Intraoperative Pedal Pressure Changes Offers Another Quantitative Assessment for Revascularization.

BACKGROUND: Lower extremity angiography is one of the most prevalent vascular procedures performed, generally via the contralateral common femoral artery. The use of retrograde pedal artery access to perform angiography has long been reserved as a "bail-out" technique to help cross chronic total occlusions that were not amenable from an antegrade approach. Recently, there have been reports and discussions involving increased utilization of pedal access for primary revascularization. The purpose of this study is to describe the outcomes of pedal access as a primary approach and to propose a novel evaluation of distal perfusion changes associated with interventions using direct pressure measurements. METHODS: A retrospective observational study evaluating all patients who underwent lower extremity angiography via retrograde pedal access between December 1, 2020, and June 30, 2021, within a single health-care system spanning 3 hospitals was performed. Demographics, comorbidities, procedural indications, and details were all recorded. Hemodynamic measurements were obtained and recorded upon initial pedal access and post intervention with a pressure transducer connected directly to the access sheath. Outcomes were analyzed with paired t-test. RESULTS: Twenty-eight angiograms using primary pedal access for endovascular intervention were performed during the study period. Most patients were African American (75%) females (57.1%) with hypertension (89.3%), hyperlipidemia (78.6%), diabetes (85.7%), coronary artery disease (64.3%), and current tobacco users (57.1%). The most prevalent indication for angiography was nonhealing wounds (67.9%). Pedal access was mostly achieved via the anterior tibial artery (79%). Sixty-three vessels were treated during the 28 angiograms (averaging 2.3 vessels per angiogram), most commonly the superficial femoral (27%), anterior tibial (25%), and popliteal (22%) arteries. Balloon angioplasty with or without stenting (98.5%) was predominately performed with an overall technical success rate of 94%. The mean preintervention and postintervention pressures were 36.5 mm Hg (standard deviation [SD] 25.7) and 83.4 mm Hg (SD 19.5), respectively. The mean change in pressure after intervention was 46.9 mm Hg (SD 23.3) (Table 3). There was a statistically significant difference detected between preintervention and postintervention pressure (P < 0.001) (Figure 1). There were no major amputations or adverse cardiovascular events at a mean first follow-up duration of 89 days. Six of the total 28 patients (21.4%) underwent repeat endovascular intervention on the ipsilateral extremity within a median of 45 (interquartile range 22.5-62.3) days. CONCLUSIONS: Primary pedal access is a viable option for performing lower extremity angiographic interventions. A significant increase in pedal artery pressure can be observed after angiographic intervention from retrograde pedal artery access. Further studies are necessary to define the clinical prognostic importance of these findings in relation to wound healing rates.

Absence of cannabinoid 1 receptor in beta cells protects against high-fat/high-sugar diet-induced beta cell dysfunction and inflammation in murine islets.

