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Get Fit to Cut Your Diabetes Risk During Pregnancy

Title: Get Fit to Cut Your Diabetes Risk During Pregnancy
Category: Health News
Created: 4/27/2018 12:00:00 AM
Last Editorial Review: 4/30/2018 12:00:00 AM




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Scientists Pinpoint Dozens of Genes That Increase Risk of Depression

Title: Scientists Pinpoint Dozens of Genes That Increase Risk of Depression
Category: Health News
Created: 4/27/2018 12:00:00 AM
Last Editorial Review: 4/30/2018 12:00:00 AM




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Mid-Life Stresses May Be Tied to Late-Life Dementia Risk

Title: Mid-Life Stresses May Be Tied to Late-Life Dementia Risk
Category: Health News
Created: 4/30/2018 12:00:00 AM
Last Editorial Review: 5/1/2018 12:00:00 AM




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Caterpillar Invasion in London Puts People at Risk of Deadly Allergic Reactions

Title: Caterpillar Invasion in London Puts People at Risk of Deadly Allergic Reactions
Category: Health News
Created: 4/30/2018 12:00:00 AM
Last Editorial Review: 5/1/2018 12:00:00 AM




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Blood Type May Play Role in Death Risk After Trauma

Title: Blood Type May Play Role in Death Risk After Trauma
Category: Health News
Created: 5/2/2018 12:00:00 AM
Last Editorial Review: 5/2/2018 12:00:00 AM




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Could Time in a Sauna Lower Your Stroke Risk?

Title: Could Time in a Sauna Lower Your Stroke Risk?
Category: Health News
Created: 5/2/2018 12:00:00 AM
Last Editorial Review: 5/3/2018 12:00:00 AM




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Kids of Youngest, Oldest Moms at Risk of Developmental Issues: Study

Title: Kids of Youngest, Oldest Moms at Risk of Developmental Issues: Study
Category: Health News
Created: 5/2/2018 12:00:00 AM
Last Editorial Review: 5/3/2018 12:00:00 AM




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What Drives Millennials to Tan, Knowing the Risks?

Title: What Drives Millennials to Tan, Knowing the Risks?
Category: Health News
Created: 5/2/2018 12:00:00 AM
Last Editorial Review: 5/3/2018 12:00:00 AM




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Further Signs That Too Much Sitting Can Raise Clot Risk

Title: Further Signs That Too Much Sitting Can Raise Clot Risk
Category: Health News
Created: 5/3/2018 12:00:00 AM
Last Editorial Review: 5/4/2018 12:00:00 AM




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AHA News: Director John Singleton's Fatal Stroke Spotlights Black Americans' Hypertension Risk

Title: AHA News: Director John Singleton's Fatal Stroke Spotlights Black Americans' Hypertension Risk
Category: Health News
Created: 5/2/2019 12:00:00 AM
Last Editorial Review: 5/2/2019 12:00:00 AM




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HIV Meds Cut Transmission Risk to Zero, Even Without Condoms: Study

Title: HIV Meds Cut Transmission Risk to Zero, Even Without Condoms: Study
Category: Health News
Created: 5/2/2019 12:00:00 AM
Last Editorial Review: 5/3/2019 12:00:00 AM




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What Are the Risks of Vertebroplasty?

Title: What Are the Risks of Vertebroplasty?
Category: Procedures and Tests
Created: 4/24/2020 12:00:00 AM
Last Editorial Review: 4/24/2020 12:00:00 AM




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Could Cellphone, Microwave Radiation During Pregnancy Raise ADHD Risk?

