Showing papers in "American Journal of Therapeutics in 2020"

Vitamin D Supplementation in COVID-19 Patients: A Clinical Case Series.

Abstract: Background Coronavirus disease 2019 (COVID-19) has infected more than 4.4 million people and caused more than 300,000 deaths partly through acute respiratory distress syndrome with propensity to affect African American and Hispanic communities disproportionately. Patients with worse outcomes have exhibited higher blood plasma levels of proinflammatory cytokines. Activation of the vitamin D receptor expressed on immune cells has been shown to directly reduce the secretion of inflammatory cytokines, such as interleukin-6, and indirectly affect C-reactive protein. Areas of uncertainty The significance of the vitamin D pathway in patients diagnosed with COVID-19. Therapeutic innovation Vitamin D supplementation in patients after diagnosis of COVID-19. Patients and pharmacological interventions We report 4 vitamin D deficient patients diagnosed with COVID-19 in April 2020 who were provided with either cholecalciferol of 1000 IU daily (standard dose) or ergocalciferol 50,000 IU daily for 5 days (high dose) as part of supplementation. Clinical outcomes Patients that received a high dose of vitamin D supplementation achieved normalization of vitamin D levels and improved clinical recovery evidenced by shorter lengths of stay, lower oxygen requirements, and a reduction in inflammatory marker status. Conclusions Vitamin D supplementation may serve as a viable alternative for curtailing acute respiratory distress syndrome in patients in underserved communities where resources to expensive and sought-after medications may be scarce. Randomized clinical trials will serve as an appropriate vessel to validate the efficacy of the therapeutic regimen and dissection of the pathway.

Use of Direct Oral Anticoagulants in the Treatment of Left Ventricular Thrombus: Systematic Review of Current Literature.

Abstract: Background Left ventricular thrombus (LVT) is an important complication in the setting of systolic dysfunction, particularly after acute myocardial infarction. Current guidelines recommend the vitamin-K antagonist, warfarin, for the treatment of LVT. Area of uncertainty and study question The direct oral anticoagulants (DOACs) are being increasingly used for the management of this entity, despite lack of randomized trials in support of it or knowledge about their efficacy. We aimed to assess the frequency of use and the efficacy of DOACs in the treatment of LVT. Data sources We searched published articles in Google Scholar, PubMed, MEDLINE, and Embase from the introduction of DOACs in any therapy until April 2018. Reports describing patients diagnosed with LVT and who were treated with a DOAC were examined. Patient characteristics, comorbidities, pharmacologic treatments, and outcomes were collected. The primary end points of this study were thrombus resolution and time to resolution. Other end points were bleeding and thromboembolic events. Results Thirty articles describing 41 patients were analyzed. The most common risk factors for LVT formation were male gender, ischemic heart disease, and low ejection fraction. Most patients were treated with rivaroxaban (51.2%), followed by apixaban (26.8%) and dabigatran (22%). Patients were treated with DOAC alone (46.3%), DOAC and aspirin (12.2%), DOAC and clopidogrel (2.4%), and triple therapy (39%). Thrombus resolution success rate was 81%, 100%, and 88.9% for rivaroxaban, apixaban, and dabigatran, respectively. The median time of thrombus resolution was 40 days, 36 days, and 24 days for rivaroxaban, apixaban, and dabigatran, respectively. One nonfatal bleeding event and one stroke event were reported while on a DOAC. Conclusions The use of DOACs is a reasonable alternative to vitamin-K antagonists in the management of LVT.

Insulin Pump Therapy.

Abstract: Background Advances in pump technology have increased the popularity of this treatment modality among patients with type 1 diabetes and recently also among patients with type 2 diabetes. Areas of uncertainty Four decades after the incorporation of the insulin pump in clinical use, questions regarding its efficacy, occurrence rate of short-term complications as hypoglycemia and diabetes ketoacidosis, timing of pump initiation, and selected populations for use remain unanswered. Data sources A review of the literature was performed using the PubMed database to identify all articles published up till December 2018, with the search terms including insulin pump therapy/continuous subcutaneous insulin delivery. The Cochrane database was searched for meta-analysis evaluating controlled randomized trials. Consensuses guidelines published by the International Society for Pediatric and Adolescent Diabetes, American Diabetes Association, and Advanced Technologies and Treatments for Diabetes year books were additionally reviewed for relevant cited articles. Therapeutic advances Insulin pump therapy offers flexible management of diabetes. It enables adjustment of basal insulin to daily requirements and circadian needs, offers more precise treatment for meals and physical activity, and, when integrated with continuous glucose monitoring, allows glucose responsive insulin delivery. The ability to download and transmit data for analysis allow for treatment optimization. Newer pumps are simple to operate and increase user experience. Studies support the efficacy of pump therapy in improving glycemic control and reducing the occurrence of hypoglycemia without increasing episodes of diabetes ketoacidosis. They also improve quality of life. Recent evidence suggests a role for pump therapy in reducing microvascular and macrovascular diabetes-related complications. Conclusions Insulin pump therapy appears to be effective and safe in people with T1D regardless of age. Future advancements will include incorporation of closed loop and various decision support systems to aid and improve metabolic control and quality of life.

COVID-19 and Avoiding Ibuprofen. How Good Is the Evidence?

Abstract: Ibuprofen is an over-the-counter medication that is used widely for the treatment of pain and fever during COVID-19 pandemic. A concern was raised regarding the safety of ibuprofen use because of its role in increasing ACE2 levels within the Renin-Angiotensin-Aldosterone system. ACE2 is the coreceptor for the entry of SARS-CoV-2 into cells, and so, a potential increased risk of contracting COVID-19 disease and/or worsening of COVID-19 infection was feared with ibuprofen use. However, available data from limited studies show administration of recombinant ACE2 improves lung damage caused by respiratory viruses, suggesting ibuprofen use may be beneficial in COVID-19 disease. At this time, there is no supporting evidence to discourage the use of ibuprofen.

Insulin Therapy in Hospitalized Patients.