AIMS/HYPOTHESIS: The cannabinoid 1 receptor (CB1R) regulates insulin sensitivity and glucose metabolism in peripheral tissues. CB1R is expressed on pancreatic beta cells and is coupled to the G protein Gαi, suggesting a negative regulation of endogenous signalling in the beta cell. Deciphering the exact function of CB1R in beta cells has been confounded by the expression of this receptor on multiple tissues involved in regulating metabolism. Thus, in models of global genetic or pharmacological CB1R blockade, it is difficult to distinguish the indirect effects of improved insulin sensitivity in peripheral tissues from the direct effects of inhibiting CB1R in beta cells per se. To assess the direct contribution of beta cell CB1R to metabolism, we designed a mouse model that allows us to determine the role of CB1R specifically in beta cells in the context of whole-body metabolism. METHODS: We generated a beta cell specific Cnr1 (CB1R) knockout mouse (ß-CB1R-/-) to study the long-term consequences of CB1R ablation on beta cell function in adult mice. We measured beta cell function, proliferation and viability in these mice in response to a high-fat/high-sugar diet and induction of acute insulin resistance with the insulin receptor antagonist S961. RESULTS: ß-CB1R-/- mice had increased fasting (153 ± 23% increase at 10 weeks of age) and stimulated insulin secretion and increased intra-islet cAMP levels (217 ± 33% increase at 10 weeks of age), resulting in primary hyperinsulinaemia, as well as increased beta cell viability, proliferation and islet area (1.9-fold increase at 10 weeks of age). Hyperinsulinaemia led to insulin resistance, which was aggravated by a high-fat/high-sugar diet and weight gain, although beta cells maintained their insulin secretory capacity in response to glucose. Strikingly, islets from ß-CB1R-/- mice were protected from diet-induced inflammation. Mechanistically, we show that this is a consequence of curtailment of oxidative stress and reduced activation of the NLRP3 inflammasome in beta cells. CONCLUSIONS/INTERPRETATION: Our data demonstrate CB1R to be a negative regulator of beta cell function and a mediator of islet inflammation under conditions of metabolic stress. Our findings point to beta cell CB1R as a therapeutic target, and broaden its potential to include anti-inflammatory effects in both major forms of diabetes. DATA AVAILABILITY: Microarray data have been deposited at GEO (GSE102027).

Dietary Indoles Suppress Delayed-Type Hypersensitivity by Inducing a Switch from Proinflammatory Th17 Cells to Anti-Inflammatory Regulatory T Cells through Regulation of MicroRNA.

Aryl hydrocarbon receptor (AhR) has been shown to have profound influence on T cell differentiation, and use of distinct AhR ligands has shown that whereas some ligands induce regulatory T cells (Tregs), others induce Th17 cells. In the present study, we tested the ability of dietary AhR ligands (indole-3-carbinol [I3C] and 3,3'-diindolylmethane [DIM]) and an endogenous AhR ligand, 6-formylindolo(3,2-b)carbazole (FICZ), on the differentiation and functions of Tregs and Th17 cells. Treatment of C57BL/6 mice with indoles (I3C or DIM) attenuated delayed-type hypersensitivity (DTH) response to methylated BSA and generation of Th17 cells while promoting Tregs. In contrast, FICZ exacerbated the DTH response and promoted Th17 cells. Indoles decreased the induction of IL-17 but promoted IL-10 and Foxp3 expression. Also, indoles caused reciprocal induction of Tregs and Th17 cells only in wild-type (AhR(+/+)) but not in AhR knockout (AhR(-/-)) mice. Upon analysis of microRNA (miR) profile in draining lymph nodes of mice with DTH, treatment with I3C and DIM decreased the expression of several miRs (miR-31, miR-219, and miR-490) that targeted Foxp3, whereas it increased the expression of miR-495 and miR-1192 that were specific to IL-17. Interestingly, treatment with FICZ had precisely the opposite effects on these miRs. Transfection studies using mature miR mimics of miR-490 and miR-1192 that target Foxp3 and IL-17, respectively, or scrambled miR (mock) or inhibitors confirmed that these miRs specifically targeted Foxp3 and IL-17 genes. Our studies demonstrate, to our knowledge for the first time, that the ability of AhR ligands to regulate the differentiation of Tregs versus Th17 cells may depend on miR signature profile.

Advancing learning to advance pharmacy practice.

OBJECTIVES: The objectives of this commentary are to: 1) describe advancements in the continuing professional development (CPD) model over the past decade; 2) detail an updated CPD cycle; and 3) describe how practitioners' adoption of the CPD approach may facilitate the advancement of pharmacy practice. SUMMARY: CPD is a self-directed, ongoing, systematic, and outcomes-focused approach to an individual's lifelong learning that is applied into practice. The 6 components of reflect, plan, learn, evaluate, apply, and record + review, described in a revised depiction of the CPD cycle, have evolved over the past 10 years alongside the evolution of the profession of pharmacy. The thinking around the value of building CPD habits has also advanced. New emphasis is being placed on mechanisms for applying and sharing CPD-related work, as well as the importance of employer support of CPD. CONCLUSION: As practice change has progressed, the individual's need to learn has also changed. To succeed in the evolving health care system, regular, robust, and intentional CPD is needed. Moreover, for learning to have maximum impact, it must facilitate, motivate and result in changes in learner behavior. Employers, educators, and pharmacy organizations should facilitate lifelong learning by creating CPD supportive environments that foster learner success and community. The adoption of a CPD approach by pharmacy practitioners may facilitate the advancement of pharmacy practice.

