Effectiveness of telepharmacy diabetes services: A systematic review and meta-analysis.

PURPOSE: Although pharmacist-provided diabetes services have been shown to be effective, the effectiveness of telepharmacy (TP) in diabetes management has not been clearly established. This systematic review and meta-analysis aims to evaluate the effectiveness of diabetes TP services. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched (from inception through September 2021) to identify published studies that evaluated the effect of TP services in patients with diabetes mellitus and reported either glycosylated hemoglobin (HbA1c) or fasting blood glucose (FBG) outcomes. Mean difference (MD), weighted mean difference (WMD), relative risk (RR), and 95% confidence intervals were calculated using the DerSimonian and Laird random-effects model. RESULTS: 36 studies involving 13,773 patients were included in the systematic review, and 23 studies were included in the meta-analysis. TP was associated with a statistically significant decrease in HbA1c (MD, -1.26%; 95% CI, -1.69 to -0.84) from baseline. FBG was not significantly affected (MD, -25.32 mg/dL; 95% CI, -57.62 to 6.98). Compared to non-TP service, TP was associated with a lower risk of hypoglycemia (RR, 0.48; 95% CI, 0.30-0.76). In a subset of studies that compared TP to face-to-face (FTF) pharmacy services, no significant difference in HbA1c lowering was seen between the 2 groups (WMD, -0.09%; 95% CI, -1.07 to 0.90). CONCLUSION: Use of TP was associated with reduction of HbA1c and the risk of hypoglycemia in patients with diabetes mellitus. High-quality randomized controlled trials are needed to validate the effectiveness of diabetes TP services relative to FTF services.

Effect of Probiotic Supplementation on Glycemic Outcomes in Patients with Abnormal Glucose Metabolism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The effectiveness of probiotics in patients with abnormal glucose metabolism has not been clearly demonstrated. It is also unclear if outcomes are consistent across different probiotic formulations. METHODS: A literature search was conducted using PubMed, EMBASE, and Cochrane CENTRAL database from inception through May 2020. Randomized controlled trials that evaluated the effect of probiotics on fasting blood glucose (FBG) or hemoglobin A1c (HbA1c) in patients with prediabetes, type 2 diabetes mellitus, or gestational diabetes were included. Outcomes of interest included FBG, HbA1c, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of ß-cell function (HOMA-B), and quantitative insulin sensitivity check index (QUICKI). Weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated using the DerSimonian and Laird random-effects model. RESULTS: 31 studies involving 1,948 participants were included in this analysis. Compared to control, probiotics had a significant favorable effect on FBG (WMD -5.77 mg/dL, 95% CI -8.48 to -3.06), HbA1c (WMD -0.32%, 95% CI -0.47 to -0.18), fasting insulin (WMD -2.95 µIU/mL, 95% CI -3.76 to -2.14), HOMA-IR (WMD -0.82, 95% CI -1.05 to -0.59), HOMA-B (WMD -14.86, 95% CI -24.57 to -5.16), and QUICKI (WMD 0.015, 95% CI 0.011-0.019). Further, probiotics were associated with favorable outcomes on all parameters at doses between 1 and 10 × 109 colony-forming unit per day (p < 0.004 for all) and formulations containing 2-4 strains (p < 0.05 for all). DISCUSSION/CONCLUSION: Probiotics appear to have a modest effect on glycemic parameters in patients with abnormal glucose metabolism. Due to the limited number of trials conducted in patients with prediabetes, more studies are warranted in this population.

Energy Drink-Associated Electrophysiological and Ischemic Abnormalities: A Narrative Review.

