Fracture risk assessment in celiac disease: a registry-based cohort study.

Celiac disease is associated with an increased fracture risk but is not a direct input to the FRAX® calculation. When celiac disease is considered as a secondary osteoporosis risk factor or BMD is included in the FRAX assessment, FRAX accurately predicts fracture risk. INTRODUCTION: The fracture risk assessment tool (FRAX®) uses clinical factors and bone mineral density (BMD) measurement to predict 10-year major osteoporotic (MOF) fracture probability. The study aim was to determine whether celiac disease affects MOF risk independent of FRAX score. METHODS: The Manitoba BMD Registry includes clinical data, BMD measurements, 10-year probability of MOF calculated for each individual using the Canadian FRAX tool and diagnosed celiac disease. Using linkage to population-based healthcare databases, we identified incident MOF diagnoses over the next 10 years for celiac disease and general population cohorts. RESULTS: Celiac disease (N = 693) was associated with increased fracture risk adjusted for FRAX score computed without secondary osteoporosis or BMD (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.11-1.86). Celiac disease was no longer a significant risk factor for fracture when secondary osteoporosis or BMD were included in the FRAX calculation (p > 0.1). In subjects with celiac disease, each SD increase in FRAX score (calculated with and without secondary osteoporosis or BMD) was associated with higher risk of incident MOF (adjusted HR 1.66 to 1.80), similar to the general population (p-interaction > 0.2). Including celiac disease as secondary osteoporosis or including BMD in FRAX 10-year MOF probability calculations (10.1% and 8.6% respectively) approximated the observed cumulative 10-year MOF probability (10.8%, 95% CI 7.8-13.9%). CONCLUSIONS: Celiac disease is associated with an increased risk of major osteoporotic fractures. When celiac disease is considered as a secondary osteoporosis risk factor or BMD is included in FRAX assessment, FRAX accurately predicts fracture risk.

Living gluten-free: adherence, knowledge, lifestyle adaptations and feelings towards a gluten-free diet.

BACKGROUND: A gluten-free diet (GFD) requires tremendous dedication, involving substantive changes to diet and lifestyle that may have a significant impact upon quality of life. The present study aimed io assess dietary adherence, knowledge of a GFD, and the emotional and lifestyle impact of a GFD. METHODS: Community dwelling adults following a GFD completed a questionnaire with items related to reasons for avoiding gluten, diagnostic testing, GFD adherence, knowledge and sources of information about a GFD, the Work and Social Adjustment Scale, and the effect of a GFD diet on lifestyle, feelings and behaviours. RESULTS: Strict GFD adherence among the 222 coeliac disease (CD) patients was 56%. Non-CD individuals (n = 38) were more likely to intentionally ingest gluten (odds ratio = 3.7; 95% confidence interval = 1.4-9.4). The adverse impact of a GFD was modest but most pronounced in the social domain. Eating shifted from the public to the domestic sphere and there were feelings of social isolation. Affective responses reflected resilience because acceptance and relief were experienced more commonly than anxiety or anger. Non-CD respondents were less knowledgeable and less likely to consult health professionals. They experienced less anger and depression and greater pleasure in eating than CD respondents. CONCLUSIONS: The findings obtained in the present suggest there is good potential for positive adaptation to the demands of a GFD; nevertheless, there is a measurable degree of social impairment that merits further study. The GFD may be a viable treatment option for conditions other than CD; however, education strategies regarding the need for diagnostic testing to exclude CD are required.

A comparison of antibody testing, permeability testing, and zonulin levels with small-bowel biopsy in celiac disease patients on a gluten-free diet.