3,3'-diindolylmethane ameliorates experimental autoimmune encephalomyelitis by promoting cell cycle arrest and apoptosis in activated T cells through microRNA signaling pathways.

3,3'-Diindolylmethane (DIM) is a naturally derived indole found in cruciferous vegetables that has great potential as a novel and effective therapeutic agent. In the current study, we investigated the effects of DIM post-treatment on the regulation of activated T cells during the development of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. We demonstrated that the administration of DIM 10 days after EAE induction was effective at ameliorating disease parameters, including inflammation and central nervous system cellular infiltration. MicroRNA (miRNA) microarray analysis revealed an altered miRNA profile in brain infiltrating CD4(+) T cells following DIM post-treatment of EAE mice. Additionally, bioinformatics analysis suggested the involvement of DIM-induced miRNAs in pathways and processes that halt cell cycle progression and promote apoptosis. Additional studies confirmed that DIM impacted these cellular processes in activated T cells. Further evidence indicated that DIM treatment significantly upregulated several miRNAs (miR-200c, miR-146a, miR-16, miR-93, and miR-22) in brain CD4(+) T cells during EAE while suppressing their associated target genes. Similarly, we found that overexpression of miR-16 in primary CD4(+) T cells led to significant downregulation of both mRNA and protein levels of cyclin E1 and B-cell lymphoma-2, which play important roles in regulating cell cycle progression and apoptosis. Collectively, these studies demonstrate that DIM post-treatment leads to the amelioration of EAE development by suppressing T-cell responses through the induction of select miRNAs that control cell cycle progression and mediate apoptosis.

R.I.M.E. and reason: multi-station OSCE enhancement to neutralize grade inflation.

To offset grade inflation, many clerkships combine faculty evaluations with objective assessments including the Medical Examiners Subject Examination (NBME-SE) or Objective Structured Clinical Examination (OSCE), however, standardized methods are not established. Following a curriculum transition removing faculty clinical evaluations from summative grading, final clerkship designations of fail (F), pass (P), and pass-with-distinction (PD) were determined by combined NBME-SE and OSCE performance, with overall PD for the clerkship requiring meeting this threshold in both. At the time, 90% of students achieved PD on the Internal Medicine (IM) OSCE resulting in overall clerkship grades primarily determined by the NBME-SE. The clerkship sought to enhance the OSCE to provide a more thorough objective clinical skills assessment, offset grade inflation, and reduce the NBME-SE primary determination of the final clerkship grade. The single-station 43-point OSCE was enhanced to a three-station 75-point OSCE using the Reporter-Interpreter-Manager-Educator (RIME) framework to align patient encounters with targeted assessments of progressive skills and competencies related to the clerkship rotation. Student performances were evaluated pre- and post-OSCE enhancement. Student surveys provided feedback about the clinical realism of the OSCE and the difficulty. Pre-intervention OSCE scores were more tightly clustered (SD = 5.65%) around a high average performance with scores being highly negatively skewed. Post-intervention OSCE scores were more dispersed (SD = 6.88%) around a lower average with scores being far less skewed resulting in an approximately normal distribution. This lowered the total number of students achieving PD on the OSCE and PD in the clerkship, thus reducing the relative weight of the NMBE-SE in the overall clerkship grade. Student response was positive, indicating the examination was fair and reflective of their clinical experiences. Through structured development, OSCE assessment can provide a realistic and objective measurement of clinical performance as part of the summative evaluation of students.

