Dysregulated Immunity to Clostridioides difficile in IBD Patients Without a History of Recognized Infection.

BACKGROUND & AIMS: Clostridioides difficile is a toxin-secreting bacteria that is an urgent antimicrobial resistance threat, with approximately 25% of patients developing recurrent infections. Inflammatory bowel disease (IBD) patients are at increased risk of severe, recurrent C. difficile infection. METHODS: To investigate a role for C. difficile infection in IBD pathogenesis, we collected peripheral blood and stool from 20 each of ulcerative colitis patients, Crohn's disease patients, and healthy control subjects. We used a flow cytometric activation induced marker assay to quantify C. difficile toxin-specific CD4+ T cells and 16S ribosomal RNA sequencing to study microbiome diversity. RESULTS: We found IBD patients had significantly increased levels of C. difficile toxin B-specific CD4+ T cells, but not immunoglobulin G or immunoglobulin A, compared with healthy control subjects. Within antigen-specific CD4+ T cells, T helper type 17 cells and cells expressing the gut homing receptor integrin ß7 were reduced compared with healthy control subjects, similar to our previous study of non-IBD patients with recurrent C. difficile infection. Stool microbiome analysis revealed that gut homing, toxin-specific CD4+ T cells negatively associated with microbial diversity and, along with T helper type 17 cells, positively associated with bacteria enriched in healthy control subjects. CONCLUSIONS: These data suggest that IBD patients, potentially due to underlying intestinal dysbiosis, experience undiagnosed C. difficile infections that result in impaired toxin-specific immunity. This may contribute to the development of inflammatory T cell responses toward commensal bacteria and provide a rationale for C. difficile testing in IBD patients.

Crohn's disease and ulcerative colitis patients with no history of Clostridioides difficile infection had dysregulated T cell immunity to C. difficile toxin B. This was significantly different from healthy control subjects but similar to non­inflammatory bowel disease patients with recurrent C. difficile infection.

A Narrative Review of Point of Care Ultrasound Assessment of the Optic Nerve in Emergency Medicine.

Point of care ultrasound (POCUS) of the optic nerve is easy to learn and has great diagnostic potential. Within emergency medicine, research has primarily focused on its use for the assessment of increased intracranial pressure, but many other applications exist, though the literature is heterogeneous and largely observational. This narrative review describes the principles of POCUS of the optic nerve including anatomy and scanning technique, as well as a summary of its best studied clinical applications of relevance in emergency medicine: increased intracranial pressure, idiopathic intracranial hypertension, optic neuritis, acute mountain sickness, and pediatric intracranial pressure assessment. In many of these applications, sonographic optic nerve sheath diameter (ONSD) has moderately high sensitivity and specificity, but the supporting studies are heterogeneous. Further studies should focus on standardization of the measurement of ONSD, establishment of consistent diagnostic thresholds for elevated intracranial pressure, and automation of ONSD measurement.

Can plain film radiography improve the emergency department detection of clinically important urinary stones?

OBJECTIVE: Physicians frequently use ultrasound to assess hydronephrosis in patients with suspected renal colic, but ultrasound has limited diagnostic sensitivity and rarely clarifies stone size or location. Consequently, up to 80% of emergency department (ED) renal colic patients undergo confirmatory CT imaging. Our goal was to estimate x-ray sensitivity for urinary stones and determine whether x-ray substantially improves stone detection (sensitivity) compared to hydronephrosis assessment alone. METHODS: We reviewed imaging reports from all renal colic patients who underwent x-ray and CT at four EDs. For each patient, we documented stone size, location and hydronephrosis severity on CT and whether stones were identified on x-ray. We considered moderate and severe hydronephrosis (MS-Hydro) as significant positive findings, then calculated the sensitivity (detection rate) of MS-Hydro and x-ray for large stones ≥5 mm and for stones likely to require intervention (all ureteral stones >7 mm and proximal or middle stones >5 mm). We then tested a diagnostic algorithm adding x-ray to hydronephrosis assessment. RESULTS: Among 1026 patients with 1527 stones, MS-Hydro sensitivity was 39% for large stones and 60% for interventional stones. X-ray sensitivity was 46% for large stones and 52% for interventional stones. Adding x-ray to hydronephrosis assessment increased sensitivity in all stone categories, specifically from 39% to 68% for large stones (gain = 29%; 95%CI, 23% to 35%) and from 60% to 82% for interventional stones (gain = 22%; 95%CI, 13% to 30%). Because CT and ultrasound show strong agreement for MS-Hydro identification, physicians who depend on ultrasound-based hydronephrosis assessment could achieve similar gains by adding x-ray. CONCLUSIONS: Adding x-ray to hydronephrosis assessment substantially improves diagnostic sensitivity, enabling the detection of nearly 70% of large stones and over 80% of interventional stones. This level of sensitivity may be sufficient to reassure physicians about a renal colic diagnosis without CT imaging for many patients.

