bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pseudoexfoliative Glaucoma, Endothelial Dysfunction, and Arterial Stiffness: The Role of Circulating Apoptotic Endothelial Microparticles
Authors: Bourouki Evgenia , Oikonomou Evangelos , Moschos Marilita , Siasos Gerasimos , Siasou Georgia , Gouliopoulos Nikos , Deftereos Spyridon , Miliou Antigoni , Zacharia Effimia , Tousoulis Dimitris 
Published: June 2019

Précis:
Pseudoexfoliative glaucoma (PExG) patients present with not only endothelial dysfunction and arterial stiffness but also with a specific profile of circulating apoptotic endothelial microparticles which may be owing to the accumulation of pseudoexfoliative material in vessels walls.

Purpose:
PExG is characterized by the deposition of pseudoexfoliative material in several tissues and organs including in the cardiovascular system. This study aimed to evaluate the vascular endothelial function, arterial stiffness, inflammatory status, and circulating microparticle (MP) levels in PExG patients compared with those in primary open-angle glaucoma (POAG) patients and control subjects.

Methods:
Vascular endothelial function was evaluated by flow-mediated dilation. Pulse wave velocity and augmentation index were measured as indices of aortic stiffness and arterial wave reflections, respectively. Growth-differentiation factor-15 and intercellular adhesion molecule1 levels were measured to evaluate the systemic inflammatory status. Circulating MPs that constitute an emerging marker of vascular endothelial dysfunction and platelet activation were isolated and analyzed by flow cytometry.

Results:
There was a stepwise impairment from the control to the POAG patients and PExG subjects in the flow-mediated dilation (8.21%±2.94% vs. 7.56%±3.12% vs. 5.79±3.13, P=0.005), pulse wave velocity (8.14±1.79 vs. 9.21±2.27 vs. 9.95±3.28 m/s, P=0.007), augmentation index (24.71%±7.84% vs. 26.78%±7.21% vs. 29.96%±7.58%, P=0.02), and growth-differentiation factor-15 (P=0.001) and intercellular adhesion molecule1 levels (P=0.08). PExG patients expressed greater levels of total circulating MPs (Annexin V+) (P=0.004) and endothelial-derived MPs (CD144+) (P<0.001) compared with POAG and control subjects.

Conclusions:
PExG patients with an accumulation of pseudoexfoliative microfibrillar material presented with vascular endothelial dysfunction and arterial wall impairment associated with the levels of circulating proinflammatory molecules and circulating apoptotic endothelial MPs. These findings highlight the underlying systemic pathophysiological mechanisms associated with the progress of the pseudoexfoliative syndrome.
A randomized controlled trial testing a virtual perspective-taking intervention to reduce race and socioeconomic status disparities in pain care
Authors: Hirsh Adam T. , Miller Megan M. , Hollingshead Nicole A. , Anastas Tracy , Carnell Stephanie T. , Lok Benjamin C. , Chu Chenghao , Zhang Ying , Robinson Michael E. , Kroenke Kurt , Ashburn-Nardo Leslie 
Published: June 2019

AbstractWe conducted a randomized controlled trial of an individually tailored, virtual perspective-taking intervention to reduce race and socioeconomic status (SES) disparities in providers' pain treatment decisions. Physician residents and fellows (n = 436) were recruited from across the United States for this two-part online study. Providers first completed a bias assessment task in which they made treatment decisions for virtual patients with chronic pain who varied by race (black/white) and SES (low/high). Providers who demonstrated a treatment bias were randomized to the intervention or control group. The intervention consisted of personalized feedback about their bias, real-time dynamic interactions with virtual patients, and videos depicting how pain impacts the patients' lives. Treatment bias was re-assessed 1 week later. Compared with the control group, providers who received the tailored intervention had 85% lower odds of demonstrating a treatment bias against black patients and 76% lower odds of demonstrating a treatment bias against low SES patients at follow-up. Providers who received the intervention for racial bias also showed increased compassion for patients compared with providers in the control condition. Group differences did not emerge for provider comfort in treating patients. Results suggest an online intervention that is tailored to providers according to their individual treatment biases, delivers feedback about these biases, and provides opportunities for increased contact with black and low SES patients, can produce substantial changes in providers' treatment decisions, resulting in more equitable pain care. Future studies should examine how these effects translate to real-world patient care and the optimal timing/dose of the intervention.
A Proof-of-Concept Study Evaluating the Phosphodiesterase 10A Inhibitor PF-02545920 in the Adjunctive Treatment of Suboptimally Controlled Symptoms of Schizophrenia
Authors: DeMartinis Nicholas , Lopez Rene N. , Pickering Eve H. , Schmidt Christopher J. , Gertsik Lev , Walling David P. , Ogden Adam 
Published: June 2019