The influence of microbial colonization on inflammatory versus pro-healing trajectories in combat extremity wounds.

A combination of improved body armor, medical transportation, and treatment has led to the increased survival of warfighters from combat extremity injuries predominantly caused by blasts in modern conflicts. Despite advances, a high rate of complications such as wound infections, wound failure, amputations, and a decreased quality of life exist. To study the molecular underpinnings of wound failure, wound tissue biopsies from combat extremity injuries had RNA extracted and sequenced. Wounds were classified by colonization (colonized vs. non-colonized) and outcome (healed vs. failed) status. Differences in gene expression were investigated between timepoints at a gene level, and longitudinally by multi-gene networks, inferred proportions of immune cells, and expression of healing-related functions. Differences between wound outcomes in colonized wounds were more apparent than in non-colonized wounds. Colonized/healed wounds appeared able to mount an adaptive immune response to infection and progress beyond the inflammatory stage of healing, while colonized/failed wounds did not. Although, both colonized and non-colonized failed wounds showed increasing inferred immune and inflammatory programs, non-colonized/failed wounds progressed beyond the inflammatory stage, suggesting different mechanisms of failure dependent on colonization status. Overall, these data reveal gene expression profile differences in healing wounds that may be utilized to improve clinical treatment paradigms.

Relationship between clinical signs and symptoms of convergence insufficiency.

PURPOSE: The percentage of children who are symptomatic has been shown to increase with the number of signs of convergence insufficiency (CI). Our goal was to investigate whether there is a relationship between the severity of the clinical signs of CI and symptom level reported in children with a three-sign symptomatic CI. METHODS: The Convergence Insufficiency Treatment Trial enrolled 221 children with symptomatic CI from ages 9 to 17 years. Inclusion criteria included the following three signs of CI: (1) exophoria at near at least 4Δ greater than at distance, (2) insufficient positive fusional vergence (PFV) at near, and (3) a receded near point of convergence (NPC) of 6 cm break or greater. The relationships between the severity of each sign of CI (mild, moderate, and severe) and the level of symptoms as measured by the Convergence Insufficiency Symptom Survey (CISS) at baseline were evaluated. RESULTS: Mean CISS scores were not significantly different between mild, moderate, and severe exophoria (p = 0.60), PFV blur (p = 0.99), Sheard's criterion (p = 0.89), or NPC break (p = 0.84). There was also no difference between the frequency of subjects scoring at mild, moderate, or severe levels on the CISS and the severity of each sign of CI. Correlations between individual clinical signs and the CISS score were very low and not statistically significant. CONCLUSIONS: Among symptomatic children with a CISS score of 16 or higher and three clinical signs of CI, there is no further association between the severity of the clinical signs and their level of symptoms.

SMART Pharmacists Serving the New Needs of the Post-COVID Patients, Leaving No-One Behind.

This study aims to demonstrate the improvements in clinical symptoms in patients with post-COVID syndrome after a community pharmacy-based intervention in Serbia. The Pharmaceutical Chamber of Serbia ("Chamber") invited pharmacists to deliver post-COVID patient care counselling, supported by the SMART Pharmacist Program, offering education and guidance. Present symptoms, duration and patient self-reported severity of symptoms on a scale of 1-5 on the first visit were recorded. After the counselling and proposed self-medication treatment, the time of the follow-up visit and the severity of the recorded symptoms were also recorded. The prospective data collection lasted from December 2021 to September 2022. In total, 871 patients with post-COVID symptoms were included in the study, served by 53 pharmacists. The most frequently reported post-COVID symptoms coincided with the literature, mostly related to the respiratory system (51.2%), immunity status (32.2%), fatigue and exhaustion (30.7%), skin, hair and nails (27.4%) and cognitive functions (27.9%). A total of 26.5% of patients were referred to their family physician (general practitioner), and 69.5% returned to the pharmacist for a follow-up visit. On the first visit, the median severity of patients' symptoms was three, while on the second visit it dropped to one. The pharmacists' intervention led to a significant improvement in the post-COVID patients' condition.