Abstract: BACKGROUND Hyperglycemia is prevalent and is associated with an increase in morbidity and mortality in hospitalized patients. Insulin therapy is the most appropriate method for controlling glycemia in hospital, but is associated with increased risk of hypoglycemia, which is a barrier to achieving glycemic goals. AREAS OF UNCERTAINTY Optimal glycemic targets have not been established in the critical and noncritical hospitalized patients, and there are different modalities of insulin therapy. The primary purpose of this review is to discuss controversy regarding appropriate glycemic targets and summarize the evidence about the safety and efficacy of insulin therapy in critical and noncritical care settings. DATA SOURCES A literature search was conducted through PubMed with the following key words (inpatient hyperglycemia, inpatient diabetes, glycemic control AND critically or non-critically ill patient, Insulin therapy in hospital). RESULTS In critically ill patient, blood glucose levels >180 mg/dL may increase the risk of hospital complications, and blood glucose levels <110 mg/dL have been associated with an increased risk of hypoglycemia. Continuous intravenous insulin infusion is the best method for achieving glycemic targets in the critically ill patient. The ideal glucose goals for noncritically ill patients remain undefined and must be individualized according to the characteristics of the patients. A basal-bolus insulin strategy resulted in better glycemic control than sliding scale insulin and lower risk of hypoglycemia than premixed insulin regimen. CONCLUSIONS Extremes of blood glucose lead to poor outcomes, and target glucose range of 110-180 mg/dL may be appropriate for most critically ill patients and noncritically ill patients. Insulin is the most appropriate pharmacologic agent for effectively controlling glycemia in hospital. A continuous intravenous insulin infusion and scheduled basal-bolus-correction insulin are the preferred modalities for glycemic control in critically and noncritically ill hospitalized patients, respectively.

Insulin Therapy: Future Perspectives.

Abstract: Background Insufficient insulin secretion is a core pathogenetic mechanism of diabetes mellitus and therefore, insulin therapy remains the cornerstone of management. Over the past 100 years, much progress has been made in the development of insulin therapy, including elaboration of novel insulin formulations and delivery methods. Areas of uncertainty Despite significant advances, there are still many barriers, challenges, and uncertainties involving insulin therapy. With newer pharmacological and technological approaches, there are many potential drawbacks to be addressed, such as immunogenicity, biocompatibility, degradation/clearance of delivery materials, stability, precision of dosing, reproducibility, predictability of performance, and safety over time, etc. In addition, the new formulations/delivery systems should be cost-effective and accessible. Data sources A literature search of original and review articles, editorials, and meta-analyses in Medline/PubMed and Google Scholar has been performed. ClinicalTrials.gov website was searched for ongoing relevant clinical trials. Therapeutic advances New insulin formulations (ultralong basal and ultrarapid analogues) were designed to obtain a prolonged, flatter profile, with less hypoglycemia and improvement of postprandial glucose control, respectively. The next generation of insulin therapy is probably best represented by the "smart" (glucose-responsive) insulins, which deliver it according to an endogenous glucose-sensing feedback mechanism. Another area of continuous advances includes insulin delivery systems with new jet injectors, smart pens, patch pumps, and other needle-free devices for subcutaneous administrations. Many alternative routes of insulin delivery (pulmonary, nasal, buccal, oral, and transdermal) have also been explored, with some reaching clinical use. The digitalization of diabetes care has made considerable progress in the past several years and will most probably make even more so in the near future. Conclusions The improved insulin formulations, newer delivery methods/routes, and digital technologies are rapidly becoming effective and have great potential to improve metabolic control as well as other outcomes, including quality of life of persons living with diabetes mellitus.

Venous Thromboembolism in Hospitalized COVID-19 Patients.

Abstract: Background Venous thromboembolism (VTE) is increasingly reported in seriously ill patients with COVID-19 infection. Incidence of VTE has been reported before and results varied widely in study cohorts. Area of uncertainty Incidence of major VTE (segmental pulmonary embolism and above and proximal deep vein thrombosis) which is a contributor to mortality and morbidity is not known. Also, data is unclear on the optimal anticoagulation regimen to prevent VTE. Data sources Multiple databases including PubMed were searched until May 12, 2020, to include studies reporting VTE in hospitalized COVID-19 adult patients. MOOSE guidelines were followed in selection, and 11 studies were included. We conducted a systematic review and meta-analysis to quantitatively assess the VTE burden in hospitalized COVID-19 patients and potential benefits of therapeutic dosing of anticoagulation compared with prophylaxis dosing for VTE prevention. Therapeutic advances Many societies and experts recommend routine prophylactic anticoagulation with heparin for VTE prevention in hospitalized COVID-19 patients. In this meta-analysis, the pooled rate of major VTE was 12.5% in hospitalized patients and 17.2% in intensive care unit patients. When therapeutic anticoagulation dosing was compared with prophylactic anticoagulation, the pooled odds ratio of VTE was 0.33 (95% confidence interval 0.14-0.75; P = 0.008, I = 0%) suggesting statistical significance with therapeutic dosing of anticoagulation for primary prevention of VTE in all hospitalized patients. However, this should be interpreted with caution as the bleeding events and safety profile could not be ascertained because of lack of adequate information. We recommend applying this finding to hospitalized COVID 19 patients only after carefully weighing individual bleeding risks and benefits. Conclusion Major VTE events, especially pulmonary embolism, seem to be high in COVID-19 patients admitted to the intensive care unit. Therapeutic anticoagulation dosing seems to significantly benefit the odds of preventing any VTE when compared with prophylactic dosing in all hospitalized patients.

Biosynthetic Human Insulin and Insulin Analogs.

Abstract: Background Biosynthetic human insulins and analogs have replaced animal insulins and permitted structural modifications to alter the rate of absorption, duration of action, improve reproducibility of effects, and modulate relative efficacy in various target tissues. Several forms of rapidly acting insulins nearly achieve rapid pharmacokinetics and pharmacodynamics similar to first-phase insulin release. There is need for even faster-acting analogs to mimic normal physiology and improve control of postprandial glycemic excursions. Two biosynthetic insulin analogs have sufficiently long duration of action for use as once-daily basal insulins; controversy persists regarding their respective risks of hypoglycemia and relative glycemic variability. Results Basal-bolus therapy and insulin pump therapy, including closed-loop automated insulin delivery, require rapid-acting insulin analogs. The longer acting insulins can provide stable, reproducible basal insulin with reduced rates of hypoglycemia, particularly nocturnal hypoglycemia, greater efficacy in reducing mean glucose and glucose variability while increasing time in glucose target range. Inhalable human insulin provides very rapid action. Premixture of rapid-acting analogs with protamine has been useful for some patients with type 2 diabetes. An insulin analog with preferential efficacy at the liver has been developed and tested clinically but not marketed. Current research is aimed at developing even faster-acting insulin analogs. Long-acting basal insulins coformulated with GLP-1 receptor agonists or with a rapidly acting insulin analog have valuable clinical applications. Excipients, chaperones, local heating of the infusion site, and hyaluronidase have also been used to accelerate the absorption of insulin analogs. Conclusions Biosynthetic human insulins have radically revolutionized management of both type 1 and type 2 diabetes worldwide. The ability to manipulate the structure and formulation of insulin provides for more physiologic pharmacokinetics and pharmacodynamics, enabling improved glycemic control, reduced risk of hypoglycemia, and reduced rates of long-term complications.

