PeerJ Preprints: Internal Medicinehttps://peerj.com/preprints/index.atom?journal=peerj&subject=5200Internal Medicine articles published in PeerJ PreprintsPossibility of understanding metabolic syndrome by probing dysregulation of metabolic and signaling network in bacteriahttps://peerj.com/preprints/277382019-05-162019-05-16Wenfa Ng
High fat diet and high glucose intake are commonly associated with incidence of metabolic syndrome that includes high cholesterol and diabetes. But how the two factors interplay in mediating diabetes remain poorly understood. While animal models could be used to probe the above hypothesized interplay between high fat diet and high glucose intake in mediating diabetes incidence, complex genetic background of the mammalian system seriously hamper the deciphering of the interconnection between phenotype and genes through analysis of functional genomic and epidemiological data. Furthermore, given the high conservation of central carbon metabolism across species between the three domains of life, what are analogs of the effects of high fat and high sugar diets in prokaryotic systems and what metabolic syndromes do they manifest? This work sought to trace the evolutionary ancestry of diabetes and high cholesterol syndrome as manifested in mammalian cells in prokaryotic systems. Using Escherichia coli as model organism, this work would heterologously express genes and pathways involved in mammalian fat metabolism in E. coli to help understand how a combined high fat and high glucose diet would interact in mediating prokaryotic version of diabetes and high cholesterol syndrome. Insights such as what are the genes differentially expressed during metabolization of high sugar and high fat diet by bacterial cells would hopefully inform the search for mammalian genes that predispose to metabolic syndrome by illuminating hitherto unknown genes and pathways implicated in the disease. But, what is perhaps more interesting from a fundamental perspective in this work is the search for suitable metabolic networks in which to study the prokaryotic version of diabetes and high cholesterol. Could it be overflow metabolism induced by high glucose uptake by E. coli? Or could activation of an enhanced lipid recycling pathway serve as a response to high fat infusion in bacteria? More importantly, could the manifested effects of high fat and high sugar diet be vertically inherited in bacteria similar to the incurable high cholesterol and diabetes in mammalian systems? Specifically, does manifestation of diabetes in bacteria results from epigenetic changes that mistune metabolic pathway and networks in an inheritable fashion? Finally, experiments with different types of substrates could be employed to examine the relative impact of high fat diet and high glucose intake on the extent in which central carbon metabolism in E. coli would be disturbed. Collectively, heterologous expression of mammalian genes involved in fat metabolism in E. coli opens a path to the exploration of prokaryotic version of high cholesterol and diabetes. But, what is perhaps more intriguing is tracing the evolutionary pathway that connects dysregulated sugar and fat metabolism in bacteria to their homologous clinical manifestations in mammalian systems.
High fat diet and high glucose intake are commonly associated with incidence of metabolic syndrome that includes high cholesterol and diabetes. But how the two factors interplay in mediating diabetes remain poorly understood. While animal models could be used to probe the above hypothesized interplay between high fat diet and high glucose intake in mediating diabetes incidence, complex genetic background of the mammalian system seriously hamper the deciphering of the interconnection between phenotype and genes through analysis of functional genomic and epidemiological data. Furthermore, given the high conservation of central carbon metabolism across species between the three domains of life, what are analogs of the effects of high fat and high sugar diets in prokaryotic systems and what metabolic syndromes do they manifest? This work sought to trace the evolutionary ancestry of diabetes and high cholesterol syndrome as manifested in mammalian cells in prokaryotic systems. Using Escherichia coli as model organism, this work would heterologously express genes and pathways involved in mammalian fat metabolism in E. coli to help understand how a combined high fat and high glucose diet would interact in mediating prokaryotic version of diabetes and high cholesterol syndrome. Insights such as what are the genes differentially expressed during metabolization of high sugar and high fat diet by bacterial cells would hopefully inform the search for mammalian genes that predispose to metabolic syndrome by illuminating hitherto unknown genes and pathways implicated in the disease. But, what is perhaps more interesting from a fundamental perspective in this work is the search for suitable metabolic networks in which to study the prokaryotic version of diabetes and high cholesterol. Could it be overflow metabolism induced by high glucose uptake by E. coli? Or could activation of an enhanced lipid recycling pathway serve as a response to high fat infusion in bacteria? More importantly, could the manifested effects of high fat and high sugar diet be vertically inherited in bacteria similar to the incurable high cholesterol and diabetes in mammalian systems? Specifically, does manifestation of diabetes in bacteria results from