A Simple Admission Order-set Improves Adherence to Canadian Guidelines for Hospitalized Patients With Severe Ulcerative Colitis.

Background: Individuals hospitalized with severe ulcerative colitis represent a complex group of patients. Variation exists in the quality of care of admitted patients with inflammatory bowel disease. We hypothesized that implementation of a standardized admission order set could result in improved adherence to current best practice guidelines (Toronto Consensus Statements) for the management of this patient population. Methods: A retrospective cohort study of patients admitted with severe ulcerative colitis to a Montreal tertiary center was conducted. Two cohorts were defined based on pre- and post-implementation of a standardized order set. Adherence to 11 quality indicators was assessed before and after implementation of the intervention. These included: Clostridioides difficile and stool cultures testing, ordering an abdominal X-ray and CRP, organizing a flexible sigmoidoscopy, documenting latent tuberculosis, initiating thromboprophylaxis, use of intravenous steroids, prescribing infliximab if refractory to steroids, limiting narcotics, and surgical consultation if refractory to medical therapy. Results: Adherence to 6 of the 11 quality indicators was improved in the post-intervention cohort. Significant increases were noted in adherence to C difficile testing (75.5% versus 91.9%, P < 0.05), CRP testing (71.4% versus 94.6%, P < 0.01), testing for latent tuberculosis (38.1% versus 84.6%, P < 0.01), thromboprophylaxis (28.6% versus 94.6%, P < 0.01), adequate corticosteroids prescription (72.9% versus 94.6%, P < 0.01), and limitation of narcotics prescribed (68.8% versus 38.9%, P < 0.01). Conclusions: Implementation of a standardized order set, focused on pre-defined quality indicators for hospitalized patients with severe UC, was associated with meaningful improvements to most quality indicators defined by the Toronto Consensus Statements.

Muscle Mass and Direct Oral Anticoagulant Activity in Older Adults With Atrial Fibrillation.

BACKGROUND: Direct oral anticoagulants (DOAC) are hydrophilic drugs with plasma levels inversely proportional to lean body mass. Sarcopenic patients with low muscle mass may be at risk for supra-therapeutic DOAC levels and bleeding complications. We therefore sought to examine the influence of lean body mass on DOAC levels in older adults with atrial fibrillation (AF). METHODS: A prospective cohort study was conducted with patients 65 years of age or more receiving rivaroxaban or apixaban for AF. Appendicular lean mass (ALM) was measured using a bioimpedance device and a dual X-ray absorptiometry scanner. DOAC levels were measured using a standardized anti-Xa assay 4 hours after (peak) and 1 hour before (trough) ingestion. RESULTS: The cohort consisted of 62 patients (47% female, 77.0 ± 6.1 years). The prescribed DOACs were apixaban 2.5 mg (21%), apixaban 5 mg (53%), and rivaroxaban 20 mg (26%). Overall, 16% had supra-therapeutic DOAC levels at trough and 25% at peak. In the multivariable logistic regression model, lower ALM was independently associated with supra-therapeutic DOAC levels at trough (odds ratio per ↓ 1-kg 1.23, 95% confidence interval 1.02 to 1.49) and peak (odds ratio per ↓ 1-kg 1.18, 95% confidence interval 1.02 to 1.37). Addition of ALM to a model consisting of age, total body weight, and renal function resulted in improved discrimination for supra-therapeutic DOAC levels. CONCLUSION: Our proof-of-concept study has identified an association between ALM and DOAC levels in older adults with AF. Further research is needed to determine the impact of ALM on bleeding complications and the potential role of ALM-guided dosing for sarcopenic patients.

Hypersensitivity reactions to high osmolality Total Parenteral Nutrition: a case report.