Sex-related differences in opioid administration in the emergency department: a population-based study.

BACKGROUND: Sex differences in pain experience and expression may influence ED pain management. Our objective was to evaluate the effect of sex on ED opioid administration. METHODS: We conducted a multicentre population-based observational cohort study using administrative data from Calgary's four EDs between 2017 and 2018. Eligible patients had a presenting complaint belonging to one of nine pain categories or an arrival pain score >3. We performed multivariable analyses to identify predictors of opioid administration and stratified analyses by age, pain severity and pain category. RESULTS: We studied 119 510 patients (mean age 47.4 years; 55.4% female). Opioid administration rates were similar for men and women. After adjusting for age, hospital site, pain category, ED length of stay and pain severity, male sex was not a predictor of opioid treatment (adjusted OR (aOR)=0.93; 95% CI 0.85 to 1.02). However, men were more likely to receive opioids in the categories of trauma (aOR=1.58, 95% CI 1.40 to 1.78), flank pain (aOR=1.24, 95% CI 1.11 to 1.38), headache (aOR=1.18, 95% CI 1.03 to 1.34) and abdominal pain (aOR=1.11, 95% CI 1.08 to 1.18). Pain category appears to be a strong determinant of opioid administration, especially back pain (aOR=6.56, 95% CI 5.99 to 7.19) and flank pain (aOR=6.04, 95% CI 5.48 to 6.65). There was significant variability in opioid provision by ED site (aOR 0.76 to 1.24). CONCLUSIONS: This population-based study demonstrated high variability in opioid use across different settings. Overall, men and women had similar likelihood of receiving opioids; however men with trauma, flank pain, headache and abdominal pain were much more likely to receive opioids. ED physicians should self-examine their analgesic practices with respect to possible sex biases, and departments should introduce evidence-based, indication-specific analgesic protocols to reduce practice variability and optimise opioid analgesia.

Gabapentin for uremic pruritus in hemodialysis patients: a qualitative systematic review.

PURPOSE OF THE REVIEW: Uremic pruritus (UP) is a common discomfort of dialysis-dependent end-stage renal disease. Some studies suggest a neuropathic cause of UP. Gabapentin, an anticonvulsant, has shown promising results as an emerging drug to treat this condition. OBJECTIVE: An updated qualitative systematic review was conducted to evaluate its efficacy and safety in hemodialysis patients. SOURCE OF INFORMATION: Ovid MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and Google Scholar through June 2015 were used as sources of information. PATIENTS: Patients are adult hemodialysis patients receiving gabapentin for UP. METHODS: All randomized controlled trials (RCTs), quasi-RCTs, observational studies, open-label studies, and retrospective studies were included. Case series and case reports were excluded. All descriptions and data were extracted independently by two authors. RESULTS: Seven studies evaluating gabapentin with a total of 179 patients were included. Most patients were refractory to antihistamines and topical emollients. Statistically significant favorable outcomes on pruritus scores were found in six studies. Five studies evaluated antipruritic efficacy based on a 10-point visual analog scale (VAS), and improvements in the range of an absolute decrease of 5.7 to 9.4 points from baseline were achieved on average by 3-8 weeks of treatment. Side effects are common with six studies reporting at least 26 incidences of side effects such as somnolence, dizziness, and fatigue. A total of four patients reportedly discontinued gabapentin due to intolerability. LIMITATIONS: Our review is limited by the inclusion of generally small, lower quality studies that lacked comparator groups or were open-label studies. Since the first two randomized controlled trials were published, no further high-quality studies have been conducted. IMPLICATIONS: Our review supports a trial of gabapentin for the management of UP in hemodialysis patients refractory to antihistamines and/or emollients. The results should be interpreted cautiously due to the lower quality of included studies. We recommend a starting dose of 100 mg orally after hemodialysis to minimize adverse events in this population.

