Drug-Related Problems and Recommendations Made during Home Medicines Reviews for Sick Day Medication Management in Australia.

Backgrounds and Objectives: Using certain medications during an intercurrent illness can increase the risk of drug related problems (DRP) occurring such as acute kidney injury (AKI). Medications that increase this risk include sulfonylureas, angiotensin converting enzyme inhibitors, diuretics, metformin, angiotensin receptor blockers, non-steroidal anti-inflammatories drugs, and sodium glucose co-transporter 2 inhibitors (SADMANS). Sick day medication guidance (SDMG) recommends withholding SADMANS medications during an intercurrent illness where adequate fluid intake cannot be maintained. But uptake of these recommendations is poor, and it is not known whether Australian pharmacists currently provide these recommendations during home medicine reviews (HMR) as per SDMG. We aimed to gain an understanding of the characteristics of DRP identified by pharmacists during HMR, especially those relating to SADMANS medications. Materials and Methods: We conducted a retrospective audit of 201 randomly selected HMR reports, conducted by accredited pharmacists from 2020 to 2022, that were analysed in 2023. All DRP and recommendations were categorised using a modified DOCUMENT system. Results: Overall, over 98% of participants experienced a DRP and a total of 710 DRP were found, where participants experienced an average of 4.0 ± 2.0 DRP each. Non-SADMANS medications accounted for 83.1% of all DRPs, with nervous system medications contributing the most. Common problems seen in non-SADMANS medications were related to toxicity, over/underdosing and undertreating. Diuretics contributed most to DRP in SADMANS medications. Problems with SADMANS were mainly related to toxicity and contraindications. No pharmacists provided SDMG despite 71.1% of participants using at least one SADMANS medication. Conclusions: We conclude that DRP remain prevalent in community pharmacy settings. Sick day recommendations were not provided in the HMRs included in our study, possibly due to lack of pharmacist knowledge and awareness. To ensure best practice, more research should be conducted to determine pharmacists' knowledge of and barriers to provision of sick day recommendations.

Drug-Related Problems and Sick Day Management Considerations for Medications that Contribute to the Risk of Acute Kidney Injury.

BACKGROUND: Medication use during acute illness increases the risk of experiencing drug related problems (DRPs), including acute kidney injuries. It is recommended that potentially nephrotoxic medications are withheld during acute illness, including sulfonylureas, angiotensin converting enzyme inhibitors, diuretics, metformin, angiotensin receptor blockers, non-steroidal anti-inflammatories and sodium glucose co-transporter 2 inhibitors (SADMANS). It is unknown if Australian pharmacists currently provide sick day medication management advice regarding SADMANS medications. Hence, we aimed to identify current DRPs and the recommendations made during residential medication management reviews (RMMRs), especially with SADMANS medications. METHODS: A retrospective review of 408 RMMRs was conducted. DRPs and pharmacist recommendations were classified according to a modified DOCUMENT system. General practitioners' (GP) recommendations were also categorised. RESULTS: Over 97% of residents experienced at least one DRP. Common problems for non-SADMANS medications were "toxicity or adverse drug reaction", "drug selection" and "over/underdosing" and those for SADMANS medications included "toxicity or adverse drug reaction", "monitoring" and "drug selection". GPs agreed with pharmacist recommendations approximately 40% of the time. No pharmacists provided sick day medication management advice for SADMANS medications. CONCLUSION: DRPs remain highly prevalent in aged care facilities. Medication reviews effectively identify and resolve DRPs approximately 40% of the time, but do not currently minimise the risk associated with using SADMANS medications during sick days, which is a potential area of improvement.

Sick day management in people with chronic kidney disease: a scoping review.

BACKGROUND: Use of certain medications during an acute illness may put patients at an increased risk of acute kidney injury (AKI). Patients with chronic kidney disease (CKD) are at higher risk of developing superimposed AKI. The aim of this scoping review is to collate and characterise existing evidence on sick day management considerations and practices during acute illness in people with CKD. METHODS: We searched Embase, CINAHL, MEDLINE, International Pharmaceutical Abstract, Scopus, Google Scholar and grey literature sources. We followed the methodological framework for scoping reviews, while information was extracted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Findings are presented thematically. RESULTS: Ten studies and seven guidelines met the inclusion criteria. Studies were targeted at patients, general practitioners, pharmacists, and nurses. The major themes identified included development and feasibility testing of a sick day management protocol, current practice of temporary medication discontinuation, and outcomes. Most guidelines provided recommendations for sick day management largely based on expert consensus. A digital intervention was deemed highly acceptable and easy to use, whereas patient handouts were more effective when provided along with dialogue with a health professional. While there is little evidence on the impact of sick day protocols on outcomes, a single randomised trial reported no significant association between sick day protocols and change in kidney function, AKI incidents or risk of hospitalisation. CONCLUSION: The nascent literature on sick day management in patients with CKD revealed the limited available evidence to provide guidance on implementation and on outcomes. Future research needs to clarify sick day recommendations and assess their impact on clinical outcomes including prevention of superimposed AKI or hospitalisations, as well as to address barriers to implementation.

