bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and safety of maraviroc in neonates
Authors: Rosebush Julia C. , Best Brookie M. , Chadwick Ellen G. , Butler Kevin , Moye John , Smith Elizabeth , Bradford Sarah , Reding Christina A. , Mathiba Sisinyana R. , Hanley Sherika , Aziz Mariam , Homans James , Acosta Edward P. , Murtaugh William , Vourvahis Manoli , Mcfadyen Lynn , Hayward Katy , Mirochnick Mark , Samson Pearl 
Published: November 2020

Objective:
The aim of this study was to evaluate safety and pharmacokinetics of maraviroc administered with standard antiretroviral prophylaxis to HIV-1 exposed infants and to determine the appropriate dose of maraviroc during the first 6 weeks of life.

Design:
A phase I, multicentre, open-label study enrolling two sequential cohorts.

Methods:
IMPAACT 2007 participants enrolled by day 3 of life and were stratified by exposure to maternal efavirenz. Cohort 1 participants received two single 8 mg/kg maraviroc doses 1 week apart with pharmacokinetic sampling after each dose. Cohort 2 participants received 8 mg/kg maraviroc twice daily through 6 weeks of life with pharmacokinetic sampling at weeks 1 and 4. Maraviroc exposure target was Cavg at least 75 ng/ml. Laboratory and clinical evaluations assessed safety.

Results:
Fifteen Cohort 1 and 32 Cohort 2 HIV-exposed neonates were enrolled (median gestational age 39 weeks, 51% male). All 13 evaluable Cohort 1 infants met the pharmacokinetic target. Median exposure for the 25 evaluable Cohort 2 infants met the pharmacokinetic target but variability was high, with 17–33% of infants below target at Weeks 1 and 4. Pharmacokinetic target achievement was similar between efavirenz exposure strata. No Grade 3+ toxicities, early study or treatment discontinuations due to maraviroc occurred.

Conclusion:
Median maraviroc exposure met the Cavg target in neonates receiving 8 mg/kg twice daily, although exposures were variable. Maternal efavirenz use did not impact maraviroc exposure and no discontinuations were due to maraviroc toxicity/intolerance. No infants acquired HIV-1 infection during follow-up. Maraviroc 8 mg/kg twice daily appears well tolerated during the first 6 weeks of life.
Impact of rosuvastatin on atherosclerosis in people with HIV at moderate cardiovascular risk: a randomised, controlled trial
Authors: Trevillyan Janine M. , Dart Anthony , Paul Eldho , Cavassini Matthias , Fehr Jan , Staehelin Cornelia , Dewar Elizabeth M. , Hoy Jennifer F. , Calmy Alexandra 
Published: November 2020

Background: :
People living with HIV-1 (PLHIV) are at increased risk for cardiovascular disease.

Objective:
This study aimed to determine if PLHIV would benefit from starting statins at a lower threshold than currently recommended in the general population.

Design:
A double-blind multicentre, randomised, placebo-controlled trial was performed.

Methods:
Participants (n = 88) with well controlled HIV, at moderate cardiovascular risk (Framingham score of 10–15%), and not recommended for statins were recruited from Australia and Switzerland. They were randomized 1 : 1 to rosuvastatin (n = 44) 20 mg daily, 10 mg if co-administered with ritonavir/cobicistat-boosted antiretroviral therapy, or placebo (n = 40) for 96 weeks. Assessments including fasting blood collection and carotid--intima media thickness (CIMT) were performed at baseline, and weeks 48 and 96. The primary outcome was the change from baseline to week 96 in CIMT (clinicaltrials.gov: NCT01813357).

Results:
Participants were predominantly men [82 (97.6%); mean age 54 years (SD 6.0)]. At 96 weeks, there was no difference in the progression of CIMT between the rosuvastatin (mean 0.004 mm, SE 0.0036) and placebo (0.0062 mm, SE 0.0039) arms (P = 0.684), leading to no difference in CIMT levels between groups at week 96 [rosuvastatin arm, 0.7232 mm (SE 0.030); placebo arm 0.7785 mm (SE 0.032), P = 0.075].
Adverse events were common (n = 146) and predominantly in the rosuvastatin arm [108 (73.9%)]. Participants on rosuvastatin were more likely to cease study medication because of an adverse event [7 (15.9%) vs. 2 (5.0%), P = 0.011].

