Attribution of functional limitation to cancer decreases in the year following breast cancer diagnosis in older patients

Objectives

To examine the prevalence of self-reported functional limitations in a breast cancer population, identify whether these reported limitations are attributed to breast cancer versus other coexisting illnesses, and examine how this attribution changes over time from early in treatment to 9 months later.

Design

Longitudinal, observational study.

Setting

Community dwelling adults in Detroit metropolitan area.

Participants

2033 participants (1011 breast cancer patients, 1022 controls) aged 40-84 years.

Measurements

Participants were asked about each of 23 possible coexisting illnesses in addition to breast cancer and whether or not each illness, including breast cancer, caused any activity limitation.

Results

Of the 933 cancer patients who completed both baseline and follow-up evaluations, 45% were aged 65 years and older. At baseline, 56% of patients 65 years and older reported functional limitation compared with 50% of patients younger than 65 years (p = 0.005). Of those patients who reported limitation at baseline, 59% of older patients and 78% of younger patients attributed their limitation to breast cancer (p < 0.001). At follow-up, 53% of older and 37% of younger patients reported functional limitation (p < 0.001), with 27% of older patients compared with 57% of younger patients (p < 0.001) attributing limitation to breast cancer.

Conclusion

Self-reported functional limitations are common 3 months after breast cancer diagnosis, being attributed primarily to breast cancer. By 1 year after diagnosis, much of the limitation due to breast cancer resolves. Older women are less likely to have resolution of their limitations, which are most commonly due to other coexisting illnesses.     

Cross-sectional epidemiology of hepatitis C virus detection and treatment in HIV-infected patients

Background

Sustained virologic response to peginterferon plus ribavirin reduces liver-related complications and mortality in patients co-infected with HIV and hepatitis C virus. Therefore, the presence of any barriers to start hepatitis C virus therapy should be identified and eliminated in order to recruit all eligible patients.

Methods

Cross-sectional study. In a HIV referral clinic we assessed the proportion of patients eligible for hepatitis C virus evaluation and treatment according to consensus guidelines.

Results

We identified 134 patients with hepatitis C virus and HIV co-infection. Twenty-one patients were excluded from the analysis due to never attending the HIV clinic (n = 12) or having hepatitis C virus RNA not detectable (n = 9). In the remaining 113 patients, only 61% had identification of hepatitis C virus genotype and quantification of hepatitis C viral load. Thirty-six patients started peginterferon plus ribavirin, and 16 (44%) achieved sustained virologic response. Seventy-seven patients did not receive treatment for hepatitis C virus due to the presence of medical contraindications (n = 22), provider barriers (n = 15), or patient barriers (n = 40). Multivariate analysis identified lower education degree (odds ratio: 4.53; 95% confidence intervals: 1.36-15.16, p = 0.014) and patient civil status single, separated or widower (odds ratio: 4.81; 95% confidence intervals: 1.54-14.99, p = 0.007) as the independent determinants associated to not initiating therapy for hepatitis C virus infection in patients with barriers.

Conclusion

A minor proportion of HIV-infected patients received appropriate assessment and treatment for hepatitis C virus infection. Social disadvantages require multidisciplinary models of health care to improve hepatitis C virus treatment initiation and success.     

Impact of body composition, fat distribution and sustained weight loss on cardiac function in obesity

Background

Older age is an independent predictor of all-cause mortality in patients with mild to moderate heart failure (HF). Whether older age is also an independent predictor of mortality in patients with more advanced HF is unknown.

Methods

Of the 2707 Beta-Blocker Evaluation of Survival Trial (BEST) participants with ambulatory chronic HF (New York Heart Association class III/IV and left ventricular ejection fraction < 35%), 1091 were elderly (≥ 65 years). Propensity scores for older age, estimated for each of the 2707 patients, were used to assemble a cohort of 603 pairs of younger and older patients, balanced on 66 baseline characteristics.

