bluuebunny/crossref_metadata_2025 huggingface dataset:
Snip the Tip
Authors: Highton Mary , Joseph Rachel , Dyer Natasha , Haydon Danielle
Published: July 2022

Male circumcision originated as a covenant of God with Abraham in biblical times. This practice is rooted in the Jewish and Islamic religions as both claim ancestry with Abraham. Although neonatal male circumcision was mostly performed in these cultures, it became a common practice in the United States in the 1800s. As this is not medically necessary, the frequency of male circumcision is decreasing in some parts of the world, although circumcision in older men is increasing because of the health benefits reported. Although there are several techniques to perform the procedure, pain management during and after the procedure is important. The nurse must ensure that the infant is the right candidate for the procedure, support the parental decision, and monitor the infant for any complications. Research around male circumcision on the long-term effects, reduction of complications, and economic and health benefits earlier in life may be important.
Moyamoya Disease
Authors: S.D. Shani , Sudhir B. Jayanand
Published: July 2022

Moyamoya disease is a rare disease that causes progressive narrowing of the intracranial internal carotid arteries, resulting in reduced blood supply to the brain, leading to strokes. It is a major cause of childhood stroke. A 10-year-old boy presented with recurrent left-hemispheric transient ischemic attack and seizures. On evaluation, the child was diagnosed as having bilateral moyamoya disease. The child was prescribed antiplatelets and antiepileptics and advised to drink 2 liters of water a day and to avoid dehydration. He was admitted for an elective revascularization surgery. Left-side superficial temporal artery to middle cerebral artery bypass with encephaloduroarteriomyosynangiosis was done. The child was monitored in the postoperative neurosurgery intensive care unit for 1 day for any postprocedure complications. Postoperative course was uneventful, and the child was discharged on the sixth postoperative day with instruction to continue antiplatelets and antiseizure medications. The outcome of cerebral revascularization in moyamoya disease is good, with reduction in ischemic events and seizures. Postoperative nursing care in neurosurgery units is important in preventing complications and achieving better outcomes.
Management of patients with ST-segment myocardial infarction and multivessel disease: what are the options in 2022?
Authors: Ong Peter , Martínez Pereyra Valeria , Sechtem Udo , Bekeredjian Raffi
Published: July 2022

Multivessel coronary disease is a frequent finding in patients with STEMI. However, choosing the optimal treatment strategy for these patients can be challenging. The benefit of complete versus culprit-vessel-only revascularization demonstrated by several studies led to a change in the current 2018 ESC/EACTS revascularization guidelines recommending treatment of nonculprit lesions before hospital discharge. This article summarizes current data in this area, looks at remaining knowledge gaps and gives an outlook regarding ongoing trials. The latter will provide further robust evidence for the optimal management of patients with STEMI and multivessel disease.
Effect of Helicobacter pylori Infection on Macromineral and Trace Element Status—Systematic Review and Meta‐Analysis
Authors: Simões Ana M. , Araújo Daniela , Teixeira Pedro M. , Antunes Henedina
Published: July 2022

Objectives:

To explore the effect of Helicobacter pylori (Hp) infection on zinc, copper, calcium, magnesium, phosphorus, and iodine status in the pediatric population.

Methods:

A protocol was registered on PROSPERO. A literature search was conducted on Embase, PubMed MEDLINE, and Web of Science, from inception to September 2020, including all studies in English, Spanish, and Portuguese languages. Reference lists were manually searched. Primary studies describing at least one micronutrient status in Hp‐positive and Hp‐negative or control children were included. PRISMA recommendations were applied. Pooled mean differences (MDs) and 95% confidence intervals were estimated using a random‐effects model. A total of 1011 citations were screened. Six cross‐ sectional studies were included. No publications regarding phosphorus and iodine were identified.

Results:

Included studies in meta‐analyses comprised an overall age range of 4–18 years, with Hp positivity ranging between 29.5% and 72.3%. These meta‐analyses demonstrated a lack of evidence of an association between Hp‐positive and Hp‐negative or control children regarding serum zinc (vs Hp‐negative: MD −1.36 µg/dL; vs control: MD 326.22 µg/dL), copper (MD −0.83 µg/dL), and calcium (MD 0.09 mg/dL) status. Considerable heterogeneity was recognized, except for calcium analysis (I2 = 0%). Meta‐analysis for magnesium was not performed. Five studies presented a low risk of bias.

Conclusions:

The study demonstrated a lack of evidence of an effect of Hp infection on serum zinc, copper, and calcium status. Studies concerning magnesium, phosphorus, and iodine status are warranted. Furthermore, larger and well‐controlled studies are recommended.
Profiles of Symptom Suffering and Functioning in Children and Adolescents Receiving Chemotherapy
Authors: Cheng Lei , Reeve Bryce B. , Withycombe Janice S. , Jacobs Shana S. , Mack Jennifer W. , Weaver Meaghann , Mann Courtney M. , Waldron Mia K. , Maurer Scott H. , Baker Justin N. , Wang Jichuan , Hinds Pamela S.
Published: July 2022

Background

Some children and adolescents receiving chemotherapy experience few symptom-related adverse events, whereas others experience multiple adverse events. If oncology nurses could identify patients likely to have pronounced chemotherapy-related adverse events, tailored supportive care could be matched to these patients’ symptom burdens.

Objective

The aim of this study was to identify symptom profiles in children and adolescents before and after chemotherapy, and the sociodemographic and psychological factors associated with profile classification and change.

