bluuebunny/crossref_metadata_2025 huggingface dataset:
Response to Exercise Training During Cardiac Rehabilitation Differs by Sex
Authors: Rengo Jason L. , Khadanga Sherrie , Savage Patrick D. , Ades Philip A.
Published: August 2020

Purpose:

Directly measured peak aerobic capacity or oxygen uptake (

) is a powerful predictor of prognosis in individuals with cardiovascular disease. Women enter phase 2 cardiac rehabilitation (CR) with lower

and their response to training, compared with men, is equivocal. We analyzed

at entry and exit in patients participating in CR and improvements by diagnosis to assess training response. We also identified sex differences that may influence change in

.

Methods:

The cohort included consecutive patients enrolled in CR between January 1996 and December 2015 who performed entry exercise tolerance tests. Data collected included demographics, index diagnosis,

, and exercise training response.

Results:

The cohort consisted of 3925 patients (24% female). There was a significant interaction between baseline

and diagnosis (P < .001), with percutaneous coronary intervention and myocardial infarction greater than other diagnoses. Surgical patients demonstrated greater improvement in

than nonsurgical diagnoses (n = 1789; P < .001). Women had lower

than men for all diagnoses (P < .02) and demonstrated less improvement (13 vs 17%, P < .001). Percent improvement using estimated metabolic equivalents of task (METs) were similar for women and men (33 vs 31%, P = NS). Despite overall increases in

, 18% of patients (24% women, 16% men) failed to demonstrate any improvement (exit

≤ entry

).

Conclusions:

While there were no differences in training effect estimated by METs, directly measured

showed a significantly lower training response for women despite adjusting for covariates. In addition, 18% of patients did not see any improvement in

. Alternatives to traditional CR exercise programming need to be considered.
GENDER DIFFERENCES IN SELF-REPORTED PROCEDURAL VOLUME AMONG VITREORETINAL FELLOWS
Authors: Reyes-Capo Daniela P. , Yannuzzi Nicolas A. , Chan R.V. Paul , Murray Timothy G. , Berrocal Audina M. , Sridhar Jayanth
Published: August 2020

Purpose:

A prior study revealed discrepancies in self-reported surgical numbers between male and female ophthalmology residents. This study further investigates the gender differences in self-reported procedural volume among vitreoretinal surgery fellows and examines the differences for surgical, medical, and total self-reported procedural volume between male and female vitreoretinal fellows.

Methods:

A retrospective review of case logs submitted to the American Society of Retina Specialists by first-year and second-year vitreoretinal fellows from July 1, 2018, to June 30, 2019, was performed. Fellows who reported fewer than 100 pars plana vitrectomies were excluded. A total of 133 fellows were included.

Results:

Overall, 37 of 57 (65%) first-year fellows and 59 of 76 (78%) second-year fellows were male. An average of 1,120 procedures were self-reported among all vitreoretinal fellows. In the group of second-year fellows at the completion of fellowship, men reported more total procedures (1,171 [864–1,600] vs. 1,005 [719–1,257]; P = 0.072). Women reported statistically significant fewer endolaser (P = 0.018), internal limiting membrane peel (P = 0.042), and cryoretinopexy (P = 0.002) procedures compared with men. When splitting the data by total surgical versus medical procedures, men reported more procedures than women both surgically (1,077 [799–1,490] vs. 925 [622–1,208]; P = 0.085) and medically (72 [41–116] vs. 56 [20–94]; P = 0.141), although these differences were not statistically significant.

Conclusion:

There is a trend for female vitreoretinal fellows to report fewer surgical procedures than their male counterparts, raising concerns for gender gaps in vitreoretinal surgical training. Further research is needed to verify this discrepancy and identify potential barriers that female vitreoretinal surgeons are facing in training.
PHACOVITRECTOMY FOR PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT REPAIR
Authors: Benson Matthew D. , Sia David , Seamone Mark E. , Greve Mark , Hinz Brad , Tennant Matthew T. S. , Baker Chad , Somani Rizwan , Ehmann David S.
Published: August 2020

Purpose:

To analyze the single surgery success rate and anterior segment complications related to phacoemulsification and intraocular lens implantation in a series of patients undergoing phacovitrectomy for all types of primary rhegmatogenous retinal detachment.

