Responding to the workforce crisis: consensus recommendations from the Second Workforce Summit of the American Society of Pediatric Nephrology.

IMPORTANCE: Pediatric patients with complex medical problems benefit from pediatric sub-specialty care; however, a significant proportion of children live greater than 80 mi. away from pediatric sub-specialty care. OBJECTIVE: To identify current knowledge gaps and outline concrete next steps to make progress on issues that have persistently challenged the pediatric nephrology workforce. EVIDENCE REVIEW: Workforce Summit 2.0 employed the round table format and methodology for consensus building using adapted Delphi principles. Content domains were identified via input from the ASPN Workforce Committee, the ASPN's 2023 Strategic Plan survey, the ASPN's Pediatric Nephrology Division Directors survey, and ongoing feedback from ASPN members. Working groups met prior to the Summit to conduct an organized literature review and establish key questions to be addressed. The Summit was held in-person in November 2023. During the Summit, work groups presented their preliminary findings, and the at-large group developed the key action statements and future directions. FINDINGS: A holistic appraisal of the effort required to cover inpatient and outpatient sub-specialty care will help define faculty effort and time distribution. Most pediatric nephrologists practice in academic settings, so work beyond clinical care including education, research, advocacy, and administrative/service tasks may form a substantial amount of a faculty member's time and effort. An academic relative value unit (RVU) may assist in creating a more inclusive assessment of their contributions to their academic practice. Pediatric sub-specialties, such as nephrology, contribute to the clinical mission and care of their institutions beyond their direct billable RVUs. Advocacy throughout the field of pediatrics is necessary in order for reimbursement of pediatric sub-specialist care to accurately reflect the time and effort required to address complex care needs. Flexible, individualized training pathways may improve recruitment into sub-specialty fields such as nephrology. CONCLUSIONS AND RELEVANCE: The workforce crisis facing the pediatric nephrology field is echoed throughout many pediatric sub-specialties. Efforts to improve recruitment, retention, and reimbursement are necessary to improve the care delivered to pediatric patients.

Tools to measure barriers to medication management capacity in older adults: a scoping review.

BACKGROUND: Medication management capacity is a crucial component of medication adherence, particularly among older adults. Various factors, including physical abilities, cognitive functions, sensory capabilities, motivational, and environmental factors, influence older adults' ability to manage medications. It is, therefore, crucial to identify appropriate tools that allow clinicians to determine which factors may impact medication management capacity and, consequently, nonadherence to medications. PURPOSE: 1)To identify tools that measure physical, cognitive, sensory (vision, hearing, touch), motivational, and environmental barriers to medication self-management in older adults, and 2) to understand the extent to which these tools assess various barriers. METHODS: The scoping review was conducted using Arksey and O'Malley's scoping review framework and the PRISMA Extension for Scoping Reviews checklist. In June 2022, the relevant literature was identified by searching PubMed (MEDLINE), Ovid Embase, Ovid IPA, EBSCOhost CINAHL, APA PsycINFO, and Scopus. RESULTS AND DISCUSSION: In total, 7235 studies were identified. Following the removal of duplicates, 4607 articles were screened by title and abstract, of which 4253 did not meet the inclusion criteria. Three reviewers reviewed the full texts of the remaining 354 articles; among them, 41 articles, 4 theses and 1 conference abstract met the inclusion criteria. From the included studies, 44 tools were identified that measured a combination of physical, cognitive, sensory, motivational, and environmental barriers (n=19) or only cognition (n=13), vision (n=5), environmental factors (n=3), auditory (n=1), and motivational factors (n=1). The review also examined the psychometric properties of the identified tools and found that most of them had reported validity and reliability data. Several tools have demonstrated promise in assessing a combination of barriers with validity and reliability. These tools include the Self-Medication Assessment Tool (SMAT), ManageMed Screening (MMS), Self-Medication Risk Assessment Tool (RAT), HOME-Rx revised, and Medication Management Ability Assessment (MMAA). CONCLUSION: This scoping review identified 44 validated tools to measure various challenges that older adults encounter with medication management. However, no tool measures all five barriers (physical, cognitive, sensory, motivational, and environmental) to medication-taking at home. Therefore, utilizing a combination of tools would be most appropriate to measure these different aspects comprehensively. Further research is needed to develop a new comprehensive tool that simultaneously measures various barriers to medication self-management.