Host CD3+ T-cells can significantly modulate phage treatment effects on bacterial bioburden in mouse models.

Wound healing is a complex system including such key players as host, microbe, and treatments. However, little is known about their dynamic interactions. Here we explored the interplay between: (1) bacterial bioburden and host immune responses, (2) bacterial bioburden and wound size, and (3) treatments and wound size, using murine models and various treatment modalities: Phosphate buffer saline (PBS or vehicle, negative control), doxycycline, and two doses of A. baumannii phage mixtures. We uncovered that the interplay between bacterial bioburden and host immune system may be bidirectional, and that there is an interaction between host CD3+ T-cells and phage dosage, which significantly impacts bacterial bioburden. Furthermore, the bacterial bioburden and wound size association is significantly modulated by the host CD3+ T-cells. When the host CD3+ T-cells (x on log10 scale) are in the appropriate range (1.35 < x < = 1.5), we observed a strong association between colony forming units (CFU) and wound size, indicating a hallmark of wound healing. On the basis of the findings and our previous work, we proposed an integrated parallel systems biology model.

Partnerships in public health: lessons from knowledge translation and program planning.

The purpose of this study was to better understand how partnerships are initiated, maintained, and sustained in public health practice. A qualitative design was employed to conduct individual interviews and focus groups. The participants included practitioners from 6 purposively selected public health units in the Canadian province of Ontario that developed partnerships in program planning. It was found that partnerships play an essential role in program planning but that minimal information is available regarding the partnership process. Most partnerships are formed on an ad hoc basis, with little formalization. Public health professionals rely on their experiential knowledge when seeking out and working with partners.These findings can serve to inform future public health planning and strengthen the formation and maintenance of partnerships in public health and other sectors. Understanding how partnerships are initiated, maintained, and sustained is an important first step in supporting the use of research to advance collaborative public health efforts.

Resident integration with inpatient clinical documentation improvement: a quality improvement project.

BACKGROUND: Clinical documentation improvement (CDI) is an increasing part of health system quality and patient care with clinical documentation integrity specialists (CDIS) expanding into daily physician workflow. This integration can be especially challenging for resident teams due to increased team size, lack of documentation experience, and misunderstanding of both CDIS and CDI purpose. PROBLEM: The University of Kansas Health System Internal Medicine residency programme reported challenges with CDIS and resident workflow integration specifically in navigating and understanding CDIS documentation queries, CDIS interruption of interdisciplinary huddles, and general misunderstanding of CDI and the role of CDIS. METHODS: A quality improvement project was undertaken to integrate CDIS more effectively into resident workflow. Combined with a resident debrief session to identify general areas of concern, surveys were administered to internal medicine residents, resident rounding faculty and CDIS team members to identify specific barriers to CDIS-physician integration. INTERVENTION: A collective group of CDIS member teams, internal medicine chief residents and faculty physicians was formed. Changes made to the CDI process based on survey feedback included (1) improving formatting of CDIS electronic query templates, (2) standardisation of timing for CDIS verbal queries during interdisciplinary huddles, and (3) development of a resident didactic session focused on the role of CDIS and documentation's impact on quality, safety and outcomes as related to the hospital, provider and patient. RESULTS: Surveys completed after implementation showed a positive impact on electronic query template changes and perception of CDIS at interdisciplinary huddles. The didactic curriculum was effective in helping residents understand the role and limitations of CDIS and how documentation affects quality of care. CONCLUSION: CDIS-physician integration into resident teams can occur through a collaborative focus on specific aspects of physician workflow and improving understanding of the impact of CDI on patient safety and quality of care.

Virtual Adaptation of Resident I-PASS Training Session During COVID-19.