Methods:

We performed a retrospective interventional case series on 302 eyes undergoing phacovitrectomy for primary rhegmatogenous retinal detachment repair between November 1, 2016, and February 2, 2019, in Edmonton, Canada. Primary outcomes included single surgery retinal reattachment rate and anterior segment complications. Secondary outcomes included the effects of proliferative vitreoretinopathy and macula and/or peripheral internal limiting membrane peeling on the rate of surgical success.

Results:

The single surgery success rate of phacovitrectomy for all types of primary rhegmatogenous retinal detachment was 85.1%. The presence of proliferative vitreoretinopathy was associated with lower surgical success (odds ratio, 0.33; P = 0.01). Macular internal limiting membrane peeling was associated with higher surgical success (odds ratio, 2.4; P = 0.05). Anterior segment complications included posterior capsular opacification (28.8%), posterior synechiae (10.9%), and posterior capsular rupture (2.3%).

Conclusion:

Phacovitrectomy is a safe and effective treatment option for the primary repair of rhegmatogenous retinal detachments. This study provides evidence to support the safe incorporation of phacoemulsification and intraocular lens implantation with retinal surgery.
Cannabinoids, cannabis, and cannabis-based medicine for pain management: a systematic review of randomised controlled trials
Authors: Fisher Emma , Moore R. Andrew , Fogarty Alexandra E. , Finn David P. , Finnerup Nanna B. , Gilron Ian , Haroutounian Simon , Krane Elliot , Rice Andrew S.C. , Rowbotham Michael , Wallace Mark , Eccleston Christopher
Published: August 2020

Cannabinoids, cannabis, and cannabis-based medicines (CBMs) are increasingly used to manage pain, with limited understanding of their efficacy and safety. We summarised efficacy and adverse events (AEs) of these types of drugs for treating pain using randomised controlled trials: in people of any age, with any type of pain, and for any treatment duration. Primary outcomes were 30% and 50% reduction in pain intensity, and AEs. We assessed risk of bias of included studies, and the overall quality of evidence using GRADE. Studies of <7 and >7 days treatment duration were analysed separately. We included 36 studies (7217 participants) delivering cannabinoids (8 studies), cannabis (6 studies), and CBM (22 studies); all had high and/or uncertain risk of bias. Evidence of benefit was found for cannabis <7 days (risk difference 0.33, 95% confidence interval 0.20-0.46; 2 trials, 231 patients, very low-quality evidence) and nabiximols >7 days (risk difference 0.06, 95% confidence interval 0.01-0.12; 6 trials, 1484 patients, very low-quality evidence). No other beneficial effects were found for other types of cannabinoids, cannabis, or CBM in our primary analyses; 81% of subgroup analyses were negative. Cannabis, nabiximols, and delta-9-tetrahydrocannabinol had more AEs than control. Studies in this field have unclear or high risk of bias, and outcomes had GRADE rating of low- or very low-quality evidence. We have little confidence in the estimates of effect. The evidence neither supports nor refutes claims of efficacy and safety for cannabinoids, cannabis, or CBM in the management of pain.
TRIM72 mediates lung epithelial cell death upon hyperoxia exposure
Authors: Huang Liang-Ti , Chou Hsiu-Chu , Chen Chung-Ming
Published: August 2020

Background:

Premature infants often require oxygen (O2) therapy for respiratory distress syndrome; however, excessive use of O2 can cause clinical conditions such as bronchopulmonary dysplasia. Although many treatment methods are currently available, they are not effective in preventing bronchopulmonary dysplasia. Herein, we explored the role of tripartite motif protein 72 (TRIM72), a factor involved in repairing alveolar epithelial wounds, in regulating alveolar cells upon hyperoxia exposure.

Methods:

In this in vivo study, we used Sprague–Dawley rat pups that were reared in room air or 85% O2 for 2 weeks after birth. The lungs were excised for histological analyses, and TRIM72 expression was assessed on postnatal days 7 and 14. For in vitro experiments, RLE-6TN cells (i.e., rat alveolar type II epithelial cells) and A549 cells (i.e., human lung carcinoma epithelial cells) were exposed to 85% O2 for 5 days. The cells were then analyzed for cell viability, and TRIM72 expression was determined.

Results:

Exposure to hyperoxia reduced body and lung weight, increased mean linear intercept values, and upregulated TRIM72 expression. In vitro study results revealed increased or decreased lung cell viability upon hyperoxia exposure depending on the suppression or overexpression of TRIM72, respectively.

