Acetylcholinesterase is regulated by exposure of ultraviolet B in skin keratinocytes: A potential inducer of cholinergic urticaria.

Cholinergic urticaria is a dermatological disease characterized by the presence of large patches of red skin and transient hives triggered by factors, such as exercise, sweating, and psychological tension. This skin problem is hypothesized to be attributed to a reduced expression of acetylcholinesterase (AChE), an enzyme responsible for hydrolyzing acetylcholine (ACh). Consequently, ACh is thought to the leak from sympathetic nerves to skin epidermis. The redundant ACh stimulates the mast cells to release histamine, triggering immune responses in skin. Here, the exposure of ultraviolet B in skin suppressed the expression of AChE in keratinocytes, both in in vivo and in vitro models. The decrease of the enzyme was resulted from a declined transcription of ACHE gene mediated by micro-RNAs, that is, miR-132 and miR-212. The levels of miR-132 and miR-212 were markedly induced by exposure to ultraviolet B, which subsequently suppressed the transcriptional rate of ACHE. In the presence of low level of AChE, the overflow ACh caused the pro-inflammatory responses in skin epidermis, including increased secretion of cytokines and COX-2. These findings suggest that ultraviolet B exposure is one of the factors contributing to cholinergic urticaria in skin.

Solar light induces the release of acetylcholine from skin keratinocytes affecting melanogenesis.

Cholinergic system conducts signal transmission in brain and muscle. Besides nervous system, the nonneuronal functions of cholinergic system have been proposed in various tissues. The expression of cholinergic proteins and release of acetylcholine in human skin have been reported, but its mechanism and influence on dermatological functions is not elucidated. Here, the expression profile of cholinergic markers was further investigated in skin and keratinocyte. The expression levels of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), vesicular acetylcholine transporter (VAChT), and synaptophysin, were upregulated during differentiation of keratinocytes. In cultured keratinocytes, a transient exposure of solar light induced the release of acetylcholine, which was mediated by intracellular Ca2+ mobilization. The light-induced acetylcholine release was mediated by the present of opsin. The light-induced melanogenesis was inhibited by acetylcholine or AChE inhibitor in melanocyte in vitro and mouse skin ex vivo. These results indicated that the potential role of cholinergic system could be a negative regulator in skin pigmentation.

An Optimized Extract, Named Self-Growth Colony, from Platelet-Rich Plasma Shows Robust Skin Rejuvenation and Anti-Ageing Properties: A Novel Technology in Development of Cosmetics.

INTRODUCTION: Inspired by application of platelet-rich plasma (PRP) in skin treatment during injuries, an extracting method was developed here to recover high amounts of cytokines and growth factors from PRP; this prepared extract was named as self-growth colony (SGC). METHODS: In optimization of SGC preparation, various parameters were tested, for example, centrifugation force, freeze-thaw, sonication, and inclusion of calcium chelator. The amounts of cytokines and growth factors, including platelet factor 4, ß-thromboglobulin, epidermal growth factor, vascular endothelial growth factor, platelet-derived growth factor, were measured by ELISA assay. RESULTS: By comparing to PRP, the prepared SGC contained a significant higher amount of measured growth factors. In addition, the degradation of growth factors within SGC during the storage was calibrated, which showed better stability as compared to that of PRP preparation. Having possible application in skin care, the optimized SGC was chemically standardized by using the enrichment of growth factors. Application of SGC in cultured keratinocytes stimulated the wound healing of injured cultures. In line to this notion, SGC was applied onto human skin, and thereafter the robust improvement of skin properties was revealed. CONCLUSIONS: The potential application of SGC in treating skin rejuvenation and ageing, as well as its elaborated application for medical purpose, that is, wound healing, was illustrated.

Levothyroxine prescribing and laboratory test use after a minor change in reference range for thyroid-stimulating hormone.

