scholarly journals Mechanisms and Potential Roles of Glucose-Lowering Agents in COVID-19: A Review

2021 ◽  
pp. 106002802199947
Author(s):  
Helen D. Berlie ◽  
Pramodini B. Kale-Pradhan ◽  
Tara Orzechowski ◽  
Linda A. Jaber

Objective: To explore mechanistic benefits of glucose-lowering agents that extend beyond glycemic control with the potential to mitigate coronavirus disease 2019 (COVID-19) complications. Data Sources: The following PubMed literature search terms were used from July 2020 to January 2, 2021: diabetes, COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), glucose-lowering agents, and pharmacology. Study Selection and Data Extraction: English-language studies reporting on the association between diabetes, COVID-19 adverse outcomes, and the potential roles of glucose-lowering agents were reviewed. Data Synthesis: Selected glucose-lowering agents have benefits beyond glycemic control, with the potential to reduce the risks of severe complications during SARS-CoV-2 infection. Key benefits include anti-inflammatory, anticoagulant, immune modulating, and enzyme/receptor effects. Relevance to Patient Care and Clinical Practice: This review summarizes the current knowledge of glucose-lowering agents and their potential roles in COVID-19 outcomes. Considering beneficial mechanisms on COVID-19 outcomes that extend beyond glycemic control as well as safety profiles, current data suggest that dipeptidyl peptidase-IV (DPP-IV) inhibitors and metformin may have the most promise and warrant further investigation. Conclusions: Certain glucose-lowering agents may offer additional benefits beyond glucose control—namely, by modulating the mechanisms contributing to adverse outcomes related to COVID-19 in patients with diabetes. DPP-IV inhibitors and metformin appear to have the most promise. However, current published literature on diabetes medications and COVID-19 should be interpreted with caution. Most published studies are retrospective and consist of convenience samples, and some lack adequate analytical approaches with confounding biases. Ongoing trials aim to evaluate the effects of glucose-lowering agents in reducing the severity of COVID-19 outcomes.

2017 ◽  
Vol 52 (3) ◽  
pp. 263-267 ◽  
Author(s):  
Rebecca M. Hoover ◽  
John Erramouspe

Objective: To review and summarize topical oxymetazoline’s pharmacology, pharmacokinetics, efficacy, safety, cost, and place in therapy for persistent redness associated with erythematotelangiectatic rosacea. Data Sources: Literature searches of MEDLINE (1975 to September 2017), International Pharmaceutical Abstracts (1975 to September 2017), and Cochrane Database (publications through September 2017) using the terms rosacea, persistent redness, α -agonist, and oxymetazoline. Study Selection and Data Extraction: Results were limited to studies of human subjects, English-language publications, and topical use of oxymetazoline. Relevant materials from government sources, industry, and reviews were also included. Data Synthesis: Data support the efficacy of oxymetazoline for persistent facial redness. Little study beyond clinical trials cited in the drug approval process has been conducted. Current data suggest that oxymetazoline is similar in safety and efficacy to brimonidine. Head-to-head comparisons of topical α-agonists for erythema caused by rosacea are needed. Conclusion: The topical α-agonist, oxymetazoline, is safe and effective for reducing persistent facial redness associated with erythematotelangiectatic subtype of rosacea. Health care practitioners selecting among treatments should consider not only the subtype of rosacea but also individual patient response, preference, and cost.


