Retrospective Analysis of Once-Daily Versus Twice-Daily Insulin Glargine Dosing in Noncritically Ill Individuals.

Background: Insulin is the treatment of choice for diabetes care in the hospital. There is some debate regarding the efficacy and safety of once-daily versus twice-daily insulin glargine in the hospital, particularly in the critically ill population. Objective: The purpose of this pilot study was to evaluate the efficacy and safety of insulin glargine administered as a once-daily versus twice-daily regimen in the noncritically ill population. Methods: A retrospective chart review was conducted from 1 June 2020 to 31 May 2021. Inclusion criteria were age ≥18 years and on a regimen of either once-daily or twice-daily insulin glargine for ≥72 hours during the specified time frame. The primary end point was a comparison of the number of days with all blood glucose measurements within the range of 70-180 mg/dL throughout a 24-hour period. Secondary end points included the number of hyperglycemic (>180 mg/dL) and hypoglycemic (<70 mg/dL) events that occurred in each study group. Results: Group 1 included 101 individuals who received once-daily dosing, and group 2 included 103 individuals who received twice-daily dosing. Baseline characteristics were similar between the groups except for a higher BMI at admission (P = 0.01) and a higher pre-admission A1C (P = 0.02) in group 2. No differences were found for the primary end point (P = 0.5) or for hypoglycemic (P = 0.6) or hyperglycemic (P = 0.7) events. Conclusion: There were no significant differences in efficacy or safety between once-daily and twice-daily insulin glargine in the noncritically ill population. A larger prospective study could confirm these results.

[89Zr]-CD8 ImmunoPET imaging of glioblastoma multiforme response to combination oncolytic viral and checkpoint inhibitor immunotherapy reveals CD8 infiltration differential changes in preclinical models.

Rationale: Novel immune-activating therapeutics for the treatment of glioblastoma multiforme (GBM) have shown potential for tumor regression and increased survival over standard therapies. However, immunotherapy efficacy remains inconsistent with response assessment being complicated by early treatment-induced apparent radiological tumor progression and slow downstream effects. This inability to determine early immunotherapeutic benefit results in a drastically decreased window for alternative, and potentially more effective, treatment options. The objective of this study is to evaluate the effects of combination immunotherapy on early CD8+ cell infiltration and its association with long term response in orthotopic syngeneic glioblastoma models. Methods: Luciferase positive GBM orthotopic mouse models (GSC005-luc) were imaged via [89Zr]-CD8 positron emission tomography (PET) one week following treatment with saline, anti-PD1, M002 oncolytic herpes simplex virus (oHSV) or combination immunotherapy. Subsequently, brains were excised, imaged via [89Zr]-CD8 ImmunoPET and evaluated though autoradiography and histology for H&E and CD8 immunohistochemistry. Longitudinal immunotherapeutic effects were evaluated through [89Zr]-CD8 PET imaging one- and three-weeks following treatment, with changes in tumor volume monitored on a three-day basis via bioluminescence imaging (BLI). Response classification was then performed based on long-term BLI signal changes. Statistical analysis was performed between groups using one-way ANOVA and two-sided unpaired T-test, with p < 0.05 considered significant. Correlations between imaging and biological validation were assessed via Pearson's correlation test. Results: [89Zr]-CD8 PET standardized uptake value (SUV) quantification was correlated with ex vivo SUV quantification (r = 0.61, p < 0.01), autoradiography (r = 0.46, p < 0.01), and IHC tumor CD8+ cell density (r = 0.55, p < 0.01). Classification of therapeutic responders, via bioluminescence signal, revealed a more homogeneous CD8+ immune cell distribution in responders (p < 0.05) one-week following immunotherapy. Conclusions: Assessment of early CD8+ cell infiltration and distribution in the tumor microenvironment provides potential imaging metrics for the characterization of oHSV and checkpoint blockade immunotherapy response in GBM. The combination therapies showed enhanced efficacy compared to single agent immunotherapies. Further development of immune-focused imaging methods can provide clinically relevant metrics associated with immune cell localization that can inform immunotherapeutic efficacy and subsequent treatment response in GBM patients.

Development of Quality Measures for Inpatient Diabetes Care and Education Specialists: A Call to Action.