Insulin Therapy in Type 2 Diabetes.

Abstract: Background Since the discovery of insulin, it was the only drug available for the treatment of diabetes until the development of sulfonylureas and biguanides 50 years later. But even with the availability of oral glucose-lowering drugs, insulin supplementation was often needed to achieve good glucose control in type 2 diabetes. Insulin NPH became the basal insulin therapy of choice and adding NPH to metformin and/or sulfonylureas became the standard of care until basal insulin analogs were developed and new glucose-lowering drugs became available. Areas of uncertainty The advantages in cost-benefit of insulin analogs and their combination with new glucose-lowering drugs are still a matter of debate. There is no general agreement on how to avoid inertia by prescribing insulin therapy in type 2 diabetes when really needed, as reflected by the diversity of recommendations in the current clinical practice guidelines. Data sources When necessary for this review, a systematic search of the evidence was done in PubMed and Cochrane databases. Therapeutic advances Adding new oral glucose-lowering drugs to insulin such as DPP-4 inhibitors lead to a modest HbA1c reduction without weight gain and no increase in hypoglycemia. When SGLT-2 inhibitors are added instead, there is a slightly higher HbA1c reduction, but with body weight and blood pressure reduction. The downside is the increase in genital tract infections. GLP-1 receptor agonists have become the best alternative when basal insulin fails, particularly using fixed ratio combinations. Rapid-acting insulins via the inhaled route may also become an alternative for insulin supplementation and/or intensification. "Smart insulins" are under investigation and may become available for clinical use in the near future. Conclusions Aggressive weight loss strategies together with the new glucose-lowering drugs which do not cause hypoglycemia nor weight gain should limit the number of patients with type 2 diabetes needing insulin. Nevertheless, because of therapeutic inertia and the progressive nature of the disease, many need at least a basal insulin supplementation and insulin analogs are the best choice as they become more affordable. Fixed ratio combinations with GLP1 receptor agonists are a good choice for intensification of insulin therapy.

Metabolic Monitoring of Child and Adolescent Patients on Atypical Antipsychotics by Psychiatrists and Primary Care Providers.

Abstract: Background Antipsychotic drug use in children has doubled from 2001 to 2007 with concomitant increase in obesity. Second-generation antipsychotic (SGA) medication use is associated with weight gain, metabolic derangements, and blood sugar and lipid abnormalities in children. The American Psychiatric Association and the American Diabetes Association have recommended metabolic monitoring guidelines for patients using SGA. Study question The study objective was to investigate and compare metabolic monitoring for SGA medications in psychiatry (PSY), and pediatrics and family medicine [primary care providers (PCP)] outpatient clinics of a university medical center. Study design This is a retrospective study of 149 charts of patients newly prescribed with SGA, ages 5-18 years, from their initial visit in the outpatient clinics. Measures and outcomes Compliance with recommended metabolic monitoring was evaluated for initial and subsequent clinic visits. Parameters included body mass index, waist circumference, blood pressure, fasting plasma glucose, and fasting lipid profile. Results Of the 149 charts, 110 patients were in PSY and 39 in PCP. The parameter most regularly monitored was body mass index (baseline: PSY 88.3%, PCP 97.4%; 12 weeks: PSY 86.4%, PCP 85.0%; and 24 weeks: PSY 91.8%, PCP 100%). Fasting plasma glucose (baseline: PSY 18.9%, PCP 25.6% and 12 weeks: PSY 8.6%, PCP 10.0%) and fasting lipid profile (baseline: PSY 12.7%, PCP 25.6% and 12 weeks: PSY 7.0%, PCP 10.0%) had low completions rates. No difference was seen in metabolic monitoring by sex or ethnic group. Conclusions Metabolic monitoring rate of child and adolescent patients on SGAs was low overall. No statistically significant differences were seen between psychiatry and PCP except a significantly higher rate of fasting plasma glucose level monitoring at baseline among PCP. Limitations to the study include the small sample size obtained for the period investigated and insufficient documentation in some electronic charts. Extending the period studied may increase the statistical significance of the data.

Immune Checkpoint Inhibitors-Related Cardiotoxicity

Abstract: Background Immunotherapy is a significant breakthrough in cancer therapy in the last decade. Immunotherapy is better tolerated compared with chemotherapy. However, it does have side effects, and one of the rare and serious side effects of immunotherapy is cardiotoxicity. Cardiotoxicity has been described with other cancer-related treatments such as chemotherapy and targeted therapy. A high index of suspicion is required, and prompt management with immunosuppression needs to be instituted as soon as possible to prevent fatal outcomes. Areas of uncertainty Research is still ongoing to identify biomarkers that will help us to choose the patients, who will respond well to immunotherapy. Tumor-infiltrating lymphocytes, tumor PD-L1 expression, and tumor mutational burden explored as potential biomarkers. There are no predictive biomarkers to identify patients who are at higher risk of severe cardiotoxicity. Both cardiologists and oncologists should be aware of cardiac toxicity from immune checkpoint inhibitors. Conclusion All patients who are starting immune checkpoint inhibitors should undergo baseline cardiac risk factor assessment with referral to a cardiologist in a patient with multiple risk factors or previous history of cardiovascular disease. Cardiac immune-related adverse events are higher in patients taking combination therapy with anti-CTLA-4/anti-PD-1 agents compared with monotherapy. Patients with known cardiac comorbidities require a higher level of vigilance to monitor for cardiac toxicity because nonspecific symptoms can lead to rapid clinical deterioration and a higher rate of mortality when treated with checkpoint inhibitors.

Elevations in High-Sensitive Cardiac Troponin T and N-Terminal Prohormone Brain Natriuretic Peptide Levels in the Serum Can Predict the Development of Anthracycline-Induced Cardiomyopathy.