2021 ◽  
pp. archdischild-2021-322706
Author(s):  
Moran Gal ◽  
Shirly Gamsu ◽  
Ron Jacob ◽  
Daniel M Cohen ◽  
Itai Shavit

BackgroundDespite the increased use of sedation in children undergoing stressful procedures, reduction of ileocolic intussusception (RII) is usually performed on awake children without any form of sedation.ObjectiveTo evaluate the incidence of severe complications of RII under sedation or anaesthesia.DesignA systematic review including English language original articles of any date.PatientsChildren undergoing RII (pneumatic or hydrostatic) under sedation or anaesthesia.Data sourcesOvid Embase, Scopus, PubMed, the Cochrane Database of Systematic Reviews and the internet search engine Google Scholar.Data extractionThree authors independently reviewed each article for eligibility. The Newcastle-Ottawa Scale was used to assess the quality of included studies.Main outcome measuresThe primary outcome was the incidence of intestinal perforation during RII. The secondary outcomes were the incidence of sentinel adverse events defined as death, cardiopulmonary resuscitation, permanent neurological deficit and pulmonary aspiration syndrome.ResultsThe search yielded 368 articles. Nine studies with 1391 cases were included in the analysis. Of the nine studies, six had a score of ≤6 stars in the Newcastle-Ottawa Scale assessment, indicating low-to-moderate quality. Propofol-based sedation was used in 849 (59.2%) cases; 5 (0.6%) had intestinal perforation. Intestinal perforation was not reported in patients who were sedated with other sedatives. One patient had pulmonary aspiration syndrome.ConclusionsAlthough caution remains warranted, current data suggest that the incidence of severe complications due to RII under sedation or anaesthesia is low. Due to the lack of prospective data, it is difficult to ascertain the exact incidence of severe complications.


2020 ◽  
Vol 54 (8) ◽  
pp. 780-787
Author(s):  
Rachel N. Lowe ◽  
Jennifer M. Trujillo

Objective: To review the safety, efficacy, and administration of intranasal (IN) glucagon for the management of hypoglycemia. Data Source: A literature search of PubMed/MEDLINE (1995 to November 2019) using the terms intranasal glucagon, nasal glucagon, glucagon, hypoglycemia treatment, and hypoglycemia management was completed. Study Selection and Data Extraction: English-language studies evaluating IN glucagon were evaluated. Data Synthesis: IN glucagon is a newly approved product for the treatment of hypoglycemia in patients with diabetes, 4 years and older. Administered as a 3-mg dose, it was shown to be noninferior to intramuscular (IM) glucagon. In comparison trials, more than 98% of hypoglycemic events were treated successfully with IN glucagon in both pediatric and adult patients. In simulated and real-world studies, IN glucagon was administered in less than a minute for the majority of scenarios. IM glucagon took longer to administer, ranging from 1 to 4 minutes, and often, patients did not receive the intended full dose. Nausea and vomiting, known adverse events for glucagon, as well as local adverse events were most commonly reported with IN glucagon. Relevance to Patient Care and Clinical Practice: IN glucagon is safe, effective, easy to use, and does not require reconstitution prior to use, which can lead to faster delivery in a severe hypoglycemic event. It does not require age- or weight-based dosing. This delivery method offers an option for someone who fears needles or is uncomfortable with injections. Conclusion: IN glucagon is a safe, effective, easy to use, needle-free treatment option for severe hypoglycemia.


2019 ◽  
Vol 54 (5) ◽  
pp. 496-503
Author(s):  
Alison K. Lew ◽  
Ryan L. Crass ◽  
Gregory Eschenauer

Objective: To address the background and rationale for the recent introduction of the Modification of Diet in Renal Disease (MDRD) equation for renal dose adjustment of antimicrobials and to provide recommendations for pharmacists dosing new antimicrobial agents. Data Sources: Comprehensive MEDLINE and EMBASE literature searches (from August 2018 to October 2019) were performed. Search terms included creatinine clearance, Cockcroft-Gault, MDRD, and glomerular filtration rate and a subsequent search included the preceding terms AND antimicrobials OR antibiotics. Study Selection and Data Extraction: Available English-language studies on the derivation and/or use of the Cockcroft-Gault (CG) and MDRD study equation were evaluated as well as those that specifically discussed their use for dosing antimicrobial agents. Data Synthesis: The US Food and Drug Administration (FDA) approval of delafloxacin and meropenem-vaborbactam in 2017 ushered in a new era in renal dosing of antibiotics, in that both agents are recommended to be dosed by the MDRD equation. Studies demonstrate that the CG and MDRD equations can result in discrepant dosing recommendations. Relevance to Patient Care and Clinical Practice: The renal estimation equation recommended in a new antibiotic label should dictate the dosing of that medication. It is noteworthy that these equations are not interchangeable. Conclusion: Recently approved antimicrobials utilizing the MDRD equation for renal dose adjustment will be interspersed with old and new antimicrobials utilizing the CG equation because of lack of singular guidance by the FDA. This requires pharmacists to be vigilant in evaluating drug labels to determine which equation is recommended and to understand the differences, strengths, and limitations of each equation.