Active celiac disease is associated with positive endomysial (EMA) and tissue transglutaminase (TTG) antibodies, elevated zonulin levels, and increased intestinal permeability. There is little known about what happens to these immunologic and structural abnormalities in patients on a gluten-free diet and their correlation with small-bowel biopsy changes. Adult patients previously diagnosed with celiac disease and on a gluten-free diet for greater than 1 year were considered for the study. All patients underwent the following: measurement of EMA and TTG antibodies, serum zonulin levels, intestinal permeability (IP) testing with lactulose/mannitol ratios, food diary analysis for gluten ingestion and small- bowel biopsy. A total of 21 patients on a gluten-free diet for a mean of 9.7 years completed the study. There were ten patients who had normalization of intestinal biopsies, IP and TTG, and EM antibodies. Six patients had Marsh type 2 or 3 lesions and all had either abnormal IP (5/6) or TTG antibody (4/6). In patients with Marsh type 3 lesions, there was a correlation between IP and zonulin levels. A subgroup of patients with celiac disease on a gluten-free diet has complete normalization of intestinal biopsies, intestinal permeability defects, and antibody levels. Patients with Marsh type 3 lesions have abnormal TTG antibodies and intestinal permeability with zonulin levels that correlate with IP. These abnormalities may be due to continued gluten ingestion. Further study is needed to determine the clinical utility of TTG antibodies and IP testing in following patients with celiac disease.

Ulcerative colitis and Sweet's syndrome: a case report and review of the literature.

A 47-year-old man with a history of ulcerative colitis on prednisone and azathioprine was admitted to the hospital with a four-day history of fever, skin rash, arthralgias and leukocytosis. A skin biopsy demonstrated neutrophilic infiltration of the dermis that was consistent with Sweet's syndrome. He improved after several days with an increase in his prednisone and azathioprine. Sweet's syndrome is a rare cutaneous manifestation of inflammatory bowel disease, with approximately 40 cases reported in the literature. In a previously reported case of a patient with ulcerative colitis-associated Sweet's syndrome who was on azathioprine at the time of the skin eruption, the azathioprine was stopped, raising the possibility of drug-induced Sweet's syndrome. In the present case, the azathioprine was actually increased with complete resolution of the skin manifestations. This would support the theory that immunosuppressive therapy is the mainstay of therapy for this condition. In conclusion, Sweet's syndrome is a neutrophilic dermatosis that is rarely associated with ulcerative colitis. It may occur while on immunosuppressive therapy and responds to an intensification of immunosuppression.

Symptomatic suspected gluten exposure is common among patients with coeliac disease on a gluten-free diet.

BACKGROUND: A gluten-free diet is the only recommended treatment for coeliac disease. AIM: To determine the prevalence and characteristics of reactions to gluten among persons with coeliac disease on a gluten-free diet. METHODS: Adults with biopsy proven, newly diagnosed coeliac disease were prospectively enrolled. A survey related to diet adherence and reactions to gluten was completed at study entry and 6 months. The Coeliac Symptom Index, Coeliac Diet Assessment Tool (CDAT) and Gluten-Free Eating Assessment Tool (GF-EAT) were used to measure coeliac disease symptoms and gluten-free diet adherence. RESULTS: Of the 105 participants, 91% reported gluten exposure <1 per month and median CDAT score was 9 (IQR 8-11), consistent with adequate adherence. A suspected symptomatic reaction to gluten was reported by 66%. Gluten consumption was unsuspected until a reaction occurred (63%) or resulted from problems ordering in a restaurant (29%). The amount of gluten consumed ranged from cross-contact (30%) to a major ingredient (10%). Median time to symptom onset was 1 h (range 10 min to 48 h), and median symptom duration was 24 h (range 1 h to 8 days). Common symptoms included abdominal pain (80%), diarrhoea (52%), fatigue (33%), headache (30%) and irritability (29%). CONCLUSIONS: Reactions to suspected gluten exposure are common among patients with coeliac disease on a gluten-free diet. Eating at restaurants and other peoples' homes remain a risk for unintentional gluten exposure. When following individuals with coeliac disease, clinicians should include questions regarding reactions to gluten as part of their assessment of gluten-free diet adherence.

Validity and reliability of the new Canadian Nutrition Screening Tool in the 'real-world' hospital setting.