Abstract: Author(s): Bisoc, Alina; Ciurescu, Daniel; Radoi, Mariana; Tântu, Monica M; Rogozea, Liliana; Sweidan, Alexander J; Bota, Daniela A | Abstract: BackgroundAnthracyclines remain the cornerstone of the treatment in many cancers including lymphomas, leukemia and sarcomas, and breast cancer. The cardiomyopathy that develops from anthracyclines can lead to heart failure and decreased survival. Multiple mechanisms are involved in the pathophysiology of anthracycline-induced heart failure.Study questionWe hypothesize that anthracycline-induced cardiac (AIC) pathology can be monitored using a panel of blood biomarkers including high-sensitive cardiac troponin T (hs-cTnT) for myocyte necrosis and N-terminal prohormone brain natriuretic peptide (NT-proBNP) for parietal stress.Study designA prospective, institutionally approved study recruited all patients with cancer scheduled to start anthracycline chemotherapy in the Transylvania University cancer clinics.Measures and outcomesTransthoracic 2D echocardiography and the measurements of NT-proBNP and hs-cTnT plasma levels were performed at the beginning of the study and 3 months and 6 months after anthracycline treatment initiation.ResultsThe plasma levels of hs-cTnT at 3 months (rho = 0.439, P = 0.0001) and 6 months (rho = 0.490, P = 0.0001) are correlated with AIC occurrence. For a cutoff value of hs-cTnT at 3 months g 0.008 ng/mL, we obtained 66.7% sensitivity and 67.9% specificity for developing AIC at 6 months, with a 54.5% positive predictive value and a 87.8% negative predictive value. The NT-proBNP serum levels at 3 months (rho = 0.495, P = 0.0001) and 6 months (rho = 0.638, P = 0.0001) are correlated with an AIC diagnosis at 6 months. For a cutoff value of NT-proBNP at 3 months g118.5 pg/mL, we obtained 80% sensitivity and 79.2% specificity for evolution to AIC at 6 months, with 52.2% positive predictive value and 93.3% negative predictive value.ConclusionsIn anthracycline-treated cancer patients, the increase in plasma levels of NT-proBNP and of hs-cTnT can predict the development of anthracycline-induced cardiomyopathy. Early identification of at-risk patients will potentially allow for targeted dose reductions and will diminish the number of patients developing cardiac pathology.

Propofol Infusion and Acute Pancreatitis: A Review.

Abstract: Background Propofol is a short-acting anesthetic used to induce sedation in various ambulatory and inpatient surgical procedures It is a US Food and Drug Administration approved lipid-based intravenous hypnotic agent, which has been used clinically for the induction and maintenance of anesthesia for over 3 decades In addition to general anesthesia, it is used to sedate patients undergoing mechanical ventilation or short procedures such as endoscopy, transesophageal echocardiogram, and abscess drainage An infrequent but serious complication of propofol is acute pancreatitis (AP), with potentially significant morbidity and possible mortality In this review, we will discuss the proposed mechanisms of AP secondary to propofol, a number of reported cases, studies conducted, and treatment strategies Areas of uncertainty There are several case reports in the literature that have shown an association between propofol and pancreatitis The exact mechanism behind propofol-induced pancreatitis is not fully understood, but proposed mechanisms include hypertriglyceridemia (HTG), hypersensitivity, or direct pancreatic toxicity of the drug Although the association of propofol and pancreatitis has not been proven conclusively, clinicians should be aware of this possible rare complication to prevent the devastating consequences of AP Data sources We gathered articles on previously documented case reports and up-to-date studies on propofol-induced pancreatitis by searching databases such as PubMed and Google Scholar Results Based on previous studies and case reports, we suggest that propofol should be added to a list of drugs having a direct association with AP Conclusions Although, the mechanism of propofol-induced pancreatitis is not fully understood, and the causal relationship of propofol-induced hypertriglyceridemia or idiosyncratic drug reaction has remained unproven Clinicians should be aware of the association between propofol and pancreatitis, and any patient presenting with abdominal pain after propofol infusion should be evaluated for AP and treated promptly to avoid complications

Low Response to Clopidogrel in Coronary Artery Disease.

Abstract: BACKGROUND In patients with coronary artery disease, cardiovascular mortality and other acute events showed a clear correlation with risk factors and biomarkers including platelet activation. STUDY QUESTION OF THIS RESEARCH Which was the incidence of low response to clopidogrel and its correlation with risk factors and biomarkers in coronary artery disease? STUDY DESIGN Four hundred patients (pts) with coronary artery disease-stable angina (SA) and acute coronary syndrome-were divided into 8 groups of study, consistent with low response to clopidogrel and the type of coronary artery disease. Low response to clopidogrel-defined as adenosine diphosphate test-ADP-test of >46 U by multiple electrode platelet aggregometry was evaluated in correlation with cardiovascular risk factors and biomarkers of oxidative stress, endothelial dysfunction, hypercoagulability, high platelet reactivity. RESULTS In coronary artery disease, low response to clopidogrel significantly correlated with older than 65 years, smoking, hypertension, diabetes mellitus, body mass index of >25, previous aspirin treatment (P < 0.05), high value of total and low-density lipoprotein cholesterol, low value of high-density lipoprotein cholesterol, low response to aspirin, high mean platelets volume and von Willebrand factor activity, low flow-mediated vasodilatation, total antioxidant status (P < 0.01) and only in patients with SA of male gender (P < 0.01). The incidence of other hypercoagulability biomarkers, such as reduced values of S protein, C protein, antithrombin III, and V Factor Leiden resistance to activated protein C, was very low and not correlated with low response to clopidogrel. CONCLUSIONS In coronary artery disease, low response to clopidogrel significantly correlated with the most of old cardiovascular risk factors, with previous aspirin treatment, low response to aspirin, higher mean platelets volume, higher von Willebrand factor activity, lower flow-mediated vasodilatation, and lower total antioxidant status values and only in patients with SA of male gender.

Common Pathways for Pain and Depression-Implications for Practice.

Abstract: Background Pain and depression have a high impact on caring for the people who need palliative care, but both of these are neglected compared with the approach for other symptoms encountered by these patients. Areas of uncertainty There are few studies in humans that support the existence of common neural circuits between depression and pain that also explore the use of drugs with effects in both conditions. More knowledge is needed about the relationship of these clinical entities that will lead to the optimization of the treatment and improvement of quality of life. Data sources We conducted a search in PubMed to identify relevant articles and reviews that have been published in the last 5 years, concerning the topic of common pathways between depression and pain (2014-April 2019). Therapeutic advances The connections between the 2 clinical entities start at the level of the cortical regions. The hippocampus is the main site of neural changes, modification of the immune system, neuromodulators, neurotransmitters, and signaling pathways implicated in both conditions. Increased levels of peripheral proinflammatory cytokines and neuroinflammatory changes are related to the physiopathology of these entities. Inflammation links depression and pain by altering neural circuits and changes in their common cortical regions. Antidepressants are used to treat depression and chronic, pain but more experimental studies are needed to determine which antidepressant drugs are the most effective in treating the 2 entities. Conclusions Pharmacological and nonpharmacological interventions targeting cortical changes in pain and depression are promising, but more clinical studies are needed to validate their usefulness.

