bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noninferiority Study Comparing Latanoprost 0.005% Without Versus With Benzalkonium Chloride in Open-Angle Glaucoma or Ocular Hypertension
Authors: Wirta David , Malhotra Ranjan , Peace James , Shen Lee Bridgitte , Mitchell Brittany , Sall Kenneth , McMenemy Matthew 
Published: November 2021

Objectives:
To evaluate the noninferiority of intraocular pressure (IOP)-lowering latanoprost without benzalkonium chloride (BAK) versus latanoprost with BAK (for treatment of open-angle glaucoma or ocular hypertension).

Methods:
Overall, 578 patients were randomized 1:1 to latanoprost without BAK or latanoprost with BAK once daily in the affected eye(s) for 12 weeks. The primary efficacy endpoint was IOP, measured on days 0, 7, 28, 56, and 84 (8 am, 10 am, and 4 pm). Noninferiority was established if the following criteria were met: 95% confidence interval (CI) of the mean difference between treatments included 0 mm Hg for all time points (N1), 95% CI upper limit less than 1.5 mm Hg (N2), and less than 1 mm Hg for≥7 of 12 time points (N3). Primary efficacy analysis was performed on the intent-to-treat population. Safety measurements included ocular and systemic adverse event (AE).

Results:
The 95% CI included 0 mm Hg for 7/12 time points (N1), 95% CI upper limit was less than 1.5 mm Hg for 12/12 time points (N2), and less than 1.0 mm Hg for 4/7 time points (N3). AEs were mild and similarly distributed between groups.

Conclusions:
Latanoprost without BAK did not meet two of three criteria for noninferiority and showed a similar safety profile relative to latanoprost with BAK.
Evidence-Based Blepharoplasty: An Analysis of Highly Cited Research Papers
Authors: Charles Walton N. , Lim Hong Kai , Charles Roselin C. , Basta Mhafrin , Khajuria Ankur 
Published: November 2021

Purpose:
The purpose of the study was to appraise the methodological quality of the highest impact blepharoplasty research and to describe prevalent research themes.

Methods:
The 100 most highly cited research papers relevant to blepharoplasty were obtained from Web of Science, with no journal or date limitations applied. Data extraction included the study design, main research topic and specialty, outcome measures, and citation count. Each paper’s level of evidence was independently evaluated by 2 authors according to the Oxford Centre for Evidence-Based Medicine system.

Results:
Overall, the 100 most cited blepharoplasty research papers were cited by 4,194 papers. The mean number of citations for each paper was 73 (range: 42–239). Most of the papers presented level 4 (n = 51) or level 5 (n = 35) evidence, which is consistent with the predominance of case series (n = 47) and expert opinions (n = 18) amongst study designs. No papers achieved level 1 (highest) evidence. Six papers presented level 2 evidence and 8 papers presented level 3. Significant research foci included innovative surgical techniques (n = 65) and anatomical considerations (n = 10), with reconstructive and cosmetic implications. Senior authors were mainly affiliated with centers of plastic (n = 53) or ophthalmic/oculoplastic (n = 34) surgery. Only 3 papers used validated subjective or objective cosmetic outcome measures.

Conclusions:
Despite a significant impact on current practice, the level of evidence of the highly cited blepharoplasty research was predominantly low. Robust research methodology, through well-designed studies and standardized outcome measures, is necessary to facilitate evidence synthesis and guide clinical practice.
Functional brain mapping in patients with chronic back pain shows age-related differences
Authors: Baran Timothy M. , Lin Feng V. , Geha Paul 
Published: November 2021

