Post hypoxic myoclonus: A tale of two minds.

Post hypoxic myoclonus (PHM) is considered a poor prognostic sign and may influence decisions regarding withdrawal of treatment. PHM is generally categorized in literature as either acute or chronic (also commonly referred to as Lance-Adams Syndrome) based on the onset of myoclonus. However, it may be more accurate to differentiate between the various presentations of PHM based on the clinical characteristics and electroencephalogram (EEG) findings for prognostication. Here, we describe a case of a 33-year-old female who presented after a cardiopulmonary arrest. MRI of the brain and cervical spine on admission were unremarkable. Twelve hours later, she developed generalized, stimulus-sensitive myoclonus suggestive of acute PHM. Various medications were trialed, and her symptoms eventually improved on clonazepam. On day 14, she started having resting and intention myoclonus, and dysarthria, consistent with LAS. Several adjustments were again made to her regimen, and she was eventually switched from clonazepam to baclofen which improved her resting myoclonus. This case highlights that PHM can present differently and have a markedly different outcome. It is important to develop a better understanding of the various types of PHM so as to avoid premature withdrawal of care.

Triple versus dual inhaler therapy in moderate-to-severe COPD: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Treatment of chronic obstructive pulmonary disease (COPD) is evolving specially with triple inhaler therapy. OBJECTIVES: To perform a meta-analysis to ascertain the safety and efficacy of triple inhaler therapy consisting of an inhaled-glucocorticoid (ICS), long-acting muscarinic antagonist (LAMA) and long-acting beta2-agonist (LABA) when compared with dual therapy (ICS-LABA or LAMA-LABA). METHODS: We performed an electronic database search to include randomized controlled trials (RCTs) comparing between triple and dual inhalers. Pooled rate-ratio (RR) or odds-ratio (OR) for dichotomous data and weighted mean difference (MD) for continuous data were calculated with their corresponding 95% confidence interval (CI). RESULTS: Our study included 12 RCTs totaling 19,322 patients, mean age of 65 ± 8.2 years and 68.2% were male. Pooled analysis demonstrated a significant reduction in moderate-to-severe COPD exacerbations with triple therapy (RR 0.75; 95% CI 0.69-0.83; P < 0.01). Additionally, triple therapy caused significant increase in trough FEV1 (MD 0.09 L; 95% CI 0.07-0.12; P < 0.01), significant reduction in the mean St. George's Respiratory Questionnaire (SGRQ) score (MD -1.67; 95% CI -2.02- -1.31; P < 0.01), and more patients experienced ≥ 4 points reduction of SGRQ score (OR 1.27; 95% CI 1.19-1.35; P < 0.01). Triple therapy was associated with an increased risk of pneumonia when compared to LABA/LAMA (OR 1.25; 95% 1.03-1.97; P = 0.03) but there were no significant differences in other adverse events between triple and dual inhalers. CONCLUSIONS: Among patients with moderate-to-severe COPD, triple inhaler therapy was associated with a reduction of moderate-to-severe COPD exacerbations, improved lung function and improved quality of life when compared to dual inhaler therapy but with an increased pneumonia risk.

Best duration of dual antiplatelet therapy after drug-eluting stent implantation: an updated network meta-analysis of randomized controlled trials.

Background: Drug-eluting stent(DES) implantation is the main interventional treatment for coronary artery disease, and dual antiplatelet therapy(DAPT) remains the gold standard strategy to prevent ischemic events. However, the optimal duration of DAPT after DES implantation remains controversial. Therefore, we aimed to evaluate the best duration of DAPT following DES implantation. Method: We searched PubMed, Embase, Cochrane Library, and clinicaltrials.gov for all randomized clinical trials(RCTs) that compared different durations of DAPT after DES implantation. Major adverse cardiac events(MACE) and major bleeding were the primary and secondary outcomes, respectively. Results: We included 16 RCTs (n = 42,993). The mean age of included patients was 63.1 ± 10.1. The primary outcome was statistically significant for lower MACE in patients who received DAPT for 24-48 months (mo) following DES when compared with those who received 3-6 mo of DAPT (odds ratio [OR] 0.75; 95% credible interval [CI] 0.58-0.97). There was nonstatistically significant difference in MACE when comparing those who received 12 mo of DAPT to those taking either 3-6 mo of DAPT (OR 0.86; 95% CI 0.69-1.08) or 24-48 mo of DAPT (OR 0.87; 95% CI 0.72-1.05). In contrast, major bleeding was significantly lower in those who received 3-6 mo of DAPT (OR 0.32; 95% CI 0.17-0.54) and 12 mo of DAPT (OR 0.43; 95% CI 0.27-0.63) than in those who received 24-48 mo of DAPT. Conclusion: In patients who undergo DES implantation, a longer duration of DAPT is associated with lower MACE, despite the increased risk of major bleeding events. Therefore, individualizing the duration of DAPT after DES according to the patient's risk of bleeding and recurrent ischemia is recommended.

