Efficacy and Renal Outcomes of SGLT2 Inhibitors in Patients with Type 2 Diabetes and Chronic Kidney Disease

Objective: To review glucose-lowering efficacy and changes in renal function associated with sodium-glucose co-transporter 2 (SGLT2) inhibitors among patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). Data sources: A literature search of MEDLINE and Cochrane databases was performed from 2000 to August 2018 using search terms: SGLT2 inhibitors, sodium glucose co-transporter 2, canagliflozin, empagliflozin, dapagliflozin, ertugliflozin, and chronic kidney disease. References of identified articles were also reviewed. Study selection and data extraction: English-language studies investigating glucose-lowering endpoints and/or changes in renal function with one of four U.S. approved SGLT2 inhibitors were included. A total of 10 studies met inclusion criteria and are included in this review. Results: In patients with T2DM and CKD, SGLT2 inhibitors are modestly effective in lowering hemoglobin A1C and fasting plasma glucose compared to placebo. Small reductions in eGFR are seen shortly after initiating therapy with SGLT2 inhibitors, but return to baseline levels after discontinuation. SGLT2 inhibitors are associated with a substantial reduction in albuminuria and reduced risk of progression to albuminuria. Conclusions: In patients with T2DM and CKD, SGLT2 inhibitors have a decreased glucose-lowering effect compared to patients without CKD. Renal benefits among patients with CKD are similar to those without CKD and include a significant reduction in albuminuria and reduced incidence of worsening albuminuria. Given that CKD and T2DM are both associated with increased cardiovascular risk, we believe these agents should considered as preferred add-on agents in most patients with uncontrolled T2DM and eGFR \u3e30 ml/min/1.73 m2. Ongoing studies will provide additional information as to whether these agents should be added to the current standard of care for CKD patients, with and without T2DM

Tufted capuchin monkeys (Cebus apella) spontaneously use visual but not acoustic information to find hidden food items.

Foraging choices in tufted capuchins monkeys are guided by perceptual, cognitive, and motivational factors, but only little is known about how these factors might interact. The present study investigates how different types of sensory information affect capuchins’ ability to locate hidden food. In two experiments, capuchins were presented with two cups, one baited and one empty. Monkeys were given visual, acoustic, or acoustic-visual information related to the baited cup, the empty cup, or both baited and empty cup. Results show that capuchins spontaneously used visual information to locate food, and that information indicating presence and absence of food led to higher success rates than information indicating only absence of food. In contrast, acoustic information did not lead to success rates above chance levels and failed to enhance performance in combination with visual information. Capuchins spontaneously avoided a visually empty cup, but they did not appear to associate sounds with either the presence or absence of food. Being able to locate food items with the aid of acoustic cues might be a learned process that requires interactive experiences with the task’s contingencies

Managing Chronic and Acute COPD Exacerbations

Healthcare professionals across the world utilize the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline to guide the diagnosis, management, and prevention of chronic obstructive pulmonary disease (COPD). The guideline incorporates evidence-based recommendations regarding the assessment of disease severity, choice of pharmacologic treatment, and strategies for the management and prevention of acute exacerbations. The GOLD guideline recently underwent a major revision in 2017, in addition to a minor revision in 2018, to account for new evidence surrounding the assessment of disease severity, as well as therapeutic recommendations for the management of COPD. The updated GOLD report includes a simplified version of the ABCD assessment tool, which separates symptoms and exacerbation risk from the severity of airflow limitation. Additionally, there were also modifications to the pharmacotherapy treatment algorithm and new recommendations for the prevention and management of acute COPD exacerbations

Hyponatremia after initiation and rechallenge with trimethoprim–sulfamethoxazole in an older adult