Results

All-cause mortality occurred in 33% and 36% of younger and older matched patients respectively during 4 years of follow-up (hazard ratio {HR} associated with age ≥65 years, 1.05; 95% confidence interval {CI}, 0.87-1.27; P = 0.614). HF hospitalization occurred in 38% and 40% of younger and older matched patients respectively (HR, 1.01; 95% CI, 0.84-1.21; P = 0.951). Among 603 pairs of unmatched and unbalanced patients, all-cause mortality occurred in 28% and 36% of younger and older patients respectively (HR, 1.34; 95% CI, 1.10-1.64; P = 0.004) and HF hospitalization occurred in 34% and 40% of younger and older unmatched patients respectively (HR, 1.24; 95% CI, 1.03-1.50; P = 0.024).

Conclusion

Significant bivariate associations suggest that older age is a useful marker of poor outcomes in patients with advanced chronic systolic HF. However, lack of significant independent associations suggests that older age per se has no intrinsic effect on outcomes in these patients.     

Current and new antimicrobial agents

Background

Infections may complicate cardiovascular surgery or may require surgery as an adjunct to successful treatment. Staphylococci, which are among the major pathogenic bacteria causing such infections, can be resistant to many of the older antibiotics.

Methods

The properties of several newer antimicrobial agents, recently approved or still investigational, were reviewed, with an emphasis on in vitro activities against staphylococci.

Results

The 2 approved agents, linezolid and quinupristin-dalfopristin, and several investigational agents being developed demonstrate in vitro antimicrobial activity against staphylococci. Three of these agents, daptomycin, which was approved by the US Food and Drug Administration in September 2003, and oritavancin and dalbavancin, which are in advanced stages of clinical development, are discussed.

Conclusions

Although clinical studies are required, the in vitro anti-staphylococcal activities of several agents suggest that these antimicrobial agents might be useful options for some infections in patients who are intolerant of older antibiotics or who are infected with organisms that are resistant to older agents.     

Diabetes enhances hepatocarcinogenesis in noncirrhotic, interferon-treated hepatitis C patients

Background

This retrospective cohort study assessed the impact of diabetes mellitus on hepatocarcinogenesis and determined the predictors of hepatocarcinogenesis in noncirrhotic, interferon-treated patients with hepatitis C virus infection.

Methods

A total of 2058 hepatitis C virus-positive, noncirrhotic patients treated with interferon were enrolled. The median follow-up period was 6.7 years. The primary end point was the onset of hepatocellular carcinoma. The cumulative rate of new hepatocellular carcinoma cases was computed by the Kaplan-Meier method and Cox proportional hazard analysis according to diabetic state and response to interferon therapy.

Results

The cumulative rates of hepatocellular carcinoma in diabetic patients (3.2% at 4 years, 8.5% at 8 years, and 24.4% at 12 years) were significantly higher than those of nondiabetic patients (1.3% at 4 years, 2.2% at 8 years, and 5.6% at 12 years, P <.001). In patients with a sustained virologic response, diabetes had no significant effect on the rate of hepatocarcinogenesis. In contrast, the rate in patients with a nonsustained virologic response was significantly higher in diabetic than in nondiabetic patients. Multivariate analysis identified lack of sustained virologic response (hazard ratio [HR] 7.28; 95% confidence interval [CI], 3.28-16.15; P <.001) and diabetes as independent risk factors for hepatocarcinogenesis (HR 2.00; 95% CI, 1.05-3.84; P = .036).

Conclusions

Our results highlight the enhancing effect of diabetes mellitus on hepatocarcinogenesis in noncirrhotic, interferon-treated patients with hepatitis C virus. The sustained virologic response induced by interferon therapy eliminates the influence of diabetes and markedly reduces the rate of hepatocarcinogenesis in such patients.     

Vitamin D and cognitive functioning in the elderly population in Germany

Objectives

To examine the relationship of serum 25-hydroxy vitamin D3 with cognitive functioning in higher age, using an instrument covering multiple cognitive domains in a population-based study.

Design

Follow-up study with measurement of vitamin D levels at baseline and assessment of cognitive functioning at year 5 follow-up.

Setting and participants

A subgroup of 1639 participants of the ongoing epidemiological ESTHER study of the elderly general population in Saarland State, Germany, aged 65 + years at baseline (2000-2002).

Intervention

Observational study.