BACKGROUND: The full range of allergic reactions to Total Parenteral Nutrition (TPN) remains unknown. Additionally, beyond individual allergens, there may be other factors contributing to TPN hypersensitivity reactions. CASE PRESENTATION: We present a case of a patient with negative skin testing to common TPN allergens who had recurrent urticarial reactions to TPN. Her skin reactions resolved once TPN was stopped. Following a literature review, we postulated that the reactions could be due to the high osmolality of her TPN. Consequently, lowering her TPN from 2785 to 1928 mOsm/kg and premedicating with cetirizine resulted in resolution of her urticaria. CONCLUSIONS: When looking at patients who have hypersensitivity reactions to TPN, one must consider that their reactions may be due to factors other than allergens. More studies are needed to clarify the relationship between high osmolality TPN infusions and non-IgE mediated hypersensitivity reactions.

The Comprehensive Assessment of Neurodegeneration and Dementia: Canadian Cohort Study.

BACKGROUND: The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams. METHODS: The COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here. RESULTS: The CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020. CONCLUSION: Availability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years.

Évaluation complète d'une étude de cohorte canadienne portant sur la démence et la neuro-dégénérescence. Contexte : L'évaluation globale de la neuro-dégénérescence et de la démence (COMPASS-ND), étude de cohorte du Consortium canadien en neuro-dégénérescence associée au vieillissement (CCNV), représente une initiative nationale visant à promouvoir la recherche portant sur la démence et à soutenir les programmes de recherche des équipes du CCNV. Totalisant 2310 sujets recrutés partout au pays, cette cohorte longitudinale regroupe des individus fortement « phénotypés ¼ qui présentent diverses formes de démence et de pertes de mémoire légères. En plus de sujets âgés dont les fonctions cognitives sont intactes, ces 2310 sujets ont permis de valider les hypothèses formulées par les équipes du CCNV. Méthodes : Nous avons utilisé de nombreux documents pour décrire cette étude : le protocole de la COMPASS-ND ; la demande initiale de subvention ; le cinquième rapport d'étape semi-annuel du CCNV soumis aux Instituts de recherche en santé du Canada (IRSC) en décembre 2017 ; ainsi que d'autres documents produits à la suite de modifications consécutives à la mise en œuvre de ce projet. Résultats: L'étude de cohorte COMPASS-ND du CCNV inclut des participants de partout au Canada dont les divers états cognitifs sont associés à des maladies neurodégénératives ou au risque d'en souffrir. Ils feront l'objet d'un large éventail d'examens expérimentaux, cliniques, génétiques et d'imagerie afin d'aborder de manière spécifique les causes, le diagnostic, le traitement et la prévention de ces états cognitifs chez les personnes âgées. Les données obtenues à la suite d'évaluations cliniques et cognitives, ainsi que celles issues d'échantillons biologiques, d'imagerie cérébrale, de tests génétiques et de dons de cerveaux, seront utilisées pour tester les hypothèses générées par les équipes de recherche du CCNV et d'autres chercheurs canadiens. Cette étude constitue donc à ce jour l'étude canadienne la plus complète et la plus ambitieuse au sujet de la démence. La présentation des données initiales ayant eu lieu en 2018, la cohorte devrait atteindre sa taille maximale d'ici à 2020.Conclusion : La disponibilité des données de l'étude COMPASS-ND stimulera considérablement la recherche sur la démence au Canada au cours des prochaines années.

Variation of High-Sensitivity Troponin T Results in Patients Undergoing Continuous Renal Replacement Therapy.