An increasing number of cardiovascular adverse effects, emergency room visits, and deaths have been linked to energy drinks. In this review, we summarized available published literature assessing electrophysiological and ischemic adverse effects associated with energy drink consumption. Overall, 32 case reports and 19 clinical trials are included in this review. Ventricular arrhythmia, supraventricular arrhythmia, and myocardial ischemia were amongst the most commonly reported in case reports with 3 having a fatal outcome. Although serious ischemic changes, arrhythmias, or death were not observed in clinical trials, significant electrophysiological changes, such as PR/PQ interval shortening/prolongation, QT/QTc shortening/prolongation, and ST-T changes, were noted. QT/QTc interval prolongation appears to be the most significant finding in clinical trials, and there appears to be a dose-response relationship between energy drink consumption and QTc prolongation. The exact mechanisms and the particular combination of ingredients behind energy drink-induced cardiac abnormalities require further evaluation. Until more information is available, energy drink use should be considered as part of the differential diagnosis in appropriate patients presenting with electrocardiographic changes. Further, certain patient populations should exercise caution and limit their energy drink consumption.

Effectiveness of Telepharmacy Versus Face-to-Face Anticoagulation Services in the Ambulatory Care Setting: A Systematic Review and Meta-analysis.

BACKGROUND: Effectiveness of anticoagulation services managed via telepharmacy (TP) has not been clearly demonstrated. OBJECTIVE: This systematic review and meta-analysis compares the effectiveness of TP anticoagulation services to face-to-face (FTF) anticoagulation services in the ambulatory care setting. METHODS: A literature search for studies assessing the effectiveness of TP services was conducted using PubMed, EMBASE, and Cochrane Central databases, from inception through November 18, 2020. Studies that compared TP with FTF anticoagulation services in the ambulatory care setting were included. Outcomes of interest included thromboembolic events, major bleeding, minor bleeding, any bleeding, warfarin international normalized ratio (INR) time in therapeutic range (TTR), frequency of extreme INR, anticoagulation-related emergency department visits, anticoagulation-related hospitalization, any hospitalization, and mortality. Relative risk (RR) and weighted mean difference were calculated using the DerSimonian and Laird random-effects model. RESULTS: Overall, 11 studies involving 8395 patients were included in the systematic review, and 9 studies were included in the pooled meta-analysis. Compared with FTF service, TP was associated with a lower risk of any bleeding and any hospitalization, with RRs of 0.65 (95% CI = 0.47 to 0.90; P = 0.01) and 0.59 (95% CI = 0.39 to 0.87; P = 0.01), respectively. There was no statistically significant difference in TTR or the risk of extreme supratherapeutic INR, major bleeding, minor bleeding, or thromboembolic events between the 2 groups. CONCLUSIONS: TP appears to be at least as effective as FTF anticoagulation services. Findings from this study support the utilization of TP practice models in ambulatory care anticoagulation management.

A Survey of Energy Drink Consumption and Associated Adverse Effects in Air Force Personnel.

INTRODUCTION: Energy drinks are an increasingly utilized beverage and are gaining popularity in recent years. The U.S. Air Force (USAF) represents a unique population where energy drink consumption may be higher than the general population. To better understand the safety and health impact of energy drinks, this large-scale comprehensive survey was conducted to study energy drink consumption patterns and its associated adverse effects. MATERIALS AND METHODS: A survey was conducted across 12 USAF installations to assess self-reported energy drink consumption and adverse effects in the military population. This study was approved by the David Grant USAF Medical Center Institutional Review Board. RESULTS: A total of 9,655 participants participated in the survey. Energy drink consumption was reported in 76.7% of the participants, with 12.0% consuming ≥1 energy drink per day. Male gender, younger age, and enlisted military members are more likely to be high consumers; 58.6% of participants reported having at least once tried a premixed beverage that combines alcohol, caffeine, and other stimulants. Among energy drink users, 60.0% reported experiencing ≥1 adverse effect, and 0.92% reported needing to see a physician or going to the emergency department because of adverse effects from energy drinks. Higher energy drink or premixed combination beverage consumption frequency was associated with increased likelihood of physician or emergency department visits (P ≤ 0.002 for both). CONCLUSION: Approximately three in four USAF members reported ever consuming an energy drink. Caution should be exercised on the amount of energy drink consumed to limit the risk of serious adverse effects. Future studies should identify populations at greatest risk for adverse effects and alternative sources of energy maintenance to attain optimal mission readiness.

Considerations for Optimal Blood Pressure Goals in the Elderly Population: A Review of Emergent Evidence.