Conclusion:

Hyperoxia upregulates TRIM72 expression in neonatal rat lung tissue; moreover, it initiates TRIM72-dependent alveolar epithelial cell death, leading to hyperoxia-induced lung injury.
Variation of the Vaginal Lactobacillus Microbiome in Cytolytic Vaginosis
Authors: Yang Shuhua , Liu Ying , Wang Jianhong , Li Shuxia , Zhang Yuexiang
Published: August 2020

Objective

This pilot study aimed to evaluate whether different microbial compositions cause symptoms in patients with Lactobacillus overgrowth and to investigate the variation in Lactobacillus microbiome in cytolytic vaginosis (CV).

Materials and Methods

Lactobacillus species were identified from the vaginal fluid of 70 healthy women and 79 patients with CV using molecular analysis of the 16S rRNA gene. χ2 and Fisher exact tests were used to compare the isolated rates of Lactobacillus species between the 2 groups. The capabilities of dominant Lactobacillus strain to produce acid in the 2 groups were analyzed by repeated measures analysis of variance.

Results

The isolation of 2 or more Lactobacillus species per vaginal sampling was significantly less common in the CV group (1.3%) compared with the healthy control (HC) group 12.2% (p = .013). Significant differences in Lactobacillus species were observed between the 2 groups (p < .001). Lactobacillus crispatus was more often found in the CV group (88.7%) than in the HC group (56.4%, p < .001). Compared with that in the HC group, the dominant L. crispatus strain in the CV group tended to produce more acid.

Conclusions

The CV group carried a less diverse Lactobacillus species, vaginally. Lactobacillus crispatus was common to both CV and HC groups but demonstrated enhanced acid-producing capability in the CV group. The pathogenesis of CV may be based, in part, on an overgrowth of L. crispatus with enhanced acid-producing capability.
Current opinions in otolaryngology and head and neck surgery: functional considerations in reconstruction after laryngectomy
Authors: Elson Nora C. , Martinez Daniel C. , Cervenka Brian P.
Published: August 2020

Purpose of review

To review reconstruction techniques following total laryngectomy, partial laryngopharyngectomy, and total laryngopharyngectomy with an emphasis on long-term swallow and speech outcomes.

Recent findings

Recent literature has shown that the use of fasciocutaneous free flaps in the reconstruction of laryngectomy defects may lead to improved speech and swallow outcomes as compared with regional or free musculocutaneous flaps. Radial forearm and anterolateral thigh are the most often used fasciocutaneous free flaps, with similar speech and swallow outcomes. Primary closure with myofascial flap onlay yields similar speech and swallow results to fasciocutaneous flaps following laryngectomy that spares sufficient pharyngeal mucosa.

Whenever reconstructing a salvage laryngectomy defect or a primary laryngectomy defect with mucosal deficiency, current evidence suggests that a fasciocutaneous free flap used to augment pharyngeal volume both improves fistula rates as well as long-term speech and swallow outcomes. When sufficient pharyngeal mucosa is present, myofascial onlay can be considered as well.
State of the art regeneration of the tympanic membrane
Authors: Sagiv Doron , Chin Oliver Y. , Diaz Rodney C. , Brodie Hilary A.
Published: August 2020

Purpose of review

One of the most common diseases of the tympanic membrane is a perforation, and tympanoplasty is one of the more common procedures in otolaryngology. Tympanic membrane regeneration and bioengineering aim to improve the success rate of the procedure, increase the availability of different scaffolds and provide innovative tools that will simplify the surgical technique and make it accessible for surgeons with varying expertise level. This review aims to raise awareness of current tissue engineering developments in tympanic membrane regeneration and how they may augment current clinical practices. We focus here on achievements in tympanic membrane cell cultures and on innovations in development of new scaffolds and growth factors that enhance regeneration of patient's native tympanic membranes.

Recent findings

In recent years, great achievements were reached in the field of tympanic membrane regeneration in the three hallmarks of bioengineering: cells, scaffolds and bioactive molecules. New techniques for modeling normal tympanic membrane proliferation were developed, as well as for isolation and expansion of normal tympanic membrane keratinocytes from miniature samples of scarred tissue. Ongoing clinical trials aim to seal the perforation by applying different scaffolds infiltrated by growth factors on the tympanic membrane.