Title: Could Cellphone, Microwave Radiation During Pregnancy Raise ADHD Risk?
Category: Health News
Created: 3/24/2020 12:00:00 AM
Last Editorial Review: 3/25/2020 12:00:00 AM




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Vaginal Bacteria Could Help Predict Risk of Premature Birth: Study

Title: Vaginal Bacteria Could Help Predict Risk of Premature Birth: Study
Category: Health News
Created: 4/8/2020 12:00:00 AM
Last Editorial Review: 4/9/2020 12:00:00 AM




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Rising Number of Older Americans at Risk of Vision Loss

Title: Rising Number of Older Americans at Risk of Vision Loss
Category: Health News
Created: 3/12/2020 12:00:00 AM
Last Editorial Review: 3/13/2020 12:00:00 AM




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AHA News: More Intense Blood Pressure Control May Lower Irregular Heartbeat Risk

Title: AHA News: More Intense Blood Pressure Control May Lower Irregular Heartbeat Risk
Category: Health News
Created: 5/4/2020 12:00:00 AM
Last Editorial Review: 5/5/2020 12:00:00 AM




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Heavy Drinking Tied to Raised Stroke Risk, Study Finds

Title: Heavy Drinking Tied to Raised Stroke Risk, Study Finds
Category: Health News
Created: 5/5/2020 12:00:00 AM
Last Editorial Review: 5/6/2020 12:00:00 AM




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AHA News: Traumatic Childhood Increases Lifelong Risk for Heart Disease, Early Death

Title: AHA News: Traumatic Childhood Increases Lifelong Risk for Heart Disease, Early Death
Category: Health News
Created: 4/28/2020 12:00:00 AM
Last Editorial Review: 4/29/2020 12:00:00 AM




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Loving Family May Lower Future Depression Risk in Kids

Title: Loving Family May Lower Future Depression Risk in Kids
Category: Health News
Created: 5/4/2020 12:00:00 AM
Last Editorial Review: 5/5/2020 12:00:00 AM




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COVID-19 Daily: Skin Manifestations, HCQ Heart Rhythm Risks

These are the coronavirus stories you need to know about today.




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Obesity Is Biggest Type 2 Diabetes Risk Factor

Title: Obesity Is Biggest Type 2 Diabetes Risk Factor
Category: Health News
Created: 4/16/2020 12:00:00 AM
Last Editorial Review: 4/17/2020 12:00:00 AM




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Heart Drug Combos Might Also Lower Your Dementia Risk: Study

Title: Heart Drug Combos Might Also Lower Your Dementia Risk: Study
Category: Health News
Created: 3/13/2020 12:00:00 AM
Last Editorial Review: 3/16/2020 12:00:00 AM




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Could Sleep Apnea Put You at Risk for Alzheimer's?

Title: Could Sleep Apnea Put You at Risk for Alzheimer's?
Category: Health News
Created: 3/25/2020 12:00:00 AM
Last Editorial Review: 3/26/2020 12:00:00 AM




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Certain Gene Might Help Shield At-Risk People From Alzheimer's

Title: Certain Gene Might Help Shield At-Risk People From Alzheimer's
Category: Health News
Created: 4/13/2020 12:00:00 AM
Last Editorial Review: 4/14/2020 12:00:00 AM




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Modern Livestock Farming Can Pose Public Health Risk

Title: Modern Livestock Farming Can Pose Public Health Risk
Category: Health News
Created: 5/7/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM




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Another HIV Hazard: Higher Risk for COPD

Title: Another HIV Hazard: Higher Risk for COPD
Category: Health News
Created: 2/20/2020 12:00:00 AM
Last Editorial Review: 2/21/2020 12:00:00 AM




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Rheumatoid Arthritis, Low Folate Levels Raise Heart Risks

Title: Rheumatoid Arthritis, Low Folate Levels Raise Heart Risks
Category: Health News
Created: 3/2/2020 12:00:00 AM
Last Editorial Review: 3/3/2020 12:00:00 AM




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Endometriosis Risk Can Be Predicted in Young Girls: Study

Title: Endometriosis Risk Can Be Predicted in Young Girls: Study
Category: Health News
Created: 3/10/2020 12:00:00 AM
Last Editorial Review: 3/10/2020 12:00:00 AM