ABSTRACT: Diabetes and hyperglycemia are associated with an increased risk of in-hospital complications that lead to longer lengths of stay, increased morbidity, higher mortality, and risk of readmission. Diabetes care and education specialists (DCESs) working in hospital settings are uniquely prepared and credentialed to serve as content experts to facilitate change and implement processes and programs to improve glycemic-related outcomes. A recent survey of DCESs explored the topic of productivity and clinical metrics. Outcomes highlighted the need to better evaluate the impact and value of inpatient DCESs, advocate for the role, and to expand diabetes care and education teams to optimize outcomes. The purpose of this article was to recommend strategies and metrics that can be used to quantify the work of inpatient DCESs and describe how such metrics can help to show the value of the inpatient DCES and assist in making a business case for the role.

Significant publications in diabetes pharmacotherapy and technology in 2020.

INTRODUCTION: The most significant articles on diabetes pharmacotherapy and technology in the peer-reviewed literature from 2020, as determined by a panel of pharmacists with expertise in diabetes care and education, are summarized. AREAS COVERED: Members of the Association of Diabetes Care and Education Specialists Pharmacy Community of Interest were selected to review articles published in prominent peer-reviewed journals in 2020 that most impacted diabetes pharmacotherapy and technology. A list of 37 nominated articles were compiled (22 in diabetes pharmacotherapy and 15 in diabetes technology). Based on discussion among the authors, the articles were ranked based on significant contribution, impact, and diversity to diabetes pharmacotherapy and technology. The top 10 highest ranked publications (n = 6 for diabetes pharmacotherapy and n = 4 in diabetes technology) are summarized in this article. EXPERT OPINION: With the significant number of publications in diabetes care and education, it can be challenging and overwhelming to remain current with published literature. This review article may be helpful in identifying key articles in diabetes pharmacotherapy and technology from the year 2020.

Diabetes: how to manage chronic kidney disease.

Background: Chronic kidney disease (CKD) is a prevalent and progressive condition worldwide, and diabetes is a leading risk factor of this renal disorder. People with diabetes and CKD are at high risk of complications such as cardiovascular events and death. CKD is often unrecognized and undiagnosed amongst people with diabetes. To manage CKD, multiple existing and newer agents have been studied in trials and recommended in clinical practice guidelines. Methods: A narrative review of primary and/or secondary renal outcomes from randomized, controlled trials is summarized in this article. The main objective was to provide the most up-to-date information regarding existing and new pharmacotherapy for the management of CKD amongst people with diabetes, specifically type 2 diabetes (T2D). Discussion: Traditional agents, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, have been used for 20 years to preserve kidney function. Other existing agents have received approval by the FDA for the management of CKD such as dapagliflozin, with a role in reducing intraglomerular pressure. Evidence with sodium-glucose cotransporter 2 inhibitors show a potential class effect on improving renal outcomes, independent on their effect on glycaemic parameters. Recently, finerenone was approved for people with T2D and CKD based on clinical evidence as a non-steroidal mineralocorticoid receptor antagonist. Overall, primary and secondary prevention trials have influenced changes in clinical practice guidelines regarding the use of existing and new pharmacotherapy for CKD. Additional considerations include lifestyle modifications, blood pressure management and achievement of glycaemic targets for people with diabetes and CKD, following adequate screening of glomerular filtration rate and/or severity of albuminuria. Conclusion: Due to more robust evidence, clinical practice guidelines have been modified to reflect high-level recommendations for the management of CKD in people with diabetes, specifically T2D. Additional evidence is needed amongst people with lower glomerular filtration rates and in comparison with the standard of care.

Development and Current Role of Sodium Glucose Cotransporter Inhibition in Cardiorenal Metabolic Syndrome.

ABSTRACT: Sodium-glucose cotransporter-2 inhibitors were approved as adjunct therapy for the management of type 2 diabetes and have become a high-level recommendation for this population with cardiorenal metabolic syndrome. In addition, evidence continues to grow supporting this class of medications for people with heart failure and chronic kidney disease, regardless of diabetes status. This narrative review summarizes the sodium-glucose cotransporter inhibitors for cardiorenal metabolic syndrome.

Immune Activity and Response Differences of Oncolytic Viral Therapy in Recurrent Glioblastoma: Gene Expression Analyses of a Phase IB Study.