epigenetic changes that mistune metabolic pathway and networks in an inheritable fashion? Finally, experiments with different types of substrates could be employed to examine the relative impact of high fat diet and high glucose intake on the extent in which central carbon metabolism in E. coli would be disturbed. Collectively, heterologous expression of mammalian genes involved in fat metabolism in E. coli opens a path to the exploration of prokaryotic version of high cholesterol and diabetes. But, what is perhaps more intriguing is tracing the evolutionary pathway that connects dysregulated sugar and fat metabolism in bacteria to their homologous clinical manifestations in mammalian systems.Crowdsourcing in medical research: theory and practicehttps://peerj.com/preprints/273312018-11-082018-11-08Joseph TuckerSuzanne DayWeiming TangBarry Bayus
The field of crowdsourcing for medicine has substantially expanded. We define crowdsourcing as an organization having a large group attempt to solve community problem, then share the solution with the broader public. Large groups of individuals can participate in medical research through open contests, hackathons, and related activities. The purpose of this literature review is to examine the definition, theory, and practice of crowdsourcing in medicine in order to facilitate crowdsourcing research. This multi-disciplinary review defines crowdsourcing for health, identifies theoretical antecedents (collective intelligence and open source models), and explores implications of the approach. Several critiques of crowdsourcing are also examined. Although several crowdsourcing definitions exist, there are two essential elements: (1) having a large group of individuals, including experts and non-experts, propose potential solutions; (2) sharing solutions with the public through implementation or open access materials. The public can be a central force in framing a common problem and developing feasible and compelling solutions. Crowdsourcing is related to, but distinct from other participatory research approaches. Crowdsourcing can be a useful for informing medical research, programs, and policy. A growing evidence base suggests that crowdsourcing in medicine can result in high-quality outcomes, broad community engagement, and more open science.
The field of crowdsourcing for medicine has substantially expanded. We define crowdsourcing as an organization having a large group attempt to solve community problem, then share the solution with the broader public. Large groups of individuals can participate in medical research through open contests, hackathons, and related activities. The purpose of this literature review is to examine the definition, theory, and practice of crowdsourcing in medicine in order to facilitate crowdsourcing research. This multi-disciplinary review defines crowdsourcing for health, identifies theoretical antecedents (collective intelligence and open source models), and explores implications of the approach. Several critiques of crowdsourcing are also examined. Although several crowdsourcing definitions exist, there are two essential elements: (1) having a large group of individuals, including experts and non-experts, propose potential solutions; (2) sharing solutions with the public through implementation or open access materials. The publiccan be a central force in framing a common problem and developing feasible and compelling solutions. Crowdsourcing is related to, but distinct from other participatory research approaches. Crowdsourcing can be a useful for informing medical research, programs, and policy. A growing evidence base suggests that crowdsourcing in medicine can result in high-quality outcomes, broad community engagement, and more open science.Flexible piecewise linear model for investigating dose-response relationship in meta-analysis: methodology, examples, and comparisonhttps://peerj.com/preprints/272772018-10-152018-10-15Chang XuLehana ThabaneTong-Zu LiuLing LiSayem BorhanXin Sun
Objectives: Dose-response meta-analysis (DRMA) is widely employed to establishing the potential dose-response relationship between continuous exposures and disease outcomes. However, no method is readily available for exploring the relation between a discrete exposure and a binary or continuous outcome. We proposed a piecewise linear (PL) DRMA model as a solution to this issue.
Methods: We illustrated the methodology of PL model in both one-stage DRMA approach and two-stage DRMA approach. The method by testing the equality of slopes of each piecewise was employed to judge if there is “piecewise effect” against simple linear trend. We then used sleep (continuous exposure) and parity (discrete exposure) data as examples to illustrate how to apply PL model in DRMA using the Stata code attached. We also empirically compared the slopes of PL model with simple linear as well as restricted cubic spline (RCS) model.
Results: Both one-stage and two-stage PL DRMA model fitted well in our examples, and the results were similar. Obvious “piecewise effects” were detected in both the two examples by the method we used. In our example, the PL model showed better fitting effect and practical reliable results compared to simple linear model, while similar results for to RCS model.
Conclusion: Piecewise linear function is a simple and valid method for DRMA and can be used for discrete exposures. It also represents a superior model to linear model in DRMA and may be an alternative model to non-linear model.
