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Prolonged epileptic discharges predict seizure recurrence in JME: Insights from prolonged ambulatory EEG

Epilepsia. 2021 Mar 18. doi: 10.1111/epi.16875. Online ahead of print.

ABSTRACT

OBJECTIVE: Markers of seizure recurrence are needed to personalize antiseizure medication (ASM) therapy. In the clinical practice, EEG features are considered to be related to the risk of seizure recurrence for genetic generalized epilepsies (GGE). However, to our knowledge, there are no studies analyzing systematically specific EEG features as indices of ASM efficacy in GGE. In this study, we aimed at identifying EEG indicators of ASM responsiveness in Juvenile Myoclonic Epilepsy (JME), which, among GGE, is characterized by specific electroclinical features.

METHODS: We compared the features of prolonged ambulatory EEG (paEEG, 22 h of recording) of JME patients experiencing seizure recurrence within a year (“cases”) after EEG recording, with those of patients with sustained seizure freedom for at least 1 year after EEG (“controls”). We included only EEG recordings of patients who had maintained the same ASM regimen (dosage and type) throughout the whole time period from the EEG recording up to the outcome events (which was seizure recurrence for the “cases”, or 1-year seizure freedom for “controls”). As predictors, we evaluated the total number, frequency, mean and maximum duration of epileptiform discharges (EDs) and spike density (i.e. total EDs duration/artifact-free EEG duration) recorded during the paEEG. The same indexes were assessed also in standard EEG (stEEG), including activation methods.

RESULTS: Both the maximum length and the mean duration of EDs recorded during paEEG significantly differed between cases and controls; when combined in a binary logistic regression model, the maximum length of EDs emerged as the only valid predictor. A cut-off of EDs duration of 2.68 seconds discriminated between cases and controls with a 100% specificity and a 93% sensitivity. The same indexes collected during stEEG lacked both specificity and sensitivity.

SIGNIFICANCE: The occurrence of prolonged EDs in EEG recording might represent an indicator of antiepileptic drug failure in JME patients.

PMID:33735449 | DOI:10.1111/epi.16875

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Presence of opioid safety initiatives, prescribing patterns for opioid and naloxone, and perceived barriers to prescribing naloxone: Cross-sectional survey results based on practice type, scope, and location

J Opioid Manag. 2021 Jan-Feb;17(1):19-38. doi: 10.5055/jom.2021.0611.

ABSTRACT

BACKGROUND AND OBJECTIVES: The opioid epidemic is a public health crisis in the United States (US) and is associated with devastating consequences, including opioid misuse and related overdose. In response to the opioid crisis, the US Department of Health and Human Services is advancing improved practices in pain management. Strategies to help mitigate opioid risks include physician safety programs, hospital- or practice-based initiatives, patient education, and harm reduction campaigns that include the use of naloxone. To date, little information is available regarding the use of these strategies among healthcare providers. A survey was conducted to identify the presence of opioid safety initiatives, prescribing patterns of opioids and naloxone, and perceived barriers to prescribing naloxone. The presence of these strategies was compared between different practice types (hospital-based/academic vs. private practice), practice scope (chronic pain vs. “other”), and practice location (in the US vs. outside the US) Regarding “outside the US,” the actual geographical distribution of those countries was not captured by respondents.

METHODS: A 13-question web-based anonymous cross-sectional survey was sent to members of the American Society of Regional Anesthesia and Pain Medicine and the Women in Pain Medicine online community via email and social media (Twitter and Facebook). Survey questions were designed to ascertain the presence of opioid safety initiatives, opioid and naloxone prescribing patterns, and perceived barriers to prescribing naloxone based on practice type (hospital-based/academic vs. private practice), scope (chronic pain vs. “other”), and location (in the US vs. outside the US).