Measurements

Cognitive functioning was assessed by the COGTEL phone interview developed by Kliegel et al., which was administered 5 years after ESTHER baseline. Vitamin D in baseline samples was measured by chemiluminescence methods. Additional information was obtained by standardised questionnaires.

Results

In multiple linear regression adjusted for important confounders, women in the lowest sex-specific quintile of vitamin D showed an on average 2.1 (95% confidence interval: 0.4 to 3.9) units lower COGTEL score than women in the highest quintile. A similar, albeit slightly weaker, association was seen in males (difference of 1.7 [− 0.4 to 3.8] units). Spline regression suggested non-linearity with a distinct decline in cognitive performance in the lower range of vitamin D levels.

Conclusions

Our findings support suggestions that low levels of vitamin D may be associated with reduced cognitive functioning in the elderly.     

Viral elimination reduces incidence of malignant lymphoma in patients with hepatitis C

Purpose

A high prevalence of malignant lymphoma among patients with hepatitis C virus (HCV) infection has been reported. The aim of this retrospective study was to determine the incidence of malignant lymphoma and the relationship between malignant lymphoma and viral elimination in patients with HCV.

Method

We studied 501 consecutive HCV-infected patients who had never received interferon therapy and 2708 consecutive HCV-infected patients who received interferon therapy.

Results

In the non-interferon group, the cumulative rates of malignant lymphoma development were 0.6% at the 5th year, 2.3% at the 10th year, and 2.6% at the 15th year. The cumulative rates of malignant lymphoma development in interferon-treated patients with sustained virologic response were 0% at the 5th year, 0% at the 10th year, and 0% at the 15th year. The cumulative rates of malignant lymphoma development with persistent infection were 0.4% at the 5th year, 1.5% at the 10th year, and 2.6% at the 15th year. The malignant lymphoma development rate was higher in patients with persistent infection than in patients with sustained virologic response (P = .0159). The hazard ratio of lymphomagenesis in 1048 patients with sustained virologic response was significantly lower than in patients with persistent infection (hazard ratio: 0.13; P = .049).

Conclusion

Our retrospective study is the first to determine the annual incidence of malignant lymphoma among patients with HCV at 0.23%. Our results indicate that sustained virologic response induced by interferon therapy protects against the development of malignant lymphoma in patients with chronic HCV.     

The utility of hemoglobin A1c at diagnosis for prediction of future glycemic control in children with type 1 diabetes

Introduction

We evaluated the relationships of hemoglobin A1c (A1c) at diagnosis of type 1 diabetes (T1DM) to future glycemic control and to a series of clinical variables in children with T1DM.

Materials and methods

Patients <18 years old diagnosed with T1DM during a one year period who had an A1c at diagnosis and at least one follow-up visit at our center were eligible for inclusion. Baseline variables examined included age, race, gender, symptom duration, admission acuity, anthropometrics, bicarbonate, and A1c. Annual anthropometric and A1c data were also obtained from clinic visits through 4 years after diagnosis.

Results

We identified 120 children (53 males). Mean age at diagnosis was 7.6 ± 3.9 years. Mean A1c at diagnosis was 10.9 ± 1.9%. A1c at diagnosis correlated with age at diagnosis, symptom duration, and A1c at 3-years, with trends towards correlations at 6 weeks and 4 years. A1c at 1 year correlated highly with A1c at subsequent visits. No other baseline variables correlated with subsequent glycemic control.

Conclusions

In children with newly diagnosed diabetes, A1cs at diagnosis and one year post diagnosis are related to subsequent glycemic control. Children with high A1cs particularly at one year post diagnosis may benefit from targeted intensification of resources.     

Sex and age specific time patterns and long term time trends of pre-hospital delay of patients presenting with acute ST-segment elevation myocardial infarction

Background

Prompt initiation of treatment after symptom onset of ST-elevation myocardial infarction (STEMI) is a central goal in limiting myocardial damage because of the time-dependent nature of reperfusion therapies. We examined time patterns and long term time trends of pre-hospital delay time (PHDT) of STEMI patients.