BACKGROUND: Prescribing of levothyroxine and rates of thyroid function testing may be sensitive to minor changes in the upper limit of the reference range for thyroid-stimulating hormone (TSH) that increase the proportion of abnormal results. We evaluated the population-level change in levothyroxine prescribing and TSH testing after a minor planned decrease in the upper limit of the reference range for TSH in a large urban centre with a single medical laboratory. METHODS: Using provincial administrative data, we compared predicted volumes of TSH tests with actual TSH test volumes before and after a planned change in the TSH reference range. We also determined the number of new levothyroxine prescriptions for previously untreated patients and the rate of changes to the prescribed dose for those on previously stable, long-term levothyroxine therapy before and after the change in the TSH reference range. RESULTS: Before the change in the TSH reference range, actual and predicted monthly volumes of TSH testing followed an identical course. After the change, actual test volumes exceeded predicted test volumes by 7.3% (95% confidence interval [CI] 5.3%-9.3%) or about 3000 to 5000 extra tests per month. The proportion of patients with newly "abnormal" TSH results almost tripled, from 3.3% (95% CI 3.2%-3.4%) to 9.1% (95% CI 9.0%-9.2%). The rate of new levothyroxine prescriptions increased from 3.24 (95% CI 3.15-3.33) per 1000 population in 2013 to 4.06 (95% CI 3.96-4.15) per 1000 population in 2014. Among patients with preexisting stable levothyroxine therapy, there was a significant increase in the number of dose escalations (p < 0.001) and a total increase of 500 new prescriptions per month. INTERPRETATION: Our findings suggest that clinicians may have responded to mildly elevated TSH results with new or increased levothyroxine prescriptions and more TSH testing. Knowledge translation efforts may be useful to accompany minor changes in reference ranges.

Tectorigenin, an isoflavone aglycone from the rhizome of Belamcanda chinensis, induces neuronal expression of erythropoietin via accumulation of hypoxia-inducible factor-1α.

Traditional Chinese medicines (TCMs) have been demonstrated as an important source for potential drug discovery. Flavonoids are regarded as the most common active components in TCMs because of their beneficial functions in the brain and erythropoietic system. Erythropoietin (EPO), a glycoprotein hormone, has been well-studied for its neuroprotective function. The blood circulating EPO is not able to cross the blood brain barrier, and thus there is mounting demand to search for compounds that can induce endogenous cerebral EPO. Here, tectorigenin, an active compound in the rhizome of Belamcanda chinensis (L.) DC., significantly induced the expression of EPO mRNA via accumulation of hypoxia-inducible factor (HIF)-1α in cultured neuron-like NT2/D1 cells and rat cortical neurons. Furthermore, tectorigenin induced transcription of HIF-1α and reduced degradation of HIF-1α-OH, a hydroxylated form of HIF-1α, in the culture. Thus, the upregulation of HIF-1α was assumed to play a significant role in regulating EPO during the treatment of tectorigenin in cultured neurons. Hence, we reported the neuroprotective function of tectorigenin through upregulation of EPO in neurons, which could be a good candidate in developing drugs or food supplements for the treatment of brain disorders.

Sociodemographic and geospatial associations with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in a large Canadian city: an 11 year retrospective study.

BACKGROUND: The first Canadian outbreak of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was identified in 2004 in Calgary, Alberta. Using a novel model of MRSA population-based surveillance, sociodemographic risk associations, yearly geospatial dissemination and prevalence of CA-MRSA infections over an 11 year period was identified in an urban healthcare jurisdiction of Calgary. METHODS: Positive MRSA case records, patient demographics and laboratory data were obtained from a centralized Laboratory Information System of Calgary Laboratory Services in Calgary, Alberta, Canada between 2004 and 2014. Public census data was obtained from Statistics Canada, which was used to match with laboratory data and mapped using Geographic Information Systems. RESULTS: During the study period, 52.5% of positive MRSA infections in Calgary were CA-MRSA cases. The majority were CMRSA10 (USA300) clones (94.1%; n = 4255), while the remaining case (n = 266) were CMRSA7 (USA400) clones. Period prevalence of CMRSA10 increased from 3.6 cases/100000 population in 2004, to 41.3 cases/100000 population in 2014. Geospatial analysis demonstrated wide dissemination of CMRSA10 annually in the city. Those who are English speaking (RR = 0.05, p <  0.0001), identify as visible minority Chinese (RR = 0.09, p = 0.0023) or visible minority South Asian (RR = 0.25, p = 0.015), and have a high median household income (RR = 0.27, p <  0.0001) have a significantly decreased relative risk of CMRSA10 infections. CONCLUSIONS: CMRSA10 prevalence increased between 2004 and 2007, followed by a stabilization of cases by 2014. Certain sociodemographic factors were protective from CMRSA10 infections. The model of MRSA population-surveillance and geomap outbreak events can be used to track the epidemiology of MRSA in any jurisdiction.

