Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat ...Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes,(e.g., giving unprotected enzymes at the start of the mealand acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy.展开更多
Interactions between BabA and Lewis b (Leb) related antigens are the best characterized adhesin-receptor interactions in Helicobacter pylori (H pylori). Several mechanisms for the regulation of BabA expression are pre...Interactions between BabA and Lewis b (Leb) related antigens are the best characterized adhesin-receptor interactions in Helicobacter pylori (H pylori). Several mechanisms for the regulation of BabA expression are predicted, including at both transcriptional and translational levels. The formation of chimeric proteins (babA /B or babB /A chimeras) seems to play an especially important role in translational regulation. Chimeric BabB/A protein had the potential to bind Leb; however, protein production was subject to phase variation through slipped strand mispairing. The babA gene was cloned initially from strain CCUG17875, which contains a silent babA1 gene and an expressed babA2 gene. The sequence of these two genes differs only by the presence of a 10 bp deletion in the signal peptide sequence of babA1 that eliminates its translational initiation codon. However, the babA1 type deletion was found only in strain CCUG17875. A few studies evaluated BabA status by immunoblot and confirmed that BabA-positive status in Western strains was closely associated with severe clinical outcomes. BabA-positive status also was associated with the presence of other virulence factors (e.g. cagA-positive status and vacA s1 genotype). A small class of strains produced low levels of the BabA protein and lacked Leb binding activity. These were more likely to be associated with increased mucosal inflammation and severe clinical outcomes than BabA-positive strains that exhibited Leb binding activity. The underlying mechanism is unclear, and further studies will be necessary to investigate how the complex BabA-receptor network is functionally coordinated during the interaction of H pylori with the gastric mucosa.展开更多
Nearly one fourth of individuals with human immunodeficiency virus (HIV) infection have hepatitis C virus (HCV) infection in the US and Western Europe. With the availability of highly active antiretroviral therapy and...Nearly one fourth of individuals with human immunodeficiency virus (HIV) infection have hepatitis C virus (HCV) infection in the US and Western Europe. With the availability of highly active antiretroviral therapy and the consequent reduction in opportunistic infections, resulting in the prolongation of the life span of HIV-infected patients, HCV co-infection has emerged as a signif icant factor influencing the survival of HIV patients. Patients with HIV/HCV co-infection have a faster rate of fibrosis progression resulting in more frequent occurrences of cirrhosis, end-stage liver disease, and hepatocellular carcinoma. However, the mechanism of interaction between the two viruses is not completely understood. The treatment for HCV in co-infected patients is similar to that of HCV monoinfection; i.e., a combination of pegylated interferon and ribavirin. The presence of any barriers to antiHCV therapy should be identified and eliminated in order to recruit all eligible patients. The response to treatment in co-infected patients is inferior compared to the response in patients with HCV mono-infection. The sustained virologic response rate is only 38% for genotype-1 and 75% for genotype-2 and -3 infections. Liver transplantation is no longer considered a contraindication for end-stage liver disease in coinfected patients. However, the 5 year survival rate is lower in co-infected patients compared to patients with HCV mono-infection (33% vs 72%, P = 0.07). A better understanding of liver disease in co-infected patients is needed to derive new strategies for improving outcome and survival.展开更多
Background: The association of body mass index and gastroesophageal reflux disease (CERD), including its complications (esophagitis, Barrett esophagus, and esophageal adenocarcinoma), is unclear. Purpose: To conduct a...Background: The association of body mass index and gastroesophageal reflux disease (CERD), including its complications (esophagitis, Barrett esophagus, and esophageal adenocarcinoma), is unclear. Purpose: To conduct a systematic review and meta- analysis to estimate the magnitude and determinants of an association between obesity and GERD symptoms, erosive esophagitis, Barrett esophagus, and adenocarcinoma of the esophagus and of the gastric cardia. Data Sources: MEDLINE search between 1966 and October 2004 for published full studies. Study Selection: Studies that provided risk estimates and met criteria on defining