Abstract

Background
Effective treatments for managing suboptimal clinical responses to current therapy for schizophrenia remain a critical unmet need. Phosphodiesterase 10A (PDE10A) inhibition represents a mechanistically novel approach to the treatment of schizophrenia, with preclinical studies suggesting improvements in partially responsive symptoms could be achieved via adjunctive use of the PDE10A inhibitor PF-02545920. Therefore, the adjunctive safety, tolerability, pharmacokinetics, and efficacy of multiple repeat doses of PF-02545920 were investigated in a phase 1b study and subsequent phase 2 study.

Methods
The phase 1b study randomized 37 adult patients with stable symptomatology and stable antipsychotic regimens within 3 cohorts. Study participants received ascending doses of PF-02545920 or placebo for 10 to 18 days. The phase 2 study randomized 240 outpatients with stable symptomatology but suboptimal response to current antipsychotic regimens 1:1:1 to PF-02545920 5 mg, PF-02545920 15 mg, or placebo every 12 hours for 12 weeks. The primary efficacy end point of the phase 2 study was change in the Positive and Negative Syndrome Scale total score from baseline to week 12, with changes in other clinical assessments as secondary end points.

Results
Treatment was well tolerated, and observed PF-02545920 exposures were within the range predicted to be adequate for demonstrating efficacy. However, no significant differences in the prespecified efficacy end points between the 2 PF-02545920 treatment arms and placebo were observed.

Conclusions
Current data and results of a prior monotherapy study in which PF-02545920 failed to differentiate from placebo refute the hypothesis that PDE10A inhibitors have use as antipsychotic agents for schizophrenia.
Estimating the Risk of Pneumonia in Patients With Schizophrenia Newly Receiving Clozapine
Authors: Wu Chi-Shin , Chen Tien-Yu , Tsai Shang-Ying , Chen Chiao-Chicy , Kuo Chian-Jue 
Published: June 2019

Abstract

Purpose/Background
Patients with schizophrenia are vulnerable to pneumonia. Clozapine is associated with the greatest risk of pneumonia. We investigated the risk factors of pneumonia in patients with schizophrenia who use clozapine.

Methods/Procedures
We used a large cohort of patients with schizophrenia (N = 22,774) who newly use clozapine (baseline). We divided the data set into a training cohort (entry between 1998 and 2008, n = 18,496) and test cohort (entry between 2009 and 2012, n = 4278), where 483 and 168 patients developed pneumonia requiring hospitalization within 1 year after baseline, respectively. For prediction, we developed a static model using Cox proportional hazards regression and a dynamic model using Cox regression with time-dependent modeling. Areas under receiver operating curves (AUCs) for the predictive model were estimated in the training cohort and then in the test cohort for validation.

Findings/Results
Based on the baseline characteristics, the static model for predicting pneumonia in 3 periods (90, 180, and 365 days) was unsatisfactory (AUCs, 0.64, 0.64, and 0.65, respectively). The predictors were older age, male sex, history of nonpsychiatric hospitalization, dementia, asthma, and tuberculosis within 1 year before baseline. However, the results were improved (AUCs, 0.83, 0.79, and 0.77, respectively) after control for time-dependent variables, namely, duration of clozapine use and concomitant medications (ie, benzodiazepines, valproic acid, systemic corticosteroids).

Implications/Conclusions
Several risk factors for predicting subsequent pneumonia after initial use of clozapine were explored, including older age, male, history of nonpsychiatric hospitalization, dementia, asthma, tuberculosis, benzodiazepines, valproic acid, systemic corticosteroids, and the use duration of clozapine. Clinical staff can use the risk factors to administer evidence-based treatment.
Quetiapine Poisoning and Factors Influencing Severity
Authors: Peridy Elise , Hamel Jean-François , Rolland Anne-Lise , Gohier Bénédicte , Boels David 
Published: June 2019

Abstract

Purpose/Background
Quetiapine is a relatively new atypical antipsychotic with fewer adverse effects. It is increasingly prescribed to patients. The purpose of this study was to describe the cases of poisoning observed at the western France Poison Control Centre and identify potential risk factors that increase the severity of the cases.