Sociodemographic associations with abnormal estimated glomerular filtration rate (eGFR) in a large Canadian city: a cross-sectional observation study.

BACKGROUND: Chronic kidney disease (CKD) is often asymptomatic in its early stages but is indicated and is diagnosed with an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2. Certain sociodemographic groups are known to be at risk for CKD, but it is unclear if there are strong associations between these at risk groups with abnormal eGFR test results in Canada. Using only secondary laboratory and Census data, geospatial variation and sociodemographic associations with abnormal eGFR result rate were investigated in Calgary, Alberta. METHODS: Secondary laboratory data from all adult community patients who received an eGFR test result were collected from Calgary Laboratory Service's Laboratory Information System, which is the sole supplier of laboratory services for the large metropolitan city. Group-level sociodemographic variables were inferred by combining laboratory data with the 2011 Canadian Census data. Poisson regression and relative risk (RR) were used to calculate associations between sociodemographic variables with abnormal eGFR. Geographical distribution of abnormal eGFR result rates were analyzed by geospatial analysis using ArcGIS. RESULTS: Of the 346,663 adult community patients who received an eGFR test result, 28,091 were abnormal (8.1%; eGFR < 60 ml/min/1.73m2). Geospatial analysis revealed distinct geographical variation in abnormal eGFR result rates in Calgary. Women (RR = 1.11, P < 0.0001), and the elderly (age ≥ 70 years; P < 0.0001) were significantly associated with an increased risk for CKD, while visible minority Chinese (RR = 0.73, P = 0.0011), South Asians (RR = 0.67, P < 0.0001) and those with a high median household income (RR = 0.88, P < 0.0001) had a significantly reduced risk for CKD. CONCLUSIONS: Presented here are significant sociodemographic risk associations, and geospatial clustering of abnormal eGFR result rates in a large metropolitan Canadian city. Using solely publically available secondary laboratory and Census data, the results from this study aligns with known sociodemographic risk factors for CKD, as certain sociodemographic variables were at a higher risk for having an abnormal eGFR test result, while others were protective in this analysis.

The incidence of acute myeloid leukemia in Calgary, Alberta, Canada: a retrospective cohort study.

BACKGROUND: The incidence rate of acute myeloid leukemia (AML) was determined in the Calgary Metropolitan Area, a major Canadian city. METHODS: Data from all patients diagnosed with AML between January 1, 2011 and December 31, 2015 were retrieved from a single, centralized cancer cytogenetics laboratory for bone marrow samples, the sole diagnostic facility of its kind in Southern Alberta. RESULTS: The calculated incidence rate was 2.79 cases per 100,000 person-years with a median age of 60, slightly lower than previously published data. The age-standardized incidence rate for Canada was 3.46 cases per 100,000 person-years. The higher value is reflective of Calgary's younger population compared to the rest of Canada. Higher male incidence and greatest incidence occurring at approximately the age of 85 is similar to data from other developed countries. The lower incidence rates and median age of diagnosis, in comparison with that of other high-income nations, may be due to differences in the proportion of aging citizens in the population. CONCLUSION: This is the first published incidence rate of acute myeloid leukemia (AML) in Canada across all age groups.

The UV-induced uptake of melanosome by skin keratinocyte is triggered by α7 nicotinic acetylcholine receptor-mediated phagocytosis.