Methods

Participants ranging from 7 to 18 years (n = 436) completed 6 Patient-Reported Outcomes Measurement Information System pediatric symptom measures within 72 hours preceding (T1) and 1 to 2 weeks after (T2) chemotherapy. Profile membership and change were determined by latent profile/latent transition analyses. Associations with profiles and profile transitions were examined using multinomial logit models and logistic regression.

Results

Three symptom suffering profiles were identified at T1 and T2: high, medium, and low. The high symptom suffering profile included the fewest participants (T1, n = 70; T2, n = 55); the low symptom suffering profile included the most participants (T1, n = 200; T2, n = 207). Of the participants, 57% remained in the same profile from T1 to T2. Psychological stress was significantly associated with T1 and T2 profile classifications and profile transition; age was associated with profile classification at T1.

Conclusion

Three symptom suffering profiles existed in a sample of pediatric patients undergoing chemotherapy, indicating that children and adolescents have differing cancer treatment experiences.

Implications for Practice

Oncology nurses could screen pediatric oncology patients for their symptom suffering profile membership and subsequently prioritize care efforts for those with a high suffering profile.
Telehealth Interventions in Head and Neck Cancer Patients
Authors: Caputo Mathew P. , Rodriguez Carmen S. , Padhya Tapan A. , Mifsud Matthew J.
Published: July 2022

Background

Head and neck cancer (HNC) and its treatments often result in adverse effects that impair a patient’s quality of life. Although intensive rehabilitative strategies can be used, their applicability can be limited due to patient-specific and socioeconomic barriers. Telehealth interventions represent a possible novel approach to increase access to these services and improve posttreatment quality of life in the HNC population.

Objective

The objective of this systematic review was to identify studies investigating telemedicine-based interventions for HNC patients to determine whether there is a consensus concerning the cost-effectiveness, clinical utility, and accessibility of this model for rehabilitation.

Methods

PubMed, EMBASE, Web of Science, and CINAHL were used to identify literature without time limit for publication. A critical appraisal of individual sources was conducted by 2 reviewers. Sixteen studies met inclusion criteria.

Results

Studies related to telehealth interventions in the HNC population are limited. Salient themes included feasibility of telehealth as an intervention, effects on self-management and knowledge, impact on quality of life, physical and psychiatric symptoms, and cost.

Conclusion

Although the current literature presents promising data, indicating that telehealth interventions may be both effective and cost-efficient in the management of HNC patients, more research is needed to definitively elucidate their role in management.

Implications for Practice

Telehealth interventions are valuable for clinicians as an alternative to expand access to care across the cancer continuum, to strengthen patients’ knowledge and consequently their self-management, and to provide continuity of services as well as for remote monitoring of symptoms and response to treatment.
Associations of Health-Related Quality of Life and Sleep Disturbance With Cardiovascular Disease Risk in Postmenopausal Breast Cancer Survivors
Authors: Vasbinder Alexi , Zaslavsky Oleg , Heckbert Susan R. , Thompson Hilaire , Cheng Richard K. , Saquib Nazmus , Wallace Robert , Haque Reina , Paskett Electra D. , Reding Kerryn W.
Published: July 2022

Background

Breast cancer (BC) survivors are at an increased risk of long-term cardiovascular disease (CVD), often attributed to cancer treatment. However, cancer treatment may also negatively impact health-related quality of life (HRQoL), a risk factor of CVD in the general population.

Objective

We examined whether sleep disturbance, and physical or mental HRQoL were associated with CVD risk in BC survivors.

Methods

We conducted a longitudinal analysis in the Women’s Health Initiative of postmenopausal women given a diagnosis of invasive BC during follow-up through 2010 with no history of CVD before BC. The primary outcome was incident CVD, defined as physician-adjudicated coronary heart disease or stroke, after BC. Physical and mental HRQoL, measured by the Short-Form 36 Physical and Mental Component Summary scores, and sleep disturbance, measured by the Women’s Health Initiative Insomnia Rating Scale, were recorded post BC. Time-dependent Cox proportional hazards models were used starting at BC diagnosis until 2010 or censoring and adjusted for relevant confounders.

Results

In 2884 BC survivors, 157 developed CVD during a median follow-up of 9.5 years. After adjustment, higher Physical Component Summary scores were significantly associated with a lower risk of CVD (hazard ratio, 0.90 [95% confidence interval, 0.81-0.99]; per 5-point increment in Physical Component Summary). No associations with CVD were found for Mental Component Summary or Insomnia Rating Scale.

Conclusion

In BC survivors, poor physical HRQoL is a significant predictor of CVD.

Implications for Practice

Our findings highlight the importance for nurses to assess and promote physical HRQoL as part of a holistic approach to mitigating the risk of CVD in BC survivors.
Central sensitization in opioid use disorder: a novel application of the American College of Rheumatology Fibromyalgia Survey Criteria
Authors: Hall O. Trent , Teater Julie , Rood Kara M. , Phan K. Luan , Clauw Daniel J.
Published: July 2022

Introduction:

Central sensitization (CS) involves dysfunctional central nervous system pain modulation resulting in heightened pain perception. Central sensitization is not commonly assessed among patients with opioid use disorder (OUD), despite the fact that pain has been implicated in the development, maintenance, and relapse of OUD and chronic opioid use may produce opioid-induced hyperalgesia. Central sensitization is a plausibly important mechanism underlying the complex relationship between OUD and chronic pain. However, this premise is largely untested.