exposure and reporting outcomes and sample size. Data Extraction: Two investigators independently performed standardized search and data abstraction. Unadjusted and adjusted odds ratios for individual outcomes were obtained or calculated for each study and were pooled by using a random- effects model. Data Synthesis: Nine studies examined the association of body mass index (BMI) with GERD symptoms. Six of these studies found statistically significant associations. Six of 7 studies found significant associations of BMI with erosive esophagitis, 6 of 7 found significant associations with esophageal adenocarcinoma, and 4 of 6 found significant associations with gastric cardia adenocarcinoma. In data from 8 studies, there was a trend toward a dose- response relationship with an increase in the pooled adjusted odds ratios for GERD symptoms of 1.43 (95% CI, 1.158 to 1.774) for BMI of 25 kg/m2 to 30 kg/m2 and 1.94 (CI, 1.468 to 2.566) for BMI greater than 30 kg/m 2. Similarly, the pooled adjusted odds ratios for esophageal adenocarcinoma for BMI of 25 kg/m2 to 30 kg/m2 and BMI greater than 30 kg/m2 were 1.52 (CI, 1.147 to 2.009) and 2.78 (CI, 1.850 to 4.164), respectively. Limitations: Heterogeneity in the findings was present, although it was mostly in the magnitude of statistically significant positive associations. No studies in this review examined the association between Barrett esophagus and obesity. Conclusion: Obesity is associated with a statistically significant increase in the risk for CERD symptoms, erosive esophagitis, and esophageal adenocarcinoma. The risk for these disorders seems to progressively increase with increasing weight.展开更多
Background &Aims: Our objective was to assess adherence to evidence-based guidelines by providers of the Department of Veterans Affairs nationwide. Methods: This was a cross-sectional study among veterans prescrib...Background &Aims: Our objective was to assess adherence to evidence-based guidelines by providers of the Department of Veterans Affairs nationwide. Methods: This was a cross-sectional study among veterans prescribed a nonsteroidal anti-inflammatory drug (NSAID) from January 1, 2002, to December 31, 2002. Prescrip tion data were linked to inpatient and outpatient medical records and death file s. The population was characterized as high risk based on the following: age 65 years or older, concurrent corticosteroid or anticoagulant use, history of pepti c ulcer, and high average daily dose of NSAIDs. Adherence was defined as the pre scription of a traditional NSAID with gastroprotection or a coxib in high-risk NSAID users. Univariate and multivariate analyses assessed the potential predict ors of adherence. Results: Three hundred three thousand seven hundred eighty-se ven met our definition of high risk. Most (97.3%) were male; 55.6%were white, 9.6%black, and 34.8%of other/unknown race. Age 65 years or older was the large st high-risk subset (87.1%). Overall, only 27.2%of highrisk veterans (n = 82, 766) were prescribed an adherent strategy. Among veterans with at least 2 risk f actors, adherence was 39.7%; among those with 3 risk factors, adherence was 41. 8%. Predictors of adherence included history of upper gastrointestinal events, anticoagulant use, rheumatologic disease, high Deyo comorbidity index score, use of low-dose salicylates, and concurrent corticosteroid use. Predictors of nona dherence included prescriptions≥90 days and high average daily dose of NSAIDs. Conclusions: Adherence to evidence-based guidelines for safe prescription of NS AIDs in the Department of Veterans Affairs is low (27.2%). The likelihood of ad herence is further decreased if veterans are prescribed NSAIDs for ≥90 days.展开更多
Chronic hepatitis B virus(CHB)infection affects approximately 250 million persons worldwide(1).CHB is a major risk factor for liver failure,cirrhosis,and hepatocellular carcinoma(HCC),accounting for 45-55%of HCC cases...Chronic hepatitis B virus(CHB)infection affects approximately 250 million persons worldwide(1).CHB is a major risk factor for liver failure,cirrhosis,and hepatocellular carcinoma(HCC),accounting for 45-55%of HCC cases(1).The incidence rates of HCC among CHB patients are 0.02-0.2 per 100 person-years in inactive carriers,0.3-0.6 per 100 person-years in those without cirrhosis,and 2.2-3.7 per 100 person-years for those with compensated cirrhosis(2).展开更多