Objectives: Dose-response meta-analysis (DRMA) is widely employed to establishing the potential dose-response relationship between continuous exposures and disease outcomes. However, no method is readily available for exploring the relation between a discrete exposure and a binary or continuous outcome. We proposed a piecewise linear (PL) DRMA model as a solution to this issue.Methods: We illustrated the methodology of PL model in both one-stage DRMA approach and two-stage DRMA approach. The method by testing the equality of slopes of each piecewise was employed to judge if there is “piecewise effect” against simple linear trend. We then used sleep (continuous exposure) and parity (discrete exposure) data as examples to illustrate how to apply PL model in DRMA using the Stata code attached. We also empirically compared the slopes of PL model with simple linear as well as restricted cubic spline (RCS) model.Results: Both one-stage and two-stage PL DRMA model fitted well in our examples, and the results were similar. Obvious “piecewise effects” were detected in both the two examples by the method we used. In our example, the PL model showed better fitting effect and practical reliable results compared to simple linear model, while similar results for to RCS model.Conclusion: Piecewise linear function is a simple and valid method for DRMA and can be used for discrete exposures. It also represents a superior model to linear model in DRMA and may be an alternative model to non-linear model.Type II diabetes may affect stem cell niche resulting in down regulation of glucose transporters and insulin receptors in cellshttps://peerj.com/preprints/270242018-07-062018-07-06Wenfa Ng
Characterized by high blood glucose concentration, resistance of cells to glucose uptake and reduced insulin sensitivity, Type II diabetes is a major health problem afflicting both developing and developed countries in increasing extent as populations around the world increasing adopt high energy diets. Given that, in Type II diabetes, successive generations of various cell types in the body ranging from muscles, tissues, blood, and organs are resistant to glucose uptake and exhibited reduced sensitivity to insulin, the underlying aetiology of Type II diabetes might involve the altered gene expression of stem cells in stem cell niches that adapted to a high glucose diet through an evolutionary conserved mechanism that aimed at homeostasis. Specifically, faced with a high energy and high sugar diet, stem cells in stem cell niches around the body possibly activated an evolutionary conserved mechanism aimed at reducing glucose uptake by cells for reducing weight gain by the body. Thus, successive generations of cells generated from the stem cell niche would exhibit an epigenetically controlled programme of gene expression that exhibited down regulation of genes for glucose transporters and insulin receptors. Such cells would display a phenotype of reduced glucose uptake together with reduced sensitivity to insulin; thereby, resulting in a high blood glucose concentration characteristic of Type II diabetes. The above hypothesis helped explain why high sugar intake by the body could result in impaired sensitivity to insulin and reduced glucose uptake by cells, and more importantly, the widespread nature in which many cell types (principally muscle cells) are affected by a possible epigenetically controlled gene expression programme which hitherto appeared clinically irreversible. Specifically, the most important clinical question for diabetes treatment and care remains the reasons underlying the clinically observed irreversible nature of the disease that progressively, with age and poor glucose control, worsens with complications to many organs of the body such as the eyes, kidneys, cardiovascular system and brain (stroke). Interested readers are invited to expand on the ideas presented in this abstract preprint.
Characterized by high blood glucose concentration, resistance of cells to glucose uptake and reduced insulin sensitivity, Type II diabetes is a major health problem afflicting both developing and developed countries in increasing extent as populations around the world increasing adopt high energy diets. Given that, in Type II diabetes, successive generations of various cell types in the body ranging from muscles, tissues, blood, and organs are resistant to glucose uptake and exhibited reduced sensitivity to insulin, the underlying aetiology of Type II diabetes might involve the altered gene expression of stem cells in stem cell niches that adapted to a high glucose diet through an evolutionary conserved mechanism that aimed at homeostasis. Specifically, faced with a high energy and high sugar diet, stem cells in stem cell niches around the body possibly activated an evolutionary conserved mechanism aimed at reducing glucose uptake by cells for reducing weight gain by the body. Thus, successive generations of cells generated from the stem cell niche would exhibit an epigenetically controlled programme of gene expression that exhibited down regulation of genes for glucose transporters and insulin receptors. Such cells would display a phenotype of reduced glucose uptake together with reduced sensitivity to insulin; thereby, resulting in a high blood glucose concentration characteristic of Type II diabetes. The above hypothesis helped explain why high sugar intake by the body could result in impaired sensitivity to insulin and reduced glucose uptake by cells, and more importantly, the widespread nature in which many cell types (principally muscle cells) are affected by a possible epigenetically controlled gene expression programme which hitherto appeared clinically irreversible. Specifically, the most important clinical question for diabetes treatment and care remains the reasons underlying the clinically observed irreversible nature of the disease that progressively, with age and poor glucose control, worsens with complications to many organs of the body such as the eyes, kidneys, cardiovascular system and brain (stroke). Interested readers are invited to expand on the ideas presented in this abstract preprint.The HOSPITAL score as a predictor of 30 day readmission in a university affiliated community hospitalhttps://peerj.com/preprints/20932016-06-012016-06-01Robert Robinson