Palliative Care in Heart Failure: A Public Health Emergency.

Abstract: Background Palliative care (PC) is the holistic care of patients with life-limiting illnesses focused on relief of suffering and maximizing quality of life for patients and their families. Patients with heart failure (HF) are the largest group eligible for PC services, but only a small percentage of them receive PC. Areas of uncertainty The optimal content and method of delivery of PC interventions to HF patients in resource-limited countries remain unknown. The integration of PC into existing HF disease management continues to be a challenge. Data sources PUBMED was searched to identify articles on the topic published in the last 5 years (2014-April 2019). One hundred thirty-six articles were identified-14 articles out of were included in the revision. Therapeutic advances Research concerning PC in HF is still scarce and comes predominantly from developed countries. PC in HF improves patients' and caregivers' outcomes in terms of dyspnea, sleep, depression, communication, coping, and care-giving burden. Specialized home-based PC services have a positive impact on patients' physical and emotional wellbeing while decreasing utilization of medical services. Fatigue, dyspnea, and pain are frequent symptoms. Evidence concerning use of opioids for dyspnea is increasing. Family caregivers offer a considerable amount of care during the disease trajectory. There is often incongruence between the carer's and the patient's wishes in terms of treatment decisions and preferences. Carers should be assessed for risk and supported in their roles in care management and care coordination. Conclusions Because of the unpredictability of the disease and difficulty in prognostication, PC should be introduced at the point of diagnosis of HF. Basic education in PC needs to be introduced early in the training of cardiology staff, focused on concept definition, differencing PC and terminal care, symptom management, communication, and decision-making.

A Systematic Review of Clinical Studies on the Effect of Psychoactive Cannabinoids in Psychiatric Conditions in Alzheimer Dementia

Abstract: Background The systematic reviews and meta-analyses performed until now did not provide the adequate picture of actual knowledge in the field of neuropsychiatric symptoms treatment using psychotropic cannabinoids in patients with Alzheimer disease (AD). The study question Which is the level of evidence, from quantitative and qualitative point of view, concerning the efficacy and safety of the treatment with psychotropic cannabinoids of neuropsychiatric symptoms in AD? Study design PubMed, EMBASE, Cochrane Database of Systematic Reviews, Google Scholar Data, and Clinicaltrials.gov were searched for randomized clinical trials with cannabinoids in Alzheimer dementia agitation and aggression. Measures and outcomes The rationale, the objectives, and the methods used for searching the trials have been established according to PRISMA Criteria 2009. Results The total number of patients in the 9 publications evaluated in this study, which included data from 6 clinical trials, was 422 patients-treatments, where treatment was a psychoactive cannabinoid or placebo, some of them obtained by multiplying selected patients with the number of cannabinoid treatments in the crossover studies. There are multiple sources of bias in the analyzed studies; 2 elements have prevented conclusive results. One element was polypragmazia, a major role being played by the use of psychotropic drugs other than cannabinoids, in an effort to reduce agitation and aggressive behavior. The second one was the large number of concomitant symptoms, for example, pain (commonly causing anxiety and agitation). Conclusions No clear conclusion can be drawn on the effectiveness of psychoactive cannabinoids in the treatment of psychiatric manifestations, in particular agitation and aggression, in AD. In the future, large randomized controlled trial with adequate designs, without crossover and for longer duration, adapted to cannabinoid pharmacokinetics, is required to establish the real efficacy and safety of these drugs in aggressive and/or agitated patients with AD.

Self-Medicating for Pain: A Public Health Perspective.

Abstract: Background Pain is one of the symptoms for which any man is willing not only to go to the doctor but also to resort to any means, including self-medication, to "get rid" of it Self-medication is not only a current practice but also a public health problem, under the circumstances that it can influence the way in which a disease is diagnosed and/or treated in a timely manner, and, consequently, repercussions may occur on the cost of treatment, in the case of severe forms Pain is a vital symptom, and the diminution until the disappearance of pain is a fundamental right of each individual; the analysis of ethical issues in the case of self-administration of analgesic medication has not been a major concern Areas of uncertainty Understanding the problem is important to realize whether self-medicating for pain is a necessity or an abuse, and in this respect, we review scientific articles from international databases: PubMed and ProQuest Data sources The study is based on the consultation of scientific articles from international databases-PubMed and ProQuest, the main keywords in the search being pain and self-medication, to which a stigma or public health is sequentially added Results Pain is becoming more and more a global problem and the extent of its spread can substantiate our assertion about pathology with pandemic impact Under the pressure of patient associations, of the media, and of nonmedical authorities, the opinion about the need for a stoic approach to pain has long become an outdated theory, and chronic pain, beyond a multidimensional approach, is increasingly considered not only a useless element but also even a destructive one Conclusions Pain and self-medication must be addressed, including in medical practice, starting from their multidimensionality from the following perspectives: medicobiological, sociocultural, instructive-educational, legal-political, and especially ethical They are not only individual health problems but also become, when connected with a stigma, a public health problem

Hundred Years of Insulin Therapy: Purified Early Insulins.

Abstract: Background The discovery of insulin has changed dramatically the outcome of patients with type 1 diabetes, giving them the possibility to survive. This is of particular concern due to the fact that type 1 diabetes most frequently occurs in children who were destined to die in ketoacidosis coma. Areas of uncertainty From insulin discovery to the availability of human insulin and human insulin analogs to be used in diabetes therapy, a series of problems have arisen as the difficulty of insulin purifications, the animal insulin used by the first researches were in fact contaminated by proteins, fats, and other impurities, and the presence of side effects such as allergy, antibodies generation, and lipoatrophy. Data source literature Data strictly related to the argument have been searched in Pub Med and used. Results Starting from insulin discovery in 1921 to nowadays, significant efforts have been made by a series of researches to purify animal insulin, discover the molecular structure of human insulin, and develop methods to synthetize human insulin and then insulin analogs. Conclusions The history of insulin discovery here reported is fascinating; insulin is a hormone, a product of biotechnology, a field of research that saved and save the life of many diabetic patients.