Policy recommendations to ensure that research software is openly accessible and reusable.

Research data is optimized when it can be freely accessed and reused. To maximize research equity, transparency, and reproducibility, policymakers should take concrete steps to ensure that research software is openly accessible and reusable.

Dent disease presenting with nyctalopia and electroretinographic correlates of vitamin A deficiency.

Purpose: To report a unique case of Dent Disease presenting with nyctalopia associated with vitamin A deficiency and abnormal electroretinogram findings without prior systemic symptomatology. Observations: A 16-year-old male presented with a several month history of nyctalopia and peripheral vision deficits. Central visual acuity, anterior and posterior segment examinations, and macular optical coherence tomography were unremarkable. Electroretinogram (ERG) testing revealed a rod-cone dystrophic pattern, with further workup demonstrating serum vitamin A deficiency (VAD). Laboratory evaluation revealed renal dysfunction and proteinuria with a significantly elevated urinary retinol-binding protein (RBP). Kidney biopsy showed glomerular and tubular disease.Genetic screening for inherited renal disease was performed identifying a hemizygous pathogenic variant c.2152C>T (p.Arg718*) in the Chloride Voltage-Gated Channel 5 (CLCN5) gene, confirming the diagnosis of X-linked Dent Disease. Following vitamin A supplementation, our patient reported resolution of nyctalopia and reversal of abnormal ERG findings were demonstrated. Conclusions and Importance: To our knowledge, this is the first case in the literature describing Dent disease solely presenting with ophthalmic symptoms of nyctalopia and abnormal electroretinogram findings that later reversed with vitamin A repletion. This case stresses the importance for clinicians to consider renal tubular disorders in the differential for VAD.

Acute kidney injury requiring kidney replacement therapy in childhood lupus nephritis: a cohort study of the Pediatric Nephrology Research Consortium and Childhood Arthritis and Rheumatology Research Alliance.

BACKGROUND: Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for development of chronic kidney disease. In adults with LN, AKI severity correlates with the incidence of kidney failure and patient survival. Data on AKI outcomes in children with LN, particularly those requiring kidney replacement therapy (KRT), are limited. METHODS: A multicenter, retrospective cohort study was performed in children diagnosed between 2010 and 2019 with LN and AKI stage 3 treated with dialysis (AKI stage 3D). Descriptive statistics were used to characterize demographics, clinical data, and kidney biopsy findings; treatment data for LN were not included. Logistic regression was used to examine the association of these variables with kidney failure. RESULTS: Fifty-nine patients (mean age 14.3 years, 84.7% female) were identified. The most common KRT indications were fluid overload (86.4%) and elevated blood urea nitrogen/creatinine (74.6%). Mean follow-up duration was 3.9 ± 2.9 years. AKI recovery without progression to kidney failure occurred in 37.3% of patients. AKI recovery with later progression to kidney failure occurred in 25.4% of patients, and there was no kidney recovery from AKI in 35.6% of patients. Older age, severe (> 50%) tubular atrophy and interstitial fibrosis, and National Institutes of Health (NIH) chronicity index score > 4 on kidney biopsy were associated with kidney failure. CONCLUSIONS: Children with LN and AKI stage 3D have a high long-term risk of kidney failure. Severe tubular atrophy and interstitial fibrosis at the time of AKI, but not AKI duration, are predictive of kidney disease progression. A higher resolution version of the Graphical abstract is available as Supplementary information.

Cervical Osteomyelitis, Cardiac Arrest, and Lance-Adams Syndrome: A Case Report.

Lance-Adams syndrome (LAS) is a rare complication of successful cardiopulmonary resuscitation, often accompanied by action myoclonus. Myoclonus may occur as generalized, focal, or multifocal movements and can include the face, trunk, and/or extremities. Only 100 cases of LAS have been reported worldwide. Here, we present the case of a 53-year-old female who had a cardiac arrest event after being admitted for posterior cervical wound dehiscence management following a posterior cervical fusion from C3-T1. The patient was successfully resuscitated but developed action myoclonus in all extremities shortly after. Anoxic brain injury and myoclonus led to debilitation and prolonged hospital stay. During her inpatient stay, she was treated with clonazepam, levetiracetam, and sodium valproate with mild improvement.