The melanosome is an organelle that produces melanin for skin pigmentation, which is synthesized by epidermal melanocytes, subsequently transported and internalized by epidermal keratinocytes. Exposure to ultraviolet (UV) from sunlight radiation is a major stimulator of melanosome uptake by keratinocytes. Acetylcholine (ACh) is known to be released by keratinocytes under UV exposure, which regulates melanin production in melanocytes by participating in which has been named as 'skin synapse'. Here, the role of cholinergic molecules, i.e. ACh and α7 nicotinic acetylcholine receptor (nAChR), in regulating melanosome uptake through phagocytosis by keratinocytes was illustrated. In cultured keratinocytes (HaCaT cells), the fluorescent beads at different sizes imitating melanosomes, or melanosomes, were phagocytosed under UV exposure. The UV-induced phagocytosis in keratinocytes was markedly increased by applied ACh, an acetylcholinesterase (AChE) inhibitor or an α7 nAChR agonist. By contrast, the antagonist of α7 nAChR was able to fully block the UV-induced phagocytosis, suggesting the role of α7 nAChR in this event. The intracellular Ca++ mobilization was triggered by UV exposure, accounting for the initiation of phagocytosis. The blockage of UV-mediated Ca++ mobilization, triggered by BAPTA-AM or α7 nAChR antagonist, resulted in a complete termination of phagocytosis. Besides, the phosphorylation of cofilin, as well as expression and activation of RhoA, accounting for phagocytosis was induced by UV exposure: the phosphorylation was blocked by BAPTA-AM or α7 nAChR antagonist. The result suggests that the cholinergic system, especially α7 nAChR, is playing a regulatory role in modulating melanosome uptake in keratinocytes being induced by UV exposure.

The mean abnormal result rates of laboratory tests ordered in the emergency department: shooting percentage insights from a multi-centre study.

OBJECTIVE: While there is concern about excessive laboratory test ordering in the ED, it is difficult to quantify the problem. One solution involves the Mean Abnormal Result Rate (MARR), which is the proportion of tests ordered that return abnormal results. The primary objective of this study was to calculate MARR scores, and factors associated with MARR scores, for tests ordered between April 2014 and March 2019 at adult EDs in Calgary. METHODS: Administrative data were obtained for 40 laboratory tests that met selection criteria. One possible MARR correlate, physician experience, was quantified for 209 ED physicians as number of years since licensure. Analyses were descriptive where appropriate for whole-population data. RESULTS: The condensed dataset comprised 3,395,312 test results on 415,653 unique patients. The aggregate 5-year MARR score was 40.1%. The highest per-test score was for BNP (80.5%), while the lowest was for glucose (7.9%). MARR scores were higher for nurse-initiated orders than for physician-initiated orders (44.7% vs. 38.1%). The MARR score correlated inversely with number of tests per order (r = - 0.90; 95% confidence interval [CI] - 0.65 to - 0.94; p < 0.001) and directly with physician experience (r = 0.28, 95% CI 0.20 to 0.27; p < 0.001). CONCLUSION: This is the first study to measure MARR scores in an ED setting. While lower scores (close to 5%) are less optimal in principle, ideal scores will depend on the clinical context in which tests are used. However, once departmental benchmarks are established, MARR score-monitoring allows efficient tracking of ordering practices across millions of tests.

RéSUMé: OBJECTIFS: Bien que l'on s'inquiète d'une commande excessive de tests de laboratoire dans le service d'urgence, il est difficile de quantifier le problème. Une solution implique le taux de résultat anormal moyen (MARR), qui est la proportion de tests commandés qui renvoient des résultats anormaux. L'objectif principal de cette étude était de calculer les scores MARR, et les facteurs associés aux scores MARR, pour les tests commandés entre avril 2014 et mars 2019 dans les services d'urgence pour adultes à Calgary. LES MéTHODES: Des données administratives ont été obtenues pour 40 tests de laboratoire répondant aux critères de sélection. Une corrélation possible du MARR, soit l'expérience des médecins, a été quantifié pour 209 médecins urgentistes en nombre d'années depuis l'autorisation d'exercer. Les analyses étaient descriptives, le cas échéant, pour les données sur l'ensemble de la population. RéSULTATS: L'ensemble de données condensé comprenait 3,395,312 résultats de tests sur 415 653 patients uniques. Le score MARR global à 5 ans était de 40,1%. Le score le plus élevé par test était pour le peptide cérébral natriurétique BNP (80,5%), tandis que le plus bas était pour le glucose (7,9%). Les scores de MARR sont plus élevés pour les ordonnances initiées par les infirmières que pour les ordonnances initiées par les médecins (44,7% contre 38,1%). Le score MARR s'est corrélé inversement avec le nombre de tests par ordre (r = − 0,90; intervalle de confiance de 95 % [IC] − 0.65 to − 0,94; p < 0.001) et directement avec l'expérience du médecin (r = 0.28, IC à 95 % 0.20­0.27; p < 0.001). CONCLUSIONS: Il s'agit de la première étude à mesurer les scores du MARR dans un contexte de service d'urgence. Bien que des scores inférieurs (près de 5%) sont moins optimaux en principe, les scores idéaux dépendront du contexte clinique dans lequel les tests sont utilisés. Cependant, une fois les points de repère ministériels établis, la surveillance des scores du MARR permet de suivre efficacement les pratiques de commande sur des millions de tests.

