyses will assess the biological relevance of these results

    Genome sequence of adherent-invasive Escherichia coli and comparative genomic analysis with other E. coli pathotypes

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    <p>Abstract</p> <p>Background</p> <p>Adherent and invasive <it>Escherichia coli </it>(AIEC) are commonly found in ileal lesions of Crohn's Disease (CD) patients, where they adhere to intestinal epithelial cells and invade into and survive in epithelial cells and macrophages, thereby gaining access to a typically restricted host niche. Colonization leads to strong inflammatory responses in the gut suggesting that AIEC could play a role in CD immunopathology. Despite extensive investigation, the genetic determinants accounting for the AIEC phenotype remain poorly defined. To address this, we present the complete genome sequence of an AIEC, revealing the genetic blueprint for this disease-associated <it>E. coli </it>pathotype.</p> <p>Results</p> <p>We sequenced the complete genome of <it>E. coli </it>NRG857c (O83:H1), a clinical isolate of AIEC from the ileum of a Crohn's Disease patient. Our sequence data confirmed a phylogenetic linkage between AIEC and extraintestinal pathogenic <it>E. coli </it>causing urinary tract infections and neonatal meningitis. The comparison of the NRG857c AIEC genome with other pathogenic and commensal <it>E. coli </it>allowed for the identification of unique genetic features of the AIEC pathotype, including 41 genomic islands, and unique genes that are found only in strains exhibiting the adherent and invasive phenotype.</p> <p>Conclusions</p> <p>Up to now, the virulence-like features associated with AIEC are detectable only phenotypically. AIEC genome sequence data will facilitate the identification of genetic determinants implicated in invasion and intracellular growth, as well as enable functional genomic studies of AIEC gene expression during health and disease.</p
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