Methods:

Participants with OUD (n = 141) were recruited from an academic addiction treatment center in Columbus, Ohio. An established surrogate measure of CS, the American College of Rheumatology 2011 Fibromyalgia Survey Criteria, was administered using electronic survey. Participants also responded to questions about pain interference (Brief Pain Inventory), quality of life (RAND-36), and items regarding pain beliefs and expectations of pain and addiction treatment. Descriptive analyses, Spearman rho correlations, and Mann–Whitney U tests were performed.

Results:

Hypothesized relationships were confirmed between degree of CS, pain interference, and health-related quality of life. Degree of CS was also positively correlated with greater endorsement of pain as a reason for the onset, maintenance, and escalation of OUD; treatment delay; and OUD relapse. Participants with the American College of Rheumatology 2011 Fibromyalgia Survey Criteria ≥13 had significantly greater endorsement of pain as a reason for delaying OUD treatment, continuing and increasing opioid use, and precipitating OUD relapse.

Conclusions:

This study provides early evidence CS may underlie previously observed connections between clinically salient features of chronic pain and OUD, potentially informing future mechanistic research and precision treatment.
Change in Substance Use and the Effects of Social Distancing on Health-Related Quality of Life and Depressive Symptoms During the COVID-19 Pandemic in People Living With and Without HIV
Authors: Schaaf Reja E. A. , Verburgh Myrthe L. , Boyd Anders , Wit Ferdinand W. , Nieuwkerk Pythia T. , Schim van der Loeff Maarten F. , Reiss Peter ,   for the AGEhIV Study Group
Published: July 2022

Background:

Little is known about the impact of social distancing on health-related quality of life and depressive symptoms in older people with HIV during the COVID-19 pandemic.

Setting:

HIV-positive and HIV-negative AGEhIV Cohort Study participants.

Method:

In September-November 2020, participants completed questionnaires on social distancing, change in substance use, health-related quality of life (EQ-6D, including EQ-VAS), and depressive symptoms (PHQ-9). Associations between social distancing and (1) EQ-VAS or (2) PHQ-9 score ≥10 (clinically relevant depressive symptoms) were analyzed using fractional and binomial logistic regression, respectively.

Results:

Two hundred fourteen HIV-positive and 285 HIV-negative participants were analyzed. 77.4% found social distancing important and 66.9% reported good adherence to these measures, without significant differences between HIV-positive and HIV-negative participants. In both groups, <5% reported increased smoking or recreational drug use, but more HIV-positive (12.2%) than HIV-negative (4.9%) participants (P = 0.005) reported increased/more frequent alcohol use. Median EQ-VAS was slightly lower in HIV-positive (80 IQR = 73–90) than HIV-negative (84 IQR = 75–90) participants (P = 0.041). The prevalence of clinically relevant depressive symptoms was similar (HIV-positive, 8.4% and HIV-negative, 8.8%). Worrying about contracting COVID-19 and having ≥3 (vs no) comorbidities were associated with lower EQ-VAS and finding social distancing easy with higher EQ-VAS. Worrying about contracting COVID-19 and younger than 60 years (vs ≥65) were associated with higher odds of clinically relevant depressive symptoms. HIV status was associated with neither outcome.

Conclusions:

Initially during the COVID-19 pandemic in the Netherlands, a similar majority of HIV-positive and HIV-negative participants reported adhering to social distancing. Irrespective of HIV status, concerns about contracting COVID-19 negatively affected participants' perceived current health and increased risk of depressive symptoms.
Perception of Treatment Success and Impact on Function with Antibiotics or Appendectomy for Appendicitis
Authors: Thompson Callie M. , Voldal Emily C. , Davidson Giana H. , Sanchez Sabrina E. , Ayoung-Chee Patricia , Victory Jesse , Guiden Mary , Bizzell Bonnie , Glaser Jacob , Hults Christopher , Price Thea P. , Siparsky Nicole , Ohe Kristin , Mandell Katherine A. , DeUgarte Daniel A. , Kaji Amy H. , Uribe Lisandra , Kao Lillian S. , Mueck Krislynn M. , Farjah Farhood , Self Wesley H. , Clark Sunday , Drake F. Thurston , Fischkoff Katherine , Minko Elizaveta , Cuschieri Joseph , Faine Brett , Skeete Dionne A. , Dhanani Naila , Liang Mike K. , Krishnadasan Anusha , Talan David A. , Fannon Erin , Kessler Larry G. , Comstock Bryan A. , Heagerty Patrick J. , Monsell Sarah E. , Lawrence Sarah O. , Flum David R. , Lavallee Danielle C. ,   Writing Group for the CODA Collaborative
Published: July 2022

Objective:

To compare secondary patient reported outcomes of perceptions of treatment success and function for patients treated for appendicitis with appendectomy vs. antibiotics at 30 days.

Summary Background Data:

The Comparison of Outcomes of antibiotic Drugs and Appendectomy trial found antibiotics noninferior to appendectomy based on 30-day health status. To address questions about outcomes among participants with lower socioeconomic status, we explored the relationship of sociodemographic and clinical factors and outcomes.

Methods:

We focused on 4 patient reported outcomes at 30 days: high decisional regret, dissatisfaction with treatment, problems performing usual activities, and missing >10 days of work. The randomized (RCT) and observational cohorts were pooled for exploration of baseline factors. The RCT cohort alone was used for comparison of treatments. Logistic regression was used to assess associations.

Results:

The pooled cohort contained 2062 participants; 1552 from the RCT. Overall, regret and dissatisfaction were low whereas problems with usual activities and prolonged missed work occurred more frequently. In the RCT, those assigned to antibiotics had more regret (Odd ratios (OR) 2.97, 95% Confidence intervals (CI) 2.05–4.31) and dissatisfaction (OR 1.98, 95%CI 1.25–3.12), and reported less missed work (OR 0.39, 95%CI 0.27–0.56). Factors associated with function outcomes included sociodemographic and clinical variables for both treatment arms. Fewer factors were associated with dissatisfaction and regret.