RESULTS: Opioid safety initiatives: The presence of physician safety initiatives was found to be statistically higher among hospital-based/academic practices. No statistical difference was found for hospital- or practice-based, patient education, or harm reduction initiatives for different practice types (hospital-based/academic vs. private practice). The presence of patient education initiatives is statistically higher for chronic pain providers versus others. No statistical difference was found for physician safety, hospital- or practice-based, or harm reduction initiatives among the different practice scopes (chronic pain vs. others). The presence of opioid safety initiatives is statistically higher in the US compared with outside the US Prescribing patterns for opioids: Hospital-based/academic practices are more likely to prescribe opioids to patients suspected of the following: illicit or nonmedical drug use, recently released from prison or correctional facility, in opioid detoxification, a mandatory medication treatment program, and/or a current methadone maintenance program, and those having difficulty accessing emergency medical services. Chronic pain providers are more likely to prescribe opioids to patients taking antidepressants compared with “other” providers. Other providers are more likely to prescribe opioids to patients suspected of the following: illicit or nonmedical drug use, recently released from prison or correctional facility, in opioid detoxification, in mandatory medication treatment programs, in current methadone maintenance programs, and patients having difficulty accessing emergency medical services. There is no difference in opioid prescribing patterns based on practice location. Prescribing pattern for naloxone: Chronic pain providers and providers in the US are more likely to prescribe/recommend naloxone and are more aware of a state’s medical board guidelines on naloxone prescribing. There is no statistical difference between practice types. Most providers, regardless of practice type, scope, or location, will coprescribe naloxone at a morphine milligram equivalent per day threshold of >50. Hospital-based/academic practices are more likely to prescribe naloxone to patients with opioid prescriptions and coexisting respiratory disease. Chronic pain providers are more likely to prescribe naloxone for patients with methadone prescriptions in opioid-naïve populations, coexisting respiratory, hepatic and/or renal dysfunction, known or suspected alcohol use, coprescribed benzodiazepine or antidepressants, and those having difficulty accessing emergency medical services. Based on practice location, providers in the US are more likely to prescribe naloxone for patients with opioid prescriptions and coexisting hepatic and/or renal dysfunction, known or suspected alcohol use, coprescribed benzodiazepine or antidepressants, recently released from a correctional facility, opioid detoxification program or mandatory abstinence program, and those having difficulty accessing emergency medical services. Perceived barriers to prescribing naloxone: We found no statistical difference regarding obstacles to prescribing naloxone based on practice type. The cost of the medication and lack of interest from patients are perceived barriers encountered by chronic pain providers versus other providers who do not have enough knowledge regarding when and how to prescribe for a patient. Based on practice location, perceived barriers for providers in the US are related to medication costs and lack of interest from patients.

CONCLUSION: While some improvements have been achieved in the fight against the opioid epidemic, our survey results indicate that further knowledge is needed to determine the potential obstacles to implementing opioid safety initiatives, understanding prescribing practices for opioids and naloxone, and lowering the barriers to prescribing naloxone based on practice type, scope, and location.

PMID:33735425 | DOI:10.5055/jom.2021.0611

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Introduction of a modified analgesic ladder in the emergency depart-ment: Effect on oxycodone use for back pain

J Opioid Manag. 2021 Jan-Feb;17(1):55-61. doi: 10.5055/jom.2021.0613.

ABSTRACT

OBJECTIVE: The aim of this study was to assess the introduction of an analgesic ladder and targeted education on oxycodone use for patients presenting to the emergency department (ED).

DESIGN: A retrospective pre-post implementation study was conducted. Data were extracted for patients presenting from June to July 2016 (preintervention) and June to July 2017 (post-intervention).

SETTING: The EDs of a major metropolitan health service and an affiliated community-based hospital.

PARTICIPANTS: Patients with back pain where nonpharmacological interventions such as mobilization and physiotherapy are recommended as the mainstay of treatment.

INTERVENTIONS: A modified analgesic ladder introduced in May 2017. The ladder promoted the use of simple analgesics such as paracetamol and nonsteroidal anti-inflammatory drug (NSAIDs) prior to opioids and tramadol in preference to oxycodone in selected patients.

MAIN OUTCOME MEASURE(S): The proportion of patients prescribed oxycodone and total doses administered.

RESULTS: There were 107 patients pre and 107 post-intervention included in this study. After implementation of the analgesic ladder, 78 (72.9 percent) preintervention patients and 55 (51.4 percent) post-intervention patients received oxycodone in ED (p = 0.001). The median oxycodone doses administered in the ED was 14 mg (interquartile range: 5-20 mg) and 5 mg (interquartile range: 5-10 mg; p < 0.001), respectively. On discharge from hospital, a prescription for oxycodone was issued for 36 (33.6 percent) patients preintervention and 26 (24.3 percent) patients post-intervention (p = 0.13).

CONCLUSIONS: Among patients with back pain, implementation of a modified analgesic ladder was associated with a statistically significant but modest reduction in oxycodone prescription. Consideration of multifaceted interventions to produce major and sustained changes in opioid prescribing is required.

PMID:33735427 | DOI:10.5055/jom.2021.0613

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Extensions of the distributed lag non-linear model (DLNM) to account for cumulative mortality

Environ Sci Pollut Res Int. 2021 Mar 18. doi: 10.1007/s11356-021-13124-0. Online ahead of print.

