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Objectives: Our aim in this work was to 1) explore barriers and enablers to patient and health-care provider (HCP) behaviours related to sick-day medication guidance (SDMG), 2) identify theory-informed strategies to advise SDMG intervention design, and 3) obtain perspectives on an eHealth tool for this purpose., Methods: A qualitative descriptive study using qualitative conventional content analysis was undertaken. Interviews and focus groups were held with patients and HCPs from January 2021 to April 2022. Data were analyzed using the Behaviour Change Wheel and Theoretical Domains Framework to inform intervention design., Results: Forty-eight people (20 patients, 13 pharmacists, 12 family physicians, and 3 nurse practitioners) participated in this study. Three interventions were designed to address the identified barriers and enablers: 1) prescriptions provided by a community-based care provider, 2) pharmacists adding a label to at-risk medications, and 3) built-in prompts for prescribing and dispensing software. Most participants accepted the concept of an eHealth tool and identified pharmacists as the ideal point-of-care provider. Challenges for an eHealth tool were raised, including credibility, privacy of data, medical liability, clinician remuneration and workload impact, and equitable access to use of the tool., Conclusions: Patients and HCPs endorsed non-technology and eHealth innovations as strategies to aid in the delivery of SDMG. These findings can guide the design of future theory-informed SDMG interventions., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pulmonary embolism (PE) is a serious condition that presents a diagnostic challenge for which diagnostic errors often happen. The literature suggests that a gap remains between PE diagnostic guidelines and adherence in healthcare practice. While system-level decision support tools exist, the clinical impact of a human-centred design (HCD) approach of PE diagnostic tool design is unknown., Design: Before-after (with a preintervention period as non-concurrent control) design study., Setting: Inpatient units at two tertiary care hospitals., Participants: General internal medicine physicians and their patients who underwent PE workups., Intervention: After a 6-month preintervention period, a clinical decision support system (CDSS) for diagnosis of PE was deployed and evaluated over 6 months. A CDSS technical testing phase separated the two time periods., Measurements: PE workups were identified in both the preintervention and CDSS intervention phases, and data were collected from medical charts. Physician reviewers assessed workup summaries (blinded to the study period) to determine adherence to evidence-based recommendations. Adherence to recommendations was quantified with a score ranging from 0 to 1.0 (the primary study outcome). Diagnostic tests ordered for PE workups were the secondary outcomes of interest., Results: Overall adherence to diagnostic pathways was 0.63 in the CDSS intervention phase versus 0.60 in the preintervention phase (p=0.18), with fewer workups in the CDSS intervention phase having very low adherence scores. Further, adherence was significantly higher when PE workups included the Wells prediction rule (median adherence score=0.76 vs 0.59, p=0.002). This difference was even more pronounced when the analysis was limited to the CDSS intervention phase only (median adherence score=0.80 when Wells was used vs 0.60 when Wells was not used, p=0.001). For secondary outcomes, using both the D-dimer blood test (42.9% vs 55.7%, p=0.014) and CT pulmonary angiogram imaging (61.9% vs 75.4%, p=0.005) was lower during the CDSS intervention phase., Conclusion: A clinical decision support intervention with an HCD improves some aspects of the diagnostic decision, such as the selection of diagnostic tests and the use of the Wells probabilistic prediction rule for PE., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Clostridioides difficile infection (CDI) is associated with considerable morbidity and mortality in hospitalized patients, especially among older adults. Probiotics have been evaluated to prevent hospital-acquired (HA) CDI in patients who are receiving systemic antibiotics, but the implementation of timely probiotic administration remains a challenge. We evaluated methods for effective probiotic implementation across a large health region as part of a study to assess the real-world effectiveness of a probiotic to prevent HA-CDI (Prevent CDI-55 +)., Methods: We used a stepped-wedge cluster-randomized controlled trial across four acute-care adult hospitals (n = 2,490 beds) to implement the use of the probiotic Bio-K + ® (Lactobacillus acidophilus CL1285®, L. casei LBC80R® and L. rhamnosus CLR2®; Laval, Quebec, Canada) in patients 55 years and older receiving systemic antimicrobials. The multifaceted probiotic implementation strategy included electronic clinical decision support, local site champions, and both health care provider and patient educational interventions. Focus groups were conducted during study implementation to identify ongoing barriers and facilitators to probiotic implementation, guiding needed adaptations of the implementation strategy. Focus groups were thematically analyzed using the Theoretical Domains Framework and the Consolidated Framework of Implementation Research., Results: A total of 340 education sessions with over 1,800 key partners and participants occurred before and during implementation in each of the four hospitals. Site champions were identified for each included hospital, and both electronic clinical decision support and printed educational resources were available to health care providers and patients. A total of 15 individuals participated in 2 focus group and 7 interviews. Key barriers identified from the focus groups resulted in adaptation of the electronic clinical decision support and the addition of nursing education related to probiotic administration. As a result of modifying implementation strategies for identified behaviour change barriers, probiotic adherence rates were from 66.7 to 75.8% at 72 h of starting antibiotic therapy across the four participating acute care hospitals., Conclusions: Use of a barrier-targeted multifaceted approach, including electronic clinical decision support, education, focus groups to guide the adaptation of the implementation plan, and local site champions, resulted in a high probiotic adherence rate in the Prevent CDI-55 + study., (© 2023. The Author(s).)