BACKGROUND: Cardiac troponins are the preferred biomarker to diagnose myocardial injury. Complicating the interpretation of serial troponins in patients with end-stage renal disease, it has been shown that the hemodialysis procedure results in a small but significant decline in high-sensitivity cardiac troponins (hs-cTnT). This raises the possibility that continuous renal replacement therapy (CRRT) might similarly alter cardiac troponin levels and affect their interpretation when cardiac ischemia is being considered. OBJECTIVE: We sought to determine the effect of CRRT on hs-cTnT levels over time in a group of patients without active myocardial injury. DESIGN: Prospective, observational study. SETTING: Single tertiary care hospital, Montreal, Quebec. PATIENTS: Ten critically ill patients with acute kidney injury (AKI) undergoing CRRT. Cardiac ICU (intensive care unit) patients and acute coronary syndrome patients were excluded from the study. The CRRT prescription was at the discretion of the treating intensivist and relatively high doses were used in this study. MEASUREMENTS: The hs-cTnT levels were drawn pre-CRRT, within 6 hours of initiation, and approximately every 6 hours thereafter along with routine CRRT blood work. METHODS: Changes in hs-cTnT, creatinine, and albumin levels were recorded over the course of CRRT. Mean change in serum analyte concentration and 95% confidence interval was determined for specified time intervals relative to baseline, with paired t tests used to determine statistical significance. RESULTS: Among the 10 patients included in the study, the cause of AKI was primarily acute tubular necrosis from septic shock or hemorrhagic shock. Compared with baseline hs-cTnT levels prior to CRRT initiation, mean hs-cTnT level fell by 42% at 5 to 10 hours post-CRRT initiation, followed by a plateauing of levels for the duration of time on CRRT. LIMITATIONS: Single-center study only applicable to hs-cTnT assay. CONCLUSIONS: This study demonstrates a significant decrease in hs-cTnT within 5 to 10 hours of CRRT initiation. This suggests that interpretation of cardiac troponin changes during CRRT must take into consideration the timing of dialysis initiation relative to the time of sample collection.

CONTEXTE: Les troponines cardiaques constituent le biomarqueur de choix pour diagnostiquer les lésions myocardiques. L'hémodialyse, qui provoque un léger et significatif déclin des troponines cardiaques à haute sensibilité (hs-cTnT), complique leur interprétation chez les patients atteints d'insuffisance rénale terminale. Cette observation suggère que la thérapie de remplacement rénal continue (TRRC) pourrait modifier similairement les taux de troponines cardiaques et affecter leur interprétation lorsqu'une ischémie cardiaque est examinée. OBJECTIF: Nous souhaitions évaluer l'effet dans le temps d'une TRRC sur les taux de hs-cTnT chez des patients sans lésions myocardiques actives. TYPE D'ÉTUDE: Une étude observationnelle prospective. CADRE: Un hôpital de soins tertiaires de Montréal (Québec). SUJETS: Un groupe de dix patients gravement malades, souffrant d'insuffisance rénale aiguë (IRA) et suivant une TRRC. Les patients hospitalisés aux soins intensifs cardiaques ou atteints d'un syndrome coronarien aigu ont été exclus. La prescription d'une TRRC était laissée à la discrétion du médecin intensiviste traitant et des doses relativement élevées ont été administrées au cours de l'étude. MESURES: Les taux de hs-cTnT ont été mesurés conjointement aux prélèvements sanguins de routine requis pour une TRRC; soit avant son initiation, dans les six heures suivantes, puis aux six heures environ par la suite. MÉTHODOLOGIE: Les variations des taux de hs-cTnT, de créatinine et d'albumine ont été colligées pour la durée de la TRRC. La variation moyenne des concentrations d'analytes sériques par rapport aux valeurs initiales et les intervalles de confiance à 95 % ont été déterminés pour des périodes de temps précises. Des tests t couplés ont été employés pour établir la signification statistique des résultats. RÉSULTATS: Chez les patients examinés, l'IRA était principalement due à une nécrose tubulaire aiguë causée par un choc septique ou hémorragique. Le taux moyen de hs-cTnT a chuté de 42 % dans les 5 à 10 heures suivant l'initiation de la TRRC par rapport aux valeurs observées pré-TRRC. Les taux ont ensuite plafonné pour la durée de la TRRC. LIMITES: Il s'agit d'une étude monocentrique applicable uniquement aux mesures de hs-cTnT. CONCLUSION: Cette étude démontre une baisse significative des hs-cTnT dans les 5 à 10 heures suivant l'initiation d'une TRRC. Ce résultat suggère que l'interprétation des variations observées dans les taux de troponines cardiaques au cours d'une TRRC devrait tenir compte du moment où l'échantillon est prélevé par rapport à son initiation.

Effect of Hemodialysis on Levels of High-Sensitivity Cardiac Troponin T.