Introduction: Effective communication during the patient handoff process is critical for ensuring patient safety. At our academic medical center, first-year interns complete hand-off training before starting clinical rotations. The purpose of this study was to evaluate a virtual handoff training for residents as an alternative to in-person sessions due to limitations imposed by COVID-19. Methods: Fifty residents were administered pre/post surveys to gauge the helpfulness of the training for clinical practice, familiarity and confidence in providing a hand-off, and whether they would recommend the virtual format for incoming interns. Additionally, faculty rated the virtual form of the hand-off activity, made comparisons to in-person sessions, and assessed the helpfulness of the session for residents in clinical practice. Results: Forty-four residents (88%) and 11 faculty (85%) completed surveys. After the training session, residents who received instruction and feedback reported significant improvements in familiarity with the hand-off tool and confidence in their hand-off abilities (both p < 0.001). Both residents and faculty were satisfied with the virtual format of hand-off training. Most faculty felt the virtual platform was comparable to in-person sessions and would recommend ongoing use of the virtual platform when in-person sessions were not possible. Conclusions: Teaching hospitals mandate resident training to include strategies for a uniform hand-off method to avoid medical errors. Adaptation to a virtual platform can be a successful instruction strategy, allowing for didactic and interactive sessions with direct faculty observation and feedback.

ISBARR Huddle: First-Year Medical Students Managing Critical Hypoglycemia as an Interprofessional Team.

Introduction: Recognizing a patient requiring urgent or emergent care and initiating evaluation and management must include elements that support teams working and thinking together. Although team communication strategies exist, a standardized approach for communicating about patients with urgent or emergent conditions is lacking. This simulation was designed to provide first-semester medical students with the opportunity to deliberately practice the foundational teamwork skills required to think as a team while caring for a patient with critical hypoglycemia. Methods: Students were introduced to a team huddle that was structured using ISBARR (identify, situation, background, assessment, recommend, recap) to assist in synthesizing gathered information and arriving at a diagnosis and associated care plan. Students practiced in small groups with faculty coaches and then applied the skills learned to two cases of a patient with critical hypoglycemia followed by debriefing. Results: Two hundred eight first-semester medical students participated in the simulation course across three campuses. We surveyed a single campus subset of 172 students. One hundred thirty-three students completed a postevent survey. The majority felt that the difficulty of the simulation was appropriate for their educational level (94%) and that the training would be applicable to real-life clinical events (76%) and would improve the quality and safety of care (100%). Survey comments highlighted teamwork and the use of the ISBARR huddle communication tool. Discussion: The course provided first-semester medical students with standardized practice of a team-based approach using huddle communication to advance patient care.

The first nationwide implementation of pharmaceutical care practices through a continuing professional development approach for community pharmacists.

BACKGROUND: Noncommunicable diseases account for the majority of all deaths and impose a high socioeconomic burden, causing disability and premature deaths. Pharmacists can contribute to the prevention and management of these diseases through the provision of pharmaceutical care services. AIM: The aim of this study was to implement a nationwide practice developed by the Turkish Pharmacists' Association aiming to realize pharmaceutical care provision of standard quality to patients with asthma, chronic obstructive pulmonary disease, diabetes and hypertension at community pharmacies through a continuing professional development approach. SETTING: Community pharmacies in Turkey. DEVELOPMENT: A project with the involvement of all community pharmacists who were willing to participate was developed. After piloting, the 'project' turned into a 'practice' with a focus on asthma, chronic obstructive pulmonary disease, diabetes and hypertension management. IMPLEMENTATION: The training process occurred as a peer-training activity. Consultants and academic staff trained the trainer pharmacists during a 3-day course. Community pharmacists (n = 6161) received training regarding pharmaceutical care, asthma, chronic obstructive pulmonary disease, diabetes and hypertension from their peer trainers (n = 341) and began to practice pharmaceutical care and follow-up of patients' outcomes on a regular basis. EVALUATION: Among all community pharmacists in Turkey (n = 26,177), 24% attended training. Among these pharmacists, 21% started to implement practice. With community pharmacists' contribution to patient care, significant improvements in the majority of the outcome parameters regarding asthma, chronic obstructive pulmonary disease, diabetes and hypertension management were noted. CONCLUSION: This first nationwide practice showed us that community pharmacists can help improve the health outcomes of patients with asthma, chronic obstructive pulmonary disease, diabetes and hypertension through the provision of pharmaceutical care services.