Rationale & Objective: Sick day medication guidance (SDMG) involves withholding or adjusting specific medications in the setting of acute illnesses that could contribute to complications such as hypotension, acute kidney injury (AKI), or hypoglycemia. We sought to achieve consensus among clinical experts on recommendations for SDMG that could be studied in future intervention studies., Study Design: A modified Delphi process following guidelines for conducting and reporting Delphi studies., Setting & Participants: An international group of clinicians with expertise relevant to SDMG was recruited through purposive and snowball sampling. A scoping review of the literature was presented, followed by 3 sequential rounds of development, refinement, and voting on recommendations. Meetings were held virtually and structured to allow the participants to provide their input and rapidly prioritize and refine ideas., Outcome: Opinions of participants were measured as the percentage who agreed with each recommendation, whereas consensus was defined as >75% agreement., Analytical Approach: Quantitative data were summarized using counts and percentages. A qualitative content analysis was performed to capture the context of the discussion around recommendations and any additional considerations brought forward by participants., Results: The final panel included 26 clinician participants from 4 countries and 10 clinical disciplines. Participants reached a consensus on 42 specific recommendations: 5 regarding the signs and symptoms accompanying volume depletion that should trigger SDMG; 6 regarding signs that should prompt urgent contact with a health care provider (including a reduced level of consciousness, severe vomiting, low blood pressure, presence of ketones, tachycardia, and fever); and 14 related to scenarios and strategies for patient self-management (including frequent glucose monitoring, checking ketones, fluid intake, and consumption of food to prevent hypoglycemia). There was consensus that renin-angiotensin system inhibitors, diuretics, nonsteroidal anti-inflammatory drugs, sodium/glucose cotransporter 2 inhibitors, and metformin should be temporarily stopped. Participants recommended that insulin, sulfonylureas, and meglitinides be held only if blood glucose was low and that basal and bolus insulin be increased by 10%-20% if blood glucose was elevated. There was consensus on 6 recommendations related to the resumption of medications within 24-48 hours of the resolution of symptoms and the presence of normal patterns of eating and drinking., Limitations: Participants were from high-income countries, predominantly Canada. Findings may not be generalizable to implementation in other settings., Conclusions: A multidisciplinary panel of clinicians reached a consensus on recommendations for SDMG in the presence of signs and symptoms of volume depletion, as well as self-management strategies and medication instructions in this setting. These recommendations may inform the design of future trials of SDMG strategies., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: Sick day medication guidance has been promoted to prevent adverse events for people with chronic conditions. Our aim was to summarize the existing sick day medication guidance and the evidence base for the effectiveness of interventions for implementing this guidance., Study Design: Scoping review of quantitative and qualitative studies., Setting & Population: Sick day medication guidance for people with chronic conditions including diabetes mellitus, kidney diseases, and cardiovascular diseases., Selection Criteria for Studies: A search of 6 bibliographic databases (Ovid MEDLINE, Ovid Embase, CINAHL, Scopus, Web of Science Core Collection, and Cochrane Library [via Wiley]) and a comprehensive gray literature search were completed in June 2021., Data Extraction: Intervention and study characteristics were extracted using standardized tools., Analytical Approach: Data were summarized descriptively, and our approach observed the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews., Results: The literature search identified 2,308 documents, which were screened against the eligibility criteria, leading to 74 documents that were included. The majority of the identified documents (n = 55) were guidelines or educational resources. Of the 19 primary research studies identified, 10 studies described an intervention, with only 2 examining the effect of sick day medication guidance interventions within clinical care and no studies reporting beneficial effects on clinical outcomes. Most documents (n = 58) included guidance specific to patients with diabetes mellitus, with fewer including guidance for patients with chronic kidney disease (n = 9) or heart failure (n = 2)., Limitations: Risk of bias was not assessed., Conclusions: Many resources promoting sick day medication guidance have been developed; however, there is very little empirical evidence for the effectiveness of current approaches in implementing sick day medication guidance into practice. Recommendations for the use of sick day medication guidance will require further research to develop consistent, understandable, and usable approaches for its implementation within self-management strategies as well as empirical studies to demonstrate the effectiveness of these interventions., (© 2022 The Authors.)