Ranolazine for Symptomatic Management of Microvascular Angina.

Abstract: BACKGROUND Ranolazine is approved in the United States and Europe for chronic stable angina. Microvascular angina (MVA) is defined as angina with no obstructive coronary artery disease. STUDY QUESTION Our objective was to assess the effectiveness of ranolazine at improving angina scores and quality of life in a Canadian cohort with severe refractory angina due to MVA. STUDY DESIGN We administered questionnaires to 31 patients at baseline and after at least 6 weeks of ranolazine treatment. MEASURES AND OUTCOMES Validated, clinically significant changes for each Seattle Angina Questionnaire domain and the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form were obtained from the literature. Score changes between baseline and postranolazine use were analyzed using sign test. RESULTS Patients were mostly female (27 of 31 patients) with a median age of 57 years. After initiation of ranolazine treatment, patients experienced improvements in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form scores (80.6%; P < 0.01) and in 3 of the 4 domains of the Seattle Angina Questionnaire (physical limitation: 73.3%; P = 0.02; treatment satisfaction: 80.6%; P < 0.01; and disease perception: 77.4%; P < 0.01). Patients were less likely to have interactions with the health care system after ranolazine treatment as compared with before (35.5% vs. 93.5%; P < 0.01). CONCLUSIONS Ranolazine significantly improves symptom control and quality of life in patients with MVA and severe refractory angina and reduces their interaction with the health care system. Given the potentially debilitating effect of chronic angina in MVA, ranolazine may be an effective treatment option.

Experiences of First Insulin-Treated Patients (1922-1923).

Abstract: Background Historical description of first insulin trials just after its discovery. Areas of uncertainty The review includes first initiatives of insulin treatment. The probability of other trials, not reported to the Insulin Committee of the University of Toronto and conducted in the years 1922 and 1923, is quite low. Data sources (1) Archival Collections, University of Toronto: Insulin Discovery and Early Developments of Insulin (University of Toronto Libraries digital special collection, with a particular section entitled "From a Patient's Point of View" containing letters, patient charts, newspaper clippings, and photographs). (2) Thomas Fisher Rare Book Library: Academy of Medicine Collection, F. G. Banting Papers, C. H. Best Papers, J. B.Collip Papers, W. R. Feasby Papers, E. Hugues Papers, J. J. R. Macleod Papers. (3) National Library of Medicine: PubMed search for the topic of history of insulin, History of Medicine-on syllabus archive. (4) Selected Journals for History of Medicine: Bulletin of the History of Medicine, Journal of the History of Medicine and Allied Sciences, Medical History. (5) Selected books: The Discovery of Insulin (M. Bliss); Diabetes, Its Medical and Cultural History (D. von Engelhardt); H. C. Hagedorn and Danish Insulin (T.Deckert), Continuing Quest (W. A. Tomkins). Therapeutic advances This historical review shows the quick progress from impure pancreatic extract to the selective isoelectric precipitation of the hormone, which made possible the introduction of insulin in the clinic. Conclusions The coordination between the Departments of Physiology (Connaught Laboratories) and Medicine (Toronto General Hospital) was essential for the discovery and implementation of insulin therapy. The Insulin Committee was decisive for the negotiation with the pharmaceutical industry, the purification, grand-scale production, patents' achievement, and provision of licenses to expert clinicians and prestigious health centers. At the end of the year 1923, insulin treatment was already extended to Europe (mainly Scandinavia, Great Britain, and Spain). Insulin discovery and treatment changed the clinical spectrum of diabetes.

Repositioning or Redirection of Antidepressant Drugs in the Treatment of Bacterial and Fungal Infections.

Abstract: increases in temperature produced by MPD could trigger compensatory cooling mechanisms, which would explain the increased yawn frequency. Moreover, the abrupt and complete eradication of yawning after the discontinuation of MPD and introduction of atomoxetine is consistent with this interpretation. Atomoxetine does not appear to produce associated increases in brain or body temperature, and, in fact, it has been linked with hypothermia in at least one case.13 This appears to be the first documented case of MPDinduced yawning, and thus, future research should be aimed at more closely examining the connection between MPD, hyperthermia, and excessive yawning. Although further investigations are needed to support this interpretation, such research could have important clinical applications related to the recognition and treatment of cases of excessive yawning triggered by druginduced abnormalities in thermoregulation.

Automated Insulin Delivery: The Artificial Pancreas Technical Challenges.

Abstract: Background The automation of glucose control has been an important goal of diabetes treatment for many decades. The first artificial pancreas experiences were in-hospital, closely supervised, small-scale, and short-term studies that demonstrated their superiority over continuous subcutaneous insulin infusion therapy. At present, long-term outpatient studies are being conducted in free-living scenarios. Areas of uncertainty The integration of multiple devices increases patients' burden and the probability of technical risks. Control algorithms must be robust to manage disturbance variables, such as physical exercise, meal composition, stress, illness, and circadian variations in insulin sensitivity. Extra layers of safety could be achieved through remote supervision. Dual-hormone systems reduce the incidence and duration of hypoglycemia, but the availability of stable pumpable glucagon needs to be solved. Faster insulin analogues are expected to improve all types of artificial pancreas. Therapeutic advances Artificial pancreas safety and feasibility are being demonstrated in outpatient studies. Artificial pancreas use increases the time of sensor-measured glucose in near-normoglycemia and reduces the risk of hyperglycemia and hypoglycemia. The benefits are observed both in single- and dual-hormone algorithms and in full- or semi-closed loop control. A recent meta-analysis including 41 randomized controlled trials showed that artificial pancreas use achieves a reduction of time in hyperglycemia (2 hours less than control treatment) and in hypoglycemia (20 minutes less); mean levels of continuous glucose sensor fell by 8.6 mg/dL over 24 hours and by 14.6 mg/dL overnight. The OpenAPS community uses Do It Yourself artificial pancreas in the real world since 2013, and a recent retrospective cross-over study (n = 20) compared continuous glucose sensor readings before and after initiation: mean levels of blood glucose fell by 7.4 mg/dL over 24 hours and time in range increased from 75.8% to 82.2% (92 minutes more). Conclusions The outpatient use of artificial pancreas is safe and improves glucose control in outpatients with type 1 diabetes compared with the use of any type of insulin-based treatment. The availability of open-source solutions and data sharing is needed to foster the development of new artificial pancreas approaches and to promote the wide use of Big Data tools for knowledge discovery, decision support, and personalization.

Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Mortality Among COVID-19 Patients: A Systematic Review and Meta-Analysis.

Abstract: Background Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are known to increase the expression of angiotensin converting enzyme 2 receptor, which has been shown to be the receptor for the acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2). Areas of uncertainty Based on these observations, speculations raised the concerns that ACEIs/ARBs users would be more susceptible to SARS-CoV-2 infection and would be at higher risk for severe COVID-19 disease and death. Therefore, we systematically reviewed the literature and performed a meta-analysis of the association between prior use of ACEIs and ARBs and mortality due to COVID-19 disease. Data sources A comprehensive search of several databases from November 2019 to June 18, 2020 was conducted. The databases included Ovid MEDLINE(R) and Epub Ahead of Print, In-Process and Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, and Scopus. Medrxiv.org was also searched for unpublished data. Therapeutic advances Nine studies with a total of 18,833 patients infected with SARS-CoV-2 met our eligibility criteria. Prior use of ACEIs and/or ARBs was associated with reduced mortality among SARS-CoV-2-infected patients, with a pooled adjusted relative risk (aRR) from 6 studies of 0.63, 95% confidence interval (CI) (0.42-0.94) (I = 65%). Three studies reported separately on ACEIs or ARBs and their association with survival among SARS-CoV-2-infected patients, with a pooled adjusted relative risk of 0.78, 95% CI (0.58-1.04) (I = 0%) and 0.97, 95% CI (0.73-1.30) (I = 0%) respectively. The results of sensitivity analyses were consistent with the main analysis. Conclusion Our meta-analysis suggests that use of ACEIs/ARBs is associated with a decreased risk of death among SARS-CoV-2-infected patients. This finding provides a reassurance to the public not to stop prescribed ACEIs/ARBs because of fear of severe COVID-19.

Turmeric-Associated Liver Injury.

Abstract: nausea and vomiting due to chemotherapy. Biochim Biophys Acta. 1848;2015:2738–2746. 6. Roscoe JA, Morrow GR, Colagiuri B, et al. Insight in the prediction of chemotherapy-induced nausea. Support Care Cancer. 2010;18:869–876. 7. Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med. 2008;358:2482–2494. 8. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Antiemesis–Version 3. 2018. Available at: www.nccn.org/patients. Accessed November 26, 2019. 9. Steele RH, Limaye S, Cleland B, et al. Hypersensitivity reactions to the polysorbate contained in recombinant erythropoietin and darbepoietin. Nephrology (Carlton). 2005;10:317–320. 10. Ten Tije AJ, Verweij J, Loos WJ, et al. Pharmacological effects of formulation vehicles: implications for cancer chemotherapy. Clin Pharmacokinet. 2003;42:665–685. 11. Herrstedt J, Roila F, Warr D, et al. 2016 updated MASC/ESMO consensus recommendations: prevention of nausea and vomiting following high emetic risk chemotherapy. Support Care Cancer. 2017;25:277–288. 12. Coors EA, Seybold H, Merk HF, et al. Polysorbate 80 in medical products and nonimmunologic anaphylactoid reactions. Ann Allergy Asthma Immunol. 2005;95:593–599. 13. Navari RM, Schwartzberg LS. Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting. OTT. 2018;11:6459–6478. 14. Rojas C, Raje M, Tsukamoto T, et al. Molecular mechanisms of 5-HT3 and NK1 receptor antagonists in prevention of emesis. Eur J Pharmacol. 2014;722: 26–37. 15. Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2017;35:3240–3261. 16. Boccia R, Geller RB, Clendeninn N, et al. Hypersensitivity and infusion-site adverse events with intravenous fosaprepitant after anthracycline-containing chemotherapy: a retrospective study. Future Oncol. 2019;15:297–303. 17. Baxley A, Lee Z, Medina P. Systemic hypersensitivity to fosaprepitant–a report of two cases. J Oncol Pharm Pract. 2018;24:76–78. 18. Cass AS, Odinet JS, Valgus JM, et al. Infusion reactions following administration of intravenous rolapitant at an academic medical center. J Oncol Pharm Pract. 2019;25: 1776–1783. 19. Navari RM, Mosier MC. Crossover safety study of aprepitant: 2-min injection vs 30-min infusion in cancer patients receiving emetogenic chemotherapy. OTT. 2019;12: 3277–3284.

Prolonged Viral RNA Shedding Duration in COVID-19.

Abstract: To the Editor: Recently, coronavirus disease 2019 (COVID-19), which was caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), has been spreading rapidly in more than 100 countries, and the outbreak becomes a global public health concern.1,2 It is well known that controlling the source of infection and blocking the route of transmission were most important measurement for this disease.2 The level and duration of SARS-CoV-2 virus replication are important factors in assessing the risk of transmission and guiding decisions regarding isolation of patients. A previous study reports the median duration of viral shedding was 20 days (interquartile range 17–24) in survivors.3 Here, we report a young male patient with the viral RNA shedding duration of 45 days. A 34-year-old man without underlying diseases in Wuhan City suffered from fever (38°C) and myalgia since January 30, 2020. He received orally oseltamivir and moxifloxacin. Five days later, he reported no fever, but myalgia remains persisted and diarrhea emerged. Chest X-ray showed normal, but computed tomography (CT) scan showed multiple ground glass shadows in the right side of lung (Figures 1A–D). Routine blood tests showed leukocyte count of 6.82 3 109/L and lymphocyte count of 1.64 3 109/L. The pharyngeal swabs specimens were obtained for nucleic acid of SARS-CoV-2 PCR detection. Result was positive.