ABSTRACT

The effects of meteorological factors on health outcomes have gained popularity due to climate change, resulting in a general rise in temperature and abnormal climatic extremes. Instead of the conventional cross-sectional analysis that focuses on the association between a predictor and the single dependent variable, the distributed lag non-linear model (DLNM) has been widely adopted to examine the effect of multiple lag environmental factors health outcome. We propose several novel strategies to model mortality with the effects of distributed lag temperature measures and the delayed effect of mortality. Several attempts are derived by various statistical concepts, such as summation, autoregressive, principal component analysis, baseline adjustment, and modeling the offset in the DLNM. Five strategies are evaluated by simulation studies based on permutation techniques. The longitudinal climate and daily mortality data in Taipei, Taiwan, from 2012 to 2016 were implemented to generate the null distribution. According to simulation results, only one strategy, named MVDLNM, could yield valid type I errors, while the other four strategies demonstrated much more inflated type I errors. With a real-life application, the MVDLNM that incorporates both the current and lag mortalities revealed a more significant association than the conventional model that only fits the current mortality. The results suggest that, in public health or environmental research, not only the exposure may post a delayed effect but also the outcome of interest could provide the lag association signals. The joint modeling of the lag exposure and the delayed outcome enhances the power to discover such a complex association structure. The new approach MVDLNM models lag outcomes within 10 days and lag exposures up to 1 month and provide valid results.

PMID:33735414 | DOI:10.1007/s11356-021-13124-0

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AAAPT: Assessment of the Acute Pain Trajectory

Pain Med. 2021 Mar 18;22(3):533-547. doi: 10.1093/pm/pnaa440.

ABSTRACT

OBJECTIVE: Define and contrast acute pain trajectories vs. the aggregate pain measurements, summarize appropriate linear and nonlinear statistical analyses for pain trajectories at the patient level, and present methods to classify individual pain trajectories. Clinical applications of acute pain trajectories are also discussed.

SETTING: In 2016, an expert panel involving the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), American Pain Society (APS), and American Academy of Pain Medicine (AAPM) established an initiative to create a pain taxonomy, named the ACTTION-APS-AAPM Pain Taxonomy (AAAPT), for the multidimensional classification of acute pain. The AAAPT panel commissioned the present report to provide further details on analysis of the individual acute pain trajectory as an important component of comprehensive pain assessment.

METHODS: Linear mixed models and nonlinear models (e.g., regression splines and polynomial models) can be applied to analyze the acute pain trajectory. Alternatively, methods for classifying individual pain trajectories (e.g., using the 50% confidence interval of the random slope approach or using latent class analyses) can be applied in the clinical context to identify different trajectories of resolving pain (e.g., rapid reduction or slow reduction) or persisting pain. Each approach has advantages and disadvantages that may guide selection. Assessment of the acute pain trajectory may guide treatment and tailoring to anticipated symptom recovery. The acute pain trajectory can also serve as a treatment outcome measure, informing further management.

CONCLUSIONS: Application of trajectory approaches to acute pain assessments enables more comprehensive measurement of acute pain, which forms the cornerstone of accurate classification and treatment of pain.

PMID:33735384 | DOI:10.1093/pm/pnaa440

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Testosterone Therapy Effects on Bone Mass and Turnover in Hypogonadal Men with Type 2 Diabetes

J Clin Endocrinol Metab. 2021 Mar 18:dgab181. doi: 10.1210/clinem/dgab181. Online ahead of print.

ABSTRACT

CONTEXT: Male hypogonadism is associated with low bone mineral density (BMD) and increased fragility fracture risk. Patients with type 2 diabetes (T2D) have relatively higher BMD, but greater fracture risk.

OBJECTIVE: Evaluate the skeletal response to testosterone therapy in hypogonadal men with T2D compared to hypogonadal men without T2D.

DESIGN, METHOD AND PARTICIPANTS: Single arm, open-label clinical (NCT01378299) trial involving 105 men (40-74 years old), with average morning testosterone<300ng/dl. Subjects were injected intramuscularly with testosterone cypionate (200mg) every 2 weeks for 18 months. Testosterone and estradiol assessed by liquid-chromatography/mass-spectroscopy; serum C-telopeptide (CTX), osteocalcin and sclerostin by ELISA; A1C by high performance liquid chromatography, areal BMD (aBMD) and body composition by dual-energy x-ray absorptiometry; tibial volumetric BMD (vBMD) and bone geometry by peripheral quantitative computed tomography.