Venlafaxine, a serotonin-norepinephrine reuptake inhibitor, is a widely prescribed antidepressant drug routinely detected in the aquatic environment. However, little is known about its impact on the physiology of nontarget organisms. We tested the hypothesis that venlafaxine perturbs brain monoamine levels and disrupts molecular responses essential for stress coping and feeding activity in fish. Rainbow trout (Oncorhynchus mykiss) were exposed to waterborne venlafaxine (0.2 and 1.0 μg/L) for 7 days. This treatment elevated norepinephrine, serotonin, and dopamine levels in the brain in a region-specific manner. Venlafaxine also increased the transcript levels of genes involved in stress and appetite regulation, including corticotropin releasing factor, pro-opiomelanocortin B, and glucose transporter type 2 in distinct brain regions of trout. The drug treatment reduced the total feed consumed per day, but did not affect the feeding behavior of the dominant and subordinate fish. However, the subordinate fish from the venlafaxine-exposed group had significantly higher plasma cortisol levels compared to the subordinate fish in the control group. Collectively, our results demonstrate that venlafaxine, at environmentally realistic levels, is a neuroendocrine disruptor, impacting the stress and feeding responses in rainbow trout. We propose the midbrain region as a key target for venlafaxine impact and the mode of action involves abnormal monoamine content in trout.

The antidepressant venlafaxine is detected at parts per billion levels in tertiary-treated municipal wastewater effluent. However, the impact of this serotonin-norepinephrine reuptake inhibitor (SNRI) on non-target aquatic animals is poorly understood. We tested the hypothesis that environmentally relevant levels of venlafaxine disrupt the highly conserved cortisol and glucose response to stress in rainbow trout (Oncorhynchus mykiss). Juvenile trout were exposed to venlafaxine (0, 0.2 and 1.0 μg/L) in a static system with daily renewal for seven days. The fish were then subjected to an acute handling disturbance and sampled either prior to (0 h) or 1, 4 and 24h after stressor exposure. Venlafaxine exposure did not affect the handling disturbance-mediated transient elevation in plasma cortisol levels or target tissue glucocorticoid receptor expression. The drug exposure disrupted the interrenal steroidogenic capacity, including altered handling stressor-mediated changes in mRNA abundances of steroidogenic acute regulatory protein and cytochrome P450 side chain cleavage. The handling stressor-induced transient elevations in plasma glucose levels were significantly reduced in the venlafaxine-exposed fish. This was not accompanied by changes in liver glycogen content, glucose transporter 2 mRNA abundance or the glycolytic capacity, whereas the capacity for gluconeogenesis and amino acid catabolism were enhanced. Venlafaxine also brought about changes in the gill of trout, including enhanced lactate dehydrogenase activity and Na(+)-K(+) ATPase protein expression, while the Na(+)-K(+) ATPase enzyme activity was reduced. Collectively, our results demonstrate that venlafaxine at levels detected in the aquatic environment impacts tissue metabolic capacities and may compromise the adaptive responses to an acute stressor in rainbow trout., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A 12-year-old boy presented with a 7-year history of intermittent colicky epigastric pain. Serial abdominal ultrasound studies showed a contracted gallbladder, and single and double dose oral cholecystograms demonstrated nonfunction. All other investigation results were normal. At cholecystectomy, there was a fibrotic stricture at the junction of the gallbladder neck and cystic duct. The small, thin-walled gallbladder contained white bile. Histologically, the gallbladder was lined with normal mucous secreting columnar epithelium. The area of stricture showed diffuse fibrosis with islands of heterotopic gastric mucosa containing all gastric mucosal cell types. One year postoperatively, there have been no further episodes of abdominal pain. This is the seventh reported case of heterotopic gastric mucosa in the gallbladder of a child causing symptoms necessitating cholecystectomy. We recommend that a child with abdominal pain and a nonfunctioning gallbladder be considered for cholecystectomy even in the absence of cholelithiasis.