BACKGROUND/OBJECTIVES: Nutrition screening should be initiated on hospital admission by non-dietitians. This research aimed to validate and assess the reliability of the Canadian Nutrition Screening Tool (CNST) in the 'real-world' hospital setting. SUBJECTS/METHODS: Adult patients were admitted to surgical and medical wards only (no palliative patients). Study 1--Nutrition Care in Canadian Hospitals (n=1014): development of the CNST (3 items: weight loss, decrease food intake, body mass index (BMI)) and exploratory assessment of its criterion and predictive validity. Study 2--Inter-rater reliability and criterion validity assessment of the tool completed by untrained nursing personnel or diet technician (DT) (n=150). Subjective Global Assessment performed by site coordinators was used as a gold standard for comparison. RESULTS: Study 1: The CNST completed by site coordinators showed good sensitivity (91.7%) and specificity (74.8%). Study 2: In the subsample of untrained personnel (160 nurses; one DT), tool's reliability was excellent (Kappa=0.88), sensitivity was good (>90%) but specificity was low (47.8%). However, using a two-item ('yes' on both weight change and food intake) version of the tool improved the specificity (85.9%). BMI was thus removed to promote feasibility. The final two-item tool (study 1 sample) has a good predictive validity: length of stay (P<0.001), 30-day readmission (P=0.02; X(2) 5.92) and mortality (P<0.001). CONCLUSIONS: The simple and reliable CNST shows good sensitivity and specificity and significantly predicts adverse outcomes. Completion by several untrained nursing personnel confirms its utility in the nursing admission assessment.

Appropriate nutritional support in acute and complicated Crohn's disease.

Crohn's disease is frequently complicated by protein-calorie malnutrition. Four common clinical presentations of Crohn's disease include acute exacerbations or flares of disease, intestinal obstruction, fistulizing disease, and perianal disease. In this review, we examine the role of nutritional support in these clinical scenarios. Nutritional support is important for maintaining functional status and preventing loss of lean tissue. Determinants of lean-tissue loss include severity of underlying injury, baseline nutritional status, and duration of inadequate nutrition. One of the clinically useful measures of nutritional status is the nutritional risk index (NRI) defined on the basis of the serum albumin and weight loss. Nutritional support is important in severely malnourished patients (NRI < 83). Enteral nutrition is the route of choice, provided there are no contraindications to using the gastrointestinal tract. In acute exacerbations of Crohn's disease, enteral nutrition also has a role in the primary management of disease although it is not as effective as corticosteroids in inducing remission. The mechanisms are poorly understood and the most effective enteral formulation needs to be determined. Total parenteral nutrition is justified in severely malnourished Crohn's disease patients who are unable to tolerate enteral feeding or in whom enteral feeding is contraindicated. More clinical studies are needed on the assessment of malnutrition in Crohn's disease, the effects of nutritional management on functional status, and the timing of nutritional intervention.

An evaluation of resting energy expenditure in hospitalized, severely underweight patients.

A prospective trial was conducted with 14 hospitalized patients who were severely underweight with a mean weight of 40.9+/-5.1 kg and 70.7+/-7.8% of ideal body weight, to compare estimates of resting energy expenditure (REE) with measured values. The 9 women and 3 men, whose mean age was 66.5+/-13.9 y, underwent nutritional assessment and measurement of their REE by indirect calorimetry using the Sensormedics Deltatrac MBM100 indirect calorimeter. Their REE was also estimated by the Harris-Benedict formula (mean 1032+/-66 kcal/d) as well as a previously established empirical formula where REE = 25 x body weight in kg (mean 1023+/-129 kcal/d). Results by both estimates were significantly lower than the measured resting energy expenditure (MREE) in this group of patients (P<0.0001). The percentage difference between MREE and estimated REE by the Harris-Benedict formula was 18.4+/-9.4% and 20.9+/-7.5% by the empirical formula. The MREE exceeded the estimated REE in each individual. The correlation between MREE and body weight (r2 = 0.558, r = 0.005) was better than that between MREE and estimated REE by Harris-Benedict formula (r2 = 0.275, P = 0.08) suggesting that weight was the principal determinant rather than the other components (height, age, sex) of the Harris-Benedict formula. Our data shows that commonly employed formulae routinely underestimate the energy needs of severely underweight patients below 50 kg in body weight. The Harris-Benedict equation had limited predictive value for the individual, explaining approximately 25% of the variance in energy expenditure. Given the particular importance of matching energy intake to needs in this group of patients with limited reserves, many of whom are critically ill, we suggest an empirical equation using 30-32 kcal/kg be used to estimate the energy requirements of severely underweight patients when direct measurements are unavailable or clinically less imperative.