PURPOSE: Previously, clinical trials of experimental virotherapy for recurrent glioblastoma multiforme (GBM) demonstrated that inoculation with a conditionally replication-competent Δγ134.5 oncolytic herpes simplex virus (oHSV), G207, was safe. Following the initial safety study, a phase Ib trial enrolled 6 adult patients diagnosed with GBM recurrence from which tumor tissue was banked for future studies. PATIENTS AND METHODS: Here, we analyzed tumor RNA sequencing (RNA-seq) data obtained from pre- and posttreatment (collected 2 or 5 days after G207 injection) biopsies from the phase Ib study patients. RESULTS: Using a Spearman rank-order correlation analysis, we identified approximately 500 genes whose expression pattern correlated with survival duration. Many of these genes were enriched for the intrinsic IFN-mediated antiviral and adaptive immune functional responses, including immune cell chemotaxis and antigen presentation to T-cells. Furthermore, we show that the expression of several T-cell-related genes was highest in the patient with the longest survival after G207 inoculation. CONCLUSIONS: Our data support that the oHSV-induced type I IFN production and the subsequent recruitment of an adaptive immune response differed between enrolled patients and showed association with survival duration in patients with recurrent malignant glioma after treatment with an early generation oHSV.

The Effects of Diabetes Self-Management Education on Quality of Life for Persons With Type 1 Diabetes: A Systematic Review of Randomized Controlled Trials.

PURPOSE: It is well documented that chronic conditions, such as diabetes, impact quality of life (QoL). QoL assessment is essential when developing and evaluating diabetes self-management education support interventions. The aim of this systematic review was to evaluate the evidence and gaps in the research and the impact of diabetes self-management education (DSME) on QoL outcomes in persons with type 1 diabetes mellitus (T1DM). METHODS: A systematic review of English language studies published between January 1, 2007, and March 31, 2020, was conducted using a modified Cochrane review method. Studies were included if they were randomized controlled trials (RCTs), participants had T1DM with or without caregivers, a DSME intervention alone or a component(s) of the ADCES7™ Self-Care Behaviors was described, and QoL was a primary or secondary outcome. A 3-tiered review process was utilized for selecting articles. Retained articles were assessed for risk of bias. RESULTS: Nineteen articles, reporting on 17 RCTs, met inclusion criteria, of which 7 studies reported QoL as the primary outcome and 10 as a secondary outcome. Seven studies detected significant impact of DMSE on QoL outcomes in either the participants or family caregivers, which varied in participant populations, selection of QoL tools (generic vs diabetes-specific), intervention type, intervention length, and type of interventionist. CONCLUSION: DSME has the potential to influence QoL outcomes in people with T1DM. Research using more standardized methods are needed to delineate impact on a broader range of factors that influence QoL for those living with T1DM across the life span and their caregivers.

Clinical review of subcutaneous semaglutide for obesity.

WHAT IS KNOWN AND OBJECTIVE: The purpose of this review paper is to review the efficacy and safety of subcutaneous semaglutide, marketed as Wegovy, a glucagon-like peptide-1 receptor agonist for obesity management. METHODS: A MEDLINE search (1970 to June 2021) was conducted to identify Phase 3 trials of subcutaneous semaglutide for obesity management. Published Phase 3 trials from The Semaglutide Treatment Effect in People with obesity (STEP) program were reviewed and summarized. RESULTS AND DISCUSSION: Based on four Phase 3 trials, subcutaneous semaglutide as 2.4 mg once weekly was compared in efficacy and safety among 5000 randomized participants who were overweight or had obesity. A change in body weight from baseline to end of study was the primary outcome in the STEP program. Participants who received semaglutide had a dose-dependent reduction in body weight from baseline, compared to placebo. Higher percentages of participants had 5%-10% weight reduction from baseline when receiving subcutaneous semaglutide. The patient population was mainly middle-aged female participants with Class II obesity. Additional studies are needed, especially active-comparator trials, to determine the efficacy and safety of semaglutide in a diverse patient population. WHAT IS NEW AND CONCLUSION: Subcutaneous semaglutide is another available option as adjunct therapy to lifestyle modifications for people who are overweight or have obesity based on body weight and body mass index. It resulted in more weight reduction than placebo with gastrointestinal adverse events being the most common safety concerns. Clinical utilization of subcutaneous semaglutide will be determined, as insurance coverage will be a limitation for this new medication.

A cross-sectional study of student pharmacists' attitudes and self-awareness towards obesity and weight.