On April 13,2021,the US Centers for Disease Control and Prevention(CDC)and the US Food and Drug Administration(FDA)recommended a pause in administration of the Ad26.COV2.S(Johnson&Johnson[Janssen])coronavirus dise...On April 13,2021,the US Centers for Disease Control and Prevention(CDC)and the US Food and Drug Administration(FDA)recommended a pause in administration of the Ad26.COV2.S(Johnson&Johnson[Janssen])coronavirus disease 2019(COVID-19)vaccine for all persons[1].At that time,approximately 6.8 million doses of vaccine had been administered around the United States.The pause was prompted by 6 cases of cerebral venous sinus thrombosis(CVST)in combination with thrombocytopenia,a condition whose nomenclature is in flux but which we will refer to as thrombosis with thrombocytopenia syndrome(TTS),as used by CDC in describing the condition[2].All patients were women younger than 50 years.Of note,2 of 6 patients also had splanchnic and portal vein thrombosis.展开更多
Objectives The objective of our study was to evaluate the impact of a multifaceted stewardship intervention on adherence to the evidence-based practice guidelines on treatment of uncomplicated cystitis in primary care...Objectives The objective of our study was to evaluate the impact of a multifaceted stewardship intervention on adherence to the evidence-based practice guidelines on treatment of uncomplicated cystitis in primary care.We hypothesised that our intervention would increase guideline adherence in terms of antibiotic choice and duration of treatment.Design A preintervention and postintervention comparison with a contemporaneous control group was performed.During the first two study periods,we obtained baseline data and performed interviews exploring provider prescribing decisions for cystitis at both clinics.During the third period in the intervention clinic only,the intervention included a didactic lecture,a decision algorithm and audit and feedback.We used a difference-in differences analysis to determine the effects of our intervention on the outcome and guideline adherence to antibiotic choice and duration.Setting Two family medicine clinics(one intervention and one control)were included.Participants All female patients with uncomplicated cystitis attending the study clinics between 2016 and 2019.Results Our sample included 932 visits representing 812 unique patients with uncomplicated cystitis.The proportion of guideline-adherent antibiotic regimens increased during the intervention period(from 33.2%(95%CI 26.9 to 39.9)to 66.9%(95%CI 58.4 to 74.6)in the intervention site and from 5.3%(95%CI 2.3 to 10.1)to 17.0%(95%CI 9.9 to 26.6)in the control site).The increase in guideline adherence was greater in the intervention site compared with the control site with a difference-in differences of 22 percentage points,p=0.001.Conclusion A multifaceted intervention increased guideline adherence for antibiotic choice and duration in greater magnitude than similar trends at the control site.Future research is needed to facilitate scale-up and sustainability of case-based audit and feedback interventions in primary care.展开更多
基金Supported by The Office of Research and Development Medical Research Service Department of Veterans Affairs,Public Health Service grants No.DK067366 and No.DK56338 which funds the Texas Medical Center Digestive Diseases Center
文摘Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes,(e.g., giving unprotected enzymes at the start of the mealand acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy.
基金(in part) National Institutes of Health Grants, R01 DK62813
文摘Interactions between BabA and Lewis b (Leb) related antigens are the best characterized adhesin-receptor interactions in Helicobacter pylori (H pylori). Several mechanisms for the regulation of BabA expression are predicted, including at both transcriptional and translational levels. The formation of chimeric proteins (babA /B or babB /A chimeras) seems to play an especially important role in translational regulation. Chimeric BabB/A protein had the potential to bind Leb; however, protein production was subject to phase variation through slipped strand mispairing. The babA gene was cloned initially from strain CCUG17875, which contains a silent babA1 gene and an expressed babA2 gene. The sequence of these two genes differs only by the presence of a 10 bp deletion in the signal peptide sequence of babA1 that eliminates its translational initiation codon. However, the babA1 type deletion was found only in strain CCUG17875. A few studies evaluated BabA status by immunoblot and confirmed that BabA-positive status in Western strains was closely associated with severe clinical outcomes. BabA-positive status also was associated with the presence of other virulence factors (e.g. cagA-positive status and vacA s1 genotype). A small class of strains produced low levels of the BabA protein and lacked Leb binding activity. These were more likely to be associated with increased mucosal inflammation and severe clinical outcomes than BabA-positive strains that exhibited Leb binding activity. The underlying mechanism is unclear, and further studies will be necessary to investigate how the complex BabA-receptor network is functionally coordinated during the interaction of H pylori with the gastric mucosa.