Ashley M Huntsberry,1 Sunny A Linnebur,1 Maria Vejar2 1University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA; 2Division of Geriatrics, Department of Internal Medicine, University of Colorado School of Medicine, Aurora, CO, USA Purpose: The purpose of this study is to describe a case report of a patient experiencing hyponatremia from trimethoprim–sulfamethoxazole (TMP–SMX) upon initial use and subsequent rechallenge.Summary: An 82-year-old woman presented to the emergency department with altered mental status thought to be due to complicated cystitis and was treated with TMP–SMX 160 mg/800 mg orally twice daily for 7 days. Her basic metabolic panel prior to initiation of TMP–SMX was within normal limits, with the exception of her serum sodium of 132 mmol/L (range 133–145 mmol/L). The day after completing her 7-day course of TMP–SMX therapy the patient was evaluated by her primary care provider and another basic metabolic panel revealed a reduction in the serum sodium to 121 mmol/L. The patient’s serum sodium concentrations increased to baseline 7 days after completion of the TMP–SMX therapy, and remained normal until she was treated in the emergency department several months later for another presumed urinary tract infection. She was again started on TMP–SMX therapy empirically, and within several days her serum sodium concentrations decreased from 138 mmol/L to a low of 129 mmol/L. The TMP–SMX therapy was discontinued upon negative urine culture results and her serum sodium increased to 134 mmol/L upon discharge. Based upon the Naranjo probability scale score of 9, TMP–SMX was the probable cause of the patient’s hyponatremia.Conclusion: Our patient developed hyponatremia from TMP–SMX therapy upon initial use and rechallenge. Although hyponatremia appears to be rare with TMP–SMX therapy, providers should be aware of this potentially life-threatening adverse event. Keywords: hyponatremia, trimethoprim–sulfamethoxazole combination, aged, drug-related side effects and adverse reaction

Transitioning Competency-Based Communication Assessments to the Online Platform: Examples and Student Outcomes

In light of the COVID-19 pandemic, pharmacy education has shifted from in-person teaching and assessments to the virtual environment. Many education programs had previously adopted objective structured clinical examinations (OSCEs) to assess communication abilities in-person with standardized patients (SPs). However, comparative student outcome data between virtual and in-person methods as well as guidance on how to conduct communication-based OSCEs in the virtual environment is lacking. The University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences (SSPPS) describes its methods of conducting two types of communication-based OSCEs (patient counseling and gathering a medical history). Student performance data from the two virtual OSCEs in 2020 was compared to results from two 2019 in-person OSCEs using Mann Whitney U Tests. The 2020 cohort scored significantly higher than the 2019 cohort in all variables (i.e., using effective verbal and non-verbal communication, using patient friendly education, organizing the encounter, demonstrating empathy, establishing trust, professionalism) and in overall score. However, the effect size for these findings indicate the differences between performances are generally small and more likely due to changes in grading patterns due to the pandemic

Early Induction and Maintenance of Env-Specific T-Helper Cells following Human Immunodeficiency Virus Type 1 Infection

Mounting evidence points to a role for CD4(+) T-helper (Th) cell activities in controlling human immunodeficiency virus type 1 (HIV-1) infection. To determine the induction and evolution of Th responses following acute infection, we prospectively analyzed Env- and Gag-specific Th responses longitudinally for 92 patients with acute (n = 28) or early (n = 64) HIV-1 infection (median, 55 days postinfection [DPI]). The probability of detecting HIV-1-specific lymphoproliferative responses was remarkably low, and when present, the responses were more likely to be Gag specific than Env specific (16 versus 5%). Env-specific responses were significantly more common in patients presenting at <30 DPI than in those presenting at 30 to 365 DPI (21 versus 0.5%, P = 0.001). By contrast, Gag-specific responses occurred with similar frequencies among subjects presenting at <30 DPI and 30 to 365 DPI (13 versus 17%, P = 0.6). After treatment, and regardless of the duration of infection before therapy, Gag-specific Th responses predominated. Furthermore, some acutely infected subjects lost detectable Env-specific Th proliferative responses, which failed to reemerge upon treatment. Detailed analysis for one such subject revealed Env-specific lymphoproliferation at 11 DPI but no detectable Env-specific lymphoproliferation or ex vivo gamma interferon (IFN-γ) secretion at multiple subsequent time points. Env-specific CD4(+) T-cell clones from 11 DPI recognized six epitopes in both conserved and variable regions within gp120 and gp41, exhibited major histocompatibility complex-restricted cytotoxicity, and secreted high levels of antiviral cytokines. T-cell receptor clonal transcript analyses and autologous virus sequencing revealed that Th cells induced during acute infection were maintained and there were no Th escape mutations. Subsequent analysis for this subject and six of seven others revealed detectable IFN-γ-secreting cells, but only following in vitro gp160 stimulation. In summary, we conclude that Env-specific Th responses are elicited very early in acute infection and may precede Gag-specific responses. The inability to detect Env-specific Th responses over time and despite antiretroviral therapy may reflect low frequencies and impaired proliferative capacity, and viral escape is not necessary for this to occur