Pharmacokinetics of Commonly Used Medications in Children Receiving Continuous Renal Replacement Therapy: A Systematic Review of Current Literature.

BACKGROUND AND OBJECTIVE: The use of continuous renal replacement therapy (CRRT) for renal support has increased substantially in critically ill children compared with intermittent modalities owing to its preferential effects on hemodynamic stability. With the expanding role of CRRT, the quantification of extracorporeal clearance and the effect on primary pharmacokinetic parameters is of the utmost importance. Within this review, we aimed to summarize the current state of the literature and compare published pharmacokinetic analyses of commonly used medications in children receiving CRRT to those who are not. METHODS: A systematic search of the literature within electronic databases PubMed, EMBASE, Cochrane Library, and Web of Science was conducted. Published studies that were included contained relevant information on the use of commonly administered medications to children, from neonates to adolescents, receiving CRRT. Pharmacokinetic parameters that were analyzed included volume of distribution, total clearance, extracorporeal clearance, area under the curve, and elimination half-life. Information regarding CRRT circuit, flow rates, and membrane components was analyzed to investigate differences in pharmacokinetics between each modality. RESULTS: Forty-five studies met the final inclusion criteria within this systematic review, totaling 833 pediatric patients, with 586 receiving CRRT. Antimicrobials were the most common pharmacological class represented within the literature, representing 81% (35/43) of studies analyzed. Children receiving CRRT largely had similar volume of distribution and total clearance to critically ill children not receiving CRRT, suggesting reno-protective dose adjustments may lead to subtherapeutic dosing regimens in these patients. Overall, there was a tendency for hydrophilic agents, with a low protein binding to undergo elevated total clearance in these children. However, results should be interpreted with caution because of the large variability amongst patient populations and heterogeneity with CRRT modalities, flow rates, and use of extracorporeal membrane oxygenation within studies. This review was able to identify that variation in solute removal, or CRRT modalities, properties (i.e., flow rates), and membrane composition, may have differing effects on the pharmacokinetics of commonly administered medications. CONCLUSIONS: The current state of the literature regarding medications administered to children receiving CRRT largely focuses on antimicrobials. Significant gaps remain with other commonly used medications such as sedatives and analgesics. Overall reporting of patient clinical characteristics, CRRT settings, and circuit composition was poor, with only 10% of articles including all relevant information to assess the impact of CRRT on total clearance. Changes in pharmacokinetics because of CRRT often required higher than labeled doses, suggesting renally adjusted or reno-protective doses may lead to subtherapeutic dosing regimens. A thorough understanding of the interplay between patient, drug, and CRRT-circuit factors are required to ensure adequate delivery of dosing regimens to this vulnerable population.

The Usability, Acceptability, and Functionality of Smart Oral Multidose Dispensing Systems for Medication Adherence: A Scoping Review.

BACKGROUND: Medication non-adherence is a leading cause of non-optimal disease management, resulting in poor health outcomes, poor quality of life, and increased healthcare costs. Smart oral multidose dispensing systems (SOMDS) are being developed to address non-adherence; however, little is known about their integration into daily use by patients. METHODS: Using Arksey and O'Malley's scoping review framework, relevant literature was searched for in electronic databases (PubMed, EMBASE, International Pharmaceutical Abstracts, and Scopus). Observational and interventional studies reporting the integration and impact on adherence from SOMDS in adults ≥18 years and published after 1960 were included. RESULTS: Thirteen articles including one case study, 8 cohort studies, and 4 randomized trials were eligible. SOMDS included smart blister packaging, automated dispensers, and electronic medication trays. The number of medications dispensed per SOMDS was one (n = 3), >1 (n = 2), placebo (n = 1) and not reported (n = 7). Reported outcomes included impact on medication adherence (n = 3), integration (n = 2) and both parameters (n = 8). CONCLUSION: Although most studies reported that SOMDS appear usable, there was significant variability in the SOMDS types, patient populations, medication adherence definitions, and measurements; impacting the interpretation of results. Future studies should be designed to address effectiveness of SOMDS on medication adherence in patients with multi-drug therapy and the utilization of real-time adherence data for informing clinical decision making.