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Sleepy Seniors Have Higher Health Risks

Title: Sleepy Seniors Have Higher Health Risks
Category: Health News
Created: 3/2/2020 12:00:00 AM
Last Editorial Review: 3/3/2020 12:00:00 AM




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Heavy Drinking Into Old Age Ups Health Risks: Study

Title: Heavy Drinking Into Old Age Ups Health Risks: Study
Category: Health News
Created: 4/7/2020 12:00:00 AM
Last Editorial Review: 4/8/2020 12:00:00 AM




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Teen Moms at High Risk for Depression, Anxiety

Title: Teen Moms at High Risk for Depression, Anxiety
Category: Health News
Created: 2/28/2020 12:00:00 AM
Last Editorial Review: 3/2/2020 12:00:00 AM




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Bacterial Blood Infections Tied to Heightened Colon Cancer Risk

Title: Bacterial Blood Infections Tied to Heightened Colon Cancer Risk
Category: Health News
Created: 4/22/2020 12:00:00 AM
Last Editorial Review: 4/23/2020 12:00:00 AM




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Untreated Sleep Apnea Puts Your Heart at High Risk

Title: Untreated Sleep Apnea Puts Your Heart at High Risk
Category: Health News
Created: 2/3/2020 12:00:00 AM
Last Editorial Review: 2/4/2020 12:00:00 AM




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Erratic Sleep Habits May Boost Risk of Heart Problems: Study

Title: Erratic Sleep Habits May Boost Risk of Heart Problems: Study
Category: Health News
Created: 3/4/2020 12:00:00 AM
Last Editorial Review: 3/5/2020 12:00:00 AM




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Knowledge, Attitudes and Practices of Dental Hygienists Regarding Diabetes Risk Assessments and Screenings

Purpose: Untreated and poorly controlled diabetes causes increased levels of blood glucose associated with poor periodontal disease outcomes. Dental hygienists can play a significant role in screening patients for diabetes mellitus, leading to referral and early diagnosis. The purpose of this study was to determine the knowledge, attitudes, practices, and barriers faced by clinical dental hygienists regarding diabetes risk assessment and screenings.Methods: A mixed method design was used with a convenience sample of dental hygienists in clinical practice (n=316). A 32 item, electronic survey was validated at item-level, and participants were recruited through multiple dental hygiene Facebook groups. Descriptive statistics were used to analyze the data. The survey also included two open-ended attitude questions that were interpreted using thematic analysis to pinpoint common patterns within the data.Results: Dental hygienists had high knowledge scores regarding diabetes and oral health, although many were unaware of their states' specific statutes and regulations for screening practices. Nearly all (95.9%), were likely to educate and refer patients (82%), although fewer than half (40.9%), were likely to perform chairside screening for diabetes. Emergent themes for barriers to screening were time, money, patient acceptance/willingness, lack of education, not having the proper tools, and states' rules and regulations.Conclusion: Despite high knowledge scores regarding diabetes and oral health, there is a gap in regards to dental hygienists' willingness to perform diabetes screenings in a clinical setting. Dental hygienists should be capable of integrating chairside diabetes screening practices into the process of care with proper training.




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Linking Human Milk Oligosaccharides, Infant Fecal Community Types, and Later Risk To Require Antibiotics