Does jejunal feeding with a polymeric immune-enhancing formula increase pancreatic exocrine output as compared with TPN? A case report.

This case report compares the pancreatic output with different feeding regimes in a patient who underwent a partial pancreatectomy for carcinoma of the ampulla of Vater. A postoperative secretin stimulation test demonstrated significant pancreatic reserve. There was no difference in pancreatic exocrine secretion when the patient was fed jejunally with a polymeric immune-enhancing formula or supported with two different formulations of total parenteral nutrition. This result suggests that jejunal infusion of a polymeric immune-enhancing formula may be safe to administer in patients with acute pancreatitis.

The validity and reproducibility of clinical assessment of nutritional status in the elderly.

Malnutrition is an important predictor of morbidity and mortality. In the non-elderly, a subjective global assessment (SGA) has been developed. It has a high inter-rater agreement, correlates with other measures of nutritional status, and predicts subsequent morbidity. The purpose of this study was to determine the validity and reproducibility of the SGA in a group of patients older than 70 y of age. Consecutive patients from four geriatric/rehabilitation units were considered for the study. Each patient underwent independent nutritional assessments by a geriatrician and senior medical resident. At the completion of the assessment, skinfold caliper measurements were obtained and the patient reclassified according to the results, which were then compared with objective measures of nutritional status. Six-month follow-up was obtained on all patients. The agreement between the two clinicians was 0.48 +/- 0.17 (unweighted kappa), which represents moderate agreement and is less than the reported agreement in nonelderly subjects. Skin calipers improved the agreement between clinicians but did not improve the correlation with other nutritional markers or prediction of morbidity and mortality. There was a correlation between a patient's severely malnourished state and mortality. In addition, patients with a body mass index (BMI) of <75% or >150% age/sex standardized norms had an increased mortality. The SGA is a reproducible and valid tool for determining nutritional status in the elderly. The reproducibility is less than in the nonelderly, which may relate to changes in body composition or ability to obtain an accurate nutritional history.

Electrolyte abnormalities in patients with chronic renal failure receiving parenteral nutrition.

BACKGROUND AND METHODS: Chronic renal failure frequently is complicated by elevations in serum potassium, phosphate, and magnesium. Consequently, parenteral nutrition (PN) solutions used to treat malnourished patients with chronic renal failure usually are prepared with little supplementation of these cations. Four malnourished patients with chronic renal failure and electrolyte abnormalities are reported. RESULTS: Four patients developed significant hypophosphatemia 3 to 5 days after starting PN. Although carbohydrate infused via PN initially was not excessive (1.4 to 2.0 mg/kg/min), two patients received additional dextrose through continuous ambulatory peritoneal dialysis (CAPD). Two of the four patients received insulin during PN. Other electrolyte abnormalities included hypomagnesemia (1 patient) and hypokalemia (3 patients). CONCLUSIONS: Malnourished patients with chronic renal failure receiving PN are at risk of developing electrolyte abnormalities, particularly hypophosphatemia. The electrolytes of these patients should be monitored closely when nutrition support is begun, and supplementation should be started as levels begin to fall within a normal range.

Peripherally inserted central catheters for parenteral nutrition: a comparison with centrally inserted catheters.

BACKGROUND: Central venous access is crucial for the provision of adequate parenteral nutrition (PN). The type of central venous access device (CVAD) has evolved over the past 10 years. The most recent trend has been to use peripherally inserted central catheters (PICCs). This development has occurred without controlled clinical trials. METHODS: Over a 10-year period, the nutrition support service at a single institution has prospectively collected data on CVADs used for providing PN. The types of CVAD used for providing PN were analyzed, and the major complications associated with CVADs, thrombosis and line sepsis, were compared over three different time periods: 1988-1989; 1992-1993; 1996-1997. In addition, complications associated with PICCs were compared with other CVADs. RESULTS: The following were the dominant CVADs over each of the three time periods: 1988-1989: tunneled catheters, 80%; 1992-1993: nontunneled catheters, 46%; and 1996-1997: PICCs, 48%. There was a decreased incidence of sepsis and pneumothorax in 1996-1997 and an increase in severed or leaking catheters and phlebitis. In a comparison of PICC and non-PICC catheters over the past 3 years, there was a trend toward decreasing sepsis with PICC catheters but an increase in malposition, inadvertent removal, and severed or leaking catheters. CONCLUSIONS: PICCs have replaced tunneled and nontunneled central catheters as the most commonly used CVAD for providing PN. PICCs do not result in increased line sepsis or thrombosis but have an increased incidence of local complications such as leaking catheters, phlebitis, and malposition.