The role of pharmacists in opioid stewardship: A scoping review.

BACKGROUND: The opioid epidemic is an international public health concern. Pharmacists are in a strategic position to promote and implement effective opioid stewardship due to both their central role on health care teams and frequent interaction with patients. Despite this integral role, pharmacists do not have harmonized scopes of practice in opioid stewardship. OBJECTIVES: This scoping review was conducted to identify and critically review the role of pharmacists in opioid stewardship and identify future areas of study. METHODS: The scoping review was conducted according to the methodological framework proposed by Arksey and O'Malley, which was further modified by the Joanna Briggs Institute. Six databases were searched for original, peer-reviewed research; PubMed (MEDLINE), Ovid Embase, Ovid International Pharmaceutical Abstracts, Scopus, Cochrane Library, and APA PsycInfo. RESULTS: In 92% of the included studies (n = 77), opioid stewardship interventions led by either a pharmacist or in an interdisciplinary team resulted in improvements in at least one outcome measure, with education and medication therapy adjustments being the most predominant activities. Other areas supported by evidence include community stakeholder education, policy and guideline setting, and risk assessment. CONCLUSION: This scoping review provides valuable insight into the various roles pharmacists can have in opioid stewardship. The findings from this review identified opioid stewardship activities that can make significant contributions towards reducing the impact of the opioid crisis. This review informs future research and has the potential to influence pharmacy practice on a national and international scale.

The role of pharmacy technicians in vaccination services: a scoping review.

BACKGROUND: A busy pharmacy workload may limit a pharmacist's ability to meet the needs of vaccine-willing patients and also contribute to missed opportunities to engage with vaccine hesitant individuals. Opportunities for pharmacy technicians to support vaccination services may play a role in addressing increasing patient vaccination needs. PURPOSE: This research aims to review the role of pharmacy technicians in vaccination services that is supported by pharmacy practice research to date. METHODS: In compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocols, systematic searches were performed in PubMed, Embase, International Pharmaceutical Abstracts, Scopus, and CINAHL. Articles published through June 2020, in French, English, and Spanish, were screened for eligibility. Two independent reviewers screened titles and abstracts for inclusion. Data extraction of included study methodologies and results was performed by one reviewer and verified by a second reviewer. RESULTS: A total of 656 records were identified through the search of published literature. Full-text screening of 145 records identified 14 articles for inclusion. Most articles evaluated emerging pharmacy technician roles in patient screening (n = 8, 53%) and vaccine administration (n = 5, 36%). Implementation of both emerging roles demonstrated positive patient outcomes (n = 10, 72%). Screening activities were complicated by the complexity of the role, as well as its potential to increase overall time spent on vaccination services. Pharmacists and technicians advocated for accredited vaccine administration training owing to consistent benefits in pharmacy workflow efficiency, pharmacist clinical time, and pharmacy technician job satisfaction. CONCLUSION: This review supports the effective deployment of pharmacy technicians in delivering vaccination services. Despite pharmacy technician vaccine administration roles being highly regulated, professional advocacy by pharmacists and technicians can use the advantageous training, workflow, and patient outcomes benefits presented in this review. Early adopters of professional practice advancements for pharmacy technician vaccine administration may expand vaccination service capacity efficiently and safely, thereby reaching more patients.

Cytomegalovirus-Induced Pericarditis, Pulmonary Embolism, and Transaminitis in an Immunocompetent Patient.

Cytomegalovirus (CMV) is a global virus with a high prevalence that usually manifests in immunocompromised patients, with significant morbidity and mortality. Though fairly common in immunocompetent patients admitted in the intensive care units, the infection is usually subclinical. Healthy individuals either have a subclinical course or exhibit a mild mononucleosis-like syndrome. Due to this, little attention has been given to morbidity and mortality that CMV infection may lead to in immunocompetent patients. We report a case of a 55-year-old immunocompetent female with no significant history who was admitted to our medical service with pericarditis, complicated by a right pulmonary embolism. Infectious workup revealed CMV as the cause for the presenting symptoms.

Ayahuasca and the traveller: A scoping review of risks and possible benefits.