ABSTRACT

Human milk oligosaccharides (HMOs) may provide health benefits to infants partly by shaping the development of the early-life intestinal microbiota. In a randomized double-blinded controlled multicentric clinical trial, healthy term infants received either infant formula (control) or the same formula with two HMOs (2'-fucosyllactose and lacto-N-neotetraose; test) from enrollment (0 to 14 days) to 6 months. Then, all infants received the same follow-up formula without HMOs until 12 months of age. Breastfed infants (BF) served as a reference group. Stool microbiota at 3 and 12 months, analyzed by 16S rRNA gene sequencing, clustered into seven fecal community types (FCTs) with marked differences in total microbial abundances. Three of the four 12-month FCTs were likely precursors of the adult enterotypes. At 3 months, microbiota composition in the test group (n = 58) appeared closer to that of BF (n = 35) than control (n = 63) by microbiota alpha (within group) and beta (between groups) diversity analyses and distribution of FCTs. While bifidobacteriaceae dominated two FCTs, its abundance was significantly higher in one (FCT BiH for Bifidobacteriaceae at high abundance) than in the other (FCT Bi for Bifidobacteriaceae). HMO supplementation increased the number of infants with FCT BiH (predominant in BF) at the expense of FCT Bi (predominant in control). We explored the association of the FCTs with reported morbidities and medication use up to 12 months. Formula-fed infants with FCT BiH at 3 months were significantly less likely to require antibiotics during the first year than those with FCT Bi. Previously reported lower rates of infection-related medication use with HMOs may therefore be linked to gut microbiota community types. (This study has been registered at ClinicalTrials.gov under registration number NCT01715246.)

IMPORTANCE Human milk is the sole and recommended nutrition for the newborn infant and contains one of the largest constituents of diverse oligosaccharides, dubbed human milk oligosaccharides (HMOs). Preclinical and clinical association studies indicate that HMOs have multiple physiological functions largely mediated through the establishment of the gut microbiome. Until recently, HMOs were not available to investigate their role in randomized controlled intervention trials. To our knowledge, this is the first report on the effects of 2 HMOs on establishing microbiota in newborn infants. We provide a detailed description of the microbiota changes observed upon feeding a formula with 2 HMOs in comparison to breastfed reference infants' microbiota. Then, we associate the microbiota to long-term health as assessed by prescribed antibiotic use.




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Many people face high risk of PTSD after being injured, research finds

A significant number of injury survivors experience post-traumatic stress disorder, and better screening practices could help connect them to mental health services.




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Polygenic risk scores of several subtypes of epilepsies in a founder population

Objective

Polygenic risk scores (PRSs) are used to quantify the cumulative effects of a number of genetic variants, which may individually have a very small effect on susceptibility to a disease; we used PRSs to better understand the genetic contribution to common epilepsy and its subtypes.

Methods

We first replicated previous single associations using 373 unrelated patients. We then calculated PRSs in the same French Canadian patients with epilepsy divided into 7 epilepsy subtypes and population-based controls. We fitted a logistic mixed model to calculate the variance explained by the PRS using pseudo-R2 statistics.

Results

We show that the PRS explains more of the variance in idiopathic generalized epilepsy than in patients with nonacquired focal epilepsy. We also demonstrate that the variance explained is different within each epilepsy subtype.

Conclusions

Globally, we support the notion that PRSs provide a reliable measure to rightfully estimate the contribution of genetic factors to the pathophysiologic mechanism of epilepsies, but further studies are needed on PRSs before they can be used clinically.




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Risk of stroke after emergency department visits for neurologic complaints

Objective

To assess the risk of subsequent stroke among older patients discharged from an emergency department (ED) without a diagnosis of TIA or stroke.

Methods

Using electronic health record data from a large urban, university hospital and a community-based hospital, we analyzed patients aged 60–89 years discharged to home from the ED without an International Statistical Classification of Diseases and Related Health Problems, 9th or 10th Revision diagnosis of TIA or stroke. Based on the presence/absence of a head CT and the presence/absence of a chief complaint suggestive of TIA or stroke ("symptoms") during the index ED visit, we created 4 mutually exclusive groups (group 1, reference: head CT no, symptoms no; group 2: head CT no, symptoms yes; group 3: head CT yes, symptoms no; and group 4: head CT yes, symptoms yes). We calculated rates of stroke in the 30, 90, and 365 days after the index visit and used multivariable logistic regression to estimate odds ratios (ORs) for subsequent stroke.