文摘Nearly one fourth of individuals with human immunodeficiency virus (HIV) infection have hepatitis C virus (HCV) infection in the US and Western Europe. With the availability of highly active antiretroviral therapy and the consequent reduction in opportunistic infections, resulting in the prolongation of the life span of HIV-infected patients, HCV co-infection has emerged as a signif icant factor influencing the survival of HIV patients. Patients with HIV/HCV co-infection have a faster rate of fibrosis progression resulting in more frequent occurrences of cirrhosis, end-stage liver disease, and hepatocellular carcinoma. However, the mechanism of interaction between the two viruses is not completely understood. The treatment for HCV in co-infected patients is similar to that of HCV monoinfection; i.e., a combination of pegylated interferon and ribavirin. The presence of any barriers to antiHCV therapy should be identified and eliminated in order to recruit all eligible patients. The response to treatment in co-infected patients is inferior compared to the response in patients with HCV mono-infection. The sustained virologic response rate is only 38% for genotype-1 and 75% for genotype-2 and -3 infections. Liver transplantation is no longer considered a contraindication for end-stage liver disease in coinfected patients. However, the 5 year survival rate is lower in co-infected patients compared to patients with HCV mono-infection (33% vs 72%, P = 0.07). A better understanding of liver disease in co-infected patients is needed to derive new strategies for improving outcome and survival.
文摘Background: The association of body mass index and gastroesophageal reflux disease (CERD), including its complications (esophagitis, Barrett esophagus, and esophageal adenocarcinoma), is unclear. Purpose: To conduct a systematic review and meta- analysis to estimate the magnitude and determinants of an association between obesity and GERD symptoms, erosive esophagitis, Barrett esophagus, and adenocarcinoma of the esophagus and of the gastric cardia. Data Sources: MEDLINE search between 1966 and October 2004 for published full studies. Study Selection: Studies that provided risk estimates and met criteria on defining exposure and reporting outcomes and sample size. Data Extraction: Two investigators independently performed standardized search and data abstraction. Unadjusted and adjusted odds ratios for individual outcomes were obtained or calculated for each study and were pooled by using a random- effects model. Data Synthesis: Nine studies examined the association of body mass index (BMI) with GERD symptoms. Six of these studies found statistically significant associations. Six of 7 studies found significant associations of BMI with erosive esophagitis, 6 of 7 found significant associations with esophageal adenocarcinoma, and 4 of 6 found significant associations with gastric cardia adenocarcinoma. In data from 8 studies, there was a trend toward a dose- response relationship with an increase in the pooled adjusted odds ratios for GERD symptoms of 1.43 (95% CI, 1.158 to 1.774) for BMI of 25 kg/m2 to 30 kg/m2 and 1.94 (CI, 1.468 to 2.566) for BMI greater than 30 kg/m 2. Similarly, the pooled adjusted odds ratios for esophageal adenocarcinoma for BMI of 25 kg/m2 to 30 kg/m2 and BMI greater than 30 kg/m2 were 1.52 (CI, 1.147 to 2.009) and 2.78 (CI, 1.850 to 4.164), respectively. Limitations: Heterogeneity in the findings was present, although it was mostly in the magnitude of statistically significant positive associations. No studies in this review examined the association between Barrett esophagus and obesity. Conclusion: Obesity is associated with a statistically significant increase in the risk for CERD symptoms, erosive esophagitis, and esophageal adenocarcinoma. The risk for these disorders seems to progressively increase with increasing weight.