BACKGROUND: Ayahuasca is a psychotropic drink made from the Amazonian vine Banisteriopsis caapi. Active components include beta-carboline alkaloids and the hallucinogen N-N-dimethyltryptamine (DMT). This review aimed to identify and summarize the literature on the safety and effectiveness of ayahuasca among recreational users. METHOD: A comprehensive literature search was done on November 1, 2019 in the following six databases: PubMed(MEDLINE), Ovid Embase, Ovid International Pharmaceutical Abstracts, LILACS, Scopus, and Web of Science. Articles were included if they were original research published in English, Spanish, or Portuguese, among human participants using oral ayahuasca for neuropsychiatric effects. Chemical or pharmacological analyses, brain imaging studies, and studies examining the use of ayahuasca within a religious context were excluded. RESULTS: 5750 unique titles were identified through the database searches, with an additional 19 titles identified through manual searches. Ultimately, 39 met all the criteria for inclusion. Articles were organized into 4 themes: (1) Case reports and case series; (2) The use of ayahuasca for depression or grief; (3) The use of ayahuasca and other psychiatric or neuropsychological outcomes; and (4) Studies examining ayahuasca use and physiologic outcomes. Ayahuasca use is associated with a risk of both psychiatric and non-psychiatric events including hallucinations, agitation or aggression, vomiting, seizure, and rhabdomyolysis. Five fatalities have been reported in the literature following ayahuasca use. Open-label studies assessing ayahuasca use in depression found favorable results persisting across 21 days. Ayahuasca was also found to influence the MINDSENS scale for mindfulness, with mixed results observed for impact of ayahuasca on cognitive function and creativity, and benefits observed for measures of self-acceptance and overall wellbeing. CONCLUSIONS: To date, evidence on benefits for the management of depression, anxiety, and other mental health disorders is mixed, with some evidence suggesting improvements in mindfulness measures and creativity that are generally short-lived, and multiple case reports suggesting the potential for harm and interactions.

Including the Reason for Use on Prescriptions Sent to Pharmacists: Scoping Review.

BACKGROUND: In North America, although pharmacists are obligated to ensure prescribed medications are appropriate, information about a patient's reason for use is not a required component of a legal prescription. The benefits of prescribers including the reason for use on prescriptions is evident in the current literature. However, it is not standard practice to share this information with pharmacists. OBJECTIVE: Our aim was to characterize the research on how including the reason for use on a prescription impacts pharmacists. METHODS: We performed an interdisciplinary scoping review, searching literature in the fields of health care, informatics, and engineering. The following databases were searched between December 2018 and January 2019: PubMed, Institute of Electrical and Electronics Engineers (IEEE), Association for Computing Machinery (ACM), International Pharmaceutical Abstracts (IPA), and EMBASE. RESULTS: A total of 3912 potentially relevant articles were identified, with 9 papers meeting the inclusion criteria. The studies used different terminology (eg, indication, reason for use) and a wide variety of study methodologies, including prospective and retrospective observational studies, randomized controlled trials, and qualitative interviews and focus groups. The results suggest that including the reason for use on a prescription can help the pharmacist catch more errors, reduce the need to contact prescribers, support patient counseling, impact communication, and improve patient safety. Reasons that may prevent prescribers from adding the reason for use information are concerns about workflow and patient privacy. CONCLUSIONS: More research is needed to understand how the reason for use information should be provided to pharmacists. In the limited literature to date, there is a consensus that the addition of this information to prescriptions benefits patient safety and enables pharmacists to be more effective. Future research should use an implementation science or theory-based approach to improve prescriber buy-in and, consequently, adoption.

The Role of Growth Hormone in Chronic Kidney Disease.

Growth hormone (GH) has become a critical therapy for treating growth delay and failure in pediatric chronic kidney disease. Recombinant human GH treatment is safe and significantly improves height and height velocity in these growing patients and improved growth outcomes are associated with decreased morbidity and mortality as well as improved quality of life. However, the utility of recombinant human GH in adults with chronic kidney disease and end-stage renal disease for optimization of body habitus and reducing frailty remains uncertain. Semin Nephrol 41:x-xx © 2021 Elsevier Inc. All rights reserved.