Results

Among 35,622 patients (mean age 70 years, 59% women, and 16% African American), unadjusted rates of stroke in 365 days were as follows: group 4: 2.5%; group 3: 1.1%; group 2: 0.69%; and group 1: 0.54%. The adjusted OR for stroke was 3.30 (95% confidence interval [CI], 1.61–6.76) in group 4, 1.56 (95% CI, 1.16–2.09) in group 3, and 0.61 (95% CI, 0.22–1.67) in group 2.

Conclusions

Among patients discharged from the ED without a diagnosis of TIA or stroke, the occurrence of a head CT and/or specific neurologic symptoms established a clinically meaningful risk gradient for subsequent stroke.




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Lowering Gestational Diabetes Risk by Prenatal Weight Gain Counseling

Purpose:

Excess weight gain during pregnancy is at epidemic proportions, and pregnancy complications are also on the rise. We sought to determine whether better weight gain counseling of expectant mothers will improve obstetric outcomes.

Methods:

Our historic control study design included 2 years of preintervention data, then 6 months of physician and staff training in prenatal weight gain counseling in accordance with 2009 Institute of Medicine guidelines, and finally, 2 more years of data collection for postintervention outcomes. Seven family medicine residency clinics monitored 1571 continuity prenatal cases. Counseling recommendations were noted and the following outcomes were analyzed: gestational age, birth weight, route of delivery, and the incidences of hypertension and gestational diabetes. Multiple logistic regression was used to control for demographic variables and body mass index at enrollment.

Results:

Institute of Medicine congruent counseling increased from 10% to 63% (P < .01). Excess weight gain decreased from 46.4% to 41.5% (adjusted odds ratio [AOR] = 0.85; 95% CI, 0.63–1.16; P = .10). Gestational diabetes decreased significantly from 11.5% to 7.3% (P = .008). The difference remained statistically significant even after adjusting for prepregnancy obesity and other clinical and demographic characteristics (AOR = 0.54; 95% CI, 0.32–0.91; P = .02). Differences in gestational age, birth weight, hypertension, primary cesarean, and shoulder dystocia were not statistically significant.

Conclusions:

Improved weight gain counseling of prenatal patients by physicians did reduce the pregnancy complication of gestational diabetes. This occurred even though the trend toward less excess weight gain was not statistically significant.




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Complexities in Integrating Social Risk Assessment into Health Care Delivery




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When and How Do We Need Permission to Help Patients Address Social Risk?




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Do Patients Want Help Addressing Social Risks?

Evaluations of health care–based screening programs for social risks often report that a relatively small proportion of patients screening positive for social risk factors are interested in receiving assistance from their health care teams to address them. The relatively low number of patients who desire assistance is relevant to the growing number of initiatives in US health care settings designed to collect data on and address patients’ social risks. We highlight multiple studies that have found differences between positive risks screens and desire for assistance. We explore possible explanations for those differences—focusing on the fallibility of screening tools as well as patient preferences, priorities, and lived experiences—and the potential implications for health equity.




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Intravenous Iron Dosing and Infection Risk in Patients on Hemodialysis: A Prespecified Secondary Analysis of the PIVOTAL Trial

Background

Experimental and observational studies have raised concerns that giving intravenous (IV) iron to patients, such as individuals receiving maintenance hemodialysis, might increase the risk of infections. The Proactive IV Iron Therapy in Haemodialysis Patients (PIVOTAL) trial randomized 2141 patients undergoing maintenance hemodialysis for ESKD to a high-dose or a low-dose IV iron regimen, with a primary composite outcome of all-cause death, heart attack, stroke, or hospitalization for heart failure. Comparison of infection rates between the two groups was a prespecified secondary analysis.

Methods

Secondary end points included any infection, hospitalization for infection, and death from infection; we calculated cumulative event rates for these end points. We also interrogated the interaction between iron dose and vascular access (fistula versus catheter).