A comparison of the effect of elemental and immune-enhancing polymeric jejunal feeding on exocrine pancreatic function.

BACKGROUND: There are few studies examining the effect of jejunal feeding on pancreatic exocrine output. The purpose of this study was to compare the effects of jejunal feeding with an elemental formula (EF) and with a polymeric immune-enhancing formula (PIEF) on pancreatic exocrine function. METHODS: Patients undergoing a partial pancreatectomy had a jejunal feeding tube inserted and a pancreatic stent exteriorized, facilitating collection of pancreatic secretions. Postoperatively, patients underwent a secretin-stimulation test to document adequate pancreatic reserve. Patients were then randomized to receive jejunal feeding with EF or with PIEF for a 24-hour period, followed by a washout period of feeding with dextrose, and subsequent jejunal feeding with EF or PIEF. RESULTS: The secretin-stimulation test demonstrated significant pancreatic reserve in all patients. There was a mild increase in pancreatic exocrine secretion with jejunal feeding with EF and PIEF compared with baseline and with dextrose. There was increased bicarbonate secretion with EF compared with PIEF, but there were no other significant differences in pancreatic exocrine function. CONCLUSIONS: In this model of partial pancreatectomy, there was no significant difference in pancreatic exocrine output when use of an EF was compared with use of a PIEF for jejunal feeding. Further clinical studies are needed to determine the potential role of PIEF in pancreatic disease.

Risk of symptomatic central venous thrombotic complications in AIDS patients receiving home parenteral nutrition.

BACKGROUND: The acquired immunodeficiency syndrome (AIDS) is frequently complicated by malnutrition that may require parenteral nutritional support. In a non-AIDS population with long-term indwelling central venous catheters, low-dose warfarin therapy has been shown to prevent venous thrombosis. The purpose of this study was to determine the incidence of symptomatic central venous thrombosis in AIDS patients receiving home parenteral nutrition. The incidence of thrombosis on low-dose warfarin was compared with no prophylactic therapy. METHODS: A retrospective review of 47 malnourished AIDS patients started on home parental nutrition was performed. None of the patients had a prior history of venous thrombosis. During this period, 9 of 47 patients were treated with low-dose warfarin therapy. The incidence of clinical and radiologic venous thrombosis was compared in these two groups. RESULTS: Forty-seven patients were treated with parenteral nutrition for 296 patients-months. The rate of central venous thrombosis in patients receiving warfarin (0.016 thromboses per patient-month) was no different from those patients on no prophylactic therapy (0.009 thromboses per patient-month). The most common abnormality in coagulation observed in the entire group during follow-up was thrombocytopenia occurring in 66% of patients. Sixty percent of patients received medications that could interfere with platelet function. CONCLUSIONS: We conclude that routine thrombosis prophylaxis with low-dose warfarin may not be justified in malnourished AIDS patients receiving home parenteral nutrition. Prospective clinical trials are needed to determine the risks and benefits of prophylactic warfarin therapy in this group of patients.

The use of sodium valproate in the treatment of alcoholism.

It has been suggested that decreased central GABAergic activity may play a role in the pathogenesis of alcoholism. Sodium valproate is a commercially available anticonvulsant that increases central GABAergic activity. In this pilot study 13 adult male alcoholics received one month of oral, low dose sodium valproate (15 mg/kg/d) followed by one month of placebo followed by one month of sodium valproate at the standard anticonvulsant dosage (45 mg/kg/d). The principle objective of the study was to determine if sodium valproate is well tolerated and free of adverse effects in this high risk group. Anxiety levels and the desire to drink alcohol were also monitored throughout the study period. The results of the study revealed that low dose sodium valproate therapy is well tolerated and free of toxicity. While anxiety levels tended to fall or remained unchanged in the seven patients who completed four weeks of low dose treatment, there was no consistent change in their desire to drink values. Too few patients completed the trial to ascertain the safety or efficacy of standard dose sodium valproate. These findings suggest that controlled clinical trials of sodium valproate are feasible in adult male alcoholics.

