Feasibility of opportunistic colorectal cancer screening of hospitalized patients in tertiary care and community hospitals.

BACKGROUND: Population screening for colorectal cancer (CRC) remains low, requiring alternative approaches for increasing participation. Opportunistic screening of hospitalized patients may aid in increasing uptake rates. OBJECTIVE: To assess whether inpatients can be recruited for opportunistic CRC screening using fecal immunochemical testing (FIT). METHODS: Inpatient charts were prospectively reviewed for study eligibility on admission of patients to the medical wards of 3 hospitals in Winnipeg, Canada. Eligible patients were approached for participation and consent. Inoculated FIT specimen collection tubes were sent to the hospital laboratory for testing. Patients with positive FIT results received a follow-up colonoscopy. RESULTS: In total, 1542 inpatient charts were screened for eligibility; 53 patients were identified for enrollment (51.9% were male; median age, 59 years), of whom 13 patients consented to participate but only 7 provided a stool specimen. One of those 7 patients had a positive FIT result. The overall screening rate was low, at 0.45%. The primary reason for exclusion of patients was age (outside of the range of 50-75 years), followed by patients having recent gastrointestinal bleeding and/or known intestinal diseases. CONCLUSIONS: Our data suggest that it is infeasible to recruit inpatients for opportunistic CRC screening in routine clinical practice.

Fecal Occult Blood Test for Evaluation of Symptoms or for Diagnostic Testing.

This editorial discusses the role of fecal occult blood test (FOBT) in a diagnostic workup. Utility of FOBT in colorectal cancer screening is well documented in multiple clinical trials, although there continues to be a debate (and ongoing trials) on its merit relative to other screening tests. Over the years, FOBT has seen growth in its application for assessment of symptomatic gastrointestinal disease without clear guidelines on its use in this setting. The work of Lee et al. in this edition of the journal synthesizes evidence on diagnostic utility of FOBT and provides additional rationale to stop using FOBTs for symptoms evaluation or for diagnostic testing.

Prostate-Specific Antigen Test Utilization in a Major Canadian City.

OBJECTIVES: To review the utilization of prostate-specific antigen (PSA) testing in Winnipeg, a major Canadian city, and to compare PSA testing rates between Winnipeg and Calgary, another major Canadian city of comparable size. METHODS: PSA testing results were reviewed by year and age group. We focused our studies in years 2011 and 2016, for which census demographic data are available. RESULTS: In Winnipeg, the PSA testing rates (patients with one or two PSA tests divided by the male population) showed a declining trend over years from 2008 to 2017. For almost all age groups, PSA testing rates in 2016 decreased in comparison to those in 2011. For age older than 40 years, the relative percentage decreases were 14% to 20%.In 2011, Winnipeg PSA testing rates were consistently higher than those in Calgary for all age groups. For age older than 40 years, the relative percentage differences were 36% to 50%.In addition, 41% and 40% of patients in Winnipeg who underwent PSA testing were younger than 50 years or older than 69 years in 2011 and 2016, respectively. CONCLUSIONS: PSA testing utilization may be falling short of optimal rates. There is a need to reinforce the optimal use of clinical recommendations.

Utility of fecal immunochemical test vs guaiac fecal occult blood test for assessment of gastrointestinal bleed in hospitalized patients.

BACKGROUND: Guaiac fecal occult blood testing (gFOBT) is often used "off-label" for gastrointestinal (GI) bleeding. Fecal Immunochemical Test (FIT) is increasingly replacing gFOBT in colorectal cancer screening and may play a role in assessment for significant bowel disease. We examined the concordance of FIT with gFOBT (Hemoccult Sensa II) among inpatients and between day 1 and day 3 gFOBT results. METHODS: FIT was performed alongside gFOBT on all inpatient stool sent for occult blood to the Winnipeg Health Sciences Centre laboratory over 1 y. gFOBT was performed on days 1 and 3 post stool collection, while FIT was performed on day 1 only. RESULTS: Positivity rates were highest for Day 1 gFOBT (27.7%), and lowest for FIT (18.3%). Concordance between FIT and Days 1 and 3 gFOBT for negative test results (96.4% and 94.1%) was significantly higher than that expected by chance alone (58.7% and 61.3%, P < .001). Similarly, concordance for positive test results (55.8% and 55.6%) was significantly higher as well as for days 1 and 3 gFOBT results. CONCLUSIONS: We found no benefit in delayed testing for 3 days post collection. FIT provides equivalent results to gFOBT in hospitalized patients.

Increased rates of 25-hydroxy vitamin D testing: Dissecting a modern epidemic.