Cardiac troponin (cTn) is essential for the diagnosis of an acute coronary syndrome (ACS). However, in end-stage renal disease (ESRD) baseline cTn levels are often elevated, and it is unknown whether the hemodialysis (HD) procedure affects cTn levels. This leaves clinicians unsure of how to interpret cTn in HD patients with cardiac ischemia. We therefore sought to determine if plasma levels of high-sensitivity cardiac troponin T (hs-cTnT) vary during or after HD treatment. We prospectively enrolled 10 chronic HD patients who were admitted to our institution. All participants were receiving thrice weekly HD before admission and were medically stable. Those admitted for ACS or to critical care units were excluded. Baseline hs-cTnT was measured immediately before HD. For the subsequent 6 hours, hs-cTnT was measured every 2 hours and every 3 hours thereafter for a total collection period of 24 hours. A significant decline in mean hs-cTnT was noted with HD. During HD (2 hours after HD initiation), hs-cTnT decreased by 10.7% (confidence interval 5% to 17%). Immediately after HD (4 hours after HD initiation), a decline of 12% (confidence interval 5% to 19%) was observed. Thereafter hs-cTnT began to rise. Hs-cTnT levels returned to baseline by 11 hours after HD completion and remained stable for the reminder of the study. In conclusion, HD induces a short-lived negative bias in hs-cTnT. When measured for investigation of ACS, hs-cTnT concentration should be interpreted with respect to time of dialysis and specimen collection.

Bead-Extractor Assisted Ready-to-Use Reagent System (BEARS) for Immunoprecipitation Coupled to MALDI-MS.

Quantitative protein assays play an important role in the study of biological functions. Immunoassays and mass spectrometry are two main technologies for quantifying proteins in biological samples. The combination of immunoprecipitation (IP) with MALDI technology delivers high assay sensitivity and specificity, but the sample preparation procedure involves multiple washing and transfer steps. These steps can be performed either manually (requiring significant time and labor) or automatically (requiring the purchase of a complex liquid-handling workstation). This bottleneck has limited the widespread adoption of this technology. We present here the Bead-Extractor Assisted ready-to-use Reagent System (BEARS) technology for simplified, low cost protein and peptide immunoprecipitation combined with MALDI-MS detection. All of the reagents are stable during long-term storage and can be prepared in advance. In the BEARS technology, a magnetic-bead extractor is used to handle beads from 96 wells simultaneously. A BEARS-based method was developed for plasma renin activity (PRA) and was evaluated on fifty-three clinical samples. These experiments showed that the BEARS assay had an LOD and linear range comparable to the manual method and an automated iMALDI PRA assay, but was 4-times faster than the manual approach. The BEARS iMALDI results also correlated well with a conventional ELISA PRA assay, with a coefficient of determination of 0.98. The BEARS technology provides convenience and affordability, and extends the use of IP-based mass spectrometry technology to most research and clinical laboratories, including those in developing countries.

Successful protocol for eliminating excessive urine microscopies: Quality improvement and cost savings with physician support.

BACKGROUND: Clinical laboratories are under growing pressure to provide faster turn-around-time and maintain high quality while decreasing costs. In a setting of rising test volumes, implementation of evidence-based protocols with physician cooperation and feedback may provide frameworks and support for laboratory utilization optimization. The purpose of this study was to eliminate wasteful urine microscopy by targeting physician ordering behavior, and to ensure quality of care with physician satisfaction surveys. METHODS: We evaluated how physicians use the laboratory for routine urine testing. Urinalysis requisition was redesigned with emphasis on clinical indications for testing. In collaboration with requesting physicians, restriction in reflex microscopy testing was applied with exceptions. Cost saving analysis was conducted based on test volume. After policy change, 2 physician satisfaction surveys were conducted 5year apart to address potential complaints. RESULTS: Over 47,000 urine microscopies have been eliminated annually, while the number of urine dipsticks and cultures remained stable. This translated into a 95% reduction in manual microscopy performed, and an estimated annual saving of $200,000. In both satisfaction surveys, 9 out of 10 physicians considered the change to have "no" or "a beneficial effect" on their clinical practice. Our laboratory did not receive any formal complaints in regards to the protocol change. CONCLUSION: By implementing changes to the way physicians order urinalysis, the number of tests can be substantially reduced. Satisfaction survey proved to be an effective tool for obtaining physician feedback, and support. The results of surveys indicated that new policy achieved significant savings without compromising on patient care. This experience has provided us with strategies on taking initiatives to further optimize utilization of laboratory tests.