Conclusion:
In PLHIV, statins prescribed at a lower threshold than guidelines did not lead to improvements in CIMT but was associated with significant adverse events.
HIV-DNA content in pTfh cells is associated with residual viremia in elite controllers
Authors: García Marcial , Morcilla Vincent , Navarrete-Muñoz Maria Ángeles , Fisher Katie , Cabello Alfonso , López-Bernaldo Juan Carlos , De La Hera Francisco , Barros Carlos , Fernández-Guerrero Manuel , Estrada Vicente , Górgolas Miguel , Benito José Miguel , Palmer Sarah , Rallón Norma 
Published: November 2020

Objective:
The source of residual HIV viremia is highly debated and its potential relationship with the HIV reservoir has not been clarified. Herein, we analysed the cell-associated HIV-DNA content in two important cell compartments of the HIV reservoir, resting CD4+ T memory (Trm) and peripheral T follicular helper (pTfh) cells, and the association with the residual HIV viremia in individuals with spontaneous HIV replication control (elite controllers, EC group) and in individuals with antiretroviral therapy (ART)-mediated HIV replication control (cART group).

Design:
A cross-sectional study.

Methods:
Seventeen chronically HIV-infected patients with suppressed HIV replication were included. Cell-associated HIV-DNA was measured by ultrasensitive digital-droplet-PCR in purified Trm and pTfh cells. Residual HIV plasma viremia was quantified using a single-copy assay with a sensitivity of 0.3 HIV-RNA copies/ml.

Results:
A significant and positive correlation was demonstrated between HIV-DNA levels in pTfh cells and residual plasma viral load (rpVL) (rho = 0.928, P = 0.008) in HIV-positive elite controllers, but not in HIV-positive treated patients, despite the lower levels of cell-associated HIV-DNA found in elite controllers compared with cART patients in pTfh cells [176 (77–882) vs. 608 (361–860) copies/million cells, respectively; P = 0.05].

Conclusion:
This association suggests that pTfh cells could have an important contribution to persistent viremia in elite controllers. This could be the consequence of a more limited control of HIV replication in elite controllers with higher transcriptional activity of HIV in pTfh cells of elite controllers than that in cART patients.
Isolated Superficial Myxoma Above the Eyebrow
Authors: Kim Woojin , Kim Joohyun , Baek Sehyun 
Published: November 2020

Abstract
A 59-year-old man with a palpable mass above the left eyebrow that had appeared over a 1-year period presented to our clinic. He previously had been administered antiglaucoma eyedrops for pseudophakic glaucoma of the left eye and had undergone Ahmed glaucoma valve implant surgery. The palpable mass above the left eyebrow was soft, nontender, and large. On slit lamp examination, the Ahmed valve was positioned in the superotemporal quadrant of the limbal conjunctiva, and there was no other abnormal finding. Computerized tomography (CT) imaging showed a dense, soft tissue lesion in the left upper lateral periorbital area. The patient underwent tumor excision with biopsy under general anesthesia, and the histopathologic result was myxoma. To rule out Carney complex, dermatological and cardiac evaluation were performed, and the results were normal. Finally, the tumor was diagnosed as isolated myxoma. Isolated myxoma around the upper eyelid is very rare, and complete surgical excision is needed because it has a high recurrence rate.
Assessment of Smell and Taste Disorders in COVID-19: A Cross-sectional Study
Authors: Bulğurcu Suphi , Öztutgan Turgut , Baz Eyup , Yonem Ayşegül , Koç Niyazi Günsu , Erkul Evren , Çekin Engin 
Published: November 2020

Background:
It has been reported worldwide that patients with a diagnosis of COVID-19 usually suffer a loss of smell and taste. In this study, we aimed to evaluate the relationship between the severity of the disease and the loss of smell and taste. In addition, we evaluated patients’ smell and taste functions after recovery.