RESULTS: Among our population of hypogonadal men, 49 had T2D and 56 were non-T2D. After 18 months of testosterone therapy, there were no differences in circulating testosterone and estradiol between the groups. Hypogonadal men with T2D had increased osteocalcin, reflecting increased osteoblast activity, compared to non-T2D men (p<0.01). T2D men increased lumbar spine aBMD (p<0.05), total area at 38% tibia (p<0.01) and periosteal and endosteal circumferences at the same site (p<0.01 for both). T2D men had reduced tibial vBMD (p<0.01), but with preserved bone mineral content (p=0.01). Changes in A1c or body composition were similar between the 2 groups.

CONCLUSIONS: Testosterone therapy results in greater improvements in the skeletal health of hypogonadal men with T2D than their non-diabetic counterparts.

PMID:33735389 | DOI:10.1210/clinem/dgab181

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Analysis of mutations in cutaneous squamous cell carcinoma reveals novel genes and mutations associated with patient-specific characteristics and metastasis: a systematic review

Arch Dermatol Res. 2021 Mar 18. doi: 10.1007/s00403-021-02213-2. Online ahead of print.

ABSTRACT

Cutaneous squamous cell carcinoma (SCC) causes approximately 1,000,000 cases and 9000 deaths each year in the United States. While individual tumor sequencing studies have discovered driver mutations in SCC, there has yet to be a review and subsequent analysis synthesizing current studies. To conduct a comprehensive synthesis and analysis of SCC sequencing studies with individual patient-level data, a comprehensive literature search was performed. Statistical analyses were performed to identify trends. Studies meeting inclusion criteria included a total of 279 patients (189 localized SCCs, 90 metastatic SCCs). Several mutations were correlated with demographic characteristics (TP53, MLL4, BRCA2, COL4A1). TP53, TERT, SPEN, MLL3, and NOTCH2 mutations were significantly more likely to be found in metastatic versus localized SCCs even after the Bonferroni correction for multiple comparisons. Silent mutations were found more in localized SCCs than metastatic SCCs, and nonsense mutations were found more in metastatic SCCs than localized SCCs (p = 0.0003 and p = 0.04, respectively). Additional mutations were identified that have not yet been explored in SCC including AHNAK2, LRP1B, TRIO, MDN1, COL4A2, SVIL, VPS13C, DST, DMD, and DYSF. Overall, novel mutations were identified and differences between mutation patterns in localized and metastatic SCCs were found. These findings may have clinical applications.

PMID:33735396 | DOI:10.1007/s00403-021-02213-2

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Mobile health technologies supporting colonoscopy preparation: A systematic review and meta-analysis of randomized controlled trials

PLoS One. 2021 Mar 18;16(3):e0248679. doi: 10.1371/journal.pone.0248679. eCollection 2021.

ABSTRACT

BACKGROUND: Mobile health (mHealth) technologies are innovative solutions for delivering instructions to patients preparing for colonoscopy.

OBJECTIVE: To systematically review the literature evaluating the effectiveness of mHealth technologies supporting colonoscopy preparation on patient and clinical outcomes.

METHODS: MEDLINE, EMBASE, CINAHL and CENTRAL were searched for randomized controlled trials (RCTs) that evaluated the effectiveness of mHealth technologies for colonoscopy preparation on patient and clinical outcomes. Two reviewers independently assessed study eligibility, extracted data, and appraised methodological quality using the Cochrane Risk-of-Bias tool. Data were pooled using random effects models and when heterogeneity, assessed using I2, was statistically significant, a qualitative synthesis of the data was performed. Publication bias was assessed using a funnel plot.

RESULTS: Ten RCTs (3,383 participants) met inclusion criteria. MHealth interventions included smartphone apps, SMS text messages, videos, camera apps, and a social media app. Outcomes were bowel cleanliness quality, user satisfaction, colonoscopy quality indicators (cecal intubation time, withdrawal time, adenoma detection rate), adherence to diet, and cancellation/no-show rates. MHealth interventions were associated with better bowel cleanliness scores on the Boston Bowel Preparation Scale [standardized mean difference (SMD) 0.57, 95%CI 0.37-0.77, I2 = 60%, p = 0.08] and the Ottawa Bowel Preparation Scale [SMD -0.39, 95%CI -0.59-0.19, I2 = 45%, p = 0.16], but they were not associated with rates of willingness to repeat the colonoscopy using the same regimen [odds ratio (OR) 1.88, 95%CI 0.85-4.15, I2 = 48%, p = 0.12] or cancellations/no-shows [OR 0.96, 95%CI 0.68-1.35, I2 = 0%]. Most studies showed that adequate bowel preparation, user satisfaction and adherence to diet were better in the intervention groups compared to the control groups, while inconsistent findings were observed for the colonoscopy quality indicators. All trials were at high risk of bias for lack of participant blinding. Visual inspection of a funnel plot revealed publication bias.

