Purpose: Direct oral anticoagulants (DOACs) have been shown to be as effective or superior to warfarin, but warfarin use remains constant. Knowledge regarding the patient population who have switched from a DOAC to warfarin is limited. The objective of this study was to identify clinical predictors which may influence a patient’s likelihood of switching from a DOAC to warfarin for atrial fibrillation (AF) or venous thromboembolism (VTE). Methods: In this single-center, case-control study, patients who switched from a DOAC to warfarin were compared with patients who remained on a DOAC. Baseline demographics were compared between the switch and control groups. Independent factors that increased the likelihood of switching from a DOAC to warfarin were analyzed using logistic regression. Results: A total of 150 patients were included in the control (n = 100) and switch (n = 50) groups. Patients switched from a DOAC to warfarin had more medications at baseline (9 [7, 13] vs 11 [8, 18], P = 0.009). The presence of heart failure (HF) increased the likelihood of switching (odds ratio [OR] = 3.95, confidence interval [CI] = 1.70-9.21, P = 0.002), and for every 10 mL/min increase in creatinine clearance (CrCl), the likelihood of switching decreased ( R = 0.89 [0.80-0.99], P = 0.026). Patients with pulmonary embolism (PE) were less likely to switch from a DOAC to warfarin (OR = 0.20, CI = 0.05-0.86, P = 0.031). Explicitly listed reasons for switching included left ventricular assist device (LVAD) implantation (20%) and valve replacement procedures (20%). Conclusion: Congestive HF was a clinical predictor associated with an increased likelihood of switching from a DOAC to warfarin. Anticoagulation therapy for PE and higher CrCl was associated with a decreased likelihood in switching from DOAC to warfarin.
Objective: The objectives of this study are, first, to measure concordance between 5 different renal function estimates (methods) in terms of recommended drug doses, and, subsequently, to establish the potential for significant clinical differences between Cockroft–Gault (CG) and Modification of Diet in Renal Disease (MDRD) equations in dosing a specific medication, namely, meropenem. Design and setting: This study used a Monte Carlo simulation, and this is a computer–based study with no actual patient data. Patients: A total of 1200 and 8701 simulated cases to study the concordance for the 5 methods and the potential clinical significance of discordance between CG and MDRD, respectively, were chosen for the study. Methods: Simulated factors were age, sex, height, weight, serum creatinine, ethnicity, and albumin. We estimated the renal function using 5 formulas (ie, 10 combinations) including CG, MDRD, and Chronic Kidney Disease Epidemiology Collaboration (CKD–EPI). Next, the team evaluated concordance for each combination in dosing 22 drugs. Finally, our researchers reviewed and simulated data from the literature to show how CG versus MDRD use can result in clinically significant differences for meropenem. Results: Pairwise combinations yielded statistically significant differences ( P < .0001) except for CG and MDRD ( P < .5147). In addition, the highest concordance was for MDRD and CKD–EPI. Average discordance is in the range of 25% to 30% with the lowest being between CG and albumin–based estimates. Both CG and MDRD were largely discordant which can reach up to 40% with a drug like meropenem and may be associated with significant adverse outcomes. Conclusions: Both CG and MDRD in our simulation are statistically comparable. Clinically, nonetheless, they are significantly inconsistent in terms of recommended drug dosing. We encourage practical comparisons of outcomes for individual or groups of medications (eg, meropenem and antibiotics) empirically dosed in renal patients on the basis of equations used in distinct populations.
Direct oral anticoagulants (DOACs) are indicated by the European Medicines Agency and US Food and Drug Administration for stroke prevention in patients with nonvalvular atrial fibrillation (AF). The role of DOACs in patients with AF and concomitant valvular heart disease (VHD) is less clear. Recent subanalyses of randomized controlled trials and meta-analyses have evaluated the role of DOACs in patients with AF and VHD. Patients with native aortic valve disease, tricuspid valve disease, or mitral regurgitation will be the primary focus as these represent the majority of VHD represented in the DOAC AF trials. Limited data exist on the role in patients with rheumatic mitral stenosis, mechanical heart valves, and mitral valve repair. This review provides the current clinical and scientific data pertaining to the safety and efficacy of DOAC use in patients with VHD.