Methods

PHDT from 3093 STEMI patients derived from the Augsburg Myocardial Infarction Registry (1985-2004) surviving > 24 h after admission was obtained by a standardized bedside interview. Patients with in-hospital MI (n = 140) and resuscitation (n = 157) were excluded. Linear regression models were used to examine monthly median PHDT and individual PHDT over time.

Results

Female sex was associated with longer PHDT (189 (98-542 quartiles) min vs. 154 (85-497) min; p < 0.0003). Median PHDT in the youngest male subgroup (25-54 years) was 128 (73-458) min and mounted to 205 (107-600) min in the oldest female subgroup (65-74 years). A minority of 12.4% of patients reached hospital within 1 h of delay ranging from 8.7% (in oldest women) to 15.9% (in youngest men).The age-adjusted linear regression model for monthly PHDT revealed no significant change over 20-year time in both sexes. The corresponding average annual percentage change estimates were −0.45 (95% CI: −1.40 to 0.54) for men and −0.08 (95% CI: −1.80 to 1.67) for women. Emergency ambulance use increased over time, however transportation time remained stable.

Conclusions

PHDT in STEMI patients is constantly high over a 20-year observation period. Room for improvement especially in older women was evidenced. Preventive strategies with focused efforts on this subgroup are warranted.     

Event-free survival in adults with heart failure who engage in self-care management

Background

Self-care management in heart failure (HF) involves decision-making to evaluate, and actions to ameliorate symptoms when they occur. This study sought to compare the risks of all-cause mortality, hospitalization, or emergency-room admission among HF patients who practice above-average self-care management, those who practice below-average self-care management, and those who are symptom-free.

Methods

A secondary analysis was conducted of data collected on 195 HF patients. A Cox proportional hazards model was used to examine the association between self-care management and event risk.

Results

The sample consisted of older (mean ± standard deviation = 61.3 ± 11 years), predominantly male (64.6%) adults, with an ejection fraction of 34.7% ± 15.3%; 60.1% fell within New York Heart Association class III or IV HF. During an average follow-up of 364 ± 288 days, 4 deaths, 82 hospitalizations, and 5 emergency-room visits occurred as first events. Controlling for 15 common confounders, those who engaged in above-average self-care management (hazard ratio, .44; 95% confidence interval, .22 to .88; P < .05) and those who were symptom-free (hazard ratio, 0.48; 95% confidence interval, .24 to .97; P < .05) ran a lower risk of an event during follow-up than those engaged in below-average self-care management.

Conclusion

Symptomatic HF patients who practice above-average self-care management have an event-free survival benefit similar to that of symptom-free HF patients.     

Left ventricular function and energy homeostasis in patients with type 1 diabetes with and without microvascular complications

Background

This study was performed to assess left ventricular (LV) energy metabolism and function in patients with type 1 diabetes with or without overt microvascular complications.

Methods

We performed cardiac Magnetic Resonance Imaging (MRI) and ³¹P spectroscopy (MRS) in 24 patients with overt microvascular complications and in 15 carefully selected patients without complications in spite of a long duration of the disease (> 20 years) and matched for anthropometric features. 31 healthy subjects served as a control group.

Results

Systolic function was preserved in all study subjects. Patients with overt complications showed a higher LV wall mass/end diastolic volume ratio and altered parameters of diastolic function when compared to patients without complications and to controls. They were also characterized by lower PCr/ATP ratio (a recognized marker of energy metabolism). No effect of HbA1c was detected within groups.

Conclusions

In patients with type 1 diabetes 1) overt microvascular complications were associated with altered LV geometry, diastolic function and energy metabolism 2) in patients without complications and duration of disease > 20 years no association with these alterations were found despite poor glycemic control. The features of this highly selected subgroup of patients demonstrated that long lasting chronic hyperglycemia per se is not sufficient to induce abnormality of cardiac energy metabolism and that additional yet to be identified (metabolic or genetic) factors must be important contributing factors.     

Infarctus du myocarde chez le sujet fumeur de moins de 50 ans traité par angioplastie coronaire. Évolution hospitalière et sur le long terme d’une série consécutive de 93 patients

Aims of the study

The study evaluated in-hospital and long-term outcome of patients less than 50 years old with myocardial infarction within 12 hours after symptom onset treated by coronary angioplasty.