Introduction Hospital readmissions are common, expensive, and a key target of the Medicare Value Based Purchasing (VBP) program. Risk assessment tools have been developed to identify patients at high risk of hospital readmission so they can be targeted for interventions aimed at reducing the rate of readmission. One such tool is the HOSPITAL score that uses 7 readily available clinical variables to predict the risk of readmission within 30 days of discharge. The HOSPITAL score has been internationally validated in large academic medical centers. This study aims to determine if the HOSPITAL score is similarly useful in a moderate sized university affiliated hospital in the midwestern United States. Materials and Methods All adult medical patients discharged from the SIU-SOM Hospitalist service from Memorial Medical Center from October 15, 2015 to March 16, 2016, were studied retrospectively to determine if the HOSPITAL score was a significant predictor of hospital readmission within 30 days. Results During the study period, 998 discharges were recorded for the SIU-SOM Hospitalist service. The analysis includes data for the 963 patients who were discharged alive. Of these patients, 118 (12%) were readmitted to the same hospital within 30 days. The patients who were readmitted were less likely to have a length of stay greater than or equal to 5 days (45% vs. 59%, p = 0.003) but were more likely to have been admitted to the hospital within the last year. A receiver operating characteristic evaluation of the HOSPITAL score for this patient population shows a C statistic of 0.762 (95% CI 0.720 - 0.805), indicating good discrimination for hospital readmission. Kaplan-Meier analysis of 30-day readmission free survival showed a significant (p < 0.001) increase in the risk of readmission in patients with a HOSPITAL score of 5 or more. Discussion This single center retrospective study indicates that the HOSPITAL score has good discriminatory ability to predict hospital readmissions within 30 days for a medical hospitalist service a university-affiliated hospital. This data for all causes of hospital readmission is comparable to the discriminatory ability of the HOSPITAL score in the international validation study (C statistics of 0.72 vs. 0.762) conducted at considerably larger hospitals (975 average beds vs 507 at Memorial Medical Center) for potentially avoidable hospital readmissions. Higher risk patients, identified as having a HOSPITAL score of 5 or more, clearly show an increased risk of hospital readmission within 30 days. Conclusions The internationally validated HOSPITAL score may be a useful tool in moderate sized community hospitals to identify patients at high risk of hospital readmission within 30 days. This easy to use scoring system using readily available data can be used as part of interventional strategies to reduce the rate of hospital readmission.
Introduction Hospital readmissions are common, expensive, and a key target of the Medicare Value Based Purchasing (VBP) program. Risk assessment tools have been developed to identify patients at high risk of hospital readmission so they can be targeted for interventions aimed at reducing the rate of readmission. One such tool is the HOSPITAL score that uses 7 readily available clinical variables to predict the risk of readmission within 30 days of discharge. The HOSPITAL score has been internationally validated in large academic medical centers. This study aims to determine if the HOSPITAL score is similarly useful in a moderate sized university affiliated hospital in the midwestern United States. Materials and Methods All adult medical patients discharged from the SIU-SOM Hospitalist service from Memorial Medical Center from October 15, 2015 to March 16, 2016, were studied retrospectively to determine if the HOSPITAL score was a significant predictor of hospital readmission within 30 days. Results During the study period, 998 discharges were recorded for the SIU-SOM Hospitalist service. The analysis includes data for the 963 patients who were discharged alive. Of these patients, 118 (12%) were readmitted to the same hospital within 30 days. The patients who were readmitted were less likely to have a length of stay greater than or equal to 5 days (45% vs. 59%, p = 0.003) but were more likely to have been admitted to the hospital within the last year. A receiver operating characteristic evaluation of the HOSPITAL score for this patient population shows a C statistic of 0.762 (95% CI 0.720 - 0.805), indicating good discrimination for hospital readmission. Kaplan-Meier analysis of 30-day readmission free survival showed a significant (p < 0.001) increase in the risk of readmission in patients with a HOSPITAL score of 5 or more. Discussion This single center retrospective study indicates that the HOSPITAL score has good discriminatory ability to predict hospital readmissions within 30 days for a medical hospitalist service a university-affiliated hospital. This data for all causes of hospital readmission is comparable to the discriminatory ability of the HOSPITAL score in the international validation study (C statistics of 0.72 vs. 0.762) conducted at considerably larger hospitals (975 average beds vs 507 at Memorial Medical Center) for potentially avoidable hospital readmissions. Higher risk patients, identified as having a HOSPITAL score of 5 or more, clearly show an increased risk of hospital readmission within 30 days. Conclusions The internationally validated HOSPITAL score may be a useful tool in moderate sized community hospitals to identify patients at high risk of hospital readmission within 30 days. This easy to use scoring system using readily available data can be used as part of interventional strategies to reduce the rate of hospital readmission. The atherosclerosis of the sinus node artery is associated with an increased history of supra-ventricular arrhythmias: A retrospective study on 541 standard coronary angiogramshttps://peerj.com/preprints/12042015-07-012015-07-01Michele M CiullaMatteo AstutiStefano Carugo