Recent hypertension clinical trials and national guideline updates have created a debate on the most appropriate treatment goals in elderly patients with hypertension. In 2014, recommendations by the Eighth Joint National Committee allowed a more lenient goal for patients 60 years and older compared with previous guidelines. Since then, several large clinical trials and meta-analyses have added more information regarding strict versus lenient treatment goals. Most recently, the American College of Cardiology and American Heart Association Task Force published their highly anticipated hypertension guideline developed in conjunction with nine additional interdisciplinary organizations. This review discusses the culmination of emerging data to provide more insight into the treatment of hypertension in the elderly. A literature search was conducted using PubMed, the Cumulative Index of Nursing and Allied Health, the Cochrane database, and by hand-searching references from relevant articles. The following key terms were used: hypertension, blood pressure, systolic, and elderly. Available literature suggests that it is reasonable to target an office systolic blood pressure of less than 130 mm Hg in elderly patients with hypertension. An individualized approach is reasonable for those who are institutionalized, with high comorbidity burden, or have a short life expectancy. A diastolic blood pressure of less than 60 mm Hg should be avoided due to the potential for an increase in cardiovascular risk. The method of blood pressure measurement is extremely important to consider when determining the blood pressure goal, and proper procedures for accurate blood pressure measurement must be followed. Other factors important to consider may include the patient's comorbidities, frailty, as well as the patient's potential for adverse drug reactions.

Association of hyponatremia to diuretic response and incidence of increased serum creatinine levels in hospitalized patients with acute decompensated heart failure.

OBJECTIVES: Although hyponatremia is a prognostic factor in acute heart failure (AHF), its influence on the acute clinical course of heart failure is unknown. Our objective was to evaluate the association of hyponatremia with diuretic response, renal function, and clinical outcomes in AHF. METHODS: A retrospective study included 499 hospitalized AHF patients treated with intravenous loop diuretics for ≥48 h. Patients were grouped by nadir sodium concentrations (normonatremic, NN) ≥135 mEq/l, (mild hyponatremia, MHN) 130-134 mEq/l, and (moderate to severe hyponatremia, MSHN) <130 mEq/l. Association to diuretic response and clinical outcome was assessed. RESULTS: The incidence of hyponatremia was 54% (36% MHN, 18% MSHN). Maximum diuretic dose (furosemide equivalents: NN 84 ± 132 mg/day vs. MHN 114 ± 165 mg/day vs. MSHN 249 ± 450 mg/day, p < 0.001) and incidence of diuretic regimen escalation (NN 11% vs. MHN 16% vs. MSHN 44%, p < 0.001) were significantly higher in patients experiencing hyponatremia. Hyponatremia was also associated with a higher incidence of acute increases in serum creatinine (NN 27% vs. MHN 45% vs. MSHN 63%, p < 0.001), greater increases in blood urea nitrogen, longer hospital stay, and higher mortality. Outcome disparities to NN patients were similar whether hyponatremia was acute or present upon admission. CONCLUSIONS: Acute or admission hyponatremia, especially <130 mEq/l, in AHF patients is associated with greater diuretic requirements, higher incidence of serum creatinine increases, and a poorer outcome. Alternative treatments warrant evaluation in these patients.

Glioma Specific Extracellular Missense Mutations in the First Cysteine Rich Region of Epidermal Growth Factor Receptor (EGFR) Initiate Ligand Independent Activation.

The epidermal growth factor receptor (EGFR) is overexpressed or mutated in glioma. Recently, a series of missense mutations in the extracellular domain (ECD) of EGFR were reported in glioma patients. Some of these mutations clustered within a cysteine-rich region of the EGFR targeted by the therapeutic antibody mAb806. This region is only exposed when EGFR activates and appears to locally misfold during activation. We expressed two of these mutations (R324L and E330K) in NR6 mouse fibroblasts, as they do not express any EGFR-related receptors. Both mutants were autophosphorylated in the absence of ligand and enhanced cell survival and anchorage-independent and xenograft growth. The ECD truncation that produces the de2-7EGFR (or EGFRvIII), the most common EGFR mutation in glioma, generates a free cysteine in this same region. Using a technique optimized for detecting disulfide-bonded dimers, we definitively demonstrated that the de2-7EGFR is robustly dimerized and that ablation of the free cysteine prevents dimerization and activation. Modeling of the R324L mutation suggests it may cause transient breaking of disulfide bonds, leading to similar disulfide-bonded dimers as seen for the de2-7EGFR. These ECD mutations confirm that the cysteine-rich region of EGFR around the mAb806 epitope has a significant role in receptor activation.