Return visits to the pediatric emergency department: A multicentre retrospective cohort study.

OBJECTIVE: Return visits to the emergency department (RTED) for the same clinical complaint occur in 2.7% to 8.1% of children presenting to pediatric emergency departments (PEDs). Most studies examining RTEDs have focused solely on PEDs and do not capture children returning to other local emergency departments (EDs). Our objective was to measure the frequency and characterize the directional pattern of RTED to any of 18 EDs serving a large geographic area for children initially evaluated at a PED. METHODS: We conducted a retrospective cohort study of all visits to a referral centre PED between August 2012 and August 2013. We compared demographic variables between children with and without an RTED, measures of flow and disposition outcomes between the initial (index) visit and RTED, and between RTED to the original PED versus to other EDs in the community. RESULTS: Among all PED visits, 7.6% had an RTED within 7 days, of which 13% were to a facility other than the original PED. Children with an RTED had higher acuity and longer length of stay on their index visit. They were also more likely to be admitted on a subsequent visit than the overall PED population. RTED to the original PED had a longer waiting time (WT), length of stay, and more frequently resulted in hospitalization than RTED to a general ED. CONCLUSIONS: A significant proportion of RTED occur at a site other than where the original ED visit occurred. Examining RTED to and from only PEDs underestimates its burden on emergency health services.

Emergency Department Return Visits Within a Large Geographic Area.

BACKGROUND: Return visits to the emergency department (RTED) contribute to overcrowding and may be a quality of care indicator. Previous studies focused on factors predicting returns to and from the same center. Little is known about RTEDs across a range of community and specialty hospitals within a large geographic area. OBJECTIVE: We sought to measure the frequency of pediatric RTEDs and describe their directional pattern across centers in a large catchment area. METHODS: We conducted a multicenter, retrospective cross-sectional study of pediatric emergency visits in the Vancouver lower mainland within 1 year. Visits were linked across study sites, including one pediatric quaternary care referral center and 17 sites ranging from large regional centers to smaller community emergency departments (EDs). Returns were defined as subsequent visits to any site with a compatible diagnosis within 7 days of an index visit. RESULTS: Among a total of 139,278 index ED visits by children, 12,133 (8.7% [95% confidence interval 8.6-8.9%]) were associated with 14,645 return visits to an ED. Three quarters of all index visits occurred at a general ED center, of which 8.9% had at least one RTED and 22% of these returns occurred at the pediatric ED (PED). Among PED index visits, 8.2% had at least one RTED and 13.6% of these returned to a general center. Overall, 38.9% of all RTEDs occurred at the PED. Multivariate regression did not identify any statistically significant association between ED crowding measures and likelihood of RTEDs. CONCLUSIONS: Compared to single-center studies, this study linking hospitals within a large geographic area identified a higher proportion of RTEDs with a disproportionate burden on the PED.

Constipation and paediatric emergency department utilization.

BACKGROUND: Constipation is a common condition in children. Little is known about the acute health care utilization of constipated children, including how many present to the paediatric emergency department (ED), the spectrum of presenting complaints, investigations and treatments used. METHODS: We conducted a cross-sectional chart review of all 42,875 visits to British Columbia Children's Hospital ED between August 31, 2012 and September 1, 2013. All visits were assessed for a potential diagnosis of constipation and a total of 913 patients were included. We recorded the chief complaints, tests performed and therapies administered in the ED and measures of flow/efficiency including waiting time (WT), length of stay (LOS) and disposition. RESULTS: Constipation-related visits comprised 2.1% of overall visits. Abdominal pain was found to be the most common presenting complaint in 65.6% of patients; however, 11.9% of patients presented with complaints unrelated to the gastrointestinal tract. Abdominal radiographs were obtained in nearly one-third of patients and almost half of the patients received a fleet enema in the ED. Only a quarter of patients were discharged home on longer-term management. Measures of ED flow were similar between groups, with no meaningful difference in WT or LOS. The vast majority of children (99.7%) were discharged home. CONCLUSIONS: Constipation can be treated as an out-patient, rather than burdening the paediatric ED unnecessarily. This study demonstrates over utilization of radiologic tests and invasive ED treatments and an under utilization of outpatient medication and dietary counselling that may contribute to unnecessary return ED visits.