BACKGROUND: The ischemic damage of the sinus node (SN) is a well known cause of cardiac arrhythmias and can be a consequence of any flow abnormality in the sinus node artery (SNA). Accordingly we aimed this retrospective study to: 1. evaluate the suitability of the standard coronary angiography to study the SNA and 2. determine if the percentage of subjects with a positive retrospective history of supra-ventricular arrhythmias (SVA) differs in patients with normal and diseased SNA ascertained at the time of coronary angiography. METHODS and RESULTS: out of the 541 coronary angiograms reviewed the SNA was visible for its entire course in 486 cases (89.8%). It was found to arise from the right side of the coronary circulation in 266 cases (54.7%) slightly more often than from the left, 219 cases (45.1%). One patient had 2 distinct SNA arising from either side of the coronary circulation. For the second objective we studied the 333 patients with: a. coronary artery disease (CAD), b. properly evaluable SNA and c. complete clinical history available. In 51 (15.3%) a SNA disease was found, the 41.2% of them had a positive SVA history, mainly atrial fibrillation (AF), whereas only the 7.4% of patients with a positive history of SVA could be found in the non-SNA diseased. This difference was statistically significant (P< 0.001). CONCLUSIONS: 1- The evaluation of the SNA is feasible in clinical practice during a standard coronary angiography; 2- this may be relevant since angiographically detectable SNA disease was significantly associated with a positive history of SVA .
BACKGROUND: The ischemic damage of the sinus node (SN) is a well known cause of cardiac arrhythmias and can be a consequence of any flow abnormality in the sinus node artery (SNA). Accordingly we aimed this retrospective study to: 1. evaluate the suitability of the standard coronary angiography to study the SNA and 2. determine if the percentage of subjects with a positive retrospective history of supra-ventricular arrhythmias (SVA) differs in patients with normal and diseased SNA ascertained at the time of coronary angiography. METHODS and RESULTS: out of the 541 coronary angiograms reviewed the SNA was visible for its entire course in 486 cases (89.8%). It was found to arise from the right side of the coronary circulation in 266 cases (54.7%) slightly more often than from the left, 219 cases (45.1%). One patient had 2 distinct SNA arising from either side of the coronary circulation. For the second objective we studied the 333 patients with: a. coronary artery disease (CAD), b. properly evaluable SNA and c. complete clinical history available. In 51 (15.3%) a SNA disease was found, the 41.2% of them had a positive SVA history, mainly atrial fibrillation (AF), whereas only the 7.4% of patients with a positive history of SVA could be found in the non-SNA diseased. This difference was statistically significant (P< 0.001). CONCLUSIONS: 1- The evaluation of the SNA is feasible in clinical practice during a standard coronary angiography; 2- this may be relevant since angiographically detectable SNA disease was significantly associated with a positive history of SVA .Metabolic syndrome in hospitalized patients with chronic obstructive pulmonary diseasehttps://peerj.com/preprints/10222015-05-012015-05-01Evgeni MekovYanina SlavovaAdelina TsakovaMarianka GenovaDimitar KostadinovDelcho MinchevDora Marinova
The metabolic syndrome (MS) affects 21-53% of patients with chronic obstructive pulmonary disease (COPD) with a higher prevalence in the early stages of COPD, with results being highly variable between studies. MS may also correlate with disease characteristics. The aim of the study is to examine the prevalence of MS and its correlation with comorbidities and COPD characteristics in patients with COPD admitted for exacerbation. 152 patients with COPD admitted for exacerbation were studied for presence of MS. All of them were also assessed for vitamin D status and diabetes mellitus type 2 (DM). Data were gathered for smoking status and exacerbations during the last year. All patients completed CAT (COPD assessment test) and mMRC (Modified Medical Research Council Dyspnea scale) questionnaires and underwent spirometry. Duration of current hospital stay was recorded. 25% of patients have MS. 23,1% of the male and 29,5% of the female patients have MS (p>0.05). The prevalence of MS in this study is significantly lower when compared to a national representative study (44,6% in subjects over 45 years). 69,1% of all patients and 97,4% from MS patients have arterial hypertension. The presence of MS is associated with significantly worse cough and sleep (1st and 7th CAT questions; p=0.002 and p=0.001 respectively) and higher total CAT score (p=0.017). Average BMI is 27,31. None of the patients have MS and BMI <25. There is a correlation between the presence of MS and DM (p=0.008) and with the number of exacerbations in the last year (p=0.015). There is no correlation between the presence of MS and the pulmonary function. This study among hospitalized COPD patients finds comparable but relatively low prevalence of MS (25%) compared to previously published data (21-53%) and lower prevalence compared to general population (44,6%). MS may impact natural course and the number of exacerbations of COPD. Having in mind that MS is more common in the early stages and decreases with COPD progression, the COPD patients admitted for exacerbation may be considered as having advanced COPD.