Blast Waves Cause Immune System Dysfunction and Transient Bone Marrow Failure in a Mouse Model.

Explosive devices, either conventional or improvised, are common sources of injuries during combat, civil unrest, and terror attacks, resulting in trauma from exposure to blast. A blast wave (BW), a near-instantaneous rise in pressure followed by a negative pressure, propagates through the body in milliseconds and can affect physiology for days/months after exposure. Epidemiological data show that blast-related casualties result in significantly higher susceptibility to wound infections, suggesting long-lasting immune modulatory effects from blast exposure. The mechanisms involved in BW-induced immune changes are poorly understood. We evaluated the effects of BW on the immune system using an established murine model. Animals were exposed to BWs (using an Advanced Blast Simulator), followed by longitudinally sampling for 14 days. Blood, bone marrow, and spleen were analyzed for changes in the 1) complete blood count (CBC), and 2) composition of bone marrow cells (BMC) and splenocytes, and 3) concentrations of systemic cytokines/chemokines. Our data demonstrate that BW results in transient bone marrow failure and long-term changes in the frequency and profile of progenitor cell populations. Viability progressively decreased in hematopoietic stem cells and pluripotent progenitor cells. Significant decrease of CD4+ T cells in the spleen indicates reduced functionality of adaptive immune system. Dynamic changes in the concentrations of several cytokines and chemokines such as IL-1α and IL-17 occurred potentially contributing to dysregulation of immune response after trauma. This work lays the foundation for identifying the potential mechanisms behind BW's immunosuppressive effects to inform the recognition of this compromised status is crucial for the development of therapeutic interventions for infections to reduce recovery time of wounded patients injured by explosive devices.

Chronic sphingosine 1-phosphate 1 receptor activation attenuates early-stage diabetic nephropathy independent of lymphocytes.

Sphingosine 1-phosphate (S1P), a pleiotropic lipid mediator, binds to five related G-protein-coupled receptors to exert its effects. As S1P1 receptor (S1P1R) activation blocks kidney inflammation in acute renal injury, we tested whether activation of S1P1Rs ameliorates renal injury in early-stage diabetic nephropathy (DN) in rats. Urinary albumin excretion increased in vehicle-treated diabetic rats (single injection of streptozotocin), compared with controls, and was associated with tubule injury and increased urinary tumor necrosis factor-α (TNF-α) at 9 weeks. These effects were significantly reduced by FTY720, a non-selective, or SEW2871, a selective S1P1R agonist. Interestingly, only FTY720 was associated with reduced total lymphocyte levels. Albuminuria was reduced by SEW2871 in both Rag-1 (T- and B-cell deficient) and wild-type diabetic mice after 6 weeks, suggesting that the effect was independent of lymphocytes. Another receptor, S1P3R, did not contribute to the FTY720-mediated protection, as albuminuria was also reduced in diabetic S1P3R knockout mice. Further, both agonists restored WT-1 staining along with podocin and nephrin mRNA expression, suggesting podocyte protection. This was corroborated in vitro, as SEW2871 reduced TNF-α and vascular endothelial growth factor mRNA expression in immortalized podocytes grown in media containing high glucose. Whether targeting kidney S1P1Rs will be a useful therapeutic measure in DN will need direct testing.

Scope of contemporary pharmacy practice: roles, responsibilities, and functions of pharmacists and pharmacy technicians.