Peptic ulcer bleeding remains an important medical emergency. Important recent advances are reviewed. These include further support for a more restrictive transfusion strategy aiming for a target haemoglobin of 70-90 g/L. The Glasgow-Blatchford score remains the most useful assessment score for identifying the lowest risk patients suitable for outpatient management and predicting the need for intervention. Newer scores such as the AIMS65 and Progetto Nazionale Emorragia Digestive score (PNED) may be more accurate in predicting mortality. Pre-endoscopy erythromycin improves outcomes and is underused. A new disposable Doppler probe appears to provide more accurate determination of both rebleeding risk and the success of endoscopic therapy than purely visual guidance. Over-the-scope clips and haemostatic powders appear to have some role as endoscopic salvage therapies. Non-H. pylori, non-aspirin/non-steroidal anti-inflammatory drug (NSAID) ulcers contribute to an increasing percentage of bleeding peptic ulcers and are associated with a high rebleeding rate. The optimal management of these ulcers remains to be determined.
Aldosterone receptor antagonists have recently been added to the American College of Cardiology/American Heart Association/Heart Failure Society of America 2017 guideline update for serving a role in the reduction in morbidity in patients with heart failure with preserved ejection fraction and an ejection fraction greater than 45%. This recent addition to the heart failure with preserved ejection fraction recommendations is supported by the findings of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist study. All trials with spironolactone or eplerenone in the treatment of patients with heart failure with preserved ejection fraction are reviewed for both cardiovascular morbidity and mortality and symptom improvement. Limited positive data exist on the role aldosterone receptor antagonists has on mortality and symptom improvement in patients with heart failure with preserved ejection fraction. Ongoing trials with angiotensin receptor neprilysin inhibitor and sodium-glucose co-transporter 2 inhibitors in patients with heart failure with preserved ejection fraction are reviewed. This review provides the current clinical and scientific data pertaining to the safety and efficacy of aldosterone receptor antagonists in patients with heart failure with preserved ejection fraction.
Background:Benzodiazepine (Bz) exposure has been identified as a risk factor of community-acquired pneumonia (CAP) in some observational studies, but this remains controversial. This study was designed to quantify the risk of CAP associated with treatment with Bz. Methods:All individuals ⩾14 years of age registered in any of 3 primary health care providers in our area between January 2011 and May 2013 were included in the study. This resulted in a population of 51 912 individuals who contributed to a total of 1 496 680 person-months of observation. Previously anonymized data for each participant were obtained from their personal health records and the official prescription database. The primary outcome measures were the incidence of CAP during the study period and the relative risk (RR) that could be attributed to Bz exposure. Results:A total of 696 CAP cases were diagnosed. Incidence density was 12.4 cases per 1000 person-years in individuals exposed to Bz and 4.51 cases per 1000 person-years in those who were not. Benzodiazepine exposure increased the risk of CAP in the whole population (RR: 2.76, 95% confidence interval: 2.35-3.25) and in all the evaluated subgroups. Stratified analysis showed an interaction only with age (RR: 2.99 in patients under 65 years and 1.78 in those aged 65 or older). Benzodiazepine exposure was associated with an excess 0.79 cases of CAP per 100 person-years. Conclusions:Benzodiazepine exposure increases the risk of CAP. Given the clinical relevance of CAP, prescribers should be aware of this potentially preventable risk and consider it while newly prescribing Bz.
Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease associated with significant morbidity and mortality. Historically, IPF has been managed using combination immunosuppressive therapy; however, this has been shown to be associated with increased mortality. Over the past 5 years, 2 disease-modifying agents have been licensed for use in IPF. Pirfenidone is a novel therapy with antifibrotic and anti-inflammatory properties. Evidence from a number of randomised control trials has shown that pirfenidone slows the progression of decline in forced vital capacity in IPF. Nintedanib is a tyrosine kinase inhibitor with antifibrotic properties which has also been shown to significantly reduce disease progression. As head-to-head comparison data are lacking, treatment selection is based on patient and clinician preference and tolerability of side effects. In the future, combination therapy with pirfenidone and nintedanib or with additional therapies may further improve lung function preservation.