Scutellarin potentiates the skin regenerative function of self growth colony, an optimized platelet-rich plasma extract, in cultured keratinocytes through VEGF receptor and MAPK signaling.

BACKGROUND: Migration of keratinocyte plays an essential role in wound healing. The proprietary platelet-rich plasma from human blood, named as self-growth colony (SGC), functions in stimulating migration of wounded keratinocytes. In addition, the growth factors, including VEGF, being enriched in SGC could account for this function. Scutellarin, an active phytochemical from root of Scutellaria barbata D. Don, has been proposed to have various pharmacological functions; however, the activity in epidermal skin cells is yet to be explored. Here, the role of scutellarin in potentiating the functionality of SGC to promote the regeneration of wounded keratinocyte was probed. METHODS: Molecular docking and ultrafiltration-based LC-MS were performed to verify the binding between scutellarin and VEGF, which potentiated the VEGF-mediated functions. Scratch assay, performed on cultured keratinocytes, was to analyze the treatments of SGC and scutellarin in the process of wound healing. Western blot analysis was to confirm the involvement of signaling cascades in observed effects. RESULTS: We have identified the binding of scutellarin with VEGF. The binding accounted for the potentiation role of scutellarin in skin regeneration, as triggered by SGC. The co-treatment of scutellarin and SGC onto scratched keratinocyte cultures was able to enhance the process of wound healing, that is, scutellarin showed a potentiating effect to SGC. In addition, the potentiation of scutellarin was shown to be mediated by phosphorylation of VEGF receptor-2 (VEGFR2) and mitogen-activated protein kinase (MAPK) signaling. CONCLUSION: These findings support the application of scutellarin as an enhancing agent in potentiating the SGC-mediated wound healing.

Capsaicin, a Phytochemical From Chili Pepper, Alleviates the Ultraviolet Irradiation-Induced Decline of Collagen in Dermal Fibroblast via Blocking the Generation of Reactive Oxygen Species.

Capsaicin, a major ingredient in chili pepper, has broad pharmaceutical applications, including relieving pain, anti-inflammation, and treating psoriasis. In dermatological biology, capsaicin has been shown to prevent the ultraviolet (UV)-induced melanogenesis via TRPV1 receptor. To strengthen the roles of capsaicin in skin function, the damaged skin, triggered by exposure to UV, was reversed by capsaicin in both in vitro and in vivo models. In cultured dermal fibroblasts, the exposure to UV induced a decrease of collagen synthesis and increases expression of matrix metalloproteinases (MMPs), generation of reactive oxygen species (ROS), and phosphorylation of Erk and c-Jun, and these events subsequently led to skin damage. However, the UV-mediated damages could be reversed by pre-treatment with capsaicin in a dose-dependent manner. The effect of capsaicin in blocking the UV-mediated collagen synthesis was mediated by reducing generation of ROS in dermal fibroblasts, instead of the receptor for capsaicin. Hence, capsaicin has high potential value in applying as an agent for anti-skin aging in dermatology.

Factors Associated with Hyponatremia in Patients Newly Prescribed Citalopram: A Retrospective Observational Study.

