Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular (CV) disease. Among the well-known pathophysiologic factors, crucial roles are played by endothelial dysfunction (caused by oxidative stress and inflammation hyperglycemia-linked), increased activity of nuclear factor kB, altered macrophage polarization, and reduced synthesis of resident endothelial progenitor cells. As consequence, a potentially rapid progression of the atherosclerotic disease with a higher propensity to unstable plaque is arguable, finally leading to significantly increased cardiovascular mortality. Main managements are focused on both prevention and early diagnosis, by targeted treatment of hyperglycemia and vascular complications.
Innovative therapeutic approaches for T2DM seek to customize the antidiabetic treatment to each patient in order to optimize glucose-lowering effects, minimize hypoglycemia and adverse effects, and prevent cardiovascular events. The newer drugs (e.g., Glucagon Like Peptide-1 Receptor Agonists, GLP-1 RAs; Sodium GLucose coTransporter-2 inhibitors, SGLT2is; DiPeptidyl Peptidase-4 inhibitors, and DPP4is) impact body weight, lipid parameters, and blood pressure, as well as endothelial (dys)functions, inflammatory markers, biomarkers of both oxidative stress, and subclinical atherosclerosis. The present review summarizes the results of the main trials focused on the cardiovascular safety of these drugs from the CV standpoint.
Background: Endometrial carcinoma is the most common gynaecologic malignancy in the world and develops through preliminary stages of endometrial hyperplasia. Atypical endometrial hyperplasia suggests a significant pre-malignant state with frank progression to endometrial carcinoma, and tends to occur at a young age. Oral progestins have been used as conservative treatment in young women with atypical endometrial hyperplasia, but they are associated with poor tolerability and side effects that may limit their overall efficacy. So it has become increasingly important and necessary to find a safe and effective fertility-sparing treatment with better tolerability and fewer side effects than the options currently available. The levonorgestrel-releasing intrauterine system (LNG-IUS) has been used to provide endometrial protection in women with breast cancer who are on adjuvant tamoxifen. The antiproliferative function of levonorgestrel is thought to reduce the risk of endometrial hyperplasia. Objectives: To determine the efficacy and safety of oral and intrauterine progestogens in treating atypical endometrial hyperplasia. Search methods: In July 2018 we searched CENTRAL; MEDLINE; Embase; CINAHL, PsycINFO and the China National Knowledge Infrastructure for relevant trials. Cochrane Gynaecology and Fertility (CGF) Specialised Register and Embase were searched in November 2018. We attempted to identify trials from references in published studies. We also searched for ongoing trials in five major clinical trials registries. Selection criteria: Randomised controlled trials (RCTs) of oral and intrauterine progestogens (LNG-IUS) versus each other or placebo in women with a confirmed histological diagnosis of simple or complex endometrial hyperplasia with atypia. Data collection and analysis: Two review authors assessed trial eligibility and risk of bias and extracted the data. The primary outcomes of the review were rate of regression and adverse effects. Secondary outcomes included rate of recurrence and proportion of women undergoing hysterectomy. We have used GRADE methodology to judge the quality of the evidence. Main results: We included one RCT (153 women) comparing the LNG-IUS administering 20 micrograms (μu) levonorgestrel per day versus 10 milligrams of continuous or cyclical oral medroxyprogesterone (MPA) for treating any type of endometrial hyperplasia. Only 19 women in this study were histologically confirmed with atypical complex hyperplasia before treatment. The evidence was of low or very low quality. The included study was at low risk of bias, but the quality of the evidence was very seriously limited by imprecision and indirectness. We did not find any RCTS comparing the LNG-IUS or oral progestogens versus placebo in women with atypical endometrial hyperplasia. Among the 19 women with atypical complex hyperplasia, after six months of treatment there was insufficient evidence to determine whether there was a difference in regression rates between the LNG-IUS group and the progesterone group (odds ratio (OR) 2.76, 95% confidence interval (CI) 0.26 to 29.73; 1 RCT subgroup, 19 women, very low-quality evidence). The rate of regression was 100% in the LNG-IUS group (n = 6/6) and 77% in the progesterone group (n = 10/13). Among the total study population (N = 153), over the six months' treatment the main adverse effects were nausea and vaginal bleeding. There was no evidence of a difference between the groups in rates of nausea (OR 0.58, 95% CI 0.28 to 1.18; 1 RCT, 153 women, very low-quality evidence). Vaginal bleeding was more common in the LNG-IUS group (OR 2.89, 95% CI 1.11 to 7.52; 1 RCT, 153 women, low-quality evidence). Except for nausea and vaginal bleeding, no other adverse effects were reported. Authors' conclusions: We did not find any RCTS of women with atypical endometrial hyperplasia, and our findings derive from a subgroup of 19 women in a larger RCT. All six women who used the LNG-IUS system achieved regression of atypical hyperplasia, but there was insufficient evidence to draw any conclusions regarding the relative efficacy of LNG-IUS versus oral progesterone (MPA) in this group of women. When assessed in a population of women with any type of endometrial hyperplasia, there was no clear evidence of a difference between LNG-IUS and oral progesterone (MPA) in risk of nausea, but vaginal bleeding was more likely to occur in women using the LNG-IUS. Larger studies are necessary to assess the efficacy and safety of oral and intrauterine progestogens in treating atypical endometrial hyperplasia.