Research efforts in tympanic membrane regeneration continue to seek the ideal single tissue-engineered substitute. Recent advances in tympanic membrane bioengineering include new types of scaffolds that may augment and provide a safe and effective alternative to the current gold-standard autograft. New bioactive molecules may simplify the surgical procedure and reduce surgical time by augmenting the native tympanic membrane regeneration. Several groups of bioengineering scientists and neurotologists are continuing to move forward and develop new strategies, seeking to create a fully functional tissue-engineered tympanic membrane.
Nerve grafts in head and neck reconstruction
Authors: Hoshal Steven G. , Solis Roberto N. , Bewley Arnaud F.
Published: August 2020

Purpose of review

This article reviews recent literature on repair of peripheral nerve injuries in the head and neck with a focus on autografts, allografts, nerve conduits, and technical considerations.

Recent findings

Contemporary nerve grafting techniques offer the potential to improve peripheral nerve outcomes and reduce donor site morbidity. A variety of donor nerves autografts have been described that offer favorable outcomes for segmental reconstruction of facial nerve defects. Recent studies have demonstrated promising results in repair of inferior alveolar nerve injuries with human allografts. Animal models describe successful reinnervation of small defects with neural conduits. The latest data do not favor protocolled nerve graft polarity or use of a motor versus sensory donor nerves.

Interposition nerve grafting is the gold standard for repair of peripheral nerve injuries when a tension-free primary neurorrhaphy is not possible. Autografts are the work-horse for the majority of head and neck neural defects, however, can result in some degree of donor site morbidity. Recent developments in allografting and neural conduits have the potential to further diversify the head and neck reconstructive surgeon's armamentarium. It is unclear if nerve graft makeup or polarity affect functional outcome.
Keratinocyte growth factor signaling promotes stem/progenitor cell proliferation under p63 expression during middle ear cholesteatoma formation
Authors: Yamamoto-Fukuda Tomomi , Akiyama Naotaro
Published: August 2020

Purpose of review

Middle ear cholesteatoma is an epithelial lesion that expands into the middle ear, resulting in bone destruction. However, the pathogenesis of this has been unknown. The purpose of this review is to understand the role of keratinocyte growth factor (KGF) during epithelial stem and/or progenitor cell proliferation in middle ear cholesteatoma.

Recent findings

Many researchers have investigated the molecular mechanism of middle ear cholesteatoma to establish a conservative treatment. Recently, some studies have focused on the stem cells of middle ear cholesteatoma and their detection, but the key molecules for stem cell formation were not shown.

We established an animal model for middle ear cholesteatoma and are showing the results of our studies. KGF expression accelerates the proliferation of stem/progenitor cells through the induction of transcription factor p63 expression in the epithelium of the tympanic membrane and mucosal epithelium overlying the promontory of the cochlea and within the attic. This is typical in middle ear cholesteatoma. Moreover, the partial epithelial–mesenchymal transition under the p63 signaling pathway plays an essential role in epithelial cell growth in middle ear cholesteatoma formation. Understanding p63 expression following KGF expression and associated signaling events can improve therapeutic outcomes in patients with middle ear cholesteatoma.
Considerations and experience driving expansion of combined heart–liver transplantation
Authors: Gong Timothy , Hall Shelley
Published: August 2020

Purpose of review

Heart transplantation concomitant with a liver transplant may be warranted when end-stage heart failure results in irreversible liver failure. Previously reported outcomes have been excellent yet the specific immunoprotective role of the liver allograft is not known. We review the current literature about the immunologic benefit for combined heart and liver transplantation (CHLT).

Recent findings

The total number of combined heart and liver transplants continues to increase and accounts for approximately 25 cases per year. Familial amyloid polyneuropathy with cardiac cirrhosis is the most common indication for CHLT while adult congenital heart disease (CHD) with associated cirrhosis is increasing in frequency. The majority of recent registry data suggest a statistically equivalent to modestly improved survival advantage for CHLT compared with isolated heart transplantation. Direct mechanisms accounting for this survival advantage are not proven, but combined heart and liver transplants experience lower rates of acute cardiac rejection and cardiac allograft vasculopathy (CAV).