Dynamics of vitamin D in patients with mild or inactive inflammatory bowel disease and their families.

BACKGROUND: 25(OH) vitamin D levels may be low in patients with moderately or severely active inflammatory bowel diseases (IBD: Crohn's disease and Idiopathic Ulcerative Colitis) but this is less clear in patients with mild or inactive IBD. Furthermore there is limited information of any family influence on 25(OH) vitamin D levels in IBD. As a possible risk factor we hypothesize that vitamin D levels may also be low in families of IBD patients. OBJECTIVES: To evaluate 25[OH] vitamin D levels in patients with IBD in remission or with mild activity. A second objective is to evaluate whether there are relationships within IBD family units of 25[OH] vitamin D and what are the influences associated with these levels. METHODS: Participants underwent medical history, physical examination and a 114 item diet questionnaire. Serum 25[OH] vitamin D was measured, using a radioimmunoassay kit, (replete ≥ 75, insufficient 50-74, deficient < 25-50, or severely deficient < 25 nmol/L). Associations between 25[OH] vitamin D and twenty variables were evaluated using univariate regression. Multivariable analysis was also applied and intrafamilial dynamics were assessed. RESULTS: 55 patients and 48 controls with their respective families participated (N206). 25[OH] vitamin D levels between patients and controls were similar (71.2 ± 32.8 vs. 68.3 ±26.2 nmol/L). Vitamin D supplements significantly increased intake but correlation with serum 25[OH] vitamin D was significant only during non sunny months among patients. Within family units, patients' families had mean replete levels (82.3 ± 34.2 nmol/L) and a modest correlation emerged during sunny months between patients and family (r2 =0.209 p = 0.032). These relationships were less robust and non significant in controls and their families. CONCLUSIONS: In patients with mild or inactive IBD 25[OH] vitamin D levels are less than ideal but are similar to controls. Taken together collectively, the results of this study suggest that patient family dynamics may be different in IBD units from that in control family units. However contrary to the hypothesis, intra familial vitamin D dynamics do not pose additional risks for development of IBD.

Effects of vitamin C and vitamin D administration on mood and distress in acutely hospitalized patients.

BACKGROUND: Hypovitaminosis C and D are highly prevalent in acute-care hospitals. Malnutrition with regard to these vitamins has been linked to mood disturbance and cognitive dysfunction. OBJECTIVE: The objective was to determine whether vitamin C or D supplementation improves mood state or reduces psychological distress in acutely hospitalized patients with a high prevalence of hypovitaminosis C and D. DESIGN: A randomized, double-blind, active-control clinical trial compared the effects of vitamin C (500 mg twice daily) with those of high-dose vitamin D (5000 IU/d) on mood (Profile of Mood States) and psychological distress (Distress Thermometer). RESULTS: Vitamin C provided for a mean of 8.2 d increased plasma vitamin C concentrations to normal (P < 0.0001) and was associated with a 71% reduction in mood disturbance (P = 0.0002) and a 51% reduction in psychological distress (P = 0.0002). High-dose vitamin D provided for a mean of 8.1 d increased plasma 25-hydroxyvitamin D [25(OH)D] concentrations (P < 0.0001), but not into the normal range, and had insignificant effects on mood (P = 0.067) and distress (P = 0.45). The changes in mood and distress in the vitamin C group were greater than those in the vitamin D group (P = 0.045 for mood; P = 0.009 for distress). CONCLUSIONS: Short-term therapy with vitamin C improves mood and reduces psychological distress in acutely hospitalized patients with a high prevalence of hypovitaminosis C and D. No conclusion is possible regarding the effects of vitamin D because the dose and duration of therapy were insufficient to raise 25(OH)D concentrations into the normal range. This trial was registered at clinicaltrials.gov as NCT01630720.