An estimated 20.4% of US adults had chronic pain in 2016.1 Opioids are often prescribed for treating chronic pain, but evidence suggests that benefits may be limited, while harms may include addiction, overdose, and death.2,3 The 2016 CDC Guideline for Prescribing Opioids for Chronic Pain (CDC Guideline) recommends non-pharmacologic and non-opioid pharmacologic therapies as the preferred therapies for chronic pain.3 Prior research has examined opioid and non-opioid pharmacologic therapies,4 little is known about how non-pharmacologic therapies are utilized for chronic pain. This study examined the prevalence of non-pharmacologic and pharmacologic (opioid and non-opioid) therapies among ambulatory care visits with a non-cancer chronic pain associated primary diagnosis.
by
Dragana Nikolic;
Rosaria Vincenza Giglio;
Ali A. Rizvi;
Angelo Maria Patti;
Giuseppe Montalto;
Francesco Maranta;
Domenico Cianflone;
Anca Pantea Stoian;
Manfredi Rizzo
Introduction: Liraglutide has several non-glycemic effects, including those on plasma lipids and lipoproteins, contributing to its cardiovascular benefit; however, the exact underlying mechanisms remain unclear. We investigated a novel anti-atherogenic effect of liraglutide in a real-world prospective study on patients with type 2 diabetes (T2DM). Methods: Sixty-two patients with T2DM (31 men, 31 women; mean age ± standard deviation 61 ± 9 years) naïve to incretin-based therapies were treated with liraglutide (1.2 mg/day) as add-on therapy to metformin (1500–3000 mg/day) for 4 months. Laboratory analyses included the assessment of lipoprotein subclass profile by gel electrophoresis (Lipoprint; Quantimetrix Corp., Redondo Beach, CA, USA). Carotid intima-media thickness (cIMT) was assessed by Doppler ultrasonography. Statistical analyses included the paired t test, Spearman correlation and multiple regression analysis. Results: The addition of liraglutide to metformin monotherapy resulted in significant reductions in fasting glycemia, hemoglobin A1c, body mass index, waist circumference, total cholesterol, triglycerides and low-density lipoprotein (LDL)-cholesterol, as well as in cIMT. There was an increase in the large LDL-1 subfraction, with a concomitant reduction in atherogenic small dense LDL-3 and LDL-4 subfractions. Correlation analysis revealed a significant association between changes in cIMT and changes in small dense LDL-3 subfraction (r = 0.501; p < 0.0001). Multivariate analysis, including all of the measured anthropometric and laboratory parameters, revealed that only changes in the small dense LDL-3 subfraction were independent predictors of changes in cIMT (p < 0.0001). Conclusion: Our findings are the first to show that the vascular benefit of liraglutide in patients with T2DM is associated with reductions in atherogenic small dense LDL. This effect is independent of glycemic control and body weight reduction and may represent one of the key mechanisms by which liraglutide is able to reduce cardiovascular events. Trial Registration: ClinicalTrials.gov: NCT01715428.
Background
Due to the COVID-19 pandemic, healthcare providers were forced to shift many services quickly from in-person to virtual, including substance use disorder (SUD) and mental health (MH) treatment services. This led to a sharp increase in telehealth services, with health systems seeing patients virtually at hundreds of times the rate as before the onset of the COVID-19 pandemic.
By analyzing qualitative data about SUD and MH care organizations’ experiences using telehealth, this study aims to elucidate emergent themes related to telehealth use by the front-line behavioral health workforce.
Methods
This study uses qualitative data from large-scale web surveys distributed to SUD and MH organizations between May and August 2020. At the end of these surveys, the following question was posed in free-response form: “Is there anything else you would like to say about use of telehealth during or after the COVID-19 pandemic?” Respondents were asked to answer on behalf of their organizations. The 391 responses to this question were analyzed for emergent themes using a conventional approach to content analysis.
Results
Three major themes emerged: COVID-specific experiences with telehealth, general experiences with telehealth, and recommendations to continue telehealth delivery. Convenience, access to new populations, and lack of commute were frequently cited advantages of telehealth, while perceived ineffectiveness of and limited access to technology were frequently cited disadvantages. Also commonly mentioned was the relaxation of reimbursement regulations. Respondents supported continuation of relaxed regulations, increased institutional support, and using a combination of telehealth and in-person care in their practices.