Patients and method

This is a retrospective study with survival analysis by Kaplan-Meier method in patients included from December 2003 to February 2008.

Results

We included 93 patients aged 42,8 ± 5,2 years old with smoking estimated at 27,7 ± 12,7 pack-years. Thirty-one patients (33,3%) were dyslipidemic and 36 patients had family history of coronary artery disease. Thirty patients (32,3%) had an anterior myocardial infarction and four patients (4.4%) had Killip greater than 2. Coronary angioplasty was performed within 4.5 ± 3.0 hours after symptom onset with TIMI 3 final flow in the culprit vessel in 96.8%. One patient died from cardiogenic shock. With a follow-up of 85 patients during 20.0 ± 15.6 months, the survival without death was 98.2% and survival without major cardiac complication was 87.9% at 24 months. Seventy-two patients (85.7%) were taking a betablocker, 81 patients (96.4%) aspirin, 75 patients (89.3%) a statin and 64 patients (76.2%) an angiotensin-converting inhibitor. Only 50 patients (58.8%) were nonsmokers.

Conclusion

Thus, young smokers with acute MI treated by coronary angioplasty have a good prognosis during in-hospital stay and long-term outcome. Secondary medical treatment prevention is well followed but there is a low rate of smoking cessation.     

The burden of diabetes mellitus in elderly patients from an Asian tertiary hospital

Summary

Diabetes mellitus (DM) has been declared as a global public health threat to society. However, the burden of the disease in elderly Asian patients has not been described. The aim of the study is to assess the disease burden of DM and its associated adverse outcomes in elderly patients from an Asian hospital using the hospital inpatient database.

Methods

Retrospective study of hospital discharge database from 2004 to 2008 to identify patients aged 65 years and above with DM and its associated ‘adverse outcomes’ using International Statistical Classification of Diseases and Related Health Problems, 9th Revision, Australian Modification (ICD-9-AM) codes.

Results

Of 89,875 hospitalized patients aged 65 years and above over the 5 years, 31,124 (34.6%) patients had DM, and the percentage of DM cases increased steadily from 34.3% to 35.6%. Prevalence of DM-associated adverse outcomes was higher in DM patients than in non-DM patients (53.8% vs. 31.5%, p < 0.001). For trends over time, the adverse outcomes decreased in both DM patients (58.1% to 53.6%) and non-DM patients (34.3% to 31.4%, all p < 0.001). All disease-specific adverse outcomes except renal disease decreased over time both in DM and non-DM patients (all p < 0.05). There were increased trends over time for renal disease in both DM patients (16.1% to 23.2%, p < 0.001) and non-DM patients (6.7% to 10.4%, p < 0.001).

Conclusion

The burden of DM in this group of elderly patients is high. Elderly patients with DM experienced much higher rates of the adverse outcomes.     

Human foetal intestinal fibroblasts are hyper-responsive to lipopolysaccharide stimulation

Background

Intestinal myofibroblasts contribute to immune regulation in adults with inflammatory bowel disease but have not been characterised in neonatal intestinal inflammatory diseases.

Aims

To compare lipopolysaccharide (LPS)-stimulated interleukin-8 (IL-8) production between human foetal and mature intestinal myofibroblasts in vitro.

Methods

Foetal, neonatal and adult cells were stimulated with increasing concentrations of E. coli LPS. In LPS stimulated foetal myofibroblasts, Toll-like receptor 4 mRNA expression was assessed by real-time PCR whilst Toll-like receptor 4 receptor activity was determined using anti-Toll-like receptor 4 antibody. Mitogen activated protein kinase pathway activity was assessed using chemical inhibitors and Western blotting. IL-8 production was measured by quantitative ELISA.

Results

IL-8 production by LPS stimulated foetal myofibroblasts occurred in a dose dependent manner. Toll-like receptor 4 expression was constitutive and Toll-like receptor 4 receptor blockade reduced IL-8 production by 42% (P = 0.0262). C-Jun N-terminal kinase, p38 and NF-κB inhibitors significantly attenuated LPS stimulated IL-8 production by 42%, 33% and 2%, respectively. Mitogen activated protein kinase activity was confirmed by the presence of phosphorylated proteins on Western blots.