Chronic hepatitis C is a common cause of liver-related morbidity and mortality. Ledipasvir/sofosbuvir is a combination of 2 direct-acting antiviral agents that has been approved for use in patients with genotype 1, 4, 5, or 6. This approval is based on multiple phase 3 studies in which the rate of sustained virologic response exceeded 90% for 12 or 24 weeks of treatment, depending on the patient population. For some patients, the addition of ribavirin is required. Ledipasvir/sofosbuvir is well tolerated, with the most commonly reported adverse events being fatigue and headaches.
Chronic obstructive pulmonary disease (COPD), a common, preventable, and treatable disease characterized by persistent respiratory symptoms and airflow limitation, is rapidly becoming a global healthcare challenge. Chronic obstructive pulmonary disease is the third leading cause of death in the United States and has been ranked fourth worldwide. Its current therapies improve symptom relief but do not alter the natural history of the disease. Therefore, as COPD is a progressive condition, novel treatment strategies, and alternative therapies are desperately needed. There are now multiple lines of evidence suggesting that changes to the pulmonary vasculature are important to the development and progression of COPD, independent of pulmonary hypertension. Hence, we hypothesize that a vascular-targeted therapy can be a potent and reliable way of monitoring and possibly changing the course of COPD progression. This review focuses on the potency and promise, as well as challenges, of developing vascular-targeted therapy in alleviating the early onset of COPD signs and symptoms.
Rolapitant is a long-acting neurokinin1 receptor antagonist (NK1 RA) which is metabolized by CYP3A4 but does not inhibit or induce it, thereby reducing potential drug interactions. Four initial randomized studies compared rolapitant with placebo when added to a 5-hydroxytryptamine3 receptor antagonist (5HT3 RA) and dexamethasone for chemotherapy-induced emesis. Three were with highly emetic chemotherapy (HEC) and one with moderately emetic chemotherapy (MEC) and anthracycline/cyclophosphamide (AC). The rolapitant groups receiving HEC yielded statistically significantly improved responses in all phases of emesis (except the acute and overall phases in study 2) when compared with active controls. Overall (0-120 h), the response was better in the rolapitant arm for AC (P =.0332) and non-AC MEC (including carboplatin) (P =.0003). The efficacy of rolapitant is sustained over multiple cycles. Rolapitant 180 mg orally is well tolerated with similar side effects between the rolapitant and active control arms. It is effective in younger and older adults. Further studies will define its place among other NK1 RAs.
Cystic fibrosis (CF) is a common life-limiting genetic condition caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR protein is present in many epithelial cells in the body, and CF is characterised by suppurative lung disease, exocrine pancreatic insufficiency, and elevated sweat chloride. Traditionally, treatment of CF has involved managing the complications of defective CFTR function, such as airway clearance techniques for impaired lung mucociliary clearance and pancreatic enzyme replacement for pancreatic insufficiency. More recently, treatments have been developed which improve CFTR function. The aim of this article is to summarise the evidence surrounding treatments that improve CFTR function and their implications for clinical practice.
Obstructive sleep apnoea (OSA) is a common sleep disorder that is associated with significant negative health outcomes including cardiovascular disease, daytime sleepiness, neurocognitive deficits, and increased motor vehicle and workplace accidents. There is wide variation in OSA symptoms and other downstream effects between patients highlighting the need to individualise therapy. Continuous positive airway pressure delivered by a face mask is the gold standard treatment, but adherence to this therapy is poor and improvements in outcomes are often incomplete. A range of alternative treatments are available and may suit different patients. These include behavioural treatments such as weight loss, mandibular advancement using an oral device, sleep posture modification, upper airway surgery, and upper airway muscle stimulation. Towards individualised OSA therapy, novel phenotyping approaches are being developed to identify the specific pathophysiological causes of OSA applying to individual patients. Furthermore, research is underway to help identify patients with OSA at higher risk of daytime sleepiness and adverse cardiovascular and neurocognitive consequences and predict how individuals might respond to treatment. In this article, we review the prevalence, risk factors, and main consequences of OSA; the main treatment modalities available at present; and some new methods for phenotyping patients with OSA that hold promise for a more personalised and effective approach to screening, diagnosis, and treatment.