2019 ◽  
Vol 53 (10) ◽  
pp. 1033-1041 ◽  
Author(s):  
Erin N. Maxwell ◽  
Brittany Johnson ◽  
Joseph Cammilleri ◽  
Jason A. Ferreira

Objective: Recent literature suggests that intravenous (IV) administration may cause hypotension in hospitalized patients; data further suggest that this effect is most pronounced in the critically ill. The purpose of this review is to identify and evaluate current literature that addresses the incidence and implications of IV acetaminophen–induced hypotension. Data Sources: A literature search of MEDLINE, Cochrane, and EMBASE databases was performed (2002-2019) using the following terms: acetaminophen, paracetamol, intravenous, and hypotension. Abstracts and peer-reviewed publications were reviewed. Study Selection and Data Extraction: Relevant English-language studies conducted in humans evaluating the hemodynamic effects of IV acetaminophen were considered. Data Synthesis: A majority of the 19 studies included in this review identified a statistically significant drop in hemodynamic variables after the administration of 500 to 1000 mg IV acetaminophen as measured by changes in systolic blood pressure, diastolic blood pressure, or mean arterial pressure. Of the trials reporting vasopressor use, the authors found a significant increase in vasopressor requirements following IV acetaminophen administration. Relevance to Patient Care and Clinical Practice: This review represents the first comprehensive review of IV acetaminophen-induced hypotension. The findings raise the question of whether IV acetaminophen is an appropriate choice for inpatient pain or temperature management in the critically ill. Conclusions: Available evidence indicates that the administration of IV acetaminophen may be harmful in the critically ill. Additional monitoring is likely required when using IV acetaminophen in this specific population, particularly if a patient is hemodynamically unstable prior to administration.


2019 ◽  
Vol 161 (2) ◽  
pp. 218-226 ◽  
Author(s):  
Ethan Frank ◽  
Bradley Carlson ◽  
Amanda Hu ◽  
Derrick R. Randall ◽  
Shanalee Tamares ◽  
...  

ObjectiveTo qualitatively assess practices of periprocedural pain assessment and control and to evaluate the effectiveness of interventions for pain during in-office procedures reported in the otolaryngology literature through a systematic review.Data SourcesPubMed, CINAHL, and Web of Science searches from inception to 2018.Review MethodsEnglish-language studies reporting qualitative or quantitative data for periprocedural pain assessment in adult patients undergoing in-office otolaryngology procedures were included. Risk of bias was assessed via the Cochrane Risk of Bias or Cochrane Risk of Bias in Non-Randomized Studies of Interventions tools as appropriate. Two reviewers screened all articles. Bias was assessed by 3 reviewers.ResultsEighty-six studies describing 32 types of procedures met inclusion criteria. Study quality and risk of bias ranged from good to serious but did not affect assessed outcomes. Validated methods of pain assessment were used by only 45% of studies. The most commonly used pain assessment was patient tolerance, or ability to simply complete a procedure. Only 5.8% of studies elicited patients’ baseline pain levels prior to procedures, and a qualitative assessment of pain was done in merely 3.5%. Eleven unique pain control regimens were described in the literature, with 8% of studies failing to report method of pain control.ConclusionMany reports of measures and management of pain for in-office procedures exist but few employ validated measures, few are standardized, and current data do not support any specific pain control measures over others. Significant opportunity remains to investigate methods for improving patient pain and tolerance of in-office procedures.