文摘Background &Aims: Our objective was to assess adherence to evidence-based guidelines by providers of the Department of Veterans Affairs nationwide. Methods: This was a cross-sectional study among veterans prescribed a nonsteroidal anti-inflammatory drug (NSAID) from January 1, 2002, to December 31, 2002. Prescrip tion data were linked to inpatient and outpatient medical records and death file s. The population was characterized as high risk based on the following: age 65 years or older, concurrent corticosteroid or anticoagulant use, history of pepti c ulcer, and high average daily dose of NSAIDs. Adherence was defined as the pre scription of a traditional NSAID with gastroprotection or a coxib in high-risk NSAID users. Univariate and multivariate analyses assessed the potential predict ors of adherence. Results: Three hundred three thousand seven hundred eighty-se ven met our definition of high risk. Most (97.3%) were male; 55.6%were white, 9.6%black, and 34.8%of other/unknown race. Age 65 years or older was the large st high-risk subset (87.1%). Overall, only 27.2%of highrisk veterans (n = 82, 766) were prescribed an adherent strategy. Among veterans with at least 2 risk f actors, adherence was 39.7%; among those with 3 risk factors, adherence was 41. 8%. Predictors of adherence included history of upper gastrointestinal events, anticoagulant use, rheumatologic disease, high Deyo comorbidity index score, use of low-dose salicylates, and concurrent corticosteroid use. Predictors of nona dherence included prescriptions≥90 days and high average daily dose of NSAIDs. Conclusions: Adherence to evidence-based guidelines for safe prescription of NS AIDs in the Department of Veterans Affairs is low (27.2%). The likelihood of ad herence is further decreased if veterans are prescribed NSAIDs for ≥90 days.
文摘Chronic hepatitis B virus(CHB)infection affects approximately 250 million persons worldwide(1).CHB is a major risk factor for liver failure,cirrhosis,and hepatocellular carcinoma(HCC),accounting for 45-55%of HCC cases(1).The incidence rates of HCC among CHB patients are 0.02-0.2 per 100 person-years in inactive carriers,0.3-0.6 per 100 person-years in those without cirrhosis,and 2.2-3.7 per 100 person-years for those with compensated cirrhosis(2).
文摘On April 13,2021,the US Centers for Disease Control and Prevention(CDC)and the US Food and Drug Administration(FDA)recommended a pause in administration of the Ad26.COV2.S(Johnson&Johnson[Janssen])coronavirus disease 2019(COVID-19)vaccine for all persons[1].At that time,approximately 6.8 million doses of vaccine had been administered around the United States.The pause was prompted by 6 cases of cerebral venous sinus thrombosis(CVST)in combination with thrombocytopenia,a condition whose nomenclature is in flux but which we will refer to as thrombosis with thrombocytopenia syndrome(TTS),as used by CDC in describing the condition[2].All patients were women younger than 50 years.Of note,2 of 6 patients also had splanchnic and portal vein thrombosis.
基金This study was approved by the Baylor College of Medicine Institutional Review Board(IRB).The IRB protocol ID for this study is H-38265.
文摘Objectives The objective of our study was to evaluate the impact of a multifaceted stewardship intervention on adherence to the evidence-based practice guidelines on treatment of uncomplicated cystitis in primary care.We hypothesised that our intervention would increase guideline adherence in terms of antibiotic choice and duration of treatment.Design A preintervention and postintervention comparison with a contemporaneous control group was performed.During the first two study periods,we obtained baseline data and performed interviews exploring provider prescribing decisions for cystitis at both clinics.During the third period in the intervention clinic only,the intervention included a didactic lecture,a decision algorithm and audit and feedback.We used a difference-in differences analysis to determine the effects of our intervention on the outcome and guideline adherence to antibiotic choice and duration.Setting Two family medicine clinics(one intervention and one control)were included.Participants All female patients with uncomplicated cystitis attending the study clinics between 2016 and 2019.Results Our sample included 932 visits representing 812 unique patients with uncomplicated cystitis.The proportion of guideline-adherent antibiotic regimens increased during the intervention period(from 33.2%(95%CI 26.9 to 39.9)to 66.9%(95%CI 58.4 to 74.6)in the intervention site and from 5.3%(95%CI 2.3 to 10.1)to 17.0%(95%CI 9.9 to 26.6)in the control site).The increase in guideline adherence was greater in the intervention site compared with the control site with a difference-in differences of 22 percentage points,p=0.001.Conclusion A multifaceted intervention increased guideline adherence for antibiotic choice and duration in greater magnitude than similar trends at the control site.Future research is needed to facilitate scale-up and sustainability of case-based audit and feedback interventions in primary care.