At the end of 2015, 36.7 million people worldwide were living with human immunodeficiency virus (HIV)/AIDS with 2.1 million newly diagnosed. The development of antiretroviral therapy was a remarkable milestone that vastly transformed the manner in which HIV/AIDS patients were managed. The introduction of preexposure prophylaxis (PrEP) ushers in a new era that could again redefine the course of this global epidemic. Daily administration of oral combination tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) and TDF alone as PrEP has demonstrated efficacy in preventing new HIV cases in a number of trials. The results of these studies represent major advances in preventing HIV acquisition and provide convincing evidence that widespread use of daily oral TDF-FTC by heterosexuals, men, women, and intravenous drug users and use of vaginal TDF is safe and effective. Low adherence has been cited as reason for failures in a few studies and poses a significant challenge when implementing PrEP in the real world in highly diverse communities. Several studies investigating a variety of strategies for PrEP delivery are underway to mitigate treatment challenges. Emerging strategies include the use of alternative antiretrovirals, novel formulations, and routes of administration, as well as dosing regimens. This article reviews literature on prior studies, current concerns and challenges, and future strategies for implementing effective PrEP.
Statins are the standard of care in the treatment of hypercholesterolemia, and their use is supported by extensive evidence demonstrating their effectiveness in primary and secondary cardiovascular risk reduction. However, clinical and epidemiologic data have clearly demonstrated that patients with chronic kidney disease (CKD) are at high risk for cardiovascular disease. However, the efficacy of statins in the reduction of cardiovascular risk has not been definitively confirmed in patients with CKD and especially those with stage 5 CKD or on dialysis. This review aims to provide the current clinical and scientific data pertaining to the effects of statins on cardiovascular outcomes in patients with CKD.
Neuroblastoma is the most common extracranial tumor derived from neural crest cells in childhood, and treatment of high-risk neuroblastoma is a difficulty in oncology field. The discovery of new treatment strategies to treat pediatric patients with high-risk neuroblastoma is important. Dinutuximab (ch14.18; Unituxin), a chimeric human-mouse monoclonal antibody, is approved by Food and Drug Administration in 2015 to be used specifically in the treatment of high-risk neuroblastoma. It binds the disialoganglioside (GD2) antigen on the surface of neuroblastoma cells and induces lysis of GD2-expressed neuroblastoma cells via antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. To enhance its activity, it is used with a combination of granulocyte-macrophage colony-stimulating factor, interleukin 2, and 13-cis-retinoic acid. In this review, we discuss the use of dinutuximab in the treatment of high-risk neuroblastoma.
Background:Wound infections constitute a significant problem in surgical procedures. In cesarean sections (CS), this is particularly important as a wound infection not only results in increased morbidity but also has far-reaching implications by way of pelvic organ disease, disturbance of the bonding process between mother and baby in the puerperium, and a longer hospital stay with its inherent problems. Objective:This study was conducted with the aim to determine the incidence and risk factor associated with surgical site infection (SSI) following cesarean section. Methodology:A retrospective cross-sectional study was conducted for 400 women undergoing cesarean section procedures during an 18-month period from January 2013 to June 2014 at Hospital Pulau Pinang, Malaysia. Patients' socio-demographic, clinical data and incidence of SSI following the CS were noted using a standardized data collection form. SPSS v 21 was used for data analysis. Results:In total, 18.8% of the study participants developed SSI. Multivariate logistic regression analysis identified the following: higher body mass index (≥30 kg/m2) (odds ratio [OR]: 0.555; 95% confidence interval [CI] = 0.313-0.985, P = .044), increase in the blood loss during surgery (≥500 mL) (OR: 0.757; 95% CI = 0.423-1.354, P = .034), prolonged hospital stay (≥4 days) (OR: 0.439; 95% CI = 0.260-0.740, P = .002), spinal anesthesia (OR: 1.543; 95% CI = 1.230-1.937, P = .021), breech baby presentation (OR:2.927 95% CI = 1.020-8.400, P = .046), and intrathecal analgesia (OR:1.567; 95% CI = 1.246-1.970, P = .001) had statistically significant association with incidence of SSI. Conclusions:Surgical site infections are common among women undergoing CS at Hospital Pulau Pinang. Special attention and enhanced clinical management of patients with identified risk factors for developing SSI may decrease its incidence.