INTRODUCTION: Laboratories have noted marked increases in the analysis of 25-hydroxy vitamin D (25(OH)D) in recent decades. Our objectives were to describe the annual number of 25(OH)D tests, examine the characteristics of those tested and those ordering them, and determine the proportion of potentially unnecessary tests in Manitoba. METHODS: Manitoba residents who were tested between 2006/7 and 2012/13 had their data anonymously linked to Manitoba Centre for Health Policy comprehensive administrative datasets. Patient and physician characteristics, location of residence, and 25(OH)D concentrations were determined. Descriptive statistics and multivariable regression models were utilized. RESULTS: There was a quadrupling in testing from 2006 to 2013, with >20,000 tests performed in 2012/13. The median annual number of tests was one per patient; the maximum was >10 tests per year. Adult females had twice the number of tests compared to males (p < 0.001). There was a rise in 25(OH)D concentrations over time with hypervitaminosis D increasing disproportionately (2006/7 to 212/13 (0% vs. 0.15%, p < 0.001)). Apparently unnecessary testing rose by 1/3 over time, frequently ordered by Family Medicine practitioners. A revised 25(OH)D requisition resulted in striking reduction of 25(OH)D requests (~80%). DISCUSSION: Manitoba noted a rapid increase in testing, and rise in 25(OH)D concentrations with levels that may be associated with toxicities; both have been reported in other jurisdictions. There appeared to a striking rise in 'unnecessary' tests. We similarly report the benefit of the implementation of a mandatory requisition specifying eligibility criteria for 25(OH)D and education about appropriate testing.

Serum Vitamins and Minerals at Diagnosis and Follow-up in Children With Celiac Disease.

OBJECTIVES: Children with celiac disease (CD) may experience deficiencies of several micronutrients. The objectives of the present study were to determine the prevalence of micronutrient deficiencies in children with CD at diagnosis, 6 months, and 18 months after the start of a gluten-free diet (GFD), and examine any correlation between micronutrient deficiencies, serum tissue transglutaminase (TtG) immunoglobulin A (IgA) antibody titers, and the degree of mucosal damage at diagnosis. METHODS: Children (<17 years) with CD had their serum vitamins, minerals, and anti-TtG IgA antibodies measured at diagnosis, 6 and 18 months after starting a GFD. Histopathological changes of duodenal biopsies at diagnosis were documented using modified MARSH classification. RESULTS: The medical records of 140 children (mean age at diagnosis 7.8 ±â€Š4.01 years, 87 girls [621%]) with CD were examined. At diagnosis, serum vitamin D was the most commonly deficient vitamin in 70% of children. Serum ferritin was subnormal in 34.5% with zinc in 18.6% children but only 12 (10.9%) children had iron deficiency anemia. There was no correlation between micronutrient deficiencies at diagnosis and serum TtG IgA antibody titers or the degree of villous atrophy. The majority of serum levels of measured micronutrients had normalized after 6 months of starting GFD except for vitamin D, which improved but remained subnormal. CONCLUSIONS: At diagnosis, most children with CD have vitamin D deficiency. The degree of micronutrient deficiencies does not correlate with the degree of villous atrophy or serum titers of anti-TtG IgA antibodies.

Anti-Saccharomyces cerevisiae antibody titres correlate well with disease activity in children with Crohn's disease.

AIM: The role of noninvasive biologic markers for disease activity is very important in children with Crohn's disease. The aim of this study was to assess an association between disease activity and quantitative serum anti-Saccharomyces cerevisiae antibody (ASCA) titres. METHODS: Anti-Saccharomyces cerevisiae antibody immunoglobulin (Ig) A and immunoglobulin G titres, paediatric Crohn's disease activity index (PCDAI), serum albumin and C-reactive protein (CRP) were repeatedly measured simultaneously in children with Crohn's disease. A possible association between ASCA IgA and IgG titres and changes in PCDAI was examined. RESULTS: Serial 136 measurements of ASCA IgA and IgG titres were documented in 57 children with Crohn's disease over a mean duration of 3.1 ± 2.1 years. In a univariate linear regression model, there were significant correlations between ASCA IgA titres and PCDAI (p < 0.001), CRP (p <0.01) and low serum albumin (p < 0.001), respectively. Similarly, ASCA IgG titres significantly correlated with PCDAI, CRP and low serum albumin. CONCLUSION: Both ASCA IgA and IgG titres seemed to correlate well with clinical Crohn's disease activity in children. Measuring these antibodies may be considered during routine clinical care for those patients.

Use of fecal occult blood testing in hospitalized patients: results of an audit.