Conclusions
This study advanced our knowledge of how the behavioral health workforce experiences telehealth delivery. Further longitudinal research comparing treatment outcomes of those receiving in-person and virtual services will be necessary to undergird organizations’ financial support, and perhaps also legislative support, for virtual SUD and MH services.
In the span of a few weeks, promising results from three Covid-19 vaccine candidates trials were reported. In the United States (US), efforts to develop and deliver vaccines is under Operation Warp Speed (OWS). News of safe, effective Covid-19 vaccines injected a dose of optimism into a pandemic-stricken world. However, vaccinations—not vaccines—save lives [1]. The National Academy of Science, Engineering, and Medicine (NASEM) released Framework for Equitable Allocation of COVID-19 Vaccine [2]. Framework focused on initial vaccine access for healthcare workers and first responders followed by selected populations considered at greatest risk for contracting the virus or experiencing complications. The report is both thoughtful and timely but may require further details to monitor progress during the rollout of the vaccines. Here we offer suggestions to ensure success to this umprecedented public health challenge.
Background: The relationship between eosinophilic esophagitis (EoE) and achalasia is not completely understood. There have been reports of eosinophilic infiltration of all esophageal layers in patients with achalasia. However, a routine endoscopic biopsy of the muscular layer is usually not feasible. We evaluate the safety and efficacy of muscle layer biopsy during per-oral endoscopic myotomy (POEM) as well as the prevalence of eosinophilic infiltration of the esophageal mucosa and muscular layer in patients with achalasia. Patients and Methods: All enrolled patients had diagnosed achalasia and had simultaneous biopsies of the muscular layer at the middle esophagus and distal esophageal sphincter as well as the mucosal layer of the proximal and distal esophagus during POEM. All POEM procedures took place from August 2018 to December 2018 or September 2019 to November 2019. Various demographic, disease-related, and procedure-related data were collected from chart review. Eosinophilic infiltration in the biopsy specimen was examined. Key Results: Twenty consecutive patients (65% female, age range: 21–84) with a pre-procedure Eckardt score of >6 were enrolled during the study period, with the duration of their achalasia ranging from 1 to 32 years. Eighteen patients had clinical symptomatic improvement after POEM, as defined by an Eckardt score <3. Endoscopic examination did not reveal any signs of eosinophilic esophagitis. Pathologic examination of biopsies revealed eosinophilic infiltration in three of 20 patients (15%) in the distal esophageal mucosa (all <15 eosinophils/HPF) and none in the proximal esophageal mucosa. There was no eosinophilic infiltration in the distal esophageal sphincter and the middle esophageal muscle. No complication was noted due to muscle biopsy. Conclusions and Inferences: Submucosal tunneling during POEM provides a safe access for direct esophageal muscle biopsy. This is the first report of the simultaneous biopsy of the esophageal mucosa and muscle in patients with achalasia. Contrary to all previously published studies, the association of esophageal eosinophilic infiltration and achalasia was not observed in this small sample study. Based on our findings, immune or autoimmune reaction rather than direct eosinophilic infiltration in the muscle is more likely the cause of achalasia.
Patient similarity measurement is an important tool for cohort identification in clinical decision support applications. A reliable similarity metric can be used for deriving diagnostic or prognostic information about a target patient using other patients with similar trajectories of health-care events. However, the measure of similar care trajectories is challenged by the irregularity of measurements, inherent in health care. To address this challenge, we propose a novel temporal similarity measure for patients based on irregularly measured laboratory test data from the Multiparameter Intelligent Monitoring in Intensive Care database and the pediatric Intensive Care Unit (ICU) database of Children's Healthcare of Atlanta. This similarity measure, which is modified from the Smith Waterman algorithm, identifies patients that share sequentially similar laboratory results separated by time intervals of similar length. We demonstrate the predictive power of our method; that is, patients with higher similarity in their previous histories will most likely have higher similarity in their later histories. In addition, compared with other non-temporal measures, our method is stronger at predicting mortality in ICU patients diagnosed with acute kidney injury and sepsis.
Clinicians spend a substantial part of their workday reviewing and writing electronic medical notes. Here we describe how the current, widely accepted paradigm for electronic medical notes represents a poor organizational framework for both the individual clinician and the broader medical team. As described in this viewpoint, the medical chart-including notes, labs, and imaging results-can be reconceptualized as a dynamic, fully collaborative workspace organized by topic rather than time, writer, or data type. This revised framework enables a more accurate and complete assessment of the current state of the patient and easy historical review, saving clinicians substantial time on both data input and retrieval. Collectively, this approach has the potential to improve health care delivery effectiveness and efficiency.
I play this silly game on my phone called Wordscapes. It started as a way to pass time, in moments like those when you’re waiting for your plane to take off—post-airplane mode, pre-in-flight Wi-Fi. Then, it became a way to unwind and take my mind off things without mindlessly scrolling through social media. Lately, it has become a way to keep my mind engaged and awake during late nights and early mornings while nursing my newborn child.