Conclusion

These data demonstrate increased IL-8 production by foetal myofibroblasts that is partially mediated by Toll-like receptor 4, mitogen activated protein kinase and NF-κB cell signalling pathways. Intestinal myofibroblasts cells may contribute to the dysregulated inflammatory response in the immature intestine and may form targets that lead to new therapies to prevent neonatal intestinal inflammatory bowel diseases.     

The Cost-effectiveness of Hormone Therapy in Younger and Older Postmenopausal Women

Purpose

To evaluate the health and economic outcomes of hormone therapy in younger and older postmenopausal women.

Methods

We developed a cost-effectiveness model to evaluate outcomes associated with hormone therapy in younger and older postmenopausal women, using data sources from published literature through March 2008. The target population was 50-year-old and 65-year-old women given hormone therapy or no therapy, and then followed over their lifetime. Primary outcomes measured were quality-adjusted life-years (QALYs) and incremental cost per QALY gained.

Results

For the base-case analysis, hormone therapy for 15 years in the younger cohort resulted in a gain of 1.49 QALYs with an incremental cost of $2438 per QALY gained, compared with no therapy. The results for younger women were robust to all sensitivity analyses, and treatment remained highly cost-effective (<$10,000 per QALY gained) within the range of individual assumptions used. Treatment durations of 5 years and 30 years also were highly cost-effective. In the older cohort, treatment for 15 years resulted in a net gain of 0.11 QALYs with a cost of $27,953 per QALY gained. However, a loss of QALYs was seen in the first 9 years. The results for older women were sensitive to many of the assumptions used.

Conclusions

Hormone therapy for 5 to 30 years in younger postmenopausal women increases quality-adjusted life-years and is cost-effective. Hormone therapy started in later years results in a loss of quality-adjusted life for several years before a net gain can be realized.     

Higher Cardiovascular Disease Prevalence and Mortality among Younger Blacks Compared to Whites

Background

Blacks have higher rates of cardiovascular disease than whites. The age at which these differential rates emerge has not been fully examined.

Objective

We examined cardiovascular disease prevalence and mortality among black and white adults across the adult age spectrum and explored potential mediators of these differential disease prevalence rates.

Methods

We conducted a cross-sectional analysis of National Health and Nutrition Examination Survey data from 1999-2006. We estimated age-adjusted and age-specific prevalence ratios (PR) for cardiovascular disease (heart failure, stroke, or myocardial infarction) for blacks versus whites in adults aged 35 years and older and examined potential explanatory factors. From the National Compressed Mortality File 5-year aggregate file of 1999-2003, we determined age-specific cardiovascular disease mortality rates.

Results

In young adulthood, cardiovascular disease prevalence was higher in blacks than whites (35-44 years PR 1.9; 95% confidence interval [CI], 1.1-3.4). The black-white PR decreased with each decade of advancing age (P for trend = .04), leading to a narrowing of the racial gap at older ages (65-74 years PR 1.2; 95% CI, 0.8-1.6; ≥75 years PR 1.0; 95% CI, 0.7-1.4). Clinical and socioeconomic factors mediated some, but not all, of the excess cardiovascular disease prevalence among young to middle-aged blacks. Over a quarter (28%) of all cardiovascular disease deaths among blacks occurred in those aged <65 years, compared with 13% among whites.

Conclusions

Reducing black/white disparities in cardiovascular disease will require a focus on young and middle-aged blacks.     

Impact of introducing HbA1c into the diagnostic criteria on prevalence and cardiovascular risk profiles of individuals with newly diagnosed diabetes in Japan: the Toranomon Hospital Health Management Center Study 2 (TOPICS 2)

Objective

To evaluate the impact of HbA1c for diagnosis of diabetes and investigate whether cardiovascular risks profiles differ among individuals with diabetes diagnosed by HbA1c or fasting plasma glucose (FPG).

Methods

This cross-sectional study involved 26,884 participants (30.6% women; aged 20-91 years) without known diabetes. Subjects were categorized into 4 groups according to the presence or absence of FPG ≥7.0 mmol/L and/or HbA1c ≥6.5%, which were American Diabetes Association criteria. Oral glucose tolerance test data were not available.