Haloperidol for the management of delirium in adult intensive care unit patients: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Delirium commonly presents as a complication in critically ill patients. Our aim is to perform a meta-analysis investigating the role of haloperidol versus placebo in management (treatment and prophylaxis), of delirium in intensive care unit (ICU). MATERIALS AND METHODS: Our study is a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing haloperidol versus placebo for treatment and/or prophylaxis of ICU-related delirium. RESULTS: Six RCTs representing 2552 patients. There was no significant difference between haloperidol and placebo-treated patients in short-term all-cause mortality (risk ratio [RR] 0.96; 95% confidence interval [CI] 0.81-1.14; P = 0.67), incidence of delirium (RR 0.93; 95% CI 0.65-1.34; P = 0.70), ICU length of stay (Mean difference [MD] 0.00 days; 95% CI -0.82-0.83; P = 0.99), or delirium/coma-free days (MD 0.09; 95% CI -0.05-0.24; P = 0.21). Haloperidol was not associated with increased risk for serious adverse events (RR 0.65; 95% CI 0.23-1.88; P = 0.43), QTc prolongation (RR 0.87; 95% CI 0.63-1.19; P = 0.38), or extrapyramidal symptoms (RR 0.84; 95% CI 0.57-1.23; P = 0.37). CONCLUSION: Among critically ill patients, haloperidol administration compared with placebo does not significantly affect short-term mortality, incidence of delirium, ICU length of stay, or delirium or coma-free days. Additionally, there was no increased risk of adverse events.

Dupilumab safety and efficacy in uncontrolled asthma: a systematic review and meta-analysis of randomized clinical trials.

Objective: We aimed to perform a meta-analysis evaluating the efficacy and safety of dupilumab in patients with uncontrolled asthma. Data source: A search of electronic databases was performed using PubMed, Cochrane library and Embase. Study selection: The literature search was conducted independently by two reviewers. Only randomized controlled trials (RCTs) that compared between placebo and dupilumab in patients with uncontrolled asthma were included in this analysis. Pooled risk ratios (RRs) and mean differences (MDs) with their corresponding 95% confidence intervals (CIs) were calculated for dichotomous and continuous data, respectively. Results: A total of four RCTs representing 2,992 patients were included. Pooled analysis showed significant reductions of the annualized rate of severe asthma exacerbation in the dupilumab group compared with placebo (RR 0.44; 95% CI 0.35-0.055; P < 0.01; I2 = 42%). In addition, the absolute forced expiratory volume at 1 s (FEV1) changes were significantly increased for the dupilumab group (MD 0.14; 95% CI: 0.12-0.17; P < 0.01; I2 = 0%). Finally, there were no significant differences between both groups in the development of any adverse event, serious adverse events, adverse events leading to death, discontinuation of medication due to adverse event or the occurrence of upper respiratory tract, influenza or bronchitis infections. However, dupilumab was associated with an increased risk of injection site reactions compared with placebo (RR 1.91; 95% CI 1.41, 2.59; P < 0.01; I2 = 24%). Conclusion: Among patients with uncontrolled asthma, the addition of dupilumab was associated with a reduced risk of severe asthma exacerbations and improvement in FEV1 without an increased risk of adverse events apart from injection site reactions with dupilumab.

Anti-atherosclerotic effect of incretin mimetics: a meta-analysis of randomized controlled trials.

Background: Diabetes is a very common cause of cardiovascular disease, and metformin remains the first-line treatment of diabetes. Many trials were conducted to prove the efficacy and safety of other antidiabetic medication as the best add-on medication. Objectives: We aimed to evaluate the atherosclerotic effect of incretin mimetics in patients with diabetes.Methods: We searched in PubMed, clinicaltrials.gov and Cochrane Library for randomized controlled trials (RCTs) comparing incretin mimetic with conventional treatment. The primary outcome was the change in carotid intima-media thickness (CIMT) at the end of the trials.Results: Five RCTs (n = 1241), the mean age of patients included in the trials is 64.3 ± 11.4. The primary outcome was statistically significant for CIMT improvement in terms of long-term follow-up analysis between the incretin mimetic group and conventional group (mean difference [MD] -0.031; 95% Confidence interval [CI] -0.049 to 0.012; P = 0.001), whereas at short-term follow-up it wasn't (MD -0.004; 95% CI -0.024 to 0.016; P = 0.7) in the overall group of study participants. Additionally, the mean change in body mass index (BMI) (MD 0.064; 95% CI -0.54 to 0.67; P = 0.8), and mean change in systolic blood pressure (MD -0.42; 95% CI -3.2 to 2.3; P = 0.8) or diastolic blood pressure (MD 0.25; 95% CI -1.18 to 1.68; P = 0.7) were not significant.Conclusion: Long-term use of incretin mimetic medication results in significant improvement of atherosclerosis, which leads to fewer vascular events, with no apparent effect on blood pressure or BMI. Further dedicated trials are required to show the superiority of adding these medications to conventional treatment versus placebo.