Methods:
Between March and May 2020, 418 patients diagnosed with COVID-19 were divided into 3 groups: home-quarantined, hospitalized, and intensive care patients. The disease, smell, and taste functions of patients were evaluated with visual analog scores before diagnosis of COVID-19, during the disease, and fourth week after recovery. The types of smell loss and types of taste flavor loss occurring during the disease were questioned.

Results:
In all 3 groups, changes in smell and taste loss during the disease were statistically detected (P = 0.001). The smell loss rates determined in groups 1 to 3 were 45%, 43.7%, and 31.2%, respectively. The taste loss rates determined in groups 1 to 3were 46.6%, 32.1%, and 31.2% respectively. The rate of patients with a total recovery of smell loss in groups 1 to 3 were 95.5%, 93.7%, and 100%, respectively (P = 0.768). The rate of patients with a total recovery of taste loss in groups 1 to 3 were 97.1%, 91.4%, and 100%, respectively (P = 0.423).

Conclusion:
COVID-19 causes significant loss of smell and taste in patients. The loss of smell and taste does not correlate with the severity of COVID-19 disease. The loss of smell and taste improves at a high rate after the disease.
Thinning of Calvarial Bone by Skull Growth in a Pediatric Patient After Skull Grinding Injury
Authors: Song Jong Keun , Kim Jae Won , Lee Jun Yong 
Published: November 2020

Abstract
Several treatment options have been suggested for the treatment of scalp defects that occur following head trauma. Growth changes should be considered, especially for children. The authors report a case of delayed cranial bone absorption after successful free latissimus dorsi flap coverage following skull grinding injury in a pediatric patient.
A 3-year-old patient was referred to the reconstructive surgery department because of a 7 × 8 cm-sized scalp defect in the temporoparietal area due to dragging and grinding injury. Debridement and free latissimus dorsi musculocutaneous flap coverage with split-thickness skin graft were performed. The operation was successful and antibiotics were administered for 4 weeks to prevent the occurrence of osteomyelitis (OM). The patient was discharged after confirming the absence of OM via magnetic resonance imaging.
Thinning of cranial bone was observed in the skull series taken one year postoperatively. The size gradually increased, but no significant changes in size occurred after 5 years of patient's age. Magnetic resonance imaging was performed used to confirm the occurrence of OM and no specific findings were observed. It is well-known fact that the cranium grows to 90% of its adult capacity by the age of 5. In this regard, we believe that the current case and the demonstrated cranial thinning is due to bone absorption associated with the growth.
In the pediatric population, injuries involving the cranial vault should be considered in the context of bone resorption due to skull growth, which may lead to cranial bone thinning. Reconstructive surgeons should closely observe the presence or absence of skull defects through long-term follow-ups.
The Anxiety and Pain of Fibromyalgia Patients during the COVID-19 Pandemic
Authors: Kharko A. Y. , Hansford K. J. , Furlong P. L. , Hall S. D. , Roser M. E. 
Published: November 2020

AbstractBackgroundEarly research on the impact of the COVID-19 pandemic found persistent related anxiety in the general population. We hypothesised that this anxiety will be associated with increased pain in chronic pain patients diagnosed with fibromyalgia (FM).MethodsTo study this, we carried out a 10-day online survey with 58 female participants, diagnosed with FM and no other pain condition. We identified which aspects of the COVID-19 pandemic evoked anxiety. We then asked participants to provide daily ratings of both anxiety and pain on 101-point visual analogue scales (VAS). Key participant characteristics were included as mediators in a mixed-effects analysis, where the primary outcome was pain VAS.ResultsWe found that participants were most often anxious about“impact on relationships”, “a family member contracting COVID-19”, and“financial hardships”, but on average rated“financial hardship”, “access to medication”, and“home loss/eviction”as evoking the strongest anxiety. Mixed-effects modelling showed that an increase in pain was significantly associated with an increase in anxiety, when taking into account individual variance and daily caffeine intake. Age and intake of some mild analgesics were also linked to stronger pain.ConclusionOur results extend the initial findings from the literature about the effects of COVID-19 pandemic on chronic pain sufferers. We found that not only is pandemic anxiety in FM patients present, but it is associated with amplified self-assessed chronic pain.SignificanceThe long-term support of fibromyalgia patients is challenging for healthcare professionals due to the nature of the condition. The new normal introduced by the pandemic particularly hinders pain management, which is the leading request from this patient group. Our study demonstrates that mental health decline during the COVID-19 pandemic is directly related to the worsening of pain in fibromyalgia. Core stressors that evoke the strongest anxiety were identified thus providing guidance for where to focus patient support.
County Demographics and COVID-19 Death Rates: Comparison of relationship in the first and current stage of the pandemic in the United States of America
Authors: Urbine Emma , James Madison T , Shah Vishal 
Published: November 2020