Efficacy of vision-based treatments for children and teens with amblyopia: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To identify differences in efficacy between vision-based treatments for improving visual acuity (VA) of the amblyopic eye in persons aged 4-17 years old. DATA SOURCES: Ovid Embase, PubMed (Medline), the Cochrane Library, Vision Cite and Scopus were systematically searched from 1975 to 17 June 2020. METHODS: Two independent reviewers screened search results for randomised controlled trials of vision-based amblyopia treatments that specified change in amblyopic eye VA (logMAR) as the primary outcome measure. Quality was assessed via risk of bias and GRADE (Grading of Recommendations, Assessment, Development, and Evaluations). RESULTS: Of the 3346 studies identified, 36 were included in a narrative synthesis. A random effects meta-analysis (five studies) compared the efficacy of binocular treatments versus patching: mean difference -0.03 logMAR; 95% CI 0.01 to 0.04 (p<0.001), favouring patching. An exploratory study-level regression (18 studies) showed no statistically significant differences between vision-based treatments and a reference group of 2-5 hours of patching. Age, sample size and pre-randomisation optical treatment were not statistically significantly associated with changes in amblyopic eye acuity. A network meta-analysis (26 studies) comparing vision-based treatments to patching 2-5 hours found one statistically significant comparison, namely, the favouring of a combination of two treatment arms comparing combination and binocular treatments, against patching 2-5 hours: standard mean difference: 2.63; 95% CI 1.18 to 4.09. However, this result was an indirect comparison calculated from a single study. A linear regression analysis (17 studies) found a significant relationship between adherence and effect size, but the model did not completely fit the data: regression coefficient 0.022; 95% CI 0.004 to 0.040 (p=0.02). CONCLUSION: We found no clinically relevant differences in treatment efficacy between the treatments included in this review. Adherence to the prescribed hours of treatment varied considerably and may have had an effect on treatment success.

The role of pharmacists in opioid stewardship: Protocol.

BACKGROUND: The opioid crisis is a worldwide public health concern. In North America, evidence suggests that the increase in opioid prescriptions correlates with the observed increase in opioid-related mortality and morbidity. Pharmacists are in a strategic position to promote effective opioid stewardship as they have a central role on healthcare teams. However, in many contexts, pharmacists do not have a harmonized scope of practice and no standardized opioid stewardship approach has been implemented. OBJECTIVES: A scoping review will be conducted to identify and summarize evidence on the role of pharmacists in opioid stewardship and identify areas for future study. METHODS: The scoping review will be conducted according to the methodological framework proposed by Arksey and O'Malley, which was further modified by the Joanna Briggs Institute. Six databases will be searched which include PubMed, Embase, International Pharmaceutical Abstracts, Scopus, Cochrane Library, and APA PsycInfo. PROJECT IMPACT: The findings of this review will identify opioid stewardship activities that can contribute towards reducing the impact of the opioid crisis. Additionally, it will provide foundational strategies to promote policy level change and foster a harmonized scope of practice. This review has the potential to inform future research, impact pharmacy practice, and drive policy change.

Proteinuria and nocturnal blood pressure dipping in hypertensive children and adolescents.

BACKGROUND: The absence of nocturnal blood pressure dipping is associated with adverse cardiovascular outcomes in adults, and proteinuria is a risk factor for non-dipping in this population. Risk factors for non-dipping in children are largely unknown. METHODS: We retrospectively identified patients aged 5-19 years who underwent 24-h ambulatory blood pressure monitoring (ABPM) from August 2018 to January 2019 and had a spot urine protein-to-creatinine ratio (PCR) within 1 year of their ABPM. Dipping was defined as ≥10% reduction in systolic and diastolic blood pressure from day to night. Multivariable logistic and linear regression models evaluated the association of proteinuria with non-dipping. RESULTS: Among 77 children identified, 27 (35.1%) were non-dippers. Each two-fold higher urine PCR was associated with 38% higher odds of non-dipping, after adjusting for body mass index (BMI). Higher urine PCR was also associated with a lower diastolic dipping percentage by 1.33 (95% confidence interval 0.31-2.34), after adjusting for BMI, age, and estimated glomerular filtration rate. CONCLUSIONS: Limitations of this study include its retrospective design and the time lapse between urine PCR and ABPM. Proteinuria appears to be associated with blood pressure non-dipping in children. This finding needs to be confirmed in prospective studies. IMPACT: Our study demonstrates the association of proteinuria with non-dipping of blood pressure in children. This association has been explored in adults, but to our knowledge, this is the first time it is evaluated in children referred for evaluation of elevated blood pressure. Non-dipping is a modifiable risk factor for kidney function decline and cardiovascular disease in adulthood, and thus early identification in children is important. The association between proteinuria and non-dipping in children will allow us to more readily identify those at risk, with a future focus on interventions to modify blood pressure dipping patterns.