Combined heart and liver transplants remain a small percentage of the total heart transplants worldwide, but the majority of recent literature confirms the safety and viability of this option for patients with end-stage heart and liver disease. Equivalent to modestly improved survival outcomes, lower rates of acute cardiac rejection and CAV warrant further investigation into the liver allograft's immunoprotective effect on the transplanted heart. The key mechanisms of tolerogenicity have important implications for surgical technique and immunosuppression requirements. Future directions include development of criteria for heart–liver transplant candidacy and identification of equitable allocation protocols.
Symptomatic Persistent Fetal Ovarian Cysts
Authors: Souganidis Ellie , Chen Aaron , Friedlaender Eron
Published: August 2020

Vomiting in young infants is a common presentation to the pediatric emergency department with a broad differential diagnosis. We present 2 cases seen in our emergency department of infant females with symptomatic complex ovarian cysts who presented with vomiting. The first case study describes a patient with a prenatally diagnosed ovarian cyst that was being followed with serial ultrasounds by general surgery. The second case study describes a patient with reportedly normal prenatal ultrasounds with a subsequent diagnosis of a large complex ovarian cyst. These cases were selected to review pertinent imaging findings, discuss management decisions, and expand the differential of vomiting in the young female infants.
Two Cases of Intramuscular Hemangiomas in the Upper Limbs
Authors: Sobotová Karolína , Mezian Kamal , Abdulsalam Ahmad Jasem , Galko Jan , Özçakar Levent
Published: August 2020

Intramuscular hemangiomas are benign soft tissue tumors that are rarely found in the upper limbs. Diagnosing these tumors may be challenging owing to their pertinent nonspecific symptoms—often leading to misdiagnoses like tendinitis or muscle strain. In this article, two cases of intramuscular hemangiomas are presented—one in flexor pollicis brevis muscle and the other one in flexor digitorum superficialis muscle. Both subjects had nonspecific clinical symptoms whereby ultrasound imaging led to prompt diagnosis. To this end, the authors strongly advocate sonographic examination as an extension of physical examination in the daily clinical practice of musculoskeletal physicians.
The Time Course of Onset and Peak Effects of Phenol Neurolysis
Authors: Zhang Bei , Darji Nathan , Francisco Gerard E. , Li Sheng
Published: August 2020

Objective

The aim of this study was to explore the time course of onset and peak effects of phenol neurolysis.

Design

This is a retrospective chart review. Eleven patients with elbow flexor spasticity after brain injury were enrolled. The resting angle of the elbow joint was measured before and after the injection and up to 6 wks of follow-up.

Results

Phenol injection was performed to 13 musculocutaneous nerves under ultrasound and electrical stimulation guidance. The resting elbow angles were 84.4° ± 25.8° (before injection), 116.6° ± 20.9° (immediately after injection), 121.2° ± 21.4° (2 hrs after injection), 127.2° ± 19.7° (24 hrs after injection), 145.4° ± 11.8° (7 days after injection), 145.5° ± 10.4° (14 days after injection), and 150.3° ± 12.2° (6 wks after injection; N = 7). The mean resting angle was statistically different among the time points from preinjection to 14 days after (F
2.625, 31.505 = 36.805, P < 0.01). Post hoc tests revealed that significant improvements existed immediately after and 7 days after the injection (P < 0.01 for both). The effects seemed to reach its peak in 7 days. The effect sizes immediately and 7 days after the injection were 1.37 and 3.04, respectively. The immediate effect accounted for approximately 60% of the maximal effect.

Conclusions

Phenol neurolysis has an immediate effect on spasticity reduction and reaches its peak effect around 1 wk after injection.
Heart Rate Reactivity to Acute Psychological Stress Predicts Higher Levels of Posttraumatic Stress Disorder Symptoms During the COVID-19 Pandemic
Authors: Ginty Annie T. , Young Danielle A. , Tyra Alexandra T. , Hurley Page E. , Brindle Ryan C. , Williams Sarah E.
Published: August 2020

Objective

Increased autonomic arousal is a proposed risk factor for posttraumatic stress disorder (PTSD). Few studies have prospectively examined the association between physiological responses to acute psychological stress before a traumatic event and later PTSD symptoms. The present prospective study examined whether cardiovascular responses to an acute psychological stress task before the COVID-19 global pandemic predicted PTSD symptoms related to the ongoing pandemic.