INTRODUCTION: Neutral attitudes towards people with obesity is a necessity among student pharmacists entering the workforce and caring for this patient population. The purpose of the study was to investigate the perception towards people with obesity among student pharmacists. METHODS: A cross-sectional study using a self-administered questionnaire was sent to 237 student pharmacists. The questionnaire consisted of four demographic questions, the 14-item Fat Phobia Scale (FPS), and the 20-item Attitudes Towards Obese Persons Scale (ATOPS). Statistical analysis was completed to determine any differences between gender, age, and current status in pharmacy school. RESULTS: Eighty-four student pharmacists completed the questionnaire (35.4% response rate). Most participants were female (84.5%) and > 25 years of age (61.9%). Scores indicated an average level of fat phobia with no difference between males and females (mean score 2.8 ± 0.23 and 2.8 ± 0.29, respectively; P = .92). For attitude, the mean scores were - 0.93 ± 0.42 for males and - 0.75 ± 0.59 for females, indicating a neutral attitude towards obesity and no difference between groups (P = .35). There was no difference in age (younger vs. ≥ 25 years of age) in the FPS (P = .06) or ATOPS (P = .36). There was no difference in mean scores of FPS and ATOPS based on current year in pharmacy school (P = .69 and P = .97, respectively). CONCLUSIONS: Student pharmacists had an average level of fat phobia and neutral attitude towards people with obesity regardless of gender, age, and year in pharmacy school.

Thumb CMCJ prosthetic total joint replacement: a systematic review.

Thumb carpometacarpal joint (CMCJ) arthritis is a common and painful condition. Thumb CMCJ prosthetic replacement aims to restore thumb biomechanics and improve pain and function. Early reviews demonstrated a lack of high-quality studies, but more recently a significant number of higher-quality studies have been published. This review provides a concise and systematic overview of the evidence to date.A systematic review of several databases was conducted according to PRISMA guidelines. Studies evaluating the outcomes of thumb CMCJ prosthetic total joint replacement were included. Data extracted included patient-reported outcome measures (PROMs), pain scores, range of motion, strength, survival rates and complications.A total of 56 studies met all inclusion criteria and were analysed. There was one randomized controlled trial, three prospective comparative cohort studies, five retrospective comparative cohort studies, and 47 descriptive cohort studies. The reported studies included 2731 patients with 3048 thumb total CMCJ prosthetic joint replacements. Follow up ranged from 12 months to 13.1 years.In general, good results were demonstrated, with improvements in PROMs, pain scores and strength. Failure rates ranged from 2.6% to 19.9% depending upon implant studied. Comparative studies demonstrated promising results for replacement when compared to resection arthroplasty, with modest improvements in PROMs but at a cost of increased rates of complications.Studies reporting outcomes in thumb CMCJ prosthetic total joint replacement are increasing in both number and quality. Failure, in terms of loosening and dislocation, remains a concern, although in the medium-term follow up for modern implants this issue appears to be lower when compared to their predecessors.Functional outcomes also look promising compared to resection arthroplasty, but further high-quality studies utilizing a standardized resection arthroplasty technique and modern implants, together with standardized core outcome sets, will be of value. Cite this article: EFORT Open Rev 2021;6:316-330. DOI: 10.1302/2058-5241.6.200152.

Glucagon: Its evolving role in the management of hypoglycemia.

More than 10% of the United States population has diabetes, characterized by hyperglycemia. Insulin and other agents used to treat diabetes predispose people to hypoglycemia, which can be life threatening. Glucagon is an emergency medication that can save lives by quickly raising glucose in people who are unconscious or unable to consume glucose due to severe hypoglycemia. Although glucagon has been commercially available since 1960, earlier formulations required reconstitution of a dry powder with diluent immediately prior to injection, due to lack of long-term stability once reconstituted. Glucagon has been underutilized due to the lack of confidence or ability to administer in emergency situations. More recently, new formulations including a nasal powder glucagon and liquid-stable glucagon have become available. This article discusses the evidence surrounding new glucagon formulations compared with the original glucagon emergency kit including ease of use, efficacy, and safety with a focus on important patient counseling points and relevant clinical information on hypoglycemia.

Pharmacokinetics and Clinical Implications of Oral Semaglutide for Type 2 Diabetes Mellitus.

Since the approval of subcutaneous glucagon-like peptide-1 receptor agonists, this therapeutic class has become a preferred choice for the management of type 2 diabetes due to A1C reduction, minimal risk of hypoglycemia, weight loss, and cardiovascular benefit. An oral option, with gastrointestinal absorption, would overcome any potential fear of injection among patients. Oral semaglutide has been studied in randomized controlled trials within the PIONEER program. From a robust pool of literature with a global patient population, oral semaglutide has been an effective option as monotherapy and combination therapy to improve clinical outcomes, such as A1C and body weight from baseline to week 78, depending on the randomized controlled trial. In addition, a noninferiority result was observed with oral semaglutide versus placebo in a cardiovascular outcomes trial in patients with type 2 diabetes with established cardiovascular disease or risk factors. Similar to injectable glucagon-like peptide 1 receptor agonists, transient nausea and vomiting was seen with oral semaglutide. Overall, this new oral option may be a choice for patients with barriers to injectable therapy. This review evaluates and summarizes the pharmacokinetics, pharmacodynamics, and clinical application of oral semaglutide in patients with type 2 diabetes.