Methods
This was a retrospective study of self-poisoning with quetiapine as reported by the western France Poison Control Centre between 2007 and 2017.

Results
There were 372 cases of quetiapine poisoning. Circumstances are known in 367 of 372 cases. There were 75 cases of null severity (grade 0), 133 cases of mild severity (grade 1), 85 cases of moderate severity (grade 2), and 79 cases of high severity (grade 3). Five deaths were listed in this series. The most commonly observed symptoms were neurological and cardiovascular in nature (drowsiness, coma, tachycardia, hypotension). Of these cases, 79.8% included voluntary ingestions. Among 302 cases with coagents, the most common coagents were benzodiazepines (56%), other psychotropic drugs (41%), and antidepressants (37%). An evaluated ingested dose 1500 mg or greater and 2 or more coagents increase the risk of severe poisoning. In particular, concomitant ingestion of benzodiazepines and antidepressants with quetiapine was associated with high severity (odds ratio, 2.478 [confidence interval, 1.3–4.723]; odds ratio, 1.820 [confidence interval, 1.010–3.316]).

Conclusions
Quetiapine may lead to severe poisoning for which there is currently no specific treatment. Patients and practitioners should be aware of this when quetiapine is prescribed, particularly when used in combination with other medications, and in order to deal with cases of poisoning.
Efficacy of Varenicline in Patients With Severe Alcohol Dependence
Authors: Pfeifer Philippe , Fehr Christoph 
Published: June 2019

Abstract

Purpose/Background
Varenicline has proven its efficacy in the treatment of nicotine dependence, and there is also evidence that it could be helpful in the treatment of alcohol dependence. In our pilot study, we investigated the feasibility and acceptability of varenicline for the treatment of a population of patients with severe alcohol dependence and multiple somatic comorbidities after alcohol detoxification.

Methods/Procedures
We conducted a phase II, double-blind, placebo-controlled randomized trial of daily oral varenicline versus a placebo in alcohol-dependent men and women after alcohol detoxification (n = 28). Following our study protocol, somatic conditions and adverse events were thoroughly monitored and several study end points were investigated (percentage of abstinent days for both alcohol and nicotine, number of standardized drinks and cigarettes per day, days of heavy drinking).

Findings/Results
Compared with the placebo, varenicline did not have more side effects and did not provoke more adverse events. Patients in the varenicline group did not show a significantly higher percentage of alcohol abstinent days or fewer heavy drinking days. A trend significance was found for a reduced number of standard drinks per day (P = 0.06) in the varenicline group.

Implications/Conclusions
In this pilot trial, varenicline was shown to be well tolerated by our study population of severely alcohol-dependent patients with somatic conditions. Varenicline did not sustain alcohol abstinence or reduce the number of heavy drinking days, but it did reduce the daily amount of alcohol consumed.
The stigma of skin disease
Authors: Wu Julie H. , Cohen Bernard A. 
Published: June 2019

Purpose of review
The effects of skin disease on stigmatization are important but understudied in the pediatric population. Given the highly visible nature of dermatologic conditions, stigmatization is a common problem that requires significant attention in patients with skin diseases. In this review, we examine the recent literature addressing stigmatization of patients suffering from common dermatologic diseases with the goal to increase clinician awareness of these issues and identify new avenues for future research.

Recent findings
A number of studies have examined the impact of skin disease on psychosocial well being and quality of life. Although some skin diseases are often overlooked medically and considered to be primarily cosmetic issues, the long-term consequences of skin diseases on psychosocial health, especially in pediatric patients, can be profound.

Summary
The precipitating factors for stigma vary widely depending on age, sex, and culture. In order to effectively reduce the impact of pediatric skin diseases on psychosocial health, physicians should be able to identify specific characteristics that may increase risks for stigmatization in chidlren. Carefully monitoring psychosocial development in pediatric patients with dermatological conditions in addition to proactively guiding patients and families to appropriate resources can benefit the child's development and overall long-term well being.
Excess Cancer Cases and Medical Costs Due to Suboptimal Human Papillomavirus Vaccination Coverage in California
Authors: Baughan Eleonore B. , Keizur Erin M. , Damico Christopher A. , Arnold Elizabeth Mayfield , Ko Jamie S. , Klausner Jeffrey D. 
Published: June 2019

Background
Human papillomavirus (HPV) vaccination coverage continues to be at low to moderate levels throughout the United States. HPV infection is linked to multiple types of cancers resulting in high economic and health burden. We aimed to estimate the excess number of cancer cases and associated medical costs due to current HPV vaccination coverage for a 20-year-old birth cohort in California.