Balanced crystalloids versus isotonic saline in critically ill patients: systematic review and meta-analysis.

OBJECTIVES: Intravenous fluids are one of the most used medical therapy for patients, especially critically ill patients. We conducted a meta-analysis comparing between balanced crystalloids and normal saline in critically ill patients and its effect on various clinical outcomes. DESIGN: Meta-analysis and systematic review of randomized clinical trials (RCTs). METHODS AND DATA SOURCE: Electronic search was performed using PubMed, Cochrane library, and clinical trials.gov from inception through March 1, 2018, with inclusion of prospective studies that investigated one of the primary outcomes which were acute kidney injury (AKI) and in-hospital mortality while secondary outcomes were intensive care unit (ICU) mortality and new renal replacement therapy (RRT). RESULTS: Six RCTs were included. Total of 19,332 patients were included in the final analysis. There was no significant difference in in-hospital mortality (11.5% vs 12.2%; OR 0.92; 95% CI 0.85-1.01; P = 0.09; I2 = 0%), incidence of AKI (12% vs 12.7%, OR 0.92; 95% CI 0.84-1.01; P = 0.1; I2 = 0), overall ICU mortality (OR 0.9, 95% CI 0.81-1.01, P = 0.08, I2 = 0%), or need for new RRT (OR 0.92, 95% CI 0.67-1.28, P = 0.65, I2 = 38%) between balanced crystalloids and isotonic saline in critically ill patients. CONCLUSION: Balanced crystalloids and isotonic saline have no difference on various clinical outcomes including in-hospital mortality, AKI, overall ICU mortality, and new RRT. Further powerful clinical trials are required to determine the relationship between crystalloid fluid type and clinical outcomes.

Antiphospholipid Antibody Induced by Nivolumab.

Nivolumab is a monoclonal antibody against the programmed death protein 1 and is used for patients with advanced melanoma. It is associated with potentially immune-related adverse events, including disorders of the skin, GI tract, and the thyroid; these disorders were successfully treated with prednisone and infliximab. Other immunotherapeutic agents were observed to induce the formation of antiphospholipid antibody (APA) including α-interferon and interleukin-2. We present a case of APA development after the third dose of nivolumab in a 71-year-old male with advanced melanoma. The APA was detected after finding a prolonged aPTT; the lupus anticoagulant assay tested positive. The patient was treated with prednisone but, unfortunately, he expired a few days later.

Ventricular tachycardia after initiation of fingolimod.

Fingolimod, a sphingosine-1-phosphate receptor modulator, is used for the treatment of relapsing-remitting multiple sclerosis. It is well known to cause bradyarrhythmias. We present a 63-year-old woman who was admitted to the hospital with sustained monomorphic ventricular tachycardia 2 weeks after fingolimod initiation. Further evaluation showed that the patient's ventricular tachycardia was most likely secondary to her medication. Medical practitioners need to be aware of such possible life-threatening side effects while using fingolimod.

Factors associated with short recurrence-free survival in completely resected colon cancer.

Background: Several factors could affect disease recurrence in surgically resected colon cancer. While the role of certain factors such as cancer stage and grade is well established, the role of other factors (e.g., histological subtypes) is yet to be determined. Objective:Therefore, we conducted a study to evaluate the impact of several factors in recurrence-free survival (RFS) in patients who were disease free following surgical resection of the colon cancer. Design/Methods: Data were collected for patients with Stage I-III colon cancer who underwent complete surgical resection of the tumor between January 2010 and December 2015 in our institution. A total of 90 subjects met the inclusion criteria and were included in the study. The following factors were collected at the time of surgical resection of the colonic tumor: patient's age, gender, colon cancer stage, grade and histological subtype, body mass index, hemoglobin A1c, and smoking history. Results: A total of 28 patients (31%) developed recurrence and had a mean follow-up time of 19.8 months (range: 2-54.4 months). Median RFS was 54.4 months with a 5-year RFS of 49%. Advanced colonic cancer stage and mucinous histological subtype were associated with shorter RFS with an HR of 2.37, 95% CI = 1.38-4.06, and 95% CI = 1.02-5.90, respectively. Current smokers or those who quit less than 15 years earlier tended to have worse RFS with an HR of 2.47, 95% CI = 0.98-6.27. Conclusion: Advanced colon cancer stage and mucinous histological subtype are independent risk factors for cancer recurrence and shorter RFS in completely resected colonic tumor.