Pharmacist interventions for persons with intellectual disabilities: A scoping review.

INTRODUCTION: Persons with intellectual disabilities (ID) often have complex health needs due to the development of multiple comorbidities. Given the higher associated use of problematic medications, such as antipsychotics, and polypharmacy, persons with ID may be particularly vulnerable to adverse side effects. With their medication expertise, pharmacists have the potential to address medication related challenges experienced by this population. OBJECTIVE: Explore what is known about the care pharmacists provide to persons with ID. DESIGN: Following Arksey and O'Malley's 5-stage framework for scoping reviews, searches of the PubMed (MEDLINE), Ovid EMBASE, Ovid International Pharmaceutical Abstracts, Scopus and APA PsycINFO databases were conducted in January 2019 with no limits on publication date. Studies of participants diagnosed with ID or healthcare providers/caregivers of persons with ID that referenced a pharmacist care intervention were included. Studies with non-human populations and editorials, commentaries, letters to the editor or discussion papers were excluded. RESULTS: Twenty-six studies were included in the review. Seventy-six pharmacist care interventions were identified in cognitive pharmacy services (n = 46); educational and advisory services (n = 20); and medication prescription processing (n = 10). Fifty-one outcomes were referenced including drug-related interventions (n = 14), drug related problems (n = 9), cost/time-effectiveness (n = 7), secondary symptoms (n = 6), other outcomes (n = 5), general medication usage (n = 4), caregiver and healthcare team satisfaction levels (n = 3), and educational/knowledge (n = 3). CONCLUSION: Pharmacists perform a variety of health care services to persons with ID but the impact of these interventions cannot be accurately measured due to a lack of: 1) universal definitions for ID; 2) reporting of multifactorial conditions contributing to a spectrum of ID severity; and 3) standardized reporting of ID-specific outcomes. Addressing these gaps is necessary for the development of a comprehensive evidence base regarding pharmacist involvement for medication challenges in persons with ID.

The SWI/SNF ATPase BRG1 stimulates DNA end resection and homologous recombination by reducing nucleosome density at DNA double strand breaks and by promoting the recruitment of the CtIP nuclease.

DNA double strand breaks (DSBs) are among the most toxic DNA lesions and can be repaired accurately through homologous recombination (HR). HR requires processing of the DNA ends by nucleases (DNA end resection) in order to generate the required single-stranded DNA (ssDNA) regions. The SWI/SNF chromatin remodelers are 10-15 subunit complexes that contain one ATPase (BRG1 or BRM). Multiple subunits of these complexes have recently been identified as a novel family of tumor suppressors. These complexes are capable of remodeling chromatin by pushing nucleosomes along the DNA. More recent studies have identified these chromatin remodelers as important factors in DNA repair. Using the DR-U2OS reporter system, we show that the down regulation of BRG1 significantly reduces HR efficiency, while BRM has a minor effect. Inactivation of BRG1 impairs DSB repair and results in a defect in DNA end resection, as measured by the amount of BrdU-containing ssDNA generated after DNA damage. Inactivation of BRG1 also impairs the activation of the ATR kinase, reduces the levels of chromatin-bound RPA, and reduces the number of RPA and RAD51 foci after DNA damage. This defect in DNA end resection is explained by the defective recruitment of GFP-CtIP to laser-induced DSBs in the absence of BRG1. Importantly, we show that BRG1 reduces nucleosome density at DSBs. Finally, inactivation of BRG1 renders cells sensitive to anti-cancer drugs that induce DSBs. This study identifies BRG1 as an important factor for HR, which suggests that BRG1-mutated cancers have a DNA repair vulnerability that can be exploited therapeutically.