Efficacy and Safety of Omalizumab for Chronic Spontaneous Urticaria: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Abstract: Background Omalizumab has been proposed as a possible effective treatment of chronic spontaneous urticaria (CSU). Study question We aimed to access the efficacy and safety of omalizumab in the treatment of CSU based on qualified, randomized controlled trials (RCTs). Data sources PubMed, the Cochrane library, and Embase databases. Study design Computerized search by index words was performed to identify qualified RCTs, and relevant literature sources were also searched. Result Nine RCTs were included in the meta-analysis with 1612 patients in the omalizumab group and 1251 patients in the placebo group. Compared with the placebo group, omalizumab significantly decreased the weekly itch score after therapy [Weighted Mean Difference (WMD), -3.94; 95% confidence interval (CI), -4.64 to -3.24], the weekly hive score (WMD, -5.27; 95% CI, -6.17 to -4.38), the dermatology life quality index (DLQI; WMD, -3.58; 95% CI, -4.66 to -2.50), and the urticaria activity score over 7 days (UAS7; WMD, -9.51; 95% CI, -10.94 to -8.08). There was no significant difference in the incidence of adverse events (AE) [relative risk (RR), 1.01; 95% CI, 0.91-1.12], serious AE (RR, 0.85; 95% CI, 0.57-1.27), and severe AE (RR, 0.83; 95% CI, 0.60-1.14) between the 2 groups. Compared with the placebo, omalizumab significantly decreased the weekly itch score and weekly hive score after therapy in patients receiving 75, 150, and 300 mg omalizumab, respectively. DLQI was significantly reduced in patients receiving 150 and 300 mg of omalizumab, respectively. In all the subgroup of UAS7, omalizumab significantly decreased the score compared with the placebo. Only patients receiving 600-mg omalizumab had a significantly higher AE incidence versus placebo. There was no significant difference in serious and severe AE between the 2 groups. Conclusion Omalizumab caused a significantly greater reduction in weekly itch score, weekly hive score, DLQI, and UAS7 in CSU patients than the placebo. However, high-quality, multicenter RCTs with a larger sample size are needed to confirm the safety of omalizumab, and whether AEs are caused by omalizumab or other factors.

Advances in the Pharmacogenomics of Antiplatelet Therapy.

Abstract: Background Acute coronary syndrome (ACS) is a highly thrombotic state, and a sustained antiplatelet effect is vital to the prevention of thrombotic complications. Clopidogrel, the most widely used oral P2Y12 receptor antagonist in ACS, has attracted considerable attention because of significant variability in antiplatelet effect depending on the presence of CYP2C19 allele. Other P2Y12 receptor antagonists offer sustained and more predictable antiplatelet effects than clopidogrel albeit at an increased cost. Several studies have demonstrated the promising application of pharmacogenetics in choosing personalized antiplatelet therapy using the point-of-care genotype assays. Areas of uncertainty Guidelines regarding the genotype-guided approach to the selection of antiplatelet therapy have been conflicting, and studies evaluating the effect of pharmacogenetic-guided selection of antiplatelet therapy on the outcomes have demonstrated mixed results. Data sources A literature search was conducted using MEDLINE and EMBASE for studies reporting the association of pharmacogenetic-guided selection of antiplatelet therapy and the outcomes in patients with ACS until December 2018. Results Presence of specific CYP2C19 allele significantly influences clopidogrel metabolism and associated outcomes in patients with ACS. Thrombotic and bleeding complications are more common in patients with loss-of-function (LOF) and gain-of-function (GOF) alleles, respectively. Although the pharmacogenetic-guided approach to the selection of antiplatelet therapy appears promising in ACS, studies have shown conflicting results, and direct randomized evidence linking this approach with the better outcomes is lacking. Conclusions Genotype-guided selection of antiplatelet therapy is expected to be useful in patients undergoing percutaneous coronary intervention (PCI) with a high risk of adverse outcomes. The patient-physician discussion should be an essential part of this decision-making process. Large-scale multicenter randomized controlled trials using the point-of-care genotype assay are needed to investigate this approach further before its use can be recommended in all comers.

How to Reduce Cardiovascular Risk in Nonalcoholic Fatty Liver Disease.

Abstract: Background Nonalcoholic fatty liver disease (NAFLD) is a rapidly growing multisystem disease with extrahepatic manifestations, including effects on the cardiovascular (CV) system. The leading cause of death in NAFLD is of cardiac etiology being ischemic heart disease. Areas of uncertainty NAFLD is associated with several CV complications including cardiac structural and functional alterations. However, there are no current approved pharmacotherapies for treating NAFLD, leading to increased CV risk with an increasing morbidity and mortality. Data sources We summarize the currently available therapeutic strategies in managing NAFLD and their cardioprotective effects according to recently published data, guidelines, and practice guidance recommendations. Therapeutic advances Several therapeutic modalities evaluated in NAFLD include nonpharmacological strategies, pharmacotherapies and surgical management. Nonpharmacological strategies are recommended in early stages of NAFLD and include weight loss, physical activity, and dietary changes. Personalized management strategies with nonpharmacological lifestyle modifications are associated with reduced CV risk, improved liver enzyme levels, in addition to liver fat content, injury, and fibrosis. Several pharmacotherapies including lipid-lowering agents and antidiabetic drugs such as insulin sensitizers and incretin mimetics, in addition to antioxidants, ursodeoxycholic acid, semi-synthetic bile acid analogue, acetylsalicylic acid, and renin-angiotensin system inhibitors have been evaluated in the current literature. Despite promising results of several drugs in NAFLD with cardioprotective effects, we currently remain with no approved medical drugs for treating NAFLD. Although bariatric surgery was demonstrated to be associated with CV risk reduction and improvements in hepatic steatosis, inflammation, and fibrosis, it remains of limited use because of its invasiveness. Conclusions Management of NAFLD necessitates a multidisciplinary team with a patient-centered and individualized medicine approach. Early lifestyle modifications are essential in NAFLD to reduce CV risk. Experimental studies are required to confirm hepatic and cardioprotective effects associated with several drugs. Bariatric surgery remains of limited use.

Effect of Bisoprolol on the Level of Dabigatran.

Abstract: Background Many patients receiving dabigatran treatment might also require bisoprolol therapy. However, there is a possibility that bisoprolol as significant P-glycoprotein inhibitor might interact with dabigatran. Study question To investigate the impact of concomitant bisoprolol therapy on dabigatran plasma level in patients with nonvalvular atrial fibrillation. Study design A pilot drug interaction study in 29 patients with nonvalvular atrial fibrillation on dabigatran therapy. Bisoprolol was administrated in 18 patients. Blood samples were collected at baseline (in the morning, before any medication was administered) and at hour 2 (2 hours after administration of dabigatran and bisoprolol). Results The dabigatran plasma level was significantly higher at baseline and at hour 2 in patients treated with bisoprolol compared with patients without bisoprolol therapy. In addition, we have shown that this increase is affected by dabigatran dosage and concomitant treatment with proton-pump inhibitor and digoxin. The impact of bisoprolol on dabigatran concentration was still significant despite these confounders. Conclusions This study demonstrated the interaction between dabigatran and bisoprolol, which is modulated with dabigatran dosage and concomitant treatment with proton-pump inhibitor and digoxin.