CONCLUSIONS: MHealth technologies show promise as a way to improve bowel cleanliness, but trials to date were of low methodological quality. High-quality research is required to understand the effectiveness of mHealth technologies on colonoscopy outcomes.

PMID:33735320 | DOI:10.1371/journal.pone.0248679

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Differential N-glycosylation profiling of formalin-fixed paraffin-embedded (FFPE) invasive ductal carcinoma tissues using MALDI-TOF-MS

Mol Omics. 2021 Mar 18. doi: 10.1039/d0mo00150c. Online ahead of print.

ABSTRACT

Invasive ductal carcinoma (IDC) is the most common type of breast cancer. As dynamic changes of the glycome are closely associated with complex diseases, they have become a focal point of cancer research involving predictive and prognostic markers. Formalin-fixed paraffin-embedded (FFPE) clinical specimens are representative of the tumor environment and are thus utilized in studies on cancer related research and biomarker discovery. Further studies on differential N-glycosylation profiling of IDC cancer tissues are necessary in order to understand the biological role of glycans in cancer and to evaluate their predictive ability. In this study, matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS)-based analyses were conducted for determining differential N-glycosylation patterns of IDC. Two different derivatization methods, namely, 2-aminobenzoic acid (2-AA) labeling and linkage-specific sialic acid esterification, were used for the analysis of N-glycans. Forty-seven 2-AA labeled and fifty ethyl esterified N-glycans were identified by MALDI-MS. In statistical analyses conducted for 2-AA-labeled N-glycans, the relative amounts of 32 N-glycans and prevalence of 15 N-glycan traits showed significant (p < 0.05) differences between cancer and normal tissues; and in such analyses for the ethyl-esterified N-glycans, the relative amounts of 27 N-glycans and prevalence of 17 N-glycan traits showed significant (p < 0.05) differences between them. It was found that mainly high mannose N-glycans, including H5N2, H6N2, and H7N2, and two fucosylated compositions (H3N3F1 and H5N5F1) showed strong discrimination between IDC and controls. In addition, compared with the controls, high mannose N-glycans were observed to be up-regulated in IDC whereas bisecting N-glycans were down-regulated.

PMID:33735360 | DOI:10.1039/d0mo00150c

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Association of Stage 1 Hypertension Defined by the ACC/AHA 2017 Guideline with Asymptomatic Coronary Atherosclerosis

Am J Hypertens. 2021 Mar 18:hpab051. doi: 10.1093/ajh/hpab051. Online ahead of print.

ABSTRACT

BACKGROUND: This study sought to assess the relationship between stage 1 hypertension and subclinical coronary atherosclerosis.

METHODS: A total of 4666 individuals with available coronary computed tomography angiography (CCTA) results from a health checkup were enrolled. The classification of hypertension was adapted from the American College of Cardiology/American Heart Association (ACC/AHA) 2017 guideline. The presence of coronary plaques and its characteristics, coronary artery calcium (CAC) score, and significant stenosis defined as luminal narrowing >50% were assessed.

RESULTS: The mean age was 52.6±7.3 years, and 3311 (71.0%) were men. There was a linear relationship between blood pressure (BP), both systolic BP (SBP) and diastolic BP (DBP), and the presence of coronary plaque. Patients were classified into four groups according to the BP category: normal BP (SBP<120 mm Hg and DBP <80 mm Hg; n=2395; 51.3%), elevated BP (SBP 120-129 mm Hg and DBP <80 mm Hg; n=467; 10.0%), stage 1 hypertension (SBP 130-139 mm Hg or DBP 80-89 mm Hg; n=1139; 24.4%), and stage 2 hypertension (SBP ≥140 mm Hg or DBP ≥90 mm Hg; n=665; 14.2%). Compared to the normal BP group after multivariate adjustment, the stage 1 hypertension group was significantly associated with the presence of atherosclerotic plaque (adjusted odds ratio [95% confidential interval], 1.37 [1.17-1.62]; P<0.001), especially in non-calcified and mixed plaques. The relationship between stage 1 hypertension and stenosis >50% was not statistically significant. Isolated diastolic and isolated systolic stage 1 hypertensions were significantly related to the presence of coronary plaque. The elevated BP group was not associated with any positive CCTA findings.

CONCLUSIONS: Stage 1 hypertension was independently associated with subclinical coronary atherosclerosis.

PMID:33735371 | DOI:10.1093/ajh/hpab051