BACKGROUND: The fecal occult blood test (FOBT), widely used as a colorectal cancer screening tool, continues to be used in hospitalized patients. However, the utility of this test for hospitalized patients is unclear. OBJECTIVE: To assess FOBT use in a large urban regional health authority. METHODS: Reports of all FOBTs performed between April 1, 2011 and March 30, 2012 from two academic and four community hospitals in Winnipeg (Manitoba) were extracted. Of 650 hospitalizations with a positive FOBT result and 1254 with a negative FOBT result, random samples of 230 and 97 charts, respectively, were reviewed. Information including demographics, admission diagnos(es), indication(s) for ordering the FOBT and clinical management was extracted. RESULTS: Thirty-four percent (650 of 1904) of hospitalizations with an FOBT had a positive FOBT result. Family medicine physicians ordered approximately one-half of the reviewed FOBTs. The most common indication for ordering an FOBT was anemia. Of those with a positive FOBT, 66% did not undergo further gastrointestinal investigations. Of those with a positive FOBT and overt gastrointestinal bleeding and/or melena who underwent endoscopy, 60% had their endoscopy performed before the FOBT result being reported while 38% underwent their endoscopy ≥3 days after the stool sample was collected. There were minimal differences in clinical practices between academic and community hospitals. CONCLUSIONS: The present study suggests that FOBT results in hospitalized patients may have little beneficial impact on clinical management. Hospital laboratories may be better served in directing resources to other tests.

Use of fecal occult blood test in hospitalized patients: survey of physicians practicing in a large central Canadian health region and Canadian gastroenterologists.

BACKGROUND: Although the fecal occult blood test (FOBT) was developed for colorectal cancer screening in the outpatient setting, it continues to be used among hospitalized patients. No previous study has evaluated the knowledge, beliefs and attitudes of practicing physicians on the use of FOBT among hospitalized patients and compared practices among physicians with different medical specialty training. OBJECTIVE: To survey physicians in the Winnipeg Regional Health Authority (WRHA) and Canadian gastroenterologists (GIs) on the use of FOBT in hospitals. METHODS: A survey was distributed by e-mail to internists (n=198), emergency medicine (EM) physicians (n=118), general surgeons (n=47) and family medicine (FM) physicians with admitting privileges (n=29) in the WRHA. Canadian GIs were surveyed through the membership database of the Canadian Association of Gastroenterology (CAG) (n=449). The survey included items regarding demographics of the respondents and their current use of FOBT in hospitals. RESULTS: Response rates ranged from 18% among CAG members to 69% among FM physicians in the WRHA. General internal medicine, general surgeon and GI respondents were less likely to order a FOBT and less likely to believe that an FOBT was useful in assessing emergency room or hospitalized patients when compared with FM and EM respondents (P<0.001). The most common indications for ordering a FOBT were black stools and anemia with and without iron deficiency. Two-thirds of EM physicians preferred point-of-care testing rather than laboratory reporting of FOBT. CONCLUSIONS: The present survey suggests that FOBTs are commonly used in hospitals by EM and FM physicians for indications such as anemia and black stools.

Neuroleptic malignant syndrome versus serotonin syndrome: the search for a diagnostic tool.

OBJECTIVE: To evaluate the use of urine dopamine and catecholamine concentrations as diagnostic aids in a patient with neuroleptic malignant syndrome (NMS) in the emergency department setting. CASE SUMMARY: A 61-year-old female on multiple medications, including several antipsychotics, rapidly deteriorated, with fever, lead-pipe rigidity, and decreased level of consciousness. The patient died 20 days after initial presentation to an emergency department. The Naranjo probability scale indicated probable causality for NMS due to quetiapine, haloperidol, and risperidone in this patient, whereas the Naranjo scale assigned only possible causality for serotonin syndrome developing with serotonergic agents. Laboratory investigations of blood and urine revealed elevations in dopamine, metanephrines, and epinephrines, as well as trazodone and risperidone. Serotonin metabolites were not elevated. DISCUSSION: NMS is a rare and potentially severe adverse effect associated with the use of antipsychotic medications. It is mainly characterized by hyperthermia, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigors. It has been associated with multisystem organ failure potentially leading to rhabdomyolysis, acute respiratory distress syndrome, and disseminated intravascular coagulation. The prevalence of this syndrome is associated with the use of neuroleptics. Serotonin syndrome is another adverse drug reaction leading to NMS associated with elevated serotonin. It occurs when multiple serotonergic medications are ingested and is associated with rapid onset of altered mental status, myoclonus, and autonomic instability. Differentiating between NMS and serotonin syndrome can be challenging because of their similar clinical presentation. This case highlights the importance of a diagnostic aid being available to help distinguish between the 2 syndromes. CONCLUSIONS: We propose that laboratory findings that include dopamine and serotonin metabolites can be used as adjuncts to clinical and prescription histories in the diagnosis of NMS. The use of urinary catecholamine as a diagnostic aid in NMS needs further evaluation.