2017 ◽  
Vol 51 (11) ◽  
pp. 1008-1022 ◽  
Author(s):  
Alice Tseng ◽  
Christine A. Hughes ◽  
Janet Wu ◽  
Jason Seet ◽  
Elizabeth J. Phillips

Objective: To describe properties of cobicistat and ritonavir; compare boosting data with atazanavir, darunavir, and elvitegravir; and summarize antiretroviral and comedication interaction studies, with a focus on similarities and differences between ritonavir and cobicistat. Considerations when switching from one booster to another are discussed. Data Sources: A literature search of MEDLINE was performed (1985 to April 2017) using the following search terms: cobicistat, ritonavir, pharmacokinetic, drug interactions, booster, pharmacokinetic enhancer, HIV, antiretrovirals. Abstracts from conferences, article bibliographies, and product monographs were reviewed. Study Selection and Data Extraction: Relevant English-language studies or those conducted in humans were considered. Data Synthesis: Similar exposures of elvitegravir, darunavir, and atazanavir are achieved when combined with cobicistat or ritonavir. Cobicistat may not be as potent a CYP3A4 inhibitor as ritonavir in the presence of a concomitant inducer. Ritonavir induces CYP1A2, 2B6, 2C9, 2C19, and uridine 5′-diphospho-glucuronosyltransferase, whereas cobicistat does not. Therefore, recommendations for cobicistat with comedications that are extrapolated from studies using ritonavir may not be valid. Pharmacokinetic properties of the boosted antiretroviral can also affect interaction outcome with comedications. Problems can arise when switching patients from ritonavir to cobicistat regimens, particularly with medications that have a narrow therapeutic index such as warfarin. Conclusions: When assessing and managing potential interactions with ritonavir- or cobicistat-based regimens, clinicians need to be aware of important differences and distinctions between these agents. This is especially important for patients with multiple comorbidities and concomitant medications. Additional monitoring or medication dose adjustments may be needed when switching from one booster to another.


MicroRNA ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 8-16 ◽  
Author(s):  
Fasoulakis Zacharias ◽  
Theodora Marianna ◽  
Tsirkas Ioannis ◽  
Tsirka Theodora ◽  
Kalagasidou Sofia ◽  
...  

Aim:The study aimed to provide an overall view of current data considering the presence of microRNAs in amniotic fluid.Methods:The available literature in MEDLINE, regarding the role of the amniotic fluid in pregnancy and fetal development, was searched for related articles including terms such as “microRNA”, “Amniotic fluid”, “Adverse outcome” and others.Results:The amniotic fluid has an undoubtedly significant part in fetal nutrition, with a protecting and thermoregulatory role alongside. MicroRNAs have proven to be highly expressed during pregnancy in many body liquids including amniotic fluid and are transferred between cells loaded in exosomes, while they are also implicated in many processes during fetal development and could be potential biomarkers for early prediction of adverse outcomes.Conclusion:Current knowledge reveals that amniotic fluid microRNAs participate in many developmental and physiological processes of pregnancy including proliferation of fibroblasts, fetal development, angiogenesis, cardioprotection, activation of signaling pathways, differentiation and cell motility, while the expression profile of specific microRNAs has a potential prognostic role in the prediction of Down syndrome, congenital hydronephrosis and kidney fibrosis.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16263-e16263
Author(s):  
Livia Munhoz Rodrigues ◽  
Simone Maistro ◽  
Vinícius Marques Rocha ◽  
Rossana Veronica Mendoza Lopez ◽  
Maria A. A. Koike Folgueira