AbstractPrevious studies have discovered disparity in death rates associated with SARS-CoV-2 infection in the United States during the initial stages of the pandemic. Specifically, the death rates were higher in the population in poverty and communities of color across the United States. In the current study, we perform the secondary analysis of death rates due to COVID-19 data, obtained from the Center for Disease Control and Prevention (CDC). Results indicate that in the first phase of the pandemic (February 1 to August 1, 2020), counties with higher percentage of White, Native Hawaiian and other Pacific Islanders, and two or more races populations were found to have lower per-capita COVID-19 death rate. Whereas counties with population having higher percentage of females, Black or African American people, and persons in poverty had higher death rates. Analysis of the death rates from August 1 to September 10, 2020, indicate that disparity continues with counties having higher population of Black or African American people and female having higher death rates. Poverty is not a significant variable in determining the death rates due to COVID-19. Based on the current data and lack of detailed molecular mechanism of the disease, we suggest that more resources must be diverted to counties with higher percentages of Black or African American and female populations.
Psychological distress among people with probable COVID-19 infection: analysis of the UK Household Longitudinal Study
Authors: Niedzwiedz Claire L , Benzeval Michaela , Hainey Kirsten , Leyland Alastair H , Katikireddi Srinivasa Vittal 
Published: November 2020

SummaryStudies exploring the longer-term effects of experiencing COVID-19 infection on mental health are lacking. We explored the relationship between reporting probable COVID-19 symptoms in April 2020 and psychological distress (measured using the General Health Questionnaire) one, two, three, five and seven months later. Data were taken from the UK Household Longitudinal Study, a nationally representative household panel survey of UK adults. Elevated levels of psychological distress were found up to seven months after probable COVID-19, compared to participants with no likely infection. Associations were stronger among younger age groups and men. Further research into the psychological sequalae of COVID-19 is urgently needed.
Dental practice in Pre- COVID19 and Future Perspectives
Authors: Subramanya Ashwin Parakkaje , Prabhuji MLV 
Published: November 2020

AbstractObjectivesTo assess the trends in dental practice in pre-COVID19 times and future perspectives.MethodsThe cross-sectional study was conducted among the dental professionals across India. The snowball and convenience sampling methods were used to ensure maximum participation of the subjects. An online structured questionnaire was created using free-access Google Forms application and was sent to the dental professionals via E-mail, WhatsApp mobile application and through other social media platforms. Initially, a pilot study was conducted among 30 dentists to check for the validity. The questionnaire was administered between the months of May 2020 – July 2020 and was sent to 650 dentists from various parts of the country. Data were compiled and subjected to statistical analysis.ResultsThe questionnaire was sent to 650 dental professionals. Out of 650, 120 (18.4%) participants took part in the survey. Majority of the respondents had 1 to 3 years of experience in dental practice (n=51, 42.5%). It was noted that majority of the participants were into consultation practice (n=69, 57.5%). 65.8% participants reported that they can withstand upto 6 months from economic view point. Difficulty in paying salaries, reduced incomes is some of the main problems encountered by dental professionals. Increasing the price of treatment, reducing co-workers are a few strategies planned by dental professionals to mitigate the economic burden caused by COVID19 pandemic.ConclusionMajority of dental professionals in India are dependent on private practice and consultation practice. Due to COVID19, source of income has disrupted for majority of the younger dental professionals.
A Quality Improvement Initiative: Improving Time-to-Antibiotics for Pediatric Oncology Patients with Fever and Suspected Neutropenia
Authors: Kram David E , Salafian Kia , Reel Sarah M , Johnson Emily Nance , Borsheim Brianna , Russell Thomas B , Pearsall Will A , Mitchell Michael , McCalla Chad 
Published: November 2020