Patients with autoimmune rheumatic conditions, particularly rheumatoid arthritis, have an increased cardiovascular risk when compared with the general population. Methotrexate is a relatively old, yet effective, immunomodulatory drug for the management of autoimmune and chronic inflammatory disorders, such as rheumatoid arthritis, particularly in terms of symptom control, quality of life, and disease progression. Recent meta-analyses have also shown that methotrexate treatment is associated with a lower risk of cardiovascular events when compared with other disease-modifying antirheumatic drugs. This suggests that methotrexate might exert specific protective effects against atherosclerosis and thrombosis. This mini-review discusses the mechanisms associated with the increased cardiovascular risk in rheumatoid arthritis, the pharmacokinetics and pharmacodynamics of methotrexate, the available evidence on the in vitro and in vivo effects of methotrexate on modifiable cardiovascular risk factors, and suggestions for future research directions.
Study design: Systematic literature review. Objective: This study provided a systematic review of randomized controlled trials which assessed the therapeutic effects of stem cell treatments, surgical interventions, and nonsurgical treatments on the outcomes of patients diagnoses with intervertebral disk degeneration (IDD). Methods : A MEDLINE (2000-2017), PubMed (2000-2017), and Google scholar (1995-2000) database search was performed to identify published articles reporting on patient-reported clinical outcomes. A total of 12 articles were identified and met the inclusion criteria. Results : Literature evaluating the comparative treatment outcomes between patients who underwent surgical versus nonsurgical interventions demonstrated mixed findings in treatment efficacy. Although studies involving the manipulation of endogenous stem cells in fibrocartilage suggested that this application could be a potentially noninvasive, stem cell-based strategy to treat fibrocartilage degeneration, especially in patients with IDD. Conclusions : The reviewed literature suggested that no clinical significance exists between surgical and nonsurgical treatment for IDD. The decision to undergo surgical or conservative treatment should depend on the patient's state of health at the time of surgery, as well as any other potentially alarming factors (altered mental status, level of consciousness, comorbidities, etc) that could be exacerbated with the proposed treatment. Mesenchymal stem cells and fibrocartilage stem cells may also be an effective therapeutic option for the regeneration of a degenerated intervertebral disk. To move forward in finding an effective therapeutic treatment protocol for IDD, further research needs to be implemented that minimizes the limitation discussed in this review.
There are accumulating evidences on the role of dysregulated angiogenesis in Behçet disease. By considering that encouraging results are accumulating about the role of anti–tumor necrosis factor α (TNF-α) agents in the treatment of Behçet disease and that there are evidences of a role of anti-TNF-α agents in angiogenesis inhibition, it is conceivable that antiangiogenic effects of anti-TNF-α agents may contribute to the efficacy of these therapeutic arms in Behçet disease.
The objective of this study was to evaluate oral supplements with antioxidants in oocyte and embryonic quality in patients undergoing assisted reproductive treatments. A cohort of 120 patients was included in the study: 60 patients were included in the control group and 60 in the Seidivid group. The medication contained folic acid, myo-inositol, melatonin, and selenium (Seidivid) and was supplied for at least 2 months before the ovarian puncture. The results of the different cycles were compared, evaluating the number of follicles (9.67 vs 9.15, P = .584), the number of metaphase II (8.52 vs 8.53, P = .986), the number of embryos of A + B quality, the number of vitrified embryos (1.93 vs 2.26, P = .505), and biochemical (62.75% vs 66.00%, P = .83) and clinical pregnancy rates (52.94% vs 56.00%, P = .84). A significant fact in our study was that although the supplements with antioxidants were not statistically significant for some aspects, they were significant in terms of obtaining embryos of good quality (A + B).