OBJECTIVE: To provide an overview of the current context and scope of pharmacy practice, the range of professional services offered by pharmacists, and the supporting role of pharmacy technicians. DATA SYNTHESIS: A synopsis of the current state of pharmacy practice as it relates to the spectrum of professional roles and responsibilities, the diversity of patient populations served, the complexities of patient services provided, and various aspects of emerging pharmacy practice is provided. The current work focuses on patient care services provided by pharmacists; it does not address all possible activities of pharmacists, such as administration and general management. This is a descriptive analysis. It does not take a position regarding future changes but is intended to serve as a foundation for understanding the relationship and alignment between the profession's various mandatory and voluntary credentials and the scope of practice continuum. The key educational and credentialing standards for pharmacists and pharmacy technicians are summarized and referenced. CONCLUSION: The evolutions in health care and pharmacy practice are presenting many new opportunities for pharmacists to perform functions and provide services not considered as traditional roles. The profession of pharmacy is working to achieve a pervasive model and standard of care determined only by the needs of patients and populations. The Council on Credentialing in Pharmacy hopes that the material presented herein, including the framework for credentialing in pharmacy practice, will allow audiences to gain a better understanding of where pharmacy is today and what future pharmacy practice will look like.

Learn Today-Apply Tomorrow: The SMART Pharmacist Program.

The SMART Pharmacist Program was initiated by the Accreditation Council for Pharmacy Education (ACPE) and Pharma Expert in 2014. It was designed to introduce a new continuing education model for pharmacists for the Turkish Pharmacists' Association, and to support development of competencies for future practice. After successful implementation in Turkey, the Program spread to 16 additional countries. To assure quality, globally adopted and validated tools and best practices were used, respecting the national context. National competency frameworks and quality indicators for pharmaceutical care delivery were developed. Pharmacists' learning portfolios were introduced and patient care modules created. Under the sub-title "Learn Today-Apply Tomorrow," the changes in practice were introduced under the leadership of national host organizations. The Program showed an impact on the patient level in several countries, especially in areas of patient care in Asthma and Chronic Obstructive Pulmonary Disease (COPD), Hypertension and Dyslipidemia, Diabetes, and the patient care process in general (e.g., identifying drug-related problems, improving patient safety, collaborating with medical doctors). Changes are visible at the individual (pharmacists) and organizational levels. Barriers and facilitators to the change-management process during Program implementation are identified. In some countries, the Program is recognized as one of the most important initiatives in pharmacy education and practice, with visible support of national medicines agencies, academia, government, and WHO regional offices.

Laparoscopic EndoClose fixation of a peritoneal catheter reduces migration.

BACKGROUND: With the introduction of laparoscopic Tenckhoff catheter insertion in the early 1990s, catheter malposition resulting in malfunction remains a frequent complication, often requiring surgical or radiological intervention. In this pioneer study, we describe the technique of suturing the Tenckhoff catheter using an EndoClose (Medtronic, Macquarie Park, NSW, Australia) device to the anterior abdominal wall during laparoscopic insertion and compare its outcomes with those not sutured. METHODS: This is a retrospective study of all patients who underwent laparoscopic Tenckhoff catheter insertion at Western Health from January 2013 to June 2018. All procedures were undertaken or supervised by one surgeon. The primary outcome was catheter malposition requiring surgical revision. Secondary outcomes were time to malposition and complications. Peri- and post-operative factors were analysed to adjust for confounders using the Cochran-Mantel-Haenszel test. RESULTS: There were 82 patients in the sutured group and 63 patients in the non-sutured group. Catheter malposition occurred in 7.32% in the sutured group and 19.05% in the non-sutured group (P = 0.034; 95% confidence interval for the difference 0.007-0.237). There was an overall reduction in the odds of catheter malposition of 63% in favour of the sutured group. The median time-to-malposition was 128 and 182 days for the non-sutured and sutured group, respectively, but not statistically different. No differences were found for the number of post-operative complications. CONCLUSION: Suturing of Tenckhoff catheter with an EndoClose device to the anterior abdominal wall during laparoscopic insertion is a simple, safe and useful method of reducing catheter malposition.