MISE EN CONTEXTE: Le prurit urémique est un symptôme clinique fréquemment associé à l'insuffisance rénale chronique et des études suggèrent qu'il serait d'origine neuropathique. Un anticonvulsivant, la gabapentine, a démontré des résultats prometteurs et pourrait s'avérer la pharmacothérapie d'avenir pour aider à soulager ce symptôme. OBJECTIF DE LA REVUE: Cette revue visait à démontrer l'innocuité de la gabapentine et à évaluer son efficacité dans le traitement du prurit urémique chez les patients dialysés. PARTICIPANTS: Il s'agit de patients dialysés adultes recevant de la gabapentine pour le soulagement du prurit urémique associé à leur état. MÉTHODE ET SOURCES: Cette étude systématique a été réalisée par le passage en revue des bases de données sur Ovid MEDLINE et EMBASE ainsi que par la consultation du Cochrane Central Register of Controlled Trials, du site internet Clinitrials.gov et de Google Scholar jusqu'en juin 2015. La revue inclut tous les essais cliniques randomisés et quasi randomisés, les études observationnelles, les études ouvertes et les études rétrospectives répertoriées dans les sources susmentionnées. Toutes les descriptions et les données utilisées dans cette revue ont été recueillies par deux des auteurs, de façon indépendante. Les rapports de cas ainsi que les séries de cas relevés dans les sources consultées n'ont pas été retenus. RÉSULTATS: La revue porte sur un total de 179 patients répartis dans sept études traitant de l'effet de la gabapentine pour le traitement du prurit urémique. La plupart des patients suivaient ce traitement à la suite de l'échec des traitements par les antihistaminiques et les émollients. Des résultats positifs et statistiquement significatifs ont été répertoriés dans six des sept études passées en revue. Une échelle visuelle analogique en 10 points a servi pour l'évaluation de l'efficacité antiprurigineuse de la gabapentine dans cinq des sept études. Une baisse absolue de la sévérité du prurit allant de 5,7 à 9,4 points a été notée par rapport aux valeurs initiales, et ce pour une période moyenne de traitement de 3 à 8 semaines. En ce qui concerne les effets secondaires fréquemment associés à un traitement à la gabapentine (somnolence, étourdissement ou asthénie), ils ont été rapportés à 26 reprises parmi six des sept études révisées. De plus, quatre patients ont dû cesser la prise de gabapentine en raison d'une intolérance au médicament. LIMITES DE L'ÉTUDE: La présente revue repose sur des données recueillies à partir de la consultation d'un nombre restreint d'études. La majorité des études incluses dans la revue n'étaient pas de grande envergure et s'avéraient peu rigoureuses au plan scientifique : certaines ne comportant pas de groupe comparateur, d'autres consistant en des études ouvertes. Parmi les sept études passées en revue, seuls deux essais cliniques randomisés avaient été publiés et aucune autre étude rigoureuse n'a été réalisée depuis. CONSÉQUENCES: Cette revue recommande un essai de gabapentine pour soulager le prurit urémique chez les patients dialysés qui ne répondent pas aux traitements par les antihistaminiques et les émollients. Toutefois, l'interprétation des résultats doit être faite avec prudence en raison du manque de rigueur associé à certains types d'études incluses dans la revue. Nous suggérons une dose initiale de 100 mg de gabapentine, administrée par voie orale après la séance d'hémodialyse, afin de prévenir les effets secondaires du médicament dans cette population.

The effect of transitioning from residency to pharmacy practice on learning style.

OBJECTIVE: To describe the evolution of learning styles of pharmacy residents as they transition from residency to practice. METHODS: Cross-sectional survey and interview-based study. A complete provincial cohort of former pharmacy residents (N=28), who had their learning styles characterized with the Pharmacists' Inventory of Learning Styles (PILS) at the beginning of their residency and, 1 year post-residency, were invited to repeat the PILS. Interviews were administered to consenting participants to gain additional insight. RESULTS: Twenty-seven of the former residents (96%) completed the PILS survey and 16 (59%) completed the post-PILS interview. Thirteen (48%) changed their dominant learning style and 20 (74%) changed their secondary learning style. Six (22%) participants did not change either learning style. The overall proportion of dominant assimilators (59%) and convergers (26%) remained similar to baseline (52% and 26%, respectively), meaning participants had adopted and abandoned different learning style in similar numbers. Change in learning style was associated with being a preceptor (p<0.05), as 58% of the 12 former residents who became preceptors stated in the interview they had adjusted their teaching practices based on knowledge of their learning styles gained during their residency. CONCLUSION: Changing learning style is common for former residents after 1 year in postresidency practice. There is no overall direction to the change; former residents transition into and out of various learning styles with similar frequency and retain preferences for passive/abstract learning approaches over active/concrete ones. The early-career lability in learning style the study demonstrated may reveal an opportunity to guide pharmacists toward more active learning preferences through residency curricula, preceptorship, and mentorship.