Results

Prevalence of undiagnosed diabetes was 3.6%. Of those individuals, 47.5% fulfilled both two criteria and 26.0% fulfilled only HbA1c criterion. Individuals with diabetes according to FPG ≥7.0 mmol/L alone were characterized as having poorly controlled hypertension while those with HbA1c ≥6.5% alone were characterized as older, female, and having lower blood pressure and γ-glutamyltransferase values. Persons with newly diagnosed diabetes by HbA1c had low HDL cholesterol and high LDL or non-HDL cholesterol levels.

Conclusions

Introducing HbA1c into the diagnosis allowed detection of many previously undiagnosed cases of diabetes in Japanese individuals. Those diagnosed by FPG were characterized by hypertension and those diagnosed by HbA1c had unfavorable lipid profiles, reflecting an atherosclerotic trait.     

Bile acid malabsorption investigated by selenium-75-homocholic acid taurine (SeHCAT) scans: Causes and treatment responses to cholestyramine in 298 patients with chronic watery diarrhoea

Background

The liver produces and secretes bile acids into the small intestine. In the small intestine, most of the bile acids are absorbed in the distal ileum with portal vein transportation back to the liver and resecretion (enterohepatic recycling). Increased spillover of bile acids from the small intestine into the colon (bile acid malabsorption) may affect the secretion of colonic water and electrolytes and result in watery diarrhoea.The aim of this study was to investigate the frequency of bile acid malabsorption and treatment responses to cholestyramine with ⁷⁵SeHCAT scanning among patients suffering from chronic watery diarrhoea.

Methods

This was a retrospective study that included all patients who received a ⁷⁵SeHCAT scan over a five-year period (2004-2009).

Results

In total, 298 patients (198 females, 100 men) with a median age of 42 years (range 16-82 years) were investigated.Bile acid malabsorption (⁷⁵SeHCAT retention < 15% after seven days) was identified in 201 patients (68%, 95% confidence interval (CI): 62%-73%). Bile acid malabsorption due to ileal dysfunction (Type I) was found in 77 patients, idiopathic bile acid malabsorption (Type II) was found in 68 patients and 56 patients with other conditions had bile acid malabsorption (Type III).Of the 150 patients who were able to take cholestyramine continuously, 108 patients (71%, CI: 63%-78%) reported a positive effect on their bowel habits.

Conclusions

Bile acid malabsorption is a frequent problem in patients with chronic watery diarrhoea. Treatment with bile acid binders was effective regardless of type and severity.     

Serum lipids in primary sclerosing cholangitis

Background

Limited data are available regarding the serum lipids in primary sclerosing cholangitis.

Aims

To determine the lipid levels in patients with primary sclerosing cholangitis.

Methods

We monitored the serum lipid levels annually for up to 6 years in 157 patients included in three previous trials of ursodeoxycholic acid.

Results

The baseline lipid values were: total cholesterol = 207 mg/dL (127-433); high-density lipoprotein = 56 mg/dL (26-132); low-density lipoprotein = 129 mg/dL (48-334); triglycerides = 102 mg/dL (41-698). Cirrhotic stage was associated with lower levels of total cholesterol (186 mg/dL vs. 217 mg/dL, p = .02). A significant correlation between the liver biochemistries and total and low-density lipoprotein cholesterol levels was observed. Ursodeoxycholic acid, as compared to placebo, significantly decreased total (−27 mg/dL vs. 22 mg/dL, p = .0004) and low-density lipoprotein cholesterol (−24 mg/dL vs. 17 mg/dL, p = .0001). After extended follow-up, small changes in the lipid levels were noticed. The incidence of coronary artery disease was 4%.

Conclusions

Our findings suggest that the lipid levels in primary sclerosing cholangitis are often above levels where treatment with lipid-lowering agents is recommended. However, primary sclerosing cholangitis patients seem to have no elevated risk for cardiovascular events. The correlation of total and low-density lipoprotein cholesterol with liver biochemistries implies that mechanisms linked to cholestasis may regulate cholesterol metabolism.