The metabolic syndrome (MS) affects 21-53% of patients with chronic obstructive pulmonary disease (COPD) with a higher prevalence in the early stages of COPD, with results being highly variable between studies. MS may also correlate with disease characteristics. The aim of the study is to examine the prevalence of MS and its correlation with comorbidities and COPD characteristics in patients with COPD admitted for exacerbation. 152 patients with COPD admitted for exacerbation were studied for presence of MS. All of them were also assessed for vitamin D status and diabetes mellitus type 2 (DM). Data were gathered for smoking status and exacerbations during the last year. All patients completed CAT (COPD assessment test) and mMRC (Modified Medical Research Council Dyspnea scale) questionnaires and underwent spirometry. Duration of current hospital stay was recorded. 25% of patients have MS. 23,1% of the male and 29,5% of the female patients have MS (p>0.05). The prevalence of MS in this study is significantly lower when compared to a national representative study (44,6% in subjects over 45 years). 69,1% of all patients and 97,4% from MS patients have arterial hypertension. The presence of MS is associated with significantly worse cough and sleep (1st and 7th CAT questions; p=0.002 and p=0.001 respectively) and higher total CAT score (p=0.017). Average BMI is 27,31. None of the patients have MS and BMI <25. There is a correlation between the presence of MS and DM (p=0.008) and with the number of exacerbations in the last year (p=0.015). There is no correlation between the presence of MS and the pulmonary function. This study among hospitalized COPD patients finds comparable but relatively low prevalence of MS (25%) compared to previously published data (21-53%) and lower prevalence compared to general population (44,6%). MS may impact natural course and the number of exacerbations of COPD. Having in mind that MS is more common in the early stages and decreases with COPD progression, the COPD patients admitted for exacerbation may be considered as having advanced COPD.Staphylococcus Aureus carriage and long-term Rituximab treatment for Granulomatosis with polyangiitishttps://peerj.com/preprints/9722015-04-102015-04-10Emilio BesadaWenche KoldingsnesJohannes C Nossent
Objective: Chronic nasal carriage of Staphylococcus aureus (SA) increases the risk of relapse while Rituximab (RTX) is an effective agent for inducing and maintaining remission in patients with Granulomatosis with polyangiitis (GPA). We investigated whether B cell depletion and hypogammaglobulinemia that occur during RTX treatment increase the risk of chronic SA nasal carriage and subsequent disease flares, in GPA patients on long-term RTX maintenance therapy. Methods: Retrospective cohort study from a disease registry involving 29 GPA patients receiving RTX maintenance (median RTX dose of 9 g) during a median period of 49 months. Nasal swabs were collected prior and during RTX for a median of 3 and 9 swabs respectively. Persistent SA nasal carriage was defined with the presence of SA in more than 75 % of nasal swabs. Results: SA nasal carriage did not change during RTX (p=0.297). Persistent SA nasal carriage did not increase the risk of relapses (p=0.844) and of severe infections (p=0.144), but reduced the risk of chronic infections (p=0.044). Non-SA carriers were more prone to discontinue RTX due to hypogammaglobulinemia (p=0.122), since they had more profound decline of serum total Ig both after the first 2 g of RTX (p=0.079) and during RTX maintenance (p=0.063). Conclusion: Long-term RTX maintenance therapy in GPA patients did not significantly influence SA nasal carriage status. Persistent SA carriage during long-term RTX treatment did not increase the risk of relapses and was associated with a lower risk of hypogammaglobulinemia associated chronic infections.