Methods
We estimated the lifetime number of cancer cases caused by vaccine-preventable strains of HPV for a cohort of 20 year-olds in California. We then estimated the excess number of cancer cases in that cohort which would occur due to 2017 HPV vaccination coverage compared with an optimal coverage of 99.5%. By multiplying those excess cases by the average cost of treatment, we determined the excess cost due to current HPV vaccination coverage.

Results
With current vaccination coverage in California, the 20-year-old cohort is at risk for an excess 1352 cancer cases that could be prevented with a projected optimal vaccination coverage of 99.5%. The excess cost of treatment for those cancer cases would be US $52.2 million. Male oropharyngeal cancer accounts for the greatest projected cost burden US $21.3 million followed by cervical cancer US $16.1 million.

Conclusions
Increased HPV vaccination coverage in California is needed to reduce economic and health burdens associated with cancers caused by HPV infection.
Comparison of Outcomes between Side-to-End and End-to-End Lymphovenous Anastomoses for Early-Grade Extremity Lymphedema
Authors: AlJindan Fahad K. , Lin Chia-Yu , Cheng Ming-Huei 
Published: June 2019

Background:
Lymphovenous anastomosis is technically challenging and can be successfully performed with an advanced operating microscope, supermicrosurgical instruments, and indocyanine green lymphography. This study compared the outcomes between side-to-end and end-to-end lymphovenous anastomosis configurations for unilateral extremity lymphedema.

Methods:
Between April of 2013 and June of 2017, lymphovenous anastomosis was indicated for 58 patients who preoperatively had patent lymphatic ducts by indocyanine green lymphography, including 20 patients with upper limb lymphedema and 38 patients with lower limb lymphedema. Either an end-to-end or a side-to-end lymphovenous anastomosis was used to anastomose the subdermal venule to the lymphatic duct. The circumferential difference and episodes of cellulitis were used as outcome measurements.

Results:
Twenty-three patients underwent an end-to-end lymphovenous anastomosis and 35 patients underwent side-to-end lymphovenous anastomosis. All patients had an immediate patency evaluated by indocyanine green lymphography and patent blue assessments. All patients returned to their daily routine without the use of any compression garments. At an average follow-up of 16.5 months (range, 13.4 to 19.6 months), the improvement of circumferential difference (3.2 percent; range, 1.8 to 4.6 percent) in the side-to-end group was statistically greater than that in the end-to-end group (2.2 percent; range, 1 to 3.4 percent; p = 0.04). The overall episodes of cellulitis were significantly reduced from 1.7 times/year (range, 1.3 to 2.1 times/year) to 0.7 times/year (range, 0.3 to 1.1 times/year; p < 0.001), but no difference was observed between the two groups.

Conclusions:
Both side-to-end and end-to-end lymphovenous anastomosis configurations were effective surgical approaches for improving early-grade extremity lymphedema. Side-to-end lymphovenous anastomosis has the advantages of having greater efficacy for lymph drainage, requiring only one anastomosis and eliminating the need to use compression garments.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Conflict of Interest at Plastic Surgery Conferences: Is It Significant?
Authors: Gray Rachel , Tanna Neil , Kasabian Armen K. 
Published: June 2019

Background:
The Physician Payment Sunshine Act requires biomedical companies to disclose financial relationships between themselves and physicians. The authors compared the amount of money received by speakers at the American Society of Plastic Surgeons and the American Society for Aesthetic Plastic Surgery annual conferences with that received by the average plastic surgeon.

Methods:
General payments data were gathered from the Open Payments database for physicians listed as a presenter, moderator, panelist, lecturer, or instructor at the 2017 annual American Society of Plastic Surgeons and American Society for Aesthetic Plastic Surgery conferences. Means and medians of payments to speakers were calculated for each conference. One-tail t tests were used to evaluate differences.