Abstract
Low back pain is the most common pain condition and cause for disability in older adults. Older adults suffering from low back pain are more disabled than their healthy peers, are more predisposed to frailty, and tend to be undertreated. The cause of increased prevalence and severity of this chronic pain condition in older adults is unknown. Here, we draw on accumulating data demonstrating a critical role for brain limbic and sensory circuitries in the emergence and experience of chronic low back pain (CLBP) and the availability of resting-state brain activity data collected at different sites to study how brain activity patterns predictive of CLBP differ between age groups. We apply a data-driven multivariate searchlight analysis to amplitude of low-frequency fluctuation brain maps to classify patients with CLBP with >70% accuracy. We observe that the brain activity pattern including the paracingulate gyrus, insula/secondary somatosensory area, inferior frontal, temporal, and fusiform gyrus predicted CLBP. When separated by age groups, brain patterns predictive of older patients with CLBP showed extensive involvement of limbic brain areas including the ventromedial prefrontal cortex, the nucleus accumbens, and hippocampus, whereas only anterior insula paracingulate and fusiform gyrus predicted CLBP in the younger patients. In addition, we validated the relationships between back pain intensity ratings and CLBP brain activity patterns in an independent data set not included in our initial patterns' identification. Our results are the first to directly address how aging affects the neural signature of CLBP and point to an increased role of limbic brain areas in older patients with CLBP.
Congenital insensitivity to pain: a novel mutation affecting a U12-type intron causes multiple aberrant splicing of SCN9A
Authors: Marchi Margherita , D'Amato Ilaria , Andelic Mirna , Cartelli Daniele , Salvi Erika , Lombardi Raffaella , Gumus Evren , Lauria Giuseppe 
Published: November 2021

Abstract
Mutations in the alpha subunit of voltage-gated sodium channel 1.7 (NaV1.7), encoded by SCN9A gene, play an important role in the regulation of nociception and can lead to a wide range of clinical outcomes, ranging from extreme pain syndromes to congenital inability to experience pain. To expand the phenotypic and genotypic spectrum of SCN9A-related channelopathies, we describe the proband, a daughter born from consanguineous parents, who had pain insensitivity, diminished temperature sensation, foot burns, and severe loss of nociceptive nerve fibers in the epidermis. Next-generation sequencing of SCN9A (NM_002977.3) revealed a novel homozygous substitution (c.377+7T>G) in the donor splice site of intron 3. As the RNA functional testing is challenging, the in silico analysis is the first approach to predict possible alterations. In this case, the computational analysis was unable to identify the splicing consensus and could not provide any prediction for splicing defects. The affected intron indeed belongs to the U12 type, a family of introns characterised by noncanonical consensus at the splice sites, accounting only for 0.35% of all human introns, and is not included in most of the training sets for splicing prediction. A functional study on proband RNA showed different aberrant transcripts, where exon 3 was missing and an intron fragment was included. A quantification study using real-time polymerase chain reaction showed a significant reduction of the NaV1.7 canonical transcript. Collectively, these data widen the spectrum of SCN9A-related insensitivity to pain by describing a mutation causing NaV1.7 deficiency, underlying the nociceptor dysfunction, and highlight the importance of molecular investigation of U12 introns' mutations despite the silent prediction.
Patterns of opioid dispensing and associated wage replacement duration in workers with accepted claims for low back pain: a retrospective cohort study
Authors: Di Donato Michael , Xia Ting , Iles Ross , Buchbinder Rachelle , Collie Alex 
Published: November 2021

Abstract
This study aimed to identify patterns of opioid dispensing in Australian workers with low back pain (LBP) and determine the association of dispensing patterns with wage replacement duration. Australian workers' compensation claimants with LBP and at least 1 day of wage replacement were included. We used group-based trajectory modelling to identify opioid dispensing patterns over a two-and-a-half-year period from reported LBP onset and quantile regression to compare wage replacement duration between each dispensing pattern group. Opioids were dispensed to one-third of workers with LBP (N = 3205, 33.3%) at least once during their claim. Three dispensing patterns were identified. Most had a short-term low-volume opioid dispensing pattern (N = 2166, 67.6%), whereas 798 (24.9%) had a long-term moderate-volume pattern and 241 (7.5%) had a long-term high-volume pattern. Workers with dispensed opioids had significantly longer wage replacement duration than those without dispensed opioids (median [weeks]: 63.6 vs 7.1, respectively). In addition, moderate-volume and high-volume long-term dispensing groups had significantly longer wage replacement duration compared with the short-term dispensing group (median [weeks]: 126.9, 126.0, and 30.7, respectively). Without controlling for pain severity, these results offer limited evidence that opioids lead to longer wage replacement duration. Further research controlling for pain severity, psychosocial factors, and recovery expectations is required to confirm whether the relationship between opioid dispensing pattern and wage replacement duration is causal in nature.
Unique considerations for exercise programs to prevent future low back pain: the patient perspective
Authors: Ayre Julie , Jenkins Hazel , McCaffery Kirsten J. , Maher Christopher G. , Hancock Mark J. 
Published: November 2021