Results

We found no significant difference between the high-dose IV iron group compared with the lose-dose group in event rates for all infections (46.5% versus 45.5%, respectively, which represented incidences of 63.3 versus 69.4 per 100 patient years, respectively); rates of hospitalization for infection (29.6% versus 29.3%, respectively) also did not differ. We did find a significant association between risk of a first cardiovascular event and any infection in the previous 30 days. Compared with patients undergoing dialysis with an arteriovenous fistula, those doing so via a catheter had a higher incidence of having any infection, hospitalization for infection, or fatal infection, but IV iron dosing had no effect on these outcomes.

Conclusions

The high-dose and low-dose IV iron groups exhibited identical infection rates. Risk of a first cardiovascular event strongly associated with a recent infection.




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A Simple Clinical Tool for Stratifying Risk of Clinically Significant CKD after Nephrectomy: Development and Multinational Validation

Background

Clinically significant CKD following surgery for kidney cancer is associated with increased morbidity and mortality, but identifying patients at increased CKD risk remains difficult. Simple methods to stratify risk of clinically significant CKD after nephrectomy are needed.

Methods

To develop a tool for stratifying patients’ risk of CKD arising after surgery for kidney cancer, we tested models in a population-based cohort of 699 patients with kidney cancer in Queensland, Australia (2012–2013). We validated these models in a population-based cohort of 423 patients from Victoria, Australia, and in patient cohorts from single centers in Queensland, Scotland, and England. Eligible patients had two functioning kidneys and a preoperative eGFR ≥60 ml/min per 1.73 m2. The main outcome was incident eGFR <45 ml/min per 1.73 m2 at 12 months postnephrectomy. We used prespecified predictors—age ≥65 years old, diabetes mellitus, preoperative eGFR, and nephrectomy type (partial/radical)—to fit logistic regression models and grouped patients according to degree of risk of clinically significant CKD (negligible, low, moderate, or high risk).

Results

Absolute risks of stage 3b or higher CKD were <2%, 3% to 14%, 21% to 26%, and 46% to 69% across the four strata of negligible, low, moderate, and high risk, respectively. The negative predictive value of the negligible risk category was 98.9% for clinically significant CKD. The c statistic for this score ranged from 0.84 to 0.88 across derivation and validation cohorts.

Conclusions

Our simple scoring system can reproducibly stratify postnephrectomy CKD risk on the basis of readily available parameters. This clinical tool’s quantitative assessment of CKD risk may be weighed against other considerations when planning management of kidney tumors and help inform shared decision making between clinicians and patients.




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Risks of N95 Face Mask Use in Subjects With COPD

BACKGROUND:The N95 filtering facepiece respirator (FFR) is the most popular individual protective device to reduce exposure to particulate matter. However, concerns have been raised with regard to its use because it can increase respiratory resistance and dead space. Therefore, this study assessed the safety of N95 use in patients with COPD and air-flow limitation.METHODS:This prospective study was performed at a tertiary hospital and enrolled 97 subjects with COPD. The subjects were monitored for symptoms and physiologic variables during a 10-min rest period and 6-min walking test while wearing an N95.RESULTS:Of the 97 subjects, 7 with COPD did not wear the N95 for the entire test duration. This mask-failure group showed higher British modified Medical Research Council dyspnea scale scores and lower FEV1 percent of predicted values than did the successful mask use group. A modified Medical Research Council dyspnea scale score ≥ 3 (odds ratio 167, 95% CI 8.4 to >999.9; P = .008) or a FEV1 < 30% predicted (odds ratio 163, 95% CI 7.4 to >999.9; P = .001) was associated with a risk of failure to wear the N95. Breathing frequency, blood oxygen saturation, and exhaled carbon dioxide levels also showed significant differences before and after N95 use.CONCLUSIONS:This study demonstrated that subjects with COPD who had modified Medical Research Council dyspnea scale scores ≥ 3 or FEV1 < 30% predicted wear N95s only with care.