Conclusions:

Overall, participants reported high satisfaction, low regret, and were frequently able to resume usual activities and return to work. When comparing treatments for appendicitis, no single measure defines success or failure for all people. The reported data may inform discussions regarding the most appropriate treatment for individuals.

Trial Registration:

Clinicaltrials.gov Identifier: NCT02800785.
Morbidity, Mortality, and Pathologic Outcomes of Transanal Versus Laparoscopic Total Mesorectal Excision for Rectal Cancer Short-term Outcomes From a Multicenter Randomized Controlled Trial
Authors: Liu Huashan , Zeng Ziwei , Zhang Hong , Wu Miao , Ma Dan , Wang Quan , Xie Ming , Xu Qing , Ouyang Jun , Xiao Yi , Song Yongchun , Feng Bo , Xu Qingwen , Wang Yanan , Zhang Yi , Hao Yuantao , Luo Shuangling , Zhang Xingwei , Yang Zuli , Peng Junsheng , Wu Xiaojian , Ren Donglin , Huang Meijin , Lan Ping , Tong Weidong , Ren Mingyang , Wang Jianping , Kang Liang ,   on behalf of the Chinese Transanal Endoscopic Surgery Collaborative (CTESC) Group
Published: July 2022

Objective:

To determine the morbidity, mortality, and pathologic outcomes of transanal total mesorectal resection (taTME) versus laparoscopic total mesorectal excision (laTME) among patients with rectal cancer with clinical stage I to III rectal cancer below the peritoneal reflection.

Background:

Studies with sufficient numbers of patients allowing clinical acceptance of taTME for rectal cancer are lacking. Thus, we launched a randomized clinical trial to compare the safety and efficacy of taTME versus laTME.

Methods:

A randomized, open-label, phase 3, noninferiority trial was performed at 16 different hospitals in 10 Chinese provinces. The primary endpoints were 3-year disease-free survival and 5-year overall survival. The morbidity and mortality within 30 days after surgery, and pathologic outcomes were compared based on a modified intention­to­treat principle; this analysis was preplanned.

Results:

Between April 13, 2016, and June 1, 2021, 1115 patients were randomized 1:1 to receive taTME or laTME. After exclusion of 26 cases, modified intention­to­treat set of taTME versus laTME groups included 544 versus 545 patients. There were no significant differences between taTME and laTME groups in intraoperative complications [26 (4.8%) vs 33 (6.1%); difference, −1.3%; 95% confidence interval (CI), −4.2% to 1.7%; P=0.42], postoperative morbidity [73 (13.4%) vs 66 (12.1%); difference, 1.2%; 95% CI, −2.8% to 5.2%; P=0.53), or mortality [1 (0.2%) vs 1 (0.2%)]. Successful resection occurred in 538 (98.9%) versus 538 (98.7%) patients in taTME versus laTME groups (difference, 0.2%; 95% CI, −1.9% to 2.2%; P>0.99).

Conclusions:

Experienced surgeons can safely perform taTME in selected patients with rectal cancer.
Sharp Edge Eye Syndrome: A Case Report and Survey of Self-Identified Individuals
Authors: Reynolds Merrick S. , Katz Bradley J. , Digre Kathleen B. , Brintz Ben J. , Olson Lenora M. , Warner Judith E. A.
Published: July 2022

Background:

Sharp edge eye syndrome (SEES), sometimes known as visual looming syndrome, is a condition in which the patient experiences ocular pain or discomfort when viewing or mentally picturing sharp objects and edges. Patients may present for medical care because they perceive the condition to represent an ophthalmic problem or a sign of a more serious underlying condition. An individual case report of SEES is included to aid in illustrating syndrome characteristics. Our aim is to describe the syndrome, vision-related quality of life (VRQOL), and psychosocial characteristics in patients with self-identified SEES.

Methods:

A cross-sectional web-based survey was made available on social media webpages dedicated to SEES. The study included 22 questions developed by the research team, demographic questions, and 4 standardized questionnaires [ID Migraine, the National Eye Institute's Visual Function Questionnaire (NEI-VFQ-25), General Anxiety Disorder-2 (GAD-2), and Patient Health Questionnaire (depression) Scale-2].

Results:

Seventy-seven respondents had an average age of 29 and were 57% male. 92% reported symptoms before age 18. The main site of pain or discomfort was the eyes, with onset resulting from viewing or thinking of sharp objects and edges. Symptoms lasted from seconds to hours and could be prolonged even after closing eyes or avoiding viewing the trigger. The composite and subscale scores on the NEI-VFQ-25 were low, with a mean composite score of 78 and selected subscores of general health (61), general vision (73), ocular pain (68), driving (79), mental health (61), and role difficulties (72). Anxiety was reported in 58% of participants, and depression in 57%. Migraine or headache was reported in 46% of participants. Participants reported Alice in Wonderland syndrome, visual snow, obsessive–compulsive disorder, attention deficit hyperactivity disorder, stripe-induced visual discomfort, and synesthesia.