Clinical potential of liraglutide in cardiovascular risk reduction in patients with type 2 diabetes: evidence to date.

Metformin is the first-line therapy for the management of type 2 diabetes. After 3 months of metformin, add-on therapy can be considered if an individual's glycemic control has not been achieved for hemoglobin A1c, fasting blood glucose levels, and postprandial blood glucose levels. Liraglutide is a potential second-line option for the management of type 2 diabetes mellitus, particularly for those who are or may be at a high risk of cardiovascular disease. It can also be used an add-on therapy for those individuals with established cardiovascular disease. Liraglutide has additional benefits, such as no to minimal risk of hypoglycemia and promotion of weight loss through its mechanism of action. This particular article summarizes evidence on cardiovascular biomarkers and surrogate endpoints, along with macrovascular events, with liraglutide therapy. Overall, liraglutide has extensive cardiovascular evidence based on which it could be used as a desirable agent for glycemic control while lowering the risk of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization from heart failure.

Abaloparatide: A new pharmacological option for osteoporosis.

PURPOSE: The efficacy and safety of abaloparatide, a parathyroid hormone-related protein analog for the treatment of osteoporosis in postmenopausal women at high fracture risk, is reviewed. SUMMARY: A MEDLINE search was conducted for full text English-language articles, using the terms abaloparatide, parathyroid hormone, and osteoporosis. Published articles pertinent to the short- and long-term efficacy and safety of abaloparatide among postmenopausal women with osteoporosis were reviewed and summarized. Based on randomized, placebo-controlled and active-comparator studies, abaloparatide can reduce the risk of new vertebral and nonvertebral fractures in postmenopausal women with osteoporosis. Abaloparatide can also significantly increase bone mineral density (BMD) at the total hip, femoral neck, and lumbar spine. Patients receiving abaloparatide experience faster and more robust changes in BMD compared to those receiving teriparatide. Overall, abaloparatide is well tolerated with a mild adverse effect profile, including dizziness, headache, nausea, and palpitations. Additionally, there is a lower incidence of hypercalcemia with abaloparatide than with teriparatide. At this time, the differences demonstrated between abaloparatide and teriparatide would not be considered clinically significant. Larger and more robust studies are needed to determine future clinical significance of abaloparatide compared with other agents for use in the postmenopausal osteoporotic population. CONCLUSION: Abaloparatide is an effective anabolic agent to improve bone formation and resorption amongst postmenopausal women with osteoporosis. Based on its clinical evidence, abaloparatide can result in greater BMD increases and less hypercalcemia compared with the only current marketed anabolic agent, teriparatide. Adverse events associated with abaloparatide are generally mild in nature and include nausea, dizziness, headache, and palpitations.

Major trauma: Does weekend attendance increase 30-day mortality?

BACKGROUND: Differing mortality rates according to day of hospital admission is an area of debate, where a supposed increased rate of mortality with weekend admissions has been termed "the weekend effect". We sought to identify the 30-day mortality rates in major trauma patients attending our Major Trauma Centre (MTC) and the underlying reasons for these. METHODS: A retrospective review of data retrieved from the Trauma Audit and Research Network (TARN) database was undertaken for all patients attending between January 2013 and July 2015 with an Injury Severity Score of 9 or higher. 30-day mortality rates were calculated according to day of attendance. RESULTS: 1424 patients met the inclusion criteria. There was no significant difference in 30-day mortality between weekend attendances (7.8%) compared to those on a weekday (7.7%). 30-day mortality was highest in patients attending on Fridays (10.8%) and lowest in those attending on Sundays (5.5%). A significantly higher 30-day mortality rate was seen in patients attending on a Friday or Saturday (10.4%) compared to those attending Sunday to Thursday (6.6%) (RR 1.548). Patients with a head injury as their most serious injury on a Friday or Saturday were more likely to have GCS < 9 (34.7% vs 24.4%) and more likely to die (22.7% vs 12%) than those attending Sunday to Thursday. CONCLUSION: There is no significant difference in 30-day mortality when directly comparing weekday to weekend attendances. There is a significantly higher mortality on Friday and Saturday compared to remainder of the week which appears to be explained by a greater severity of head trauma. IMPLICATIONS: This study provides no evidence of a "weekend effect" in this MTC but the increased severity of and mortality from head injury identified on Friday and Saturday is a public health concern which warrants further investigation.