Methods

Participants (n = 120) were a subsample of an ongoing research study. Phase 1 consisted of a 10-minute baseline and 4-minute acute psychological stress task with blood pressure and heart rate recorded throughout. Phase 2 was initiated 2 weeks after the COVID-19 pandemic declaration. Participants completed the Impact of Event Scale—Revised (IES-R) with respect to the ongoing pandemic. Hierarchical linear regression analyses were used to examine whether cardiovascular stress reactivity predicted COVID-19 PTSD symptoms.

Results

Heart rate reactivity significantly predicted IES intrusion (β = −0.208, t = −2.28, p = .025, ΔR
2 = 0.041, confidence interval = −0.021 to −0.001) and IES hyperarousal (β = −0.224, t = −2.54, p = .012, ΔR
2 = 0.047, confidence interval = −0.22 to − 0.003), but not IES avoidance (p = .077). These results remained statistically significant after adjustment for sex, socioeconomic status, baseline cardiovascular activity, neuroticism, race, ethnicity, body mass index, and adverse childhood experiences. There were no statistically significant associations between blood pressure and any of the Impact of Event Scale—Revised subscales (p values > .12).

Conclusions

Diminished heart rate responses (i.e., lower physiological arousal) to acute psychological stress before the COVID-19 pandemic significantly predicted reported PTSD symptoms during the crisis.
The Oswald injury
Authors: Barr Justin , Jones Ronald C. , Pappas Theodore N.
Published: August 2020

On November 22, 1963, John F. Kennedy, the 35th president of the United States, was assassinated in Dallas, Texas. John B. Connally, the Governor of Texas, simultaneously was injured in the shooting. Both Kennedy and Connally were transported to and cared for at the Parkland Memorial Hospital. Within 3 hours, the accused assassin, Lee Harvey Oswald, was arrested and taken to the Dallas City Jail in the Downtown Municipal Building. When the authorities were transferring Oswald from the City to the County Jail at midday on November 24, Jack Ruby shot him as the event was televised and broadcast live to the nation. Oswald was rushed to Parkland Memorial Hospital where he was operated on by the same surgeons who had attended Kennedy and Connally 2 days previously. This article reviews the operative treatment that Oswald received before discussing the state of abdominal vascular trauma in the 1960s.
Outcomes and implications of a single brain death examination policy on organ donation outcomes at a high-volume trauma center
Authors: Matar Abraham J. , Wichmann Hannah , Kenney Lisa , Subramanian Anuradha , Ratcliff Jonathan , Patel Vishal , Tracy Brett M. , Gelbard Rondi B.
Published: August 2020

BACKGROUND

Despite current neurological guidelines that a single brain death examination (SBDE) is sufficient to determine brain death, a vast majority of hospitals still use a two brain death examination (TBDE) policy based on historical practice. The purpose of this study was to analyze the outcomes and implications of an SBDE policy compared with a TBDE policy with respect to organ donation outcomes.

METHODS

We retrospectively reviewed all adult patients declared dead by neurological criteria between 2010 and 2018 at a high-volume trauma center. The study population was divided into SBDE and TBDE cohorts. Primary outcomes included time to organ donation, terminal donor creatinine and bilirubin, and number of procured and transplanted organs.

RESULTS

A total of 327 patients comprised the study population: 66.7% SBDE (n = 218 of 327 patients) and 33.3% TBDE (n = 109 of 327 patients). The SBDE group had a shorter median time from examination to procurement (38 vs. 44 hours, p = 0.02) as well as lower terminal donor creatinine (1.1 vs. 1.35 mg/dL, p = 0.004) and bilirubin (0.8 vs. 1.1 mg/dL, p = 0.04). Furthermore, the SBDE group had a significantly greater proportion of kidneys (90.6% vs. 81.6%, p = 0.02), lungs (11.8% vs. 4.6%, p = 0.02), and total organs (58.2% vs. 46.6%; p = 0.0001) procured with intent to transplant and a greater proportion of total organs transplanted (53.1% vs. 42.4%, p = 0.0004). Multivariable regression analysis confirmed that SBDE was independently associated with a shorter time to procurement, lower terminal creatinine, and increased number of procured organs.

CONCLUSION

These data highlight the potential benefit of an SBDE policy with regards to organ donation outcomes at a high-volume trauma center and should facilitate future randomized prospective studies to more rigorously test this hypothesis.