Conclusion:

From this survey, we have the beginnings of an understanding of the characteristics of SEES, as well as VRQOL impacts. These survey responses lead us to postulate that SEES may be a distinct visual phenomenon and to propose SEES criteria. Systematic studies of this condition's clinical features and treatment responses will be additional steps toward improving patient care.
Nonconvulsive Status Epilepticus: Clinical Findings, EEG Features, and Prognosis in a Developing Country, Mexico
Authors: San-Juan Daniel , Ángeles Erick B. , González-Aragón María del Carmen F. , Torres Jacob Eli G. , Lorenzana Ángel L. , Trenado Carlos , Anschel David J.
Published: July 2022

Purpose:

There is a lack of clinical and epidemiological knowledge about nonconvulsive status epilepticus (NCSE) in developing countries including Mexico, which has the highest prevalence of epilepsy in the Americas. Our aim was to describe the clinical findings, EEG features, and outcomes of NCSE in a tertiary center in Mexico.

Methods:

We conducted a retrospective case series study (2010–2020) including patients (≥15 years old) with NCSE according to the modified Salzburg NCSE criteria 2015 with at least 6 months of follow-up. We extracted the clinical data (age, sex, history of epilepsy, antiseizure medications, clinical manifestations, triggers, and etiology), EEG patterns of NCSE, and outcome. Descriptive statistics and multinomial logistic regression were used.

Results:

One hundred thirty-four patients were analyzed; 74 (54.8%) women, the total mean age was 39.5 (15–85) years, and 71% had a history of epilepsy. Altered state of consciousness was found in 82% (including 27.7% in coma). A generalized NCSE pattern was the most common (32.1%). The NCSE etiology was mainly idiopathic (56%), and previous uncontrolled epilepsy was the trigger in 48% of patients. The clinical outcome was remission with clinical improvement in 54.5%. Multinomial logistic regression showed that the patient's age (P = 0.04), absence of comorbidities (P = 0.04), history of perinatal hypoxia (P = 0.04), absence of clinical manifestations (P = 0.01), and coma (P = 0.03) were negatively correlated with the outcome and only the absence of generalized slowing in the EEG (P = 0.001) had a significant positive effect on the prognosis.

Conclusions:

Age, history of perinatal hypoxia, coma, and focal ictal EEG pattern influence negatively the prognosis of NCSE.
Estimate of Patients With Missed Seizures Because of Delay in Conventional EEG
Authors: Fatima Safoora , Krishnamurthy Parimala Velpula , Sun Mengzhen , Kalkach Aparicio Mariel , Gjini Klevest , Struck Aaron F.
Published: July 2022

Purpose:

There is frequent delay between ordering and placement of conventional EEG. Here we estimate how many patients had seizures during this delay.

Methods:

Two hundred fifty consecutive adult patients who underwent conventional EEG monitoring at the University of Wisconsin Hospital were retrospectively chart reviewed for demographics, time of EEG order, clinical and other EEG-related information. Patients were stratified by use of anti-seizure medications before EEG and into low-risk, medium-risk, and high-risk groups based on 2HELPS2B score (0, 1, or >1). Monte Carlo simulations (500 trials) were performed to estimate seizures during delay.

Results:

The median delay from EEG order to performing EEG was 2.00 hours (range of 0.5–8.00 hours) in the total cohort. For EEGs ordered after-hours, it was 2.00 hours (range 0.5–8.00 hours), and during business hours, it was 2.00 hours (range 0.5–6.00 hours). The place of EEG, intensive care unit, emergency department, and general floor, did not show significant difference (P = 0.84). Anti-seizure medication did not affect time to first seizure in the low-risk (P = 0.37), medium-risk (P = 0.44), or high-risk (P = 0.12) groups. The estimated % of patients who had a seizure in the delay period for low-risk group (2HELPS2B = 0) was 0.8%, for the medium-risk group (2HELPS2B = 1) was 10.3%, and for the high-risk group (2HELPS2B > 1) was 17.6%, and overall risk was 7.2%.

Conclusions:

The University of Wisconsin Hospital with 24-hour in-house EEG technologists has a median delay of 2 hours from order to start of EEG, shorter than published reports from other centers. Nonetheless, seizures were likely missed in about 7.2% of patients.
Safety and Efficacy of Continuous Theta Burst “Intensive” Stimulation in Acute-Phase Bipolar Depression
Authors: Mallik Gunjan , Mishra Preeti , Garg Shobit , Dhyani Mohan , Tikka Sai Krishna , Tyagi Priya
Published: July 2022

Objectives

Repetitive transcranial magnetic stimulation efficacy in unipolar depression is known, but its efficacy in acute-phase bipolar depression is at best modest. Citing differential right dorsolateral prefrontal cortex hyperconnectivity implicated in BD, we aimed to study the effect of novel continuous theta burst stimulation (cTBS) targeting right dorsolateral prefrontal cortex in a randomized rater blinded placebo control design.

Material and Methods

Nineteen patients aged 18 to 59 years (baseline Hamilton Depression Rating Scale [HAM-D] 17 severity score >18) were randomly allocated to active cTBS (n = 11) and sham cTBS (n = 9) groups using block randomization method. They received 15 cTBS sessions (burst of 3 pulses delivered at 50 Hz, repeated every 200 ms at 5 Hz, 600 pulses per session), 3 sessions per day (total of 1800 pulses) for 5 days in a week at 80% resting motor threshold. The HAM-D, Beck Depression Inventory, Hamilton Anxiety Rating Scale, World Health Organization's abbreviated quality of life assessment, and Changes in Sexual Functioning Questionnaire were assessed at baseline, after the last session, and at 2 weeks after repetitive transcranial magnetic stimulation. Intention-to-treat analysis was conducted and missing values (2 patients) were replaced using the last observation carried forward method.