BACKGROUND: Hyponatremia is a common and under-recognized adverse drug reaction of selective serotonin re-uptake inhibitor (SSRI) antidepressants. Despite its clinical importance, there are few large-scale studies on the factors associated with hyponatremia. OBJECTIVE: The aim of this study was to determine the incidence of hyponatremia and to identify patient factors associated with hyponatremia in a large, population-based cohort initiating new prescriptions for citalopram. METHODS: We included all patients with a new prescription for citalopram during 2010-2017, inclusive, with baseline and post-initiation serum sodium values available. Data were obtained from an Alberta Health Pharmacy database to identify new citalopram prescriptions. Laboratory values for patients with new prescriptions were obtained from linked Calgary Laboratory Services data. Incident hyponatremia was defined as serum sodium level < 135 mmol/L, following prescription initiation. Associations were determined by performing Cox regression with time-varying covariate analysis, with the development of hyponatremia as the dependent variable. RESULTS: A total of 19,679 patients with new prescriptions were identified; 12,842 females and 6837 males. The mean age was 55.48 years (SD 21.35). Of these patients, 3250 (16.5%) developed hyponatremia, 1996 (15.5% of) females and 1254 (18.3% of) males (p = 0.002). Cox regression showed significant associations of hyponatremia with lower baseline sodium (HR 0.788), older age (HR 1.029), thiazide diuretic use (HR 1.141), and male sex (HR 1.168). Pharmaceutical manufacturer or strength of citalopram did not have significant effects on the development of hyponatremia. CONCLUSION: This study provides additional data on the predictors of hyponatremia among patients initiating citalopram therapy. We report a 16.5% incidence of hyponatremia after starting citalopram treatment, and significant new findings include a higher incidence in males. This is the first published incidence of hyponatremia following the initiation of citalopram treatment across all ages in Canada.

Edible Bird's Nest, an Asian Health Food Supplement, Possesses Moisturizing Effect by Regulating Expression of Filaggrin in Skin Keratinocyte.

Edible bird's nest (EBN) has been consumed as a Chinese delicacy for hundreds of years; the functions of which have been proposed to prevent lung disease, strengthen immune response, and restore skin youthfulness. To support the skin function of EBN, the water extract and the enzymatic digest of EBN with enriched digested peptides were tested in cultured keratinocyte, HaCaT cell line. The effects of EBN extract and digest in inducing proteins crucial for skin moisturizing were determined in both in vitro and ex vivo models. In cultured keratinocytes, the expressions of S100-fused type proteins contributing to skin barrier function in the stratum corneum, e.g. filaggrin and filaggrin-2, were determined in both mRNA and protein levels, which were markedly induced in the treatment of EBN extract or digest. The EBN-induced gene transcriptions of filaggrin and filaggrin-2 were mediated by activation of p38 MAPK pathway and various transcription factors, e.g. GATA3, PPARα, PPARß, and PPARγ: these transcriptional factors were markedly activated by the digested products of EBN, as compared to the extract, in cultured keratinocytes. By using atomic force microscopy (AFM), the EBN-treated keratinocyte was shown to have more liquid-like morphology, as compared to a control cell. The EBN digest showed better induction on these moisturizing effects as compared to the extract. These lines of evidence therefore suggested the water moisturizing effect of EBN in skin function.

A prepared platelet-rich plasma extract, namely Self-Growth Colony, inhibits melanogenesis by down-regulating microphthalmia-associated transcription factor in skin melanocyte.