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Fixed Ratio Versus Lower Limit of Normal: Health Status and Risk Factors for COPD Overdiagnosis

BACKGROUND:The threshold of the lower limit of the normal range of lung function has been suggested to be more accurate than the 0.7 fixed ratio (FEV1/FVC < 0.7) for a diagnosis of COPD. We aimed to explore the health status and risk factors of patients overdiagnosed with COPD when using the lower limit of the normal range as a diagnostic reference.METHODS:Subjects with COPD diagnosed by a pulmonologist according to guidelines of the Global Initiative for Chronic Obstructive Lung Disease were recruited from October 2016 to April 2018. Overdiagnosed COPD was defined as FEV1/FVC that meets the criterion of the 0.7 fixed ratio but not the the lower limit of the normal range criterion. Spirometry and questionnaires were performed by eligible subjects.RESULTS:Of the 513 subjects included in the final analysis, 20 (3.9%) were overdiagnosed when using the lower limit of the normal range as the diagnostic reference. The subjects who were overdiagnosed were older, weighed more, had better lung function, lower modified Medical British Research Council scores, and higher St. George's Respiratory Questionnaire and 36-item Short Form Survey scores than the subjects who were correctly diagnosed. Older age, heavier weight, exposure to cooking oil fumes, or a new-built or newly renovated home were associated with an increased risk of overdiagnosis of COPD (age adjusted odds ratio (OR) 1.17, 95% CI 1.09–1.26; weight adjusted OR 1.08, 95% CI 1.03–1.13; exposure to cooking oil fumes adjusted OR 3.00, 95% CI, 1.04–8.68; exposure to new-built or newly renovated home adjusted OR 10.88, 95% CI 1.46–80.87.CONCLUSIONS:The subjects with overdiagnosed COPD had a better health status and lung function than the subjects who were correctly diagnosed. Older age, heavier weight, and exposure to cooking oil fumes or a new-built or newly renovated home were factors associated with the overdiagnosis of COPD. These findings may help reduce overdiagnosis of COPD.




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Risk of MS relapse after yellow fever vaccination: A self-controlled case series

Objective

To determine whether live-attenuated yellow fever vaccine (YFV) was associated with MS relapse, we evaluated the clinical courses of 23 patients in the year before and the year after immunization at the university hospital of Geneva, Switzerland.

Methods

This self-controlled retrospective cohort included adult patients with MS receiving YFV between 2014 and 2018 and defined the year before vaccination, the 3 months thereafter, and the 9 months following as the pre-exposure (PEP), exposure-risk (ERP), and postrisk (PRP) periods, respectively. The primary outcome was the relative incidence of relapse in the ERP vs the PEP. Secondary end points included the presence of new T2-weighted (T2) or T1-weighted gadolinium-positive (T1Gd+) MRI lesions.

Results

Of 23 patients with MS receiving YFV (20 relapsing MS and 3 primary progressive MS), 17 (74%) were women; mean age was 34 years (SD ±10); and 10 of 23 (40%) were treated with disease-modifying therapies (DMTs). Although 9 patients experienced 12 relapses in the PEP, only one experienced a relapse in the ERP; 3 other patients experienced one relapse each in the PRP. None of the 8 patients receiving natalizumab at the time of vaccination experienced relapse thereafter. In the PEP, ERP, and PRP, 18, 2, and 9 patients had new brain and/or spinal cord lesions on T2 or T1Gd + MRI, respectively.

Conclusions

In this cohort, YF vaccination was associated with neither an increase in MS relapse nor emergence of brain and/or spinal lesions. Further studies are warranted to confirm these findings.

Classification of evidence

This study provides Class IV evidence that for persons with MS, YFV may not increase relapse risk.