A Highly Effective Component Vaccine against Nontyphoidal Salmonella enterica Infections.

UNLABELLED: Nontyphoidal Salmonella enterica (NTS) infections are a major burden to global public health, as they lead to diseases ranging from gastroenteritis to systemic infections and there is currently no vaccine available. Here, we describe a highly effective component vaccine against S. enterica serovar Typhimurium in both gastroenteritis and systemic murine infection models. We devised an approach to generate supernatants of S. enterica serovar Typhimurium, an organism that is highly abundant in virulence factors. Immunization of mice with this supernatant resulted in dramatic protection against a challenge with serovar Typhimurium, showing increased survival in the systemic model and decreased intestinal pathology in the gastrointestinal model. Protection correlated with specific IgA and IgG levels in the serum and specific secretory IgA levels in the feces of immunized mice. Initial characterization of the protective antigens in the bacterial culture supernatants revealed a subset of antigens that exhibited remarkable stability, a highly desirable characteristic of an effective vaccine to be used under suboptimal environmental conditions in developing countries. We were able to purify a subset of the peptides present in the supernatants and show their potential for immunization of mice against serovar Typhimurium resulting in a decreased level of colonization. This component vaccine shows promise with regard to protecting against NTS, and further work should significantly help to establish vaccines against these prevalent infections. IMPORTANCE: Salmonella enterica infections other than typhoid and paratyphoid fever are a major global health burden, as they cause high morbidity and mortality worldwide. Strategies that prevent Salmonella-related diseases are greatly needed, and there is a significant push for the development of vaccines against nontyphoidal Salmonella enterica serovars. In this work, we describe an S. Typhimurium supernatant-derived vaccine that is effective in reducing bacterial colonization in mouse models of gastroenteritis as well as invasive disease. This is a component vaccine that shows high stability to heat, a feature that is important for use under suboptimal conditions, such as those found in sub-Saharan Africa.

RIC-3 differentially modulates α4ß2 and α7 nicotinic receptor assembly, expression, and nicotine-induced receptor upregulation.

BACKGROUND: Recent work has shown that the chaperone resistant to inhibitors of acetylcholinesterase (RIC-3) is critical for the folding, maturation and functional expression of a variety of neuronal nicotinic acetylcholine receptors. α7 nicotinic receptors can only assemble and functionally express in select lines of cells, provided that RIC-3 is present. In contrast, α4ß2 nicotinic receptors can functionally express in many cell lines even without the presence of RIC-3. Depending on the cell line, RIC-3 has differential effects on α4ß2 receptor function - enhancement in mammalian cells but inhibition in Xenopus oocytes. Other differences between the two receptor types include nicotine-induced upregulation. When expressed in cell lines, α4ß2 receptors readily and robustly upregulate with chronic nicotine exposure. However, α7 nicotinic receptors appear more resistant and require higher concentrations of nicotine to induce upregulation. Could the coexpression of RIC-3 modulate the extent of nicotine-induced upregulation not only for α7 receptors but also α4ß2 receptors? We compared and contrasted the effects of RIC-3 on assembly, trafficking, protein expression and nicotine-induced upregulation on both α7 and α4ß2 receptors using fluorescent protein tagged nicotinic receptors and Förster resonance energy transfer (FRET) microscopy imaging. RESULTS: RIC-3 increases assembly and cell surface trafficking of α7 receptors but does not alter α7 protein expression in transfected HEK293T cells. In contrast, RIC-3 does not affect assembly of α4ß2 receptors but increases α4 and ß2 subunit protein expression. Acute nicotine (30 min exposure) was sufficient to upregulate FRET between α4 and ß2 subunits. Surprisingly, when RIC-3 was coexpressed with α4ß2 receptors nicotine-induced upregulation was prevented. α7 receptors did not upregulate with acute nicotine in the presence or absence of RIC-3. CONCLUSIONS: These results provide interesting novel data that RIC-3 differentially regulates assembly and expression of different nicotinic receptor subunits. These results also show that nicotine-mediated upregulation of α4ß2 receptors can be dynamically regulated by the presence of the chaperone, RIC-3. This could explain a novel mechanism why high affinity α4ß2 receptors are upregulated in specific neuronal subtypes in the brain and not others.