Results:
The mean and median for general payments made to conference speakers at American Society for Aesthetic Plastic Surgery (n = 75) and American Society of Plastic Surgeons (n = 249) meeting were $75,577 and $861 and $27,562 and $1021, respectively. In comparison with the average general payment received by plastic surgeons (mean, $4788; median, $3209), these differences were significant (American Society for Aesthetic Plastic Surgery, p = 0.015; American Society of Plastic Surgeons, p = 0.0004).

Conclusions:
The significant difference in payments to speakers at conferences compared with the average plastic surgeon suggests that biomedical companies may have influence over some of the conference content. Speakers must make clear the full extent of industry relationships that could potentially bias their presentations.
Meta-Analyses in Plastic Surgery: Can We Trust Their Results?
Authors: McGuire Connor , Samargandi Osama A. , Corkum Joseph , Retrouvey Helene , Bezuhly Michael 
Published: June 2019

Background:
Meta-analyses are common in the plastic surgery literature, but studies concerning their quality are lacking. The authors assessed the overall quality of meta-analyses in plastic surgery, and attempted to identify variables associated with scientific quality.

Methods:
A systematic review of meta-analyses published in seven plastic surgery journals between 2007 and 2017 was undertaken. Publication descriptors and methodologic details were extracted. Articles were assessed using the following two instruments: A Measurement Tool to Assess Systematic Reviews (AMSTAR) and AMSTAR 2.

Results:
Seventy-four studies were included. The number of meta-analyses per year increased. Most meta-analyses assessed a single intervention (59.5 percent), and pooled a mean of 20.9 studies (range, two to 134), including a mean of 2463 patients (range, 44 to 14,884). Most meta-analyses were published in Plastic and Reconstructive Surgery (44.6 percent) and included midlevel evidence (II to IV) primary studies. Only 16.2 percent of meta-analyses included randomized controlled trials. Meta-analyses generally reported positive (81.1 percent) and significant results (77.0 percent). Median AMSTAR score was 7 of 11 (interquartile range, 5 to 8). Higher AMSTAR scores correlated with more recent meta-analyses that provided a rationale for statistical pooling, and appropriately managed methodologic heterogeneity (r = 0.66; p < 0.01).

Conclusions:
Despite an increase in number and quality, meta-analyses are at high risk of bias because of the low level of evidence of included primary studies and heterogeneity within and between primary studies. Plastic surgeons should be aware of the pitfalls of conducting and interpreting meta-analyses.
An International Comparison of the Management of Gastrointestinal Surgical Emergencies in Octogenarians—England Versus United States
Authors: Markar Sheraz R. , Vidal-Diez Alberto , Holt Peter J. , Karthikesalingam Alan , Hanna George B. 
Published: June 2019

Objective:
To compare the United States and England for the utilization of surgical intervention and in-hospital mortality from 5 gastrointestinal emergencies in octogenarians.

Background:
The proportion of older adults is growing and will represent a substantial challenge to clinicians in the next decade.

Methods:
Between 2006 and 2012, the rate of surgical intervention and in-hospital mortality for 5 index conditions for octogenarians were compared between the United States and England: appendicitis, incarcerated/strangulated abdominal hernia, perforation of esophagus, small or large bowel, and peptic ulcer. Univariate and multivariate analyses were performed to adjust for underlying differences in patient demographics.

Results:
Thirty-two thousand one hundred fifty-one admissions of octogenarians in England for 5 index surgical emergencies were compared with 162,142 admissions in the USA.
Surgical intervention was significantly more common in the USA than in England for all 5 conditions: appendicitis [odds ratio (OR) 4.63, 95% confidence interval (95% CI) 4.21–5.09], abdominal hernia (OR 2.06, 95% CI 1.97–2.15), perforated esophagus (OR 1.71, 95% CI 1.31–2.24), small and large bowel perforation (OR 4.33, 95% CI 4.12–4.56), and peptic ulcer perforation (OR 4.63, 95% CI 4.27–5.02). In-hospital mortality was significantly more common in England than in the USA for all 5 conditions: appendicitis (OR 3.22, 95% CI 2.73–3.78), abdominal hernia (OR 3.49, 95% CI 3.29–3.70), perforated esophagus (OR 4.06, 95% CI 3.03–5.44), small and large bowel perforation (OR 6.97, 95% CI 6.60–7.37), and peptic ulcer perforation (OR 3.67, 95% CI 3.40–3.96).

Conclusion:
Surgery is used less commonly in England for emergency gastrointestinal conditions in octogenarians, which may be associated with a high rate of in-hospital mortality from these conditions compared with the USA.