BACKGROUND: During melanogenesis, melanocytes produce melanin through enzymatic reactions. Microphthalmia-associated transcription factor (MITF) is a major regulator in controlling the expressions of melanogenic enzymes tyrosinase (TYR), tyrosine-related protein-1 (TRP1), and dopachrome tautomerase (DCT). Self-Growth Colony (SGC) is prepared from human platelet-rich plasma (PRP) having an enrichment of growth factors, and which has claimed skin regeneration function. AIM: In this study, we aim to identify and investigate the novel role of SGC in skin melanogenesis. METHODS: MTT assay was performed to determine the cytotoxicity of applied SGC. Melanin assay was adopted to quantify the intracellular melanin after SGC treatment. Promoter-driven luciferase assay, real-time PCR, and Western blotting were performed to determine the expressions of melanogenic enzymes and MITF in SGC-treated cultured Melan-A cells, being treated with or without UV induction. Ex vivo mouse skin was treated with SGC, and then was subjected to Western blotting and histochemical staining. RESULTS: We identified that SGC inhibited melanogenesis in cultured melanocytes and ex vivo mouse skin. The phenomena were attributed to a reduction of MITF expression, which subsequently down-regulated the melanogenic enzymes, that is, TYR, TRP1, and DCT. Moreover, ERK signaling was activated in the SGC-inhibited melanogenesis. CONCLUSIONS: The findings suggest that SGC extracting from human blood can be a safe and potential agent in promoting skin whitening.

Implementation of an educational province-wide intervention to reduce redundant vitamin B12 testing: A cross-sectional study.

INTRODUCTION: We describe the implementation of an Alberta-wide intervention aimed at educating clinicians about redundant vitamin B12 testing. We hypothesized that the introduction of an educational comment outlining recommended vitamin B12 test intervals would reduce the annual number of vitamin B12 tests performed. MATERIALS AND METHODS: We performed a cross-sectional observational study that included all vitamin B12 tests ordered in Alberta between May 1, 2017 and April 30, 2018. An educational comment was appended to all vitamin B12 test results in Alberta beginning May 2, 2017. Using a simple seasonal model, we compared predicted versus observed vitamin B12 test volumes for the 12-month period following the introduction of the educational comment. The sole outcome measured was the monthly change in volume of vitamin B12 testing. A cost-analysis of the effects of the intervention on test volumes was also performed. RESULTS: Over the sum of the first 12 months of the intervention, 18,000 more vitamin B12 tests were ordered compared to the predicted value in Alberta. With an estimated cost of $7 per test, this resulted in a $126,000 increase in costs for vitamin B12 testing provincially. CONCLUSIONS: An educational intervention aimed at limiting inappropriate vitamin B12 testing in Alberta did not alter testing as desired. Multiple utilization management strategies and a longer observation period may be needed to reduce redundant vitamin B12 testing.

Is the Utilization of Helicobacter pylori Stool Antigen Tests Appropriate in an Urban Canadian Population?

OBJECTIVES: Helicobacter pylori stool antigen test (HpSAT) appropriateness was investigated by assessing its testing and positivity rates in Calgary, Canada. METHODS: The laboratory information system was accessed for all patients who received an HpSAT in 2018. Testing volume, test results, age, and sex of patients were collected. Sociodemographic risk factors and geospatial analysis were performed by matching laboratory data to the 2016 census data. Testing appropriateness was defined as a concordance between testing and positivity rates for each sociodemographic variable. RESULTS: In 2018, 25,518 H pylori stool antigen tests were performed in Calgary, with an overall positivity rate of 14.7%. Geospatial mapping demonstrated significant distribution variations of testing and positivity rates of HpSAT in the city. Certain sociodemographic groups studied (eg, recent immigrants) appeared to be appropriately tested (testing rate relative risk [RR] = 2.26, positivity rate RR = 4.32; P < .0001), while other groups (eg, male) may have been undertested (testing rate RR = 0.85, positivity rate RR = 1.14; P < .0001). CONCLUSIONS: Determining concordance of testing and positivity rate of a laboratory test can be used for assessing testing appropriateness for other diseases in other jurisdictions. This study demonstrated some at-risk patients may be missed for H pylori testing.

Dataset of test volume and tests repeated for complete blood count and electrolyte panels from hospitals in a Canadian province in 2018.