Preoperative parathyroid hormone levels as a predictor of postthyroidectomy hypocalcemia.

OBJECTIVES: The goal of the present study is to determine whether a decline in the 1-hour postoperative parathyroid hormone (PTH) level relative to the preoperative level is predictive of hypocalcemia. METHODS: This is a retrospective study involving 142 consecutive patients who underwent total thyroidectomy. Changes in preoperative PTH levels were then compared with the 1-hour levels. RESULTS: Thirty-four of 142 patients (23.9%) who underwent total thyroidectomy developed hypocalcemia. Thirty-one of the 34 patients who became hypocalcemic had a 1-hour postoperative PTH drop of 70% or more when compared with the preoperative value (sensitivity = 91%, specificity = 98%, positive predictive value = 94%, and negative predictive value = 97%). CONCLUSION: A decline in the preoperative PTH level of 70% or greater at 1 hour following total thyroidectomy appears to be a reliable predictor of patients at risk of developing hypocalcemia. By allowing thyroid surgeons to identify these patients in the early postoperative period, calcium supplementation can be initiated sooner.

Isocratic rapid liquid chromatographic method for simultaneous determination of carotenoids, retinol, and tocopherols in human serum.

An improved isocratic and rapid HPLC method was developed for the measurement of carotenoids, retinol and tocopherols in human serum. Vitamins were extracted with hexane. Mobile phase consisted of a mixture acetonitrile:methylene chloride:methanol with 20 mM ammonium acetate. This method used a small bead size (3 microm) Spherisorb ODS2 column with titane frits. Diode array and fluorescence detectors were used respectively for the detection of carotenoids and retinol/tocopherols. Chromatographic separation was complete in 13 min for beta-cryptoxanthin, cis-trans-lycopene, alpha-carotene, beta-carotene, cis-beta-carotene, retinol, delta-tocopherol, gamma-tocopherol and alpha-tocopherol. Echinenone and tocol were employed as internal standards for diode array and fluorescence detection. Accuracy was validated using standard reference material (SRM) 968C. Intra-assay and inter-assay precision were respectively 0.2-7.3% and 3.6-12.6%. Sensitivity was verified using the ICH recommendations and the limit of detection (LOD) obtained was sufficient for routine clinical application.

Cost savings associated with post-thyroidectomy parathyroid hormone levels.

OBJECTIVES: A 1-hour post-thyroidectomy parathyroid hormone (PTH) level of < or =8 ng/L is predictive of patients who will develop hypocalcemia and guides early supplementation with calcium and vitamin D. However, most hypocalcemic patients fail to meet this criterion. The goal of this study was to determine whether PTH < or = 15 ng/L could be used as a better predictor of hypocalcemia. STUDY DESIGN, SUBJECTS, AND METHODS: This retrospective study involved 270 thyroidectomy patients (2004-2006). PTH and calcium levels, length of admission, supplementation, and rates of hypocalcemia were recorded. RESULTS: Forty-three percent (26/60) of patients developing hypocalcemia met the PTH < or = 8 ng/L cut-off. In contrast, 80% (48/60) of patients developing hypocalcemia had a PTH < or = 15 ng/L. Two point two percent of patients had a 1-hour PTH < or = 15 ng/L and failed to develop hypocalcemia, for a specificity of 97%. CONCLUSIONS: A 1-hour PTH cut-off of < or =15 ng/L for prophylactic supplementation should allow the prevention of the majority of cases of hypocalcemia, leading to significant cost savings by shortening hospital stays.

Comparison of a real-time polymerase chain reaction assay for lactase genetic polymorphism with standard indirect tests for lactose maldigestion.