Diagnosis and high incidence of hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome in northern Saskatchewan.

Mutations in the SLC25A15 gene, encoding the human inner mitochondrial membrane ornithine transporter, are thought to be responsible for hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome, a rare autosomal recessive condition. HHH syndrome has been detected in several small, isolated communities in northern Saskatchewan (SK). To determine the incidence of HHH syndrome in these communities, a PCR method was set up to detect F188Δ, the common French-Canadian mutation. Neonatal blood spots collected from all newborns from the high risk area were genotyped for the F188Δ mutation for seven consecutive years. Using DNA analysis, we estimated that the heterozygote frequency for the mutant allele for HHH syndrome to be about 1 in 19 individuals, predicting one affected child with HHH syndrome for approximately every 1,500 individuals (1 in 1,550 live births; 1 child every 12 years) in this isolated population. The frequency for the mutant allele for HHH syndrome in this isolated community is probably the highest in the world for this rare disorder. We determined that ornithine levels, by tandem mass spectrometry, were not abnormal in newborns with F188Δ mutation, carriers and normals. Ornithine rises to abnormally high levels at some time after birth well past the time that the newborn screening blood spot is collected. The timing or the reasons for the delayed rise of ornithine in affected children with HHH syndrome have not been determined. Newborn screening for HHH Syndrome in this high risk population is only possible by detection of the mutant allele using DNA analysis.

Formate pharmacokinetics during formate administration in folate-deficient young swine.

The objective of the study was to investigate the effect of folate deficiency on formate pharmacokinetics during formate administration in folate-deficient young swine. Methanol is a one of the congeners found in alcoholic beverages. Methanol toxicity is mediated through formic acid and thus plays a significant role in the pathophysiology of alcoholism. Folate is a required cofactor in the metabolism of formate to CO(2) and H(2)O. We investigate the effect of folate deficiency on the pharmacokinetics of formate. Twelve young pigs were pair-matched and randomly placed into 2 groups on acquisition ( approximately 5 weeks). One group was made folate deficient (FFD) by feeding with a folic acid-deficient diet; the other group (FFC) was fed a diet supplemented with folate. Four animals (31-38 kg) from each group were infused (intravenous) with 351 mg/kg of sodium formate. The remaining 2 animals were infused with isotonic sodium chloride solution. Blood samples were collected before and at 10, 20, 30, 45, 60, 90, 120, 180, 240, and 480 minutes post dose and analyzed for formate levels by gas chromatography. Pharmacokinetic parameters were estimated using a noncompartmental approach. Formate (mean +/- SE) accumulation was higher in the FFD group than the FFC group (AUC(0-infinity) of 72.37 +/- 8.29 vs 30.08 +/- 2.58 g min/L, respectively). Elimination was also slower in the FFD group (FFD systemic clearance = 0.12 +/- 0.01 L/min compared with FFC systemic clearance = 0.27 +/- 0.02 L/min). Half-life of elimination was 2.5 times longer in FFD group (113 +/- 1 minute) than in FFC group (45 +/- 6 minutes). Folate deficiency had no influence on the volume of distribution of formate (18.84 +/- 1.05 L in FFD vs 17.21 +/- 1.35 L in FFC). Adequate folate status is important in the elimination of formate. A folate-deficiency state results in a reduction in formate elimination kinetics, which may increase the risk of formate toxicity.

Quantitative endogenous formate analysis in plasma using headspace gas chromatography without a headspace analyzer.

The objective was to develop a simple routine method for quantitative measurement of endogenous formic acid in plasma and whole blood using headspace gas chromatography-flame ionization detection. (GC-FID). Two-hundred microliters of sample was placed in a 1-mL glass vial. Fifty microliters of aqueous ethanol (10%) was added as an internal standard and a derivatizing agent. Ethylformate formation was enhanced by addition of 200 microL concentrated sulfuric acid as a catalyst. The vials were then sealed immediately and placed in a water bath for 15 min at 60 degrees C. One milliliter of this headspace gas was siphoned using a gas-tight syringe and injected into a GC-FID fitted with a capillary column. Ethanol eluted at approximately 3.0 min, and ethylformate eluted around 4.7 min. The limit of quantitation for ethylformate was 0.026 mmol/L, and the limit of detection was 0.020 mmol/L. Imprecisions for spiked plasma samples at 0.25 and 1 mmol/L were 10% and 9%, respectively and recoveries were at 100% and 108%, respectively. A simple, reliable, and highly specific headspace analysis method for quantifying endogenous formate without the use of a headspace analyzer was developed. This method enables the routine clinical analysis of formate in plasma and whole blood samples.