All laboratory tests performed within the province of Alberta in Canada are captured by three Laboratory Information Systems (LIS; Millennium, Sunquest and Meditech), which comprise the provincial Consolidated Laboratory Data Repository (CLDR). The following secondary laboratory data for electrolyte panel (EP) and complete blood count (CBC) test panels performed in emergency room (ER) and inpatient settings were collected from January 1 - December 31, 2018: total test panel volume, total number of test panels repeated, number of test panels repeated within the 24 hour period, test result, date of testing, time of test, and patient Provincial Health Number (PHN). Patient PHN were used as a linking variable to match subsequent tests performed on the same patient. The first time a test was recorded per patient was defined as the "index test". If the same test panel was performed within a 24-h period following the index test for the patient, data for the repeated test panel was also collected. The index test was defined as "normal" or "abnormal" according to established laboratory normal values and laboratory test reference ranges. For CBCs, we considered the panel to be abnormal if any of the hematocrit (Hct), hemoglobin (Hgb), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), platelet (PLT), red blood cell (RBC), red cell distribution width (RDW) or white blood cell (WBC) values were outside the normal laboratory reference range. For electrolyte panels, we considered the panel to be abnormal if any of the chloride (Cl), potassium (K), and sodium (Na) were outside of the normal laboratory reference range. All EP results were from clinical chemistry analyzers only. The reuse potential of this dataset can allow other jurisdictions in Canada to compare their redundant repeat testing in their hospital settings with this dataset as a benchmark. This article was submitted via another Elsevier journal as a co-submission ("Inappropriate repeat testing of complete blood count (CBC) and electrolytes in inpatients from Alberta, Canada" [1]), and readers should refer to the co-submission article for interpretation of the results.

Inappropriate repeat testing of complete blood count (CBC) and electrolyte panels in inpatients from Alberta, Canada.

INTRODUCTION: The avoidance of repeat chemistry testing such as Complete Blood Count (CBC) and Electrolyte Panel (EP) on clinically stable patients was identified as important utilization goals by Choosing Wisely Canada. The purpose of this study was to assess the volume of overutilization of CBC and EP in an inpatient setting in Alberta, Canada, and provide an estimated cost assessment of unnecessary testing. METHODS: The total laboratory testing volumes of two common test panels were collected retrospectively for one-year from January to December 2018. Data was collected on test panels performed in an emergency room (ER) and inpatient setting from three separate Laboratory Information Systems covering the provincial population in Alberta, Canada. Total initial test panel instances, total repeated panels, repeated panels that were previously normal or abnormal, and estimated costs were examined. Cost assessment was completed based on Reference Median Cost (RMC) analysis for each of these two common test panels. RESULTS: During the study period, 2,020,467 (CBC) and 1,455,983 (EP) initial test panel instances were recorded, of which 67.7% and 73.5% were repeated for the CBC and EP, respectively. There was a higher proportion of EP repeated inappropriately (previously normal; 35.6%) compared to CBCs (5.4%). The cost to the province for inappropriately repeating CBC and EP were estimated to be RMC $0.52 million and RMC $1.90 million CAD, respectively. CONCLUSION: Results from this study can assist policy makers in implementing utilization management initiatives and update clinical practice guidelines to reduce costs to healthcare without compromising patient care.

Solar light induces expression of acetylcholinesterase in skin keratinocytes: Signalling mediated by activator protein 1 transcription factor.

Acetylcholinesterase (AChE) hydrolyses acetylcholine to choline and acetate, playing an important role in terminating the neurotransmission in brain and muscle. Recently, the non-neuronal functions of AChE have been proposed in different tissues, in which there are various factors to regulate the expression of AChE. In mammalian skin, AChE was identified in melanocytes and keratinocytes. Our previous study has indicated that AChE in keratinocyte affects the process of solar light-induced skin pigmentation; however, the expression of AChE in keratinocytes in responding to sunlight remains unknown. Here, we provided several lines of evidence to support a notion that AChE could be upregulated at transcriptional and translational levels in keratinocytes when exposed to solar light. The light-mediated AChE expression was triggered by Ca2+, supported by an induction of Ca2+ ionophore A23187 and a blockage by Ca2+ chelator BAPTA-AM. In addition, this increase on AChE transcriptional expression was eliminated by mutagenesis on the activating protein 1 (AP1) site in ACHE gene. Hence, the solar light-induced AChE expression is mediated by Ca2+ signalling through AP1 site. This finding supports the role of solar light in affecting the cholinergic system in skin cells, and which may further influence the dermatological function.