Abstract
There is moderate quality evidence that exercise can help to prevent future low back pain (LBP). This study aimed to explore patient needs and preferences for exercise programs to prevent LBP and the outcomes of these programs that would be most important to a patient. Researchers conducted 26 semistructured interviews with people with LBP. Interviews were audio-recorded, transcribed, and analysed using framework thematic analysis. Three themes were developed. Theme 1 emphasised that everyone's LBP was different, translating to preferences for tailored prevention programs with a high level of initial supervision and individualised biomedical explanations for the program. Theme 2 highlighted important outcomes. Pain was considered not only for intensity but also for the duration, frequency, and severity of flare-ups or episodes. Other important outcomes were general fitness and capacity to engage in everyday activities, social interactions, and work. Theme 3 outlined aspects of exercise programs that were considered important for people with fluctuating pain, including how to foster a sense of “progress,” set realistic expectations, and support patients to establish exercise routines that can adapt to fluctuating pain. Theme 4 discussed participants' desire for social connection. Patients want exercise programs for LBP prevention, which are highly individualised, provide meaningful explanations of exercises, and help them maintain exercise in the long-term. Clinicians should discuss with patients the transition from a focus on treatment to the prevention of LBP. This provides greater opportunity to adjust goals and expectations and provide relevant education. Balancing the need for individualised care against affordability presents an ongoing challenge.
Use of Monospot Testing in the Diagnosis of Infectious Mononucleosis in the Collegiate Student–Athlete Population
Authors: Wang Eric X. , Kussman Andrea , Hwang Calvin E. 
Published: November 2021

Objective:
To determine the utility of monospot testing in the diagnosis of mononucleosis in the collegiate student–athlete clinical setting.

Design:
Retrospective cohort study.

Setting:
National Collegiate Athletic Association Division I sports medicine clinic.

Patients:
All varsity student athletes who had a monospot test and Epstein–Barr virus (EBV) titers obtained from January 1, 2016, through March 31, 2020, (n = 199) were included.

Independent Variables:
Monospot, EBV antibody titers, and liver transaminase results.

Main Outcome Measures:
Using EBV titers indicating acute or recent infection as the gold standard for diagnosing infectious mononucleosis (IM), the reliability of a positive monospot test and elevated liver transaminases for the diagnosis of IM were examined.

Results:
The monospot test had a sensitivity and specificity of 80.0% and 90.6%, respectively, with a positive predictive value of 36.4% and a negative predictive value of 98.5% in this cohort. All athletes diagnosed with IM also had elevated liver transaminases.

Conclusions:
The specificity of the monospot test is lower than previously reported in the literature, and a positive test is not sufficient to diagnose mononucleosis in this clinical setting. Positive monospot results should be confirmed with EBV antibody testing. Elevated transaminase levels are highly correlated with acute IM and could play a supporting role in the diagnosis.
Robot-assisted radical cystectomy: surgical technique, perioperative and oncologic outcomes
Authors: Hussein Ahmed A. , Li Qiang , Guru Khurshid A. 
Published: November 2021

Purpose of review
Radical cystectomy is a complex procedure that encompasses surgery involving the urinary, gastrointestinal tracts and the retroperitoneum, with significant morbidity. Robot-assisted radical cystectomy (RARC) has been introduced to improve perioperative outcomes.

Recent findings
It has been shown to provide equivalent oncologic outcomes to open radical cystectomy while providing some benefits in terms of perioperative outcomes. A complete intracorporeal approach utilizing intracorporeal urinary diversion may potentially offer additional benefits.

Summary
Herein, we describe our technique for RARC and intracorporeal urinary diversion, as well as a review of oncologic and perioperative outcomes.
Functional Changes in Cortical Activity of Patients Submitted to Knee Osteoarthritis Treatment
Authors: Iuamoto Leandro Ryuchi , Imamura Marta , Sameshima Koichi , Meyer Alberto , Simis Marcel , Battistella Linamara Rizzo , Fregni Felipe 
Published: November 2021

Introduction
There is evidence that brain plasticity is the central mechanism involved in the functional recovery process of patients with knee osteoarthritis. Studies involving the analysis of central nervous system mechanisms of pain control and recovery could provide more data on future therapeutic approaches.