Objective: Chronic nasal carriage of Staphylococcus aureus (SA) increases the risk of relapse while Rituximab (RTX) is an effective agent for inducing and maintaining remission in patients with Granulomatosis with polyangiitis (GPA). We investigated whether B cell depletion and hypogammaglobulinemia that occur during RTX treatment increase the risk of chronic SA nasal carriage and subsequent disease flares, in GPA patients on long-term RTX maintenance therapy. Methods: Retrospective cohort study from a disease registry involving 29 GPA patients receiving RTX maintenance (median RTX dose of 9 g) during a median period of 49 months. Nasal swabs were collected prior and during RTX for a median of 3 and 9 swabs respectively. Persistent SA nasal carriage was defined with the presence of SA in more than 75 % of nasal swabs. Results: SA nasal carriage did not change during RTX (p=0.297). Persistent SA nasal carriage did not increase the risk of relapses (p=0.844) and of severe infections (p=0.144), but reduced the risk of chronic infections (p=0.044). Non-SA carriers were more prone to discontinue RTX due to hypogammaglobulinemia (p=0.122), since they had more profound decline of serum total Ig both after the first 2 g of RTX (p=0.079) and during RTX maintenance (p=0.063). Conclusion: Long-term RTX maintenance therapy in GPA patients did not significantly influence SA nasal carriage status. Persistent SA carriage during long-term RTX treatment did not increase the risk of relapses and was associated with a lower risk of hypogammaglobulinemia associated chronic infections.Diabetes mellitus type 2 in hospitalized patients with chronic obstructive pulmonary diseasehttps://peerj.com/preprints/9392015-03-312015-03-31Evgeni MekovYanina SlavovaMarianka GenovaAdelina TsakovaDimitar KostadinovDelcho MinchevDora Marinova
Diabetes mellitus (DM) affects 2-37% of patients with chronic obstructive pulmonary disease (COPD), with results being highly variable between studies. DM may also correlate with disease characteristics.The aim of this study was to examine the prevalence of DM and its correlation with comorbidities and COPD characteristics in patients with COPD admitted for exacerbation. 152 patients were studied for presence of DM. All of them were also assessed for vitamin D status and metabolic syndrome (MS). Data were gathered for smoking status and exacerbations during the last year. All patients completed CAT (COPD assessment test) and mMRC (Modified Medical Research Council Dyspnea scale) questionnaires and underwent spirometry. Duration of current hospital stay was recorded. 13.2% (20/152) of patients are taking medications for DM. Additional 21.7% (33/152) have newly discovered DM and 30.9% (47/152) have prediabetes. Only 34.2% of the studied patients do not have DM or prediabetes. 37% (40/108) of males have DM vs. 29,5% (13/44) of females (p=0.379). The prevalence of DM in this study is significantly higher when compared to an unselected Bulgarian population (12,8% in subjects over 45 years). 91% of patients with newly discovered diabetes had glycated hemoglobin (HbA1c)≥6,5% suggesting prolonged hyperglycemia. There is a correlation between the presence of DM and MS (p=0.008). The presence of DM is associated with more severe exacerbations (hospitalizations) during the previous year (p=0.003) and a longer hospital stay (p=0.006). DM is not associated with reduced quality of life and worse pulmonary function. The patients with COPD admitted for exacerbation are at great risk for impaired glucose metabolism which is associated with worse COPD characteristics. The majority of the patients in this study are unaware of having DM.