BACKGROUND & AIMS: There is a discrepancy in outcome between the lactose tolerance and breath hydrogen tests for lactose maldigestion. The availability of a validated genetic test for lactase polymorphism allows a reevaluation of these tests. METHODS: Thirty healthy adults participated in a 50-g lactose challenge test at a university clinic. Blood was drawn for genetic and timed blood glucose testing (2 hours), and breath hydrogen was measured (4.5 hours). Lactase genetic polymorphism was assessed by a real-time polymerase chain reaction assay. Participants completed a diet questionnaire, and symptoms were recorded during the lactose challenge. Sensitivity and specificity were calculated for each indirect test. The 2-way kappa coefficient between these tests was evaluated. Student t test and Wilcoxon rank sum test were used to compare variables. RESULTS: The lactose tolerance test as a standard had an 87.5% sensitivity and 92.7% specificity for genetic status. Only a moderate agreement between lactose tolerance test and breath hydrogen test was observed (2-way kappa coefficient, .53; 95% confidence interval, .22-.83). When genetic status was used as standard, symptoms had a moderate sensitivity and specificity. Lactose tolerance test had very good sensitivity, and the breath test had excellent specificity. CONCLUSIONS: Both indirect tests independently have good to very good sensitivities and specificities for genetic lactase status. The noted disagreement likely reflects variables that affect the tests independently of intestinal lactase status. The value of these tests in the light of the availability of genetic testing is discussed.

The value of multi-modal gene screening in HNPCC in Quebec: three mutations in mismatch repair genes that would have not been correctly identified by genomic DNA sequencing alone.

Hereditary non-polyposis colorectal cancer (HNPCC) is a dominantly inherited cancer syndrome caused by a mutation in one of the mismatch repair genes, most frequently MLH1 or MSH2. The rate of mutation detection is influenced by many factors, including the diagnostic methods used. Large deletions, which occur frequently in MLH1 and MSH2, are not detected by exon-by-exon screening methods. Here, we describe three mutations in mismatch repair genes detected using a screening protocol that combines protein truncation test (PTT) analysis and multiplex ligation-dependent probe amplification (MLPA) with genomic and cDNA sequencing. Two of these mutations consist of large deletions in MLH1 that were detected by both MLPA and PTT but that would have been missed by genomic DNA sequencing. The third is a large deletion in MSH2 that could not be detected by PTT because of its location relative to the primers used to amplify the cDNA, or by sequencing. This mutation was detected by MLPA.

Postoperative parathyroid hormone levels in conjunction with corrected calcium values as a predictor of post-thyroidectomy hypocalcemia: review of outcomes 1 year after the implementation of a new protocol.

OBJECTIVES: To determine the effectiveness of post-thyroidectomy parathyroid hormone (PTH) levels in conjunction with corrected calcium values as predictors of patients at risk of developing hypocalcemia. METHODS: This is a follow-up study reviewing the results of a newly implemented post-thyroidectomy algorithm. The changes in management from the previous protocol involve decision making based on the 12-hour corrected calcium and PTH levels, as well as the 1-hour PTH value. The study involved 120 patients separated into two groups: 60 prior to implementation of the protocol and 60 following the implementation of the protocol. Patients having completion thyroidectomy, neck dissections, or parathyroidectomy were excluded. RESULTS: Since the implementation of the new protocol, there has been a reduction in the rate of transient hypocalcemia (25% to 12%; p = .059), fewer blood tests (23 to 15 per patient), and earlier patient discharges. CONCLUSIONS: The new algorithm is effective in detecting patients who are not at risk of developing hypocalcemia at 12 hours. This has led to significant cost savings at our institution. Moreover, calcium supplementation based on the 1-hour PTH level has coincided with a reduction in cases of transient hypocalcemia.

Systemic soluble Tie2 expression inhibits and regresses corneal neovascularization.

This study was designed to determine if soluble Tie2 (sTie2) expression inhibits and regresses corneal neovascularization, and if VEGF contributes to its effect. The corneas of BALB/c mice were scraped and the mice were injected with either an adenovirus expressing soluble Tie2 (Ad.sTie2) or an empty adenoviral vector. When injected at the inhibition timepoint (one day prior to corneal injury), the mean percentage of neovascularized corneal area two weeks later in Ad.sTie2-treated mice vs. controls was 56.37+/-9.15% vs. 85.79+/-3.55% (p=0.04). At the regression timepoint (4 weeks after corneal scrape), the mean area of corneal neovascularization in Ad.sTie2-treated mice was 42.89+/-4.74% vs. 75.01+/-3.22% in the control group (p=0.007). VEGF expression was significantly higher in Ad.sTie2-treated mice at the inhibition timepoint and there was no significant difference at the regression timepoint. These findings suggest that sTie2 inhibits and regresses corneal neovascularization in a VEGF-independent manner.