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Validation of an Epstein-Barr Virus Antibody Risk Stratification Signature for Nasopharyngeal Carcinoma by Use of Multiplex Serology [Virology]

Serological testing for nasopharyngeal carcinoma (NPC) has recently been reinvigorated by the implementation of novel Epstein-Barr virus (EBV)-specific IgA and IgG antibodies from a proteome array. Although proteome arrays are well suited for comprehensive antigen selection, they are not applicable for large-scale studies. We adapted a 13-marker EBV antigen signature for NPC risk identified by proteome arrays to multiplex serology to establish an assay for large-scale studies. Taiwanese NPC cases (n = 175) and matched controls (n = 175) were used for assay validation. Spearman’s correlation was calculated, and the diagnostic value of all multiplex markers was assessed independently using the area under the receiver operating characteristic curve (AUC). Two refined signatures were identified using stepwise logistic regression and internally validated with 10-fold cross validation. Array and multiplex serology showed strong correlation for each individual EBV marker, as well as for a 13-marker combined model on continuous data. Two refined signatures with either four (LF2 and BGLF2 IgG, LF2 and BMRF1 IgA) or two (LF2 and BGLF2 IgG) antibodies on dichotomous data were identified as the most parsimonious set of serological markers able to distinguish NPC cases from controls with AUCs of 0.992 (95% confidence interval [CI], 0.983 to 1.000) and 0.984 (95% CI, 0.971 to 0.997), respectively. Neither differed significantly from the 13-marker model (AUC, 0.992; 95% CI, 0.982 to 1.000). All models were internally validated. Multiplex serology successfully validated the original EBV proteome microarray data. Two refined signatures of four and two antibodies were capable of detecting NPC with 99.2% and 98.4% accuracy.




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Hepatic Transporter Alterations by Nuclear Receptor Agonist T0901317 in Sandwich-Cultured Human Hepatocytes: Proteomic Analysis and PBPK Modeling to Evaluate Drug-Drug Interaction Risk [Metabolism, Transport, and Pharmacogenomics]

In vitro approaches for predicting drug-drug interactions (DDIs) caused by alterations in transporter protein regulation are not well established. However, reports of transporter regulation via nuclear receptor (NR) modulation by drugs are increasing. This study examined alterations in transporter protein levels in sandwich-cultured human hepatocytes (SCHH; n = 3 donors) measured by liquid chromatography–tandem mass spectrometry–based proteomic analysis after treatment with N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide (T0901317), the first described synthetic liver X receptor agonist. T0901317 treatment (10 μM, 48 hours) decreased the levels of organic cation transporter (OCT) 1 (0.22-, 0.43-, and 0.71-fold of control) and organic anion transporter (OAT) 2 (0.38-, 0.38-, and 0.53-fold of control) and increased multidrug resistance protein (MDR) 1 (1.37-, 1.48-, and 1.59-fold of control). The induction of NR downstream gene expression supports the hypothesis that T0901317 off-target effects on farnesoid X receptor and pregnane X receptor activation are responsible for the unexpected changes in OCT1, OAT2, and MDR1. Uptake of the OCT1 substrate metformin in SCHH was decreased by T0901317 treatment. Effects of decreased OCT1 levels on metformin were simulated using a physiologically-based pharmacokinetic (PBPK) model. Simulations showed a clear decrease in metformin hepatic exposure resulting in a decreased pharmacodynamic effect. This DDI would not be predicted by the modest changes in simulated metformin plasma concentrations. Altogether, the current study demonstrated that an approach combining SCHH, proteomic analysis, and PBPK modeling is useful for revealing tissue concentration–based DDIs caused by unexpected regulation of hepatic transporters by NR modulators.

SIGNIFICANCE STATEMENT

This study utilized an approach combining sandwich-cultured human hepatocytes, proteomic analysis, and physiologically based pharmacokinetic modeling to evaluate alterations in pharmacokinetics (PK) and pharmacodynamics (PD) caused by transporter regulation by nuclear receptor modulators. The importance of this approach from a mechanistic and clinically relevant perspective is that it can reveal drug-drug interactions (DDIs) caused by unexpected regulation of hepatic transporters and enable prediction of altered PK and PD changes, especially for tissue concentration–based DDIs.