Results

On repeated measures analysis of variance, a significant within-group time effect (from pretreatment to 2 weeks after TBS) for HAM-D (F = 15.091, P < 0.001), Beck Depression Inventory (F = 22.376, P < 0.001), Hamilton Anxiety Rating Scale (F = 18.290, P < 0.001), Changes in Sexual Functioning Questionnaire (F = 9.281, P = 0.001), and World Health Organization's abbreviated quality of life assessment (F = 24.008, P < 0.001). The integrity of the blind assessed by the guess matrix was good. When significant between group*time effect was compared, none of the variables retained statistical significance. No major adverse effects were reported, and none of the patients discontinued the trial because of adverse effects.

Conclusions

Our trial concludes that although safe and well tolerated, the therapeutic efficacy of intensive intermittent TBS in acute-phase bipolar depression is inconclusive. Choice of lower total number to sessions and smaller intersession interval along with small sample size limit the study findings.
Combinatorial approaches for treating neuropsychiatric social impairment
Authors: Wei Don , Tsheringla Sherab , McPartland James C. , Allsop A. Z. A. Stephen Azariah
Published: July 2022

Social behaviour is an essential component of human life and deficits in social function are seen across multiple psychiatric conditions with high morbidity. However, there are currently no FDA-approved treatments for social dysfunction. Since social cognition and behaviour rely on multiple signalling processes acting in concert across various neural networks, treatments aimed at social function may inherently require a combinatorial approach. Here, we describe the social neurobiology of the oxytocin and endocannabinoid signalling systems as well as translational evidence for their use in treating symptoms in the social domain. We leverage this systems neurobiology to propose a network-based framework that involves pharmacology, psychotherapy, non-invasive brain stimulation and social skills training to combinatorially target trans-diagnostic social impairment. Lastly, we discuss the combined use of oxytocin and endocannabinoids within our proposed framework as an illustrative strategy to treat specific aspects of social function. Using this framework provides a roadmap for actionable treatment strategies for neuropsychiatric social impairment.

This article is part of the theme issue ‘Interplays between oxytocin and other neuromodulators in shaping complex social behaviours’.
Oxytocin and oxygen: the evolution of a solution to the ‘stress of life’
Authors: Carter C. Sue , Kingsbury Marcy A.
Published: July 2022

Oxytocin (OT) and the OT receptor occupy essential roles in our current understanding of mammalian evolution, survival, sociality and reproduction. This narrative review examines the hypothesis that many functions attributed to OT can be traced back to conditions on early Earth, including challenges associated with managing life in the presence of oxygen and other basic elements, including sulfur. OT regulates oxidative stress and inflammation especially through effects on the mitochondria. A related nonapeptide, vasopressin, as well as molecules in the hypothalamic–pituitary–adrenal axis, including the corticotropin-releasing hormone family of molecules, have a broad set of functions that interact with OT. Interactions among these molecules have roles in the causes and consequence of social behaviour and the management of threat, fear and stress. Here, we discuss emerging evidence suggesting that unique properties of the OT system allowed vertebrates, and especially mammals, to manage over-reactivity to the ‘side effects’ of oxygen, including inflammation, oxidation and free radicals, while also supporting high levels of sociality and a perception of safety.

This article is part of the theme issue ‘Interplays between oxytocin and other neuromodulators in shaping complex social behaviours’.
Oxytocin administration versus emotion training in healthy males: considerations for future research
Authors: Daughters Katie , Rees D. Aled , Hunnikin Laura , Wells Amy , Hall Jeremy , van Goozen Stephanie
Published: July 2022

Identifying emotions correctly is essential for successful social interaction. There is therefore a keen interest in designing therapeutic interventions to improve emotion recognition in individuals who struggle with social interaction. The neuropeptide oxytocin has been proposed as a potential physiological intervention due to its important role in emotion recognition and other aspects of social cognition. However, there are a number of caveats to consider with the current form of intranasal oxytocin commonly used in the literature. Psychological interventions, on the other hand, do not carry the same caveats, and there is, therefore, a need to understand how intranasal oxytocin administration compares to psychological interventions designed to target the same psychological phenomena; and whether a combined intervention approach may provide additive benefits. Here we present a pilot, proof-of-concept study in healthy volunteers comparing the effect of intranasal oxytocin against a validated emotion training programme, finding that the psychological intervention, and not intranasal oxytocin, improved emotion recognition specifically for angry expressions. We discuss the theoretical implications of the research for future clinical trials.

This article is part of the theme issue ‘Interplays between oxytocin and other neuromodulators in shaping complex social behaviours’.
Oxytocin and microglia in the development of social behaviour
Authors: Gonzalez Alicia , Hammock Elizabeth A. D.
Published: July 2022

Oxytocin is a well-established regulator of social behaviour. Microglia, the resident immune cells of the central nervous system, regulate brain development and maintenance in health and disease. Oxytocin and microglia interact: microglia appear to regulate the oxytocin system and are, in turn, regulated by oxytocin, which appears to have anti-inflammatory effects. Both microglia and oxytocin are regulated in sex-specific ways. Oxytocin and microglia may work together to promote experience-dependent circuit refinement through multiple developmental-sensitive periods contributing to individual differences in social behaviour.

This article is part of the theme issue ‘Interplays between oxytocin and other neuromodulators in shaping complex social behaviours’.
Interactions between theκopioid system, corticotropin-releasing hormone and oxytocin in partner loss
Authors: Bales Karen L. , Rogers Forrest D.
Published: July 2022

Selective adult social attachments, or ‘pair bonds’, represent central relationships for individuals in a number of social species, including humans. Loss of a pair mate has emotional consequences that may or may not diminish over time, and that often translate into impaired psychological and physical health. In this paper, we review the literature on the neuroendocrine mechanisms for the emotional consequences of partner loss, with a special focus on hypothesized interactions between oxytocin, corticotropin-releasing hormone and theκopioid system.