Objective
The aim of the study was to explore possible functional changes in cortical activity of patients submitted to knee osteoarthritis standardized pain treatment using electroencephalography.

Methodology
Ten patients with clinical and radiological diagnosis of painful knee unilateral or bilateral osteoarthritis were recruited to participate in clinical (Pain’s Visual Analog Scale), radiological (Kellgren-Lawrence Scale), and neurophysiological (electroencephalography) assessments to evaluate cortical activity during cortical pain modulation activity. The clinical and neurophysiological analyses were performed before and after standardized pain treatment.

Results
Eight patients participated in this study. A significant improvement in pain perception and relative increase in interhemispheric connectivity after therapies was observed. In electroencephalography analysis, tests with real movement showed a relative increase in density directed at Graph’s analysis.

Conclusions
Relative increase density directed measures at connectivity analysis in electroencephalography after pain treatment can be possible parameters to be explored in future research with a larger number of patients.
System-Level Determinants of Access to Flap Reconstruction after Abdominoperineal Resection
Authors: Dayani Fara , Sheckter Clifford C. , Rochlin Danielle H. , Nazerali Rahim S. 
Published: November 2021

Background:
Reconstruction following abdominoperineal resection improves outcomes by reducing wound-related complications, particularly in irradiated patients. Little is known regarding system-level factors that impact patients’ access to reconstructive surgery following abdominoperineal resection. This study aimed to identify barriers to undergoing reconstruction following abdominoperineal resection.

Methods:
Using the National Inpatient Sample database from 2012 to 2014, all encounters with colorectal or anorectal carcinoma patients who underwent abdominoperineal resection were extracted based on International Classification of Disease, Ninth Revision, diagnosis and procedure codes. Multivariable logistic regression analyzed the outcome of undergoing reconstruction.

Results:
The weighted sample included encounters with 19,205 abdominoperineal resection patients, of whom 1243 (6.5 percent) received a flap. Notable patient-level predictors of receiving a flap included age younger than 55 years (OR, 1.82; 95 percent CI, 1.23 to 2.74; p = 0.003) and neoadjuvant chemoradiation therapy (OR, 1.37; 95 percent CI, 1.01 to 1.88; p = 0.041). Race, sex, income level, insurance type, and Elixhauser Comorbidity Index were not associated with increased odds of receiving a flap. For facility-level factors, urban teaching hospitals (OR, 23.6; 95 percent CI, 3.29 to 169.4; p = 0.002) and larger hospital bedsize (OR, 2.64; 95 percent CI, 1.53 to 4.56; p = 0.000) were associated with higher odds of reconstruction. Plastic surgery facility volume was not found to be a significant predictor of undergoing flap reconstruction (p > 0.05).

Conclusions:
Patients undergoing abdominoperineal resection at academic centers were over 23 times more likely to undergo reconstruction, after adjusting for available confounders. Patients undergoing abdominoperineal resection at smaller, nonacademic centers may not have equitable access to reconstruction despite being appropriate candidates. Given the morbidity of abdominoperineal resection, patients should be referred to large, academic centers to have access to flap reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, III.
Intraflap Vascular Catheterization Method for Monitoring, Prevention, and Intervention of Thrombogenesis in Free-Flap Surgery
Authors: Saiga Atsuomi , Kubota Yoshitaka , Yamaji Yoshihisa , Mitsukawa Nobuyuki 
Published: November 2021

Background
Thrombosis at the anastomotic site is a significant problem in free tissue transfer with microvascular anastomosis. We report a newly developed intraflap vascular catheterization (IFVC) technique for monitoring hemodynamics, prevention of thrombogenesis, and transcatheter intervention of free-flap thrombosis.

Methods
We performed a hospital-based, prospective study. Ninety-three patients underwent free tissue transfer by a single surgeon in a single hospital. In the IFVC group (n = 40), catheters were inserted into the arterial and venous branches of the flap main pedicle vessels near the anastomoses. The catheters were connected to the pressure monitor. A bolus injection of urokinase was administered every hour to the artery, and a continuous infusion of saline was initiated to the vein. The bolus injection of urokinase solution reached the arterial anastomosis by the retrograde flow. During the postoperative period, rapid injection of urokinase or saline was performed according to the pressure monitor. Intraflap vascular catheterization monitoring was performed postoperatively for 72 hours.