Intestinal permeability in long-term follow-up of patients with celiac disease on a gluten-free diet.

Intestinal permeability is frequently abnormal in patients with celiac disease. The long-term effect of a gluten-free diet on intestinal permeability and the correlation of intestinal permeability with a gluten-free diet are not known. The objectives of this study were to determine the responses of intestinal permeability and antibody testing to gluten free diet and the degree of correlation of these measurements with gluten ingestion. In this prospective study, patients with celiac disease were divided into three groups based on length of time on a gluten-free diet: Group A, < 1 month; Group B, 1 month-1 year; Group C, > 1 year. Patients in Groups B and C were tested at baseline and at 4-12 weeks later for the following: lactulose/mannitol intestinal permeability, endomysial antibody, and 3-day food record. Permeability tests were also performed in Group A and control subjects. Intestinal permeability was elevated in newly diagnosed celiac disease and in individuals on a gluten-free diet for less than 1 year. Intestinal permeability was normal in 80% at visit 1 and 87% at visit 2 in individuals with celiac disease on a gluten-free diet for more than a year. Trace gluten ingestion was associated with increased intestinal permeability on visit 2 (P = 0.0480). The sensitivity of detecting gluten ingestion as measured by a 3-day food record was higher for permeability testing (29 and 36%) compared with endomysial antibody testing (18 and 18%) for visits 1 and 2, respectively. Intestinal permeability normalizes in the majority of individuals with celiac disease on a gluten-free diet. Gluten ingestion as measured by a 3-day food record correlates with intestinal permeability measurements. The role of permeability testing in the follow-up of patients with celiac disease warrants further investigation.

Pneumocystis carinii pneumonia complicating methotrexate treatment of primary sclerosing cholangitis.

The etiology of primary sclerosing cholangitis, a chronic progressive cholestatic liver disease, is poorly understood. Treatment with oral methotrexate may improve patient symptoms, liver biochemistry, and hepatic histology. This report describes a severe life-threatening complication of methotrexate therapy in primary sclerosing cholangitis--the development of Pneumocystis carinii pneumonia. The reported cases of methotrexate-associated P. carinii pneumonia in the literature are reviewed. With the increasing use of methotrexate in chronic inflammatory disorders, physicians should be aware of this potentially lethal complication.

Chronic hyperlipasemia caused by sarcoidosis.

A chronically elevated lipase is a rare biochemical finding and has only previously been described in patients with malignancy and macrolipasemia. We report a case of chronic hyperlipasemia caused by sarcoidosis. The literature on pancreatic sarcoidosis is reviewed and the significance of lipase isoforms is discussed. Sarcoidosis needs to be considered in patients presenting with chronic hyperlipasemia.

Co-existence of hepatitis A and adult Reye's syndrome.

Reye's syndrome is most frequently seen in children but has also been described in adults. This syndrome is usually associated with ingestion of 5-aminosalicylates (ASA) or infection with influenza A, influenza B, or varicella virus. A case of Reye's syndrome in a 47 year old, previously healthy woman precipitated by ingestion of ASA and acute hepatitis A virus infection is described. Reye's syndrome was diagnosed on the basis of her clinical course, and the presence of hepatic microvesicular steatosis and characteristic electron microscopic changes in the hepatocyte mitochondria. The diagnosis of hepatitis A was based on higher amino-transferase values than would be expected in Reye's syndrome alone, viral serology including the presence of hepatitis A IgM and the demonstration of hepatitis A virus RNA on liver biopsy by in situ hybridisation. Mitochondrial injury has been demonstrated in acute hepatitis A which, in addition to ASA, may have precipitated Reye's syndrome in this patient. The association between hepatitis A and Reye's syndrome has not been reported before. As hepatitis A virus infection is not sought routinely in patients with Reye's syndrome, the frequency of this association is unknown.