This article is part of the theme issue ‘Interplays between oxytocin and other neuromodulators in shaping complex social behaviours’.
PI3K/AKT signaling allows for MAPK/ERK pathway independency mediating dedifferentiation-driven treatment resistance in melanoma
Authors: Corrales Eyleen , Levit-Zerdoun Ella , Metzger Patrick , Mertes Ralf , Lehmann Ariane , Münch Julia , Lemke Steffen , Kowar Silke , Boerries Melanie
Published: July 2022

Current therapeutic management of advanced melanoma patients largely depends on their BRAF mutation status. However, the vast heterogeneity of the tumors hampers the success of therapies targeting the MAPK/ERK pathway alone. Dissecting this heterogeneity will contribute to identifying key players in the oncogenic progression to tailor more effective therapies. We performed a comprehensive molecular and phenotypic characterization of a panel of patient-derived BRAFV600E-positive melanoma cell lines. Transcriptional profiling was used to identify groups of coregulated genes whose expression relates to an increased migratory potential and a higher resistance. A decrease in sensitivity to MAPK/ERK pathway inhibition with vemurafenib or trametinib corresponded with an increasing quiescence and migratory properties of the cells. This was accompanied by the loss of transcriptional signatures of melanocytic differentiation, and the gain of stem cell features that conferred highly-resistant/mesenchymal-like cells with increased xenobiotic efflux capacity. Nevertheless, targeting of the implicated ABC transporters did not improve the response to vemurafenib, indicating that incomplete BRAF inhibition due to reduced drug uptake is not a main driver of resistance. Rather, indifference to MAPK/ERK pathway inhibition arose from the activation of compensatory signaling cascades. The PI3K/AKT pathway in particular showed a higher activity in mesenchymal-like cells, conferring a lower dependency on MAPK/ERK signaling and supporting stem-like properties that could be reverted by dual PI3K/mTOR inhibition with dactolisib. In case of MAPK/ERK independency, therapeutic focus may be shifted to the PI3K/AKT pathway to overcome late-stage resistance in melanoma tumors that have acquired a mesenchymal phenotype.
Assessing inhibitory control deficits in adult ADHD: A systematic review and meta-analysis of the stop-signal task
Authors: Senkowski Daniel , Ziegler Theresa , Singh Mervyn , Heinz Andreas , He Jason , Silk Tim , Lorenz Robert C.
Published: July 2022

Background

In recent years, there has been an increasing quest in improving our understanding of neurocognitive deficits underlying adult attention-deficit/hyperactivity disorder (ADHD). Current statistical manuals of psychiatric disorders emphasize inattention and hyperactivity-impulsivity symptoms, but empirical studies have also shown consistent alterations in inhibitory control. Thus far, there is no established neuropsychological test to assess inhibitory control deficits in adult ADHD. A common paradigm for assessing response inhibition is the stop-signal task (SST).

Methods

Following PRISMA-selection criteria, our systematic review and meta-analysis integrated the findings of 26 publications with 27 studies examining the SST in adult ADHD.

Results

The meta-analysis, which included 883 patients with adult ADHD and 916 control participants, revealed reliable inhibitory control deficits, as expressed in prolonged SST response times, with a moderate effect size g = 0.51. The deficits were not moderated by study quality, sample characteristics or clinical parameters, suggesting that they may be a phenotype in this disorder. The analyses of secondary outcome measures revealed greater SST omission errors and reduced go accuracy in patients, indicative of altered sustained attention. However, only few (N<10) studies were available for these measures.

Discussion

Our meta-analysis suggests that the SST could, in conjunction with other tests and questionnaires, become a valuable tool for the assessment of inhibitory control deficits in adult ADHD.
Modeling infections and deaths averted due to COVID-19 vaccination strategies in Ghana
Authors: Ofori Sylvia K. , Schwind Jessica S. , Sullivan Kelly L. , Chowell Gerardo , Cowling Benjamin J. , Fung Isaac Chun-Hai
Published: July 2022

This study assessed the impact of various COVID-19 vaccination strategies on health outcomes in Ghana using an age-stratified compartmental model. The population was stratified into three age groups: <25 years, 25-64 years, and 65+ years. Five vaccination optimization scenarios were explored, assuming that one million persons could be vaccinated in three versus six months. We also performed uncertainty analysis by assuming that the available doses were halved and doubled. The vaccine optimization strategies were assessed for the initial strain, followed by a sensitivity analysis for the delta variant by varying the reproduction number and vaccine efficacy. The results showed that vaccinating individuals <65 years was associated with the lowest cumulative infections when one million persons were vaccinated over three months for both the initial strain and the delta variant. On the contrary, prioritizing the elderly (65+) was associated with the lowest cumulative deaths for both strains.