Results
The overall flap survival rate in the IFVC group was 100% (40 of 40), whereas the overall flap survival rate in the non-IFVC group was 96% (51 of 53). In a subgroup analysis of lower extremity reconstruction, the flap survival rate was 100% (22 of 22) with no cases of reanastomosis requiring a return to the operation room in the IFVC group. By contrast, the flap survival rate was 92% (22 of 24), with 6 cases of reanastomosis requiring a return to the operation room in the non-IFVC group (P = 0.04).

Conclusions
The IFVC method enables monitoring, prevention, and intervention of thrombi at anastomotic sites of the free flap. Intraflap vascular catheterization may increase free tissue transfer success rate, especially in high-risk cases, such as free-flap reconstruction after the lower extremity trauma or venous leg ulcer.
Shifting acute stroke management to the prehospital setting
Authors: Ebinger Martin , Audebert Heinrich J. 
Published: November 2021

Purpose of review
The earlier the treatment, the better the outcomes after acute ischemic stroke. Optimizing prehospital care bears potential to shorten treatment times. We here review the recent literature on mothership vs. drip-and-ship as well as mobile stroke unit concepts.

Recent findings
Mobile stroke units result in the shortest onset-to-treatment times in mostly urban settings.

Summary
Future research should focus on further streamlining processes around mobile stroke units, especially improving dispatch algorithms and improve referral for endovascular therapy.
Conceptualization and management of personality disorders in Russian psychiatry
Authors: Kulygina Maya A. , Chetkina Anastasiya S. , Berezantsev Andrei Yu. 
Published: November 2021

Purpose of review
This article aims to present the current picture on conceptualization, diagnosis and care provision of personality disorders (PD) in modern Russia. These issues are highly relevant to Russian psychiatry, which has a rich historical tradition of analysing psychopathic constitution, personality types and dynamics.

Recent findings
This narrative review covers the main tendencies in the recent Russian academic literature devoted to PD. PD are most frequently investigated in the frames of forensic psychiatry, in which expert conclusions and assessment of the risk factors for socially dangerous behaviour are particularly important. Another area of research concerns comorbidity, since PD often affect other health conditions or are co-occurrent with other mental or behavioural problems. Specialists have also focused on the challenges of therapy in PD.

Summary
Reviewed manuscripts show a pathogenic and pathoplastic role of personality factors in manifestation of other mental, behavioural or somatic disorders. Analysis of pathocharacterological profile and self-regulation processes is a major component in assessing and diagnosing PD. The principal perspectives in this particular area focus on evidence-based research of mechanisms of personality pathology and validation of targeted personalized combined therapeutic approaches.
The unmitigated profile of COVID-19 infectiousness
Authors: Sender Ron , Bar-On Yinon M. , Park Sang Woo , Noor Elad , Dushoff Jonathan , Milo Ron 
Published: November 2021

AbstractQuantifying the temporal dynamics of infectiousness of individuals infected with SARS-CoV-2 is crucial for understanding the spread of the COVID-19 pandemic and for analyzing the effectiveness of different mitigation strategies. Many studies have tried to use data from the onset of symptoms of infector-infectee pairs to estimate the infectiousness profile of SARS-CoV-2. However, both statistical and epidemiological biases in the data could lead to an underestimation of the duration of infectiousness. We correct for these biases by curating data from the initial outbreak of the pandemic in China (when mitigation steps were still minimal), and find that the infectiousness profile is wider than previously thought. For example, our estimate for the proportion of transmissions occurring 14 days or more after infection is an order of magnitude higher - namely 19% (95% CI 10%-25%). The inferred generation interval distribution is sensitive to the definition of the period of unmitigated transmission, but estimates that rely on later periods are less reliable due to intervention effects. Nonetheless, the results are robust to other factors such as the model, the assumed growth rate and possible bias of the dataset. Knowing the unmitigated infectiousness profile of infected individuals affects estimates of the effectiveness of self-isolation and quarantine of contacts. The framework presented here can help design better quarantine policies in early stages of future epidemics using data from the initial stages of transmission.