ABSTRACTBackgroundThere is a high risk for adverse outcomes in immunocompromised, neutropenic pediatric oncology patients with fever if antibiotics are not received in a timely manner. As the absolute neutrophil count is typically unknown at the onset of fever, rapid antibiotic administration for all pediatric oncology patients with fever and suspected neutropenia is critical.Local ProblemDespite efforts over the years to meet the standard of time-to-antibiotic delivery to within 60 minutes of arrival, audits revealed a prolonged and wide-ranging time-to-antibiotics in our pediatric emergency department.MethodsWe conducted a quality improvement initiative to reduce the time to antibiotic delivery for this high risk patient population. The setting was a pediatric emergency department in an academic tertiary care hospital. We assembled a multidisciplinary team to apply quality improvement methods to understand the problem, implement interventions, and evaluate the outcomes.InterventionsWe targeted delays in patient triage, delays in antibiotic ordering, delays in antibiotic choice, and delays in bedside indwelling Port-a-Cath accessing procedure. Among other interventions, we instituted three unique measures: ceftriaxone was administered to all pediatric oncology patients with suspected neutropenia and fever; a system of ordering antibiotics that was driven by the ED pharmacist obtaining a verbal order from the ED attending; and a nurse-driven order set triggered by a unique triage category which empowered nurses to access a patient’s central line, draw and send specified blood work, and deliver an intravenous antibiotic, all potentially before an ED provider sees the patient.ResultsOver a sustained 3 year period of time, the percentage of febrile oncology patients with suspected neutropenia who met the target time-to-antibiotic delivery rose from 51% to 96%. The mean time-to-antibiotic delivery fell from 58 minutes in the pre-intervention period to 28 minutes in the post-intervention period.ConclusionsThe interventions implemented by the multidisciplinary team, using quality improvement methodology, successfully improved the percentage of febrile oncology patients receiving antibiotics within 60 minutes of arrival to a pediatric emergency department.
Heritability enrichment implicates microglia in Parkinson’s disease pathogenesis
Authors: Andersen Maren Stolp , Bandres-Ciga Sara , Reynolds Regina H. , Hardy John , Ryten Mina , Krohn Lynne , Gan-Or Ziv , Holtman Inge R. ,   International Parkinson’s Disease Genomics Consortium, Pihlstrøm Lasse 
Published: November 2020

AbstractObjectiveUnderstanding how different parts of the immune system contribute to pathogenesis in Parkinson’s disease is a burning challenge with important therapeutic implications. We studied enrichment of common variant heritability for Parkinson’s disease stratified by immune and brain cell types.MethodsWe used summary statistics from the most recent meta-analysis of genome-wide association studies in Parkinson’s disease and partitioned heritability using linkage disequilibrium score regression, stratified for specific cell types as defined by open chromatin regions. We also validated enrichment results using a polygenic risk score approach and intersected disease-associated variants with epigenetic data and expression quantitative loci to nominate and explore a putative microglial locus.ResultsWe found significant enrichment of Parkinson’s disease risk heritability in open chromatin regions of microglia and monocytes. Genomic annotations overlapped substantially between these two cell types, and only the enrichment signal for microglia remained significant in a joint model. We present evidence suggestingP2RY12, a key microglial gene and target for the anti-thrombotic agent clopidogrel, as the likely driver of a significant Parkinson’s disease association signal on chromosome 3.InterpretationOur results provide further support for the importance of immune mechanisms in PD pathogenesis, highlight microglial dysregulation as a contributing etiological factor and nominate a targetable microglial gene candidate as a pathogenic player. Immune processes can be modulated by therapy, with potentially important clinical implications for future treatment in Parkinson’s disease.