One-sentence summary

An age-stratified model of COVID-19 vaccination in Ghana found vaccinating individuals <65 years was associated with the lowest cumulative infections when one million persons were vaccinated over three months while prioritizing the elderly (65+) was associated with the lowest cumulative deaths.
Murine gammaherpesvirus 68 ORF45 stimulates B2 retrotransposon and pre-tRNA activation in a manner dependent on mitogen-activated protein kinase (MAPK) signaling
Authors: Lari Azra , Glaunsinger Britt A.
Published: July 2022

RNA polymerase III (RNAPIII) transcribes a variety of noncoding RNAs, including transfer RNA (tRNA) and the B2 family of short interspersed nuclear elements (SINEs). B2 SINEs are noncoding retrotransposons that possess tRNA-like promoters and are normally silenced in healthy somatic tissue. Infection with the murine gammaherpesvirus MHV68 induces transcription of both SINEs and tRNAs, in part through the activity of the viral protein kinase encoded by ORF36. Here, we identify the conserved MHV68 tegument protein ORF45 as an additional activator of these RNAPIII loci. MHV68 ORF45 and ORF36 form a complex, resulting in an additive induction RNAPIII and increased ORF45 expression. ORF45-induced RNAPIII transcription is dependent on its activation of the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) signaling pathway, which in turn increases the abundance of the RNAPIII transcription factor Brf1. Other viral and non-viral activators of MAPK/ERK signaling also increase the levels of Brf1 protein, B2 SINE RNA and tRNA, suggesting that this is a common strategy to increase RNAPIII activity.

Importance

Gammaherpesviral infection alters the gene expression landscape of a host cell, including through induction of non-coding RNAs transcribed by RNA polymerase III (RNAPIII). Among these are a class of repetitive genes known as retrotransposons, which are normally silenced elements that can copy and spread throughout the genome, and transfer RNAs (tRNAs), which are fundamental components of protein translation machinery. How these loci are activated during infection is not well understood. Here, we identify ORF45 from the model murine gammaherpesvirus MHV68 as a novel activator of RNAPIII transcription. To do so, it engages the MAPK/ERK signaling pathway, which is a central regulator of cellular response to environmental stimuli. Activation of this pathway leads to upregulation of a key factor required for RNAPIII activity, Brf1. These findings expand our understanding of the regulation and dysregulation of RNAPIII transcription and highlight how viral co-option of key signaling pathways can impact host gene expression.
Characterizing Variability of EHR-Driven Phenotype Definitions
Authors: Brandt Pascal S. , Kho Abel , Luo Yuan , Pacheco Jennifer A. , Walunas Theresa L. , Hakonarson Hakon , Hripcsak George , Liu Cong , Shang Ning , Weng Chunhua , Walton Nephi , Carrell David S. , Crane Paul K. , Larson Eric , Chute Christopher G. , Kullo Iftikhar , Carroll Robert , Denny Josh , Ramirez Andrea , Wei Wei-Qi , Pathak Jyoti , Wiley Laura K. , Richesson Rachel , Starren Justin B. , Rasmussen Luke V.
Published: July 2022

Objective

Analyze a publicly available sample of rule-based phenotype definitions to characterize and evaluate the types of logical constructs used.

Materials & Methods

A sample of 33 phenotype definitions used in research and published to the Phenotype KnowledgeBase (PheKB), that are represented using Fast Healthcare Interoperability Resources (FHIR) and Clinical Quality Language (CQL) was analyzed using automated analysis of the computable representation of the CQL libraries.

Results

Most of the phenotype definitions include narrative descriptions and flowcharts, while few provide pseudocode or executable artifacts. Most use 4 or fewer medical terminologies. The number of codes used ranges from 5 to 6865, and value sets from 1 to 19. We found the most common expressions used were literal, data, and logical expressions. Aggregate and arithmetic expressions are the least common. Expression depth ranges from 4 to 27.

Discussion

Despite the range of conditions, we found that all of the phenotype definitions consisted of logical criteria, representing both clinical and operational logic, and tabular data, consisting of codes from standard terminologies and keywords for natural language processing. The total number and variety of expressions is low, which may be to simplify implementation, or authors may limit complexity due to data availability constraints.

Conclusion

The phenotypes analyzed show significant variation in specific logical, arithmetic and other operators, but are all composed of the same high-level components, namely tabular data and logical expressions. A standard representation for phenotype definitions should support these formats and be modular to support localization and shared logic.
The phase angle is associated with upper arm muscle circumference but not with sarcopenia in continuous ambulatory peritoneal dialysis patients
Authors: Chen Ye , Wu Jinlan , Ran Lei , Yu Dan , Chen Xi , Liu Maodong
Published: July 2022

Aims

Limited studies on phase angle (PhA) and sarcopenia in continuous ambulatory peritoneal dialysis (CAPD) patients. We want to explore the association between PhA and sarcopenia and clarify its significance and value in diagnosing sarcopenia.

Methods

We included 87 CAPD patients. We measured the PhA and body composition by bioelectrical impedance analysis. All patients had their handgrip strength(HGS) measured. Then, we divided patients into the sarcopenia (n=25) group and non-sarcopenia(n=62) group according to the sarcopenia diagnostic strategy formulated by the Asian Working Group for Sarcopenia.

Results

Univariate analysis shows PhA is positively associated with HGS, skeletal muscle mass (SMM), and Upper arm muscle circumference (AMC). After adjustments for sex, age, diabetes, BMI, extracellular water ratio(E/T), extra water (OH), serum creatinine, total kt/v, and residual kt/v, PhA remains correlated to HGS and AMC, but not to SMM. In the multivariate logistic model, PhA is not correlated to sarcopenia. The AUROC of PhA for sarcopenia is 0.76(95% CI, 0.65-0.86, P <0.01, fig 3). The optimal cut-off value is identified as ≤5.25(sensitivity 74%, specificity 76%).

Conclusion

This study illustrates that older age and higher total kt/v are risk factors for sarcopenia. PhA is positively associated with HGS and AMC but not with sarcopenia in CAPD patients. These results suggest that PhA can predict muscle mass and strength in CAPD patients, but its diagnosis value for sarcopenia needs more studies.