e16263 Background: Despite being one of the deadliest tumors worldwide, hereditary factors involved in PC are not fully understood. Thus, our objective is to assess the prevalence of germline mutations in PC cohorts not selected for FH. Methods: A systematic review was performed, using the descriptors related to PC and germline mutations, employing Pubmed, Lilacs, Web of Science and Embase, until August/2020. Three investigators were involved in reviewing titles and abstracts by peers. Exclusions comprehended articles of non-English language, studies investigating endocrine PC or case-reports. For the present analysis, the inclusion criteria were: original full paper available for data extraction, studies with patients unselected for FH and evaluating a panel of at least 10 genes, WES or WGS. Results from our group evaluating a cohort of PC Brazilian patients were also considered. We present prevalence results for germline mutations in 8 genes, comprehending ATM, BRCA1, BRCA2, CDKN2A, CHEK2, MSH6, PALB2 (the most frequently mutated genes in PC) and FANCM (previously detected in our Brazilian cohort). Results: After exclusion of duplicate titles, 2, 035 titles were available. Using the criteria described above, 23 articles were selected for analysis and involved cohorts from Australia, Canada, USA, Japan, Czech Republic and our Brazilian cohort, totaling 11, 165 PCP evaluated. The predominant histology was adenocarcinoma (15/24 studies), 22/24 studies evaluated a panel of genes and for studies providing demographic data, the mean age of PCP was 64 (13-93) years (n = 8, 000). Six out of eight genes were evaluated in at least 10, 600 patients, among which BRCA2 mutations had the highest prevalence, followed by ATM. Mutations in CHEK2 occupied the third place in prevalence, despite being evaluated in only 74.5% of the entire cohort. BRCA1, PALB2, CDKN2A, MSH6 and FANCM showed a prevalence of less than 1%, according to the table below. Although being infrequent among PCP, it is interesting to observe that an identical FANCM mutation was detected in two unrelated Brazilian patients. Conclusions: Analysis of cohorts unselected for FH indicates that BRCA2, ATM and CHEK2 are the most frequently mutated genes in these PCP. Further studies are needed to better characterize the spectrum and prevalence of mutations in PCP from populations other than Caucasians, especially in miscegenated people.[Table: see text]


1995 ◽  
Vol 29 (7-8) ◽  
pp. 769-777 ◽  
Author(s):  
Piera T Calissi ◽  
Linda A Jaber

Objective: To review pathophysiology and current concepts in the treatment of diabetic peripheral neuropathy (PN). Data Sources: References were identified through a MEDLINE search of the English-language literature from 1976 through 1994. Additional references were obtained from reference lists of articles identified through the search. Study Selection and Data Extraction: All articles were considered for possible inclusion in the review. Clinical trials that involved an adequate number of patients and review articles were selected. Information from articles that was judged by the authors to be significant was selected for discussion. Data Synthesis: PN affects 5-50% of people with diabetes in the US and most commonly is characterized by tingling or burning sensations, particularly in the calves, ankles, and feet, with a loss of vibratory sense. Treatment of PN, for the most part, has been unsatisfactory. Therapy has been directed toward either improving nerve function or alleviating symptoms of PN, including pain and paresthesia. Glycemic control may slow the progression of PN. Hyperglycemia also is associated with decreased pain threshold in patients with diabetes mellitus. The aldose reductase inhibitors, particularly tolrestat, have been shown to improve objective and subjective neurologic function. Pain or paresthesia has been treated effectively with antidepressants, lidocaine, mexiletine, and capsaicin. The anticonvulsants phenytoin and carbamazepine may be effective, but are associated with a greater degree of adverse effects. Experimental treatments, such as gamma-linolenic acid, gangliosides, uridine, and the corticotropin4-9 analog ORG 2766, have been effective in improving neurologic function. Conclusions: Treatment of PN remains unsatisfactory. Therapy should be directed toward prevention with glycemic control and symptomatic treatment of existing PN.


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