Targeting a unique EGFR epitope with monoclonal antibody 806 activates NF-kappaB and initiates tumour vascular normalization.

Monoclonal antibodies (mAbs) and tyrosine kinase inhibitors targeting the epidermal growth factor receptor (EGFR), which is often pathogenetically overexpressed or mutated in epithelial malignancies and glioma, have been modestly successful, with some approved for human use. MAb 806 was raised against de2-7EGFR (or EGFRvIII), a constitutively active mutation expressed in gliomas, but also recognizes a subset (<10%) of wild-type (wt) EGFR when it is activated by autocrine loop, overexpression or mutation. It does not bind inactive EGFR in normal tissues like liver. Glioma xenografts expressing the de2-7EGFR treated with mAb 806 show reduced receptor autophosphorylation, increased p27(KIP1) and reduced cell proliferation. Xenografts expressing the wtEGFR activated by overexpression or autocrine ligand are also inhibited by mAb 806, but the mechanism of inhibition has been difficult to elucidate, especially because mAb 806 does not prevent wtEGFR phosphorylation or downstream signalling in vitro. Thus, we examined the effects of mAb 806 on A431 xenograft angiogenesis. MAb 806 increases vascular endothelial growth factor (VEGF) and interleukin-8 production by activating NF-kappaB and normalizes tumour vasculature. Pharmacological inhibition of NF-kappaB completely abrogated mAb 806 activity, demonstrating that NF-kappaB activation is necessary for its anti-tumour function in xenografts. Given the increase in VEGF, we combined mAb 806 with bevacizumab in vivo, resulting in additive activity.

The efficacy of epidermal growth factor receptor-specific antibodies against glioma xenografts is influenced by receptor levels, activation status, and heterodimerization.

PURPOSE: Factors affecting the efficacy of therapeutic monoclonal antibodies (mAb) directed to the epidermal growth factor receptor (EGFR) remain relatively unknown, especially in glioma. EXPERIMENTAL DESIGN: We examined the efficacy of two EGFR-specific mAbs (mAbs 806 and 528) against U87MG-derived glioma xenografts expressing EGFR variants. Using this approach allowed us to change the form of the EGFR while keeping the genetic background constant. These variants included the de2-7 EGFR (or EGFRvIII), a constitutively active mutation of the EGFR expressed in glioma. RESULTS: The efficacy of the mAbs correlated with EGFR number; however, the most important factor was receptor activation. Whereas U87MG xenografts expressing the de2-7 EGFR responded to therapy, those exhibiting a dead kinase de2-7 EGFR were refractory. A modified de2-7 EGFR that was kinase active but autophosphorylation deficient also responded, suggesting that these mAbs function in de2-7 EGFR-expressing xenografts by blocking transphosphorylation. Because de2-7 EGFR-expressing U87MG xenografts coexpress the wild-type EGFR, efficacy of the mAbs was also tested against NR6 xenografts that expressed the de2-7 EGFR in isolation. Whereas mAb 806 displayed antitumor activity against NR6 xenografts, mAb 528 therapy was ineffective, suggesting that mAb 528 mediates its antitumor activity by disrupting interactions between the de2-7 and wild-type EGFR. Finally, genetic disruption of Src in U87MG xenografts expressing the de2-7 EGFR dramatically enhanced mAb 806 efficacy. CONCLUSIONS: The effective use of EGFR-specific antibodies in glioma will depend on identifying tumors with activated EGFR. The combination of EGFR and Src inhibitors may be an effective strategy for the treatment of glioma.