Diabetes mellitus (DM) affects 2-37% of patients with chronic obstructive pulmonary disease (COPD), with results being highly variable between studies. DM may also correlate with disease characteristics.The aim of this study was to examine the prevalence of DM and its correlation with comorbidities and COPD characteristics in patients with COPD admitted for exacerbation. 152 patients were studied for presence of DM. All of them were also assessed for vitamin D status and metabolic syndrome (MS). Data were gathered for smoking status and exacerbations during the last year. All patients completed CAT (COPD assessment test) and mMRC (Modified Medical Research Council Dyspnea scale) questionnaires and underwent spirometry. Duration of current hospital stay was recorded. 13.2% (20/152) of patients are taking medications for DM. Additional 21.7% (33/152) have newly discovered DM and 30.9% (47/152) have prediabetes. Only 34.2% of the studied patients do not have DM or prediabetes. 37% (40/108) of males have DM vs. 29,5% (13/44) of females (p=0.379). The prevalence of DM in this study is significantly higher when compared to an unselected Bulgarian population (12,8% in subjects over 45 years). 91% of patients with newly discovered diabetes had glycated hemoglobin (HbA1c)≥6,5% suggesting prolonged hyperglycemia. There is a correlation between the presence of DM and MS (p=0.008). The presence of DM is associated with more severe exacerbations (hospitalizations) during the previous year (p=0.003) and a longer hospital stay (p=0.006). DM is not associated with reduced quality of life and worse pulmonary function. The patients with COPD admitted for exacerbation are at great risk for impaired glucose metabolism which is associated with worse COPD characteristics. The majority of the patients in this study are unaware of having DM.Objective pain sensitivity affects sleep quality in opioid dependent males on methadone maintenance therapyhttps://peerj.com/preprints/615v12014-11-172014-11-17Zalina ZahariChee Siong LeeSoo Choon TanNasir MohamadYeong Yeh LeeRusli Ismail
Aim Pain associated poor sleep quality has been reported among opioid dependent patients on methadone maintenance therapy (MMT) but objective pain data are lacking. This study aimed to investigate the rate of objective pain sensitivity and the relationship between pain sensitivity and sleep quality in this susceptible male population. Methods A total of 168 male patients from MMT clinic in Kelantan, Malaysia were included into the study. Objective pain tolerance to cold pressor test (CPT) was evaluated at 0 hour and at 24 hours after the first CPT. Malay version of the Pittsburgh Sleep Quality Index – PSQI and the subjective opiate withdrawal scale (SOWS) questionnaires were administered to evaluate the quality of sleep and withdrawal symptoms, respectively. Results The mean age of the study participants was 37.22 (SD 6.20) years old. The mean daily methadone dose was 76.64 (SD 37.63) mg/day. The mean averaged SOWS score was 5.43 (SD 6.91). The averaged pain tolerance time ranged from 7 to 300 s with a mean time of 32.16 (SE 2.72) s, slightly below the cut-off score of 37.53 s. More specifically, 78.6% (n = 132) of patients were identified as ‘pain-sensitive’ (averaged pain tolerance time ≤ 37.53 s), and 36 (21.4%) were ‘pain-tolerant’ patients (averaged pain tolerance time > 37.53 s). The mean global PSQI score was 5.47 (SD 2.74). The pain-sensitive patients reported poorer sleep quality with mean (SD) of 5.78 (2.80) compared with pain-tolerant patients with mean (SD) of 4.31 (2.18) (p = 0.005). With analysis of covariance, pain-sensitive patients were found to have higher global PSQI scores (adjusted mean 5.76, 95% CI 5.29; 6.22) than pain-tolerant patients (adjusted mean 4.42, 95% CI 3.52; 5.32) (p = 0.010). Conclusions Many opioid dependent male patients on MMT are pain-sensitive. A poorer sleep quality is associated with objective pain sensitivity. Pain and sleep complaints in this susceptible population should not be overlooked.
Aim Pain associated poor sleep quality has been reported among opioid dependent patients on methadone maintenance therapy (MMT) but objective pain data are lacking. This study aimed to investigate the rate of objective pain sensitivity and the relationship between pain sensitivity and sleep quality in this susceptible male population. Methods A total of 168 male patients from MMT clinic in Kelantan, Malaysia were included into the study. Objective pain tolerance to cold pressor test (CPT) was evaluated at 0 hour and at 24 hours after the first CPT. Malay version of the Pittsburgh Sleep Quality Index – PSQI and the subjective opiate withdrawal scale (SOWS) questionnaires were administered to evaluate the quality of sleep and withdrawal symptoms, respectively. Results The mean age of the study participants was 37.22 (SD 6.20) years old. The mean daily methadone dose was 76.64 (SD 37.63) mg/day. The mean averaged SOWS score was 5.43 (SD 6.91). The averaged pain tolerance time ranged from 7 to 300 s with a mean time of 32.16 (SE 2.72) s, slightly below the cut-off score of 37.53 s. More specifically, 78.6% (n = 132) of patients were identified as ‘pain-sensitive’ (averaged pain tolerance time ≤ 37.53 s), and 36 (21.4%) were ‘pain-tolerant’ patients (averaged pain tolerance time > 37.53 s). The mean global PSQI score was 5.47 (SD 2.74). The pain-sensitive patients reported poorer sleep quality with mean (SD) of 5.78 (2.80) compared with pain-tolerant patients with mean (SD) of 4.31 (2.18) (p = 0.005). With analysis of covariance, pain-sensitive patients were found to have higher global PSQI scores (adjusted mean 5.76, 95% CI 5.29; 6.22) than pain-tolerant patients (adjusted mean 4.42, 95% CI 3.52; 5.32) (p = 0.010). Conclusions Many opioid dependent male patients on MMT are pain-sensitive. A poorer sleep quality is associated with objective pain sensitivity. Pain and sleep complaints in this susceptible population should not be overlooked.