Impact of ambulance transportation on resource use in the emergency department.

OBJECTIVE: To determine how ambulance transportation is associated with resource use in the emergency department (ED). METHODS: A retrospective administrative database review of patient visits to a Montreal tertiary care hospital ED in one year (April 2000-March 2001). Measures of resource use included ED length of stay, admission to the hospital, and whether consultations and radiology/imaging tests (excluding plain-film x-rays) were ordered from the ED. RESULTS: During the study period, 39,674 patients made 59,142 visits to the ED. Ambulance transportation was used for 15.6% of these ED visits. Compared with non-ambulance visits, ambulance visits were more likely to be made by older patients (mean age: 68 vs. 47 years), to be made by females (59% vs. 55%), to have a greater triage urgency score (mean on 1-5 scale, with 1 most urgent: 2.7 vs. 3.9), and to occur after office hours, 5 PM to 9 AM (47% vs. 43%). Ambulance visits were also more likely than non-ambulance visits to result in: a longer length of stay (mean: 13.3 hours [95% CI = 13.0 to 13.6] vs. 5.9 [95% CI = 5.8 to 6.0]), hospital admission (40% vs. 10%) (odds ratio [OR]: 5.94 [95% CI = 5.59 to 6.33]), consultations (56% vs. 20%) (OR: 5.15 [95% = 4.86 to 5.45]), and radiology/imaging tests (20% vs. 12%) (OR: 1.93 [95% CI = 1.81 to 2.07]). In multivariate models that adjusted for the effects of age, gender, triage urgency, and temporal factors, ambulance transportation maintained its association with greater resource use. CONCLUSIONS: This preliminary study indicates that patients arriving at the ED by ambulance use significantly more resources than their walk-in counterparts.

Aquaporin-1 expression is decreased in human and mouse corneal endothelial dysfunction.

PURPOSE: To determine if aquaporin-1 expression is decreased in human and mouse corneal endothelial dysfunction. METHODS: Immunohistochemistry with anti-aquaporin 1 antibody and confocal microscopy were used to study a case series of human corneal specimens, and a mouse model of corneal endothelial injury was created with injection of sterile hot water into the anterior chamber with a 33 gauge needle. Western blotting of mouse and human corneas was used to provide confirmatory evidence. RESULTS: Aquaporin-1 was found to be expressed in normal human cornea and decreased in human corneas with endothelial disease but not in human corneas with non-endothelial corneal disease. Aquaporin-1 was also found to be reduced in mouse corneas subjected to corneal endothelial injury. Both results were confirmed by western blot analysis. CONCLUSIONS: Corneal endothelial injury is associated with decreased aquaporin-1 expression.

N-acetyl-L-tyrosine as a tyrosine source in adult parenteral nutrition.

BACKGROUND: N-acetyl-L-tyrosine (NAT) is commonly used in place of tyrosine in parenteral nutrition, but human studies carried out to date indicate considerable amounts of it are excreted unchanged in the urine. NAT retention has not been well studied in parenterally fed adults. METHODS: NAT retention was measured in 13 adults receiving continuous parenteral nutrition with Aminosyn II 15% (Abbott Laboratories, Abbott Park, IL). RESULTS: Approximately 35% of administered NAT was excreted unchanged in the urine, with no important effect of infusion rate, N balance, or level of renal function on this value. Sufficient NAT was retained that the prescription of 1 g total amino acids/kg x day(-1) using this product exceeded the combined recommended dietary allowance for aromatic amino acids CONCLUSION: As used in the clinical setting, the phenylalanine and NAT composition of Aminosyn II is sufficient to meet the combined aromatic amino acid needs of adults with normal phenylalanine hydroxylase activity.