LEVEL OF EVIDENCE

Therapeutic/Care Management, level IV.
Review of the burden of eating disorders: mortality, disability, costs, quality of life, and family burden
Authors: van Hoeken Daphne , Hoek Hans W.
Published: August 2020

Purpose of review

To review the recent literature on the burden of eating disorders in terms of mortality, disability, quality of life, economic cost, and family burden, compared with people without an eating disorder.

Recent findings

Estimates are that yearly over 3.3 million healthy life years worldwide are lost because of eating disorders. In contrast to other mental disorders, in anorexia nervosa and bulimia nervosa years lived with disability (YLDs) have increased. Despite treatment advances, mortality rates of anorexia nervosa and bulimia nervosa remain very high: those who have received inpatient treatment for anorexia nervosa still have a more than five times increased mortality risk. Mortality risks for bulimia nervosa, and for anorexia nervosa treated outside the hospital, are lower but still about twice those of controls. In people with an eating disorder, quality of life is reduced, yearly healthcare costs are 48% higher than in the general population, the presence of mental health comorbidity is associated with 48% lower yearly earnings, the number of offspring is reduced, and risks for adverse pregnancy and neonatal outcomes are increased.

People with a current or former eating disorder are at risk of increased mortality, high YLD rates, a reduced quality of life, increased costs, and problems with childbearing.
Developments in the psychological treatment of anorexia nervosa and their implications for daily practice
Authors: Jansingh Alberte , Danner Unna N. , Hoek Hans W. , van Elburg Annemarie A.
Published: August 2020

Purpose of review

Our aim is to give an overview of the recent literature on psychological treatment for young adults and adults with anorexia nervosa and to discuss the implications of the findings for clinical practice.

Recent findings

Three systematic reviews and meta-analyses have recently been published on psychological treatments for anorexia nervosa. Treatment outcomes are still modest and mainly focus on weight outcome, although outcomes for eating disorder disease and quality of life have also been reported. Adhering to a treatment protocol might lead to faster and better results.

For children and adolescents with anorexia nervosa, the major guidelines recommend a family-based treatment. The treatments of choice for young adults and adults with anorexia nervosa are the Maudsley Anorexia Nervosa Treatment for Adults (MANTRA), Cognitive Behaviour Therapy-Enhanced (CBT-E) and Specialist Supportive Clinical Management (SSCM), but none of these treatments seem to be superior. In search of other ways to improve outcome, shared decision making may be a way to help patients become more involved in their treatment, enhance their motivation and consequently improve the outcome.
Do damaging variants of SLC6A9, the gene for the glycine transporter 1 (GlyT-1), protect against schizophrenia?
Authors: Curtis David
Published: August 2020

The aim of the investigation was to test whether genetic variants predicted to impair the functionality of SLC6A9, which codes for the GlyT-1 glycine transporter, are protective against schizophrenia. In an exome sequenced sample of 4225 schizophrenia cases and 5834 controls, variants occurring in SLC6A9 were annotated and weights were assigned using GENEVARASSOC. Genotype counts were compared using SCOREASSOC. Variants predicted to be deleterious by SIFT and damaging by PolyPhen were examined. Genotypes at 1:44466494-G/A seemed likely to be erroneous. If these were ignored then there were 15 damaging variants in controls and five in cases. The results are consistent with the hypothesis that variants which damage SLC6A9 are protective against schizophrenia but a larger sample would be required to confirm this.
Clinical and immunological factors that distinguish COVID-19 from pandemic influenza A(H1N1)
Authors: Choreño-Parra José Alberto , Jiménez-Álvarez Luis Armando , Cruz-Lagunas Alfredo , Rodríguez-Reyna Tatiana Sofía , Ramírez-Martínez Gustavo , Sandoval-Vega Montserrat , Hernández-García Diana Lizzeth , Choreño-Parra Eduardo M. , Balderas-Martínez Yalbi I. , Martinez-Sanchez Mariana Esther , Márquez-García Eduardo , Shiutto Edda , Moreno-Rodríguez José , Barreto-Rodríguez José Omar , Vázquez-Rojas Hazel , Centeno-Sáenz Gustavo Iván , Alvarado-Peña Néstor , Salinas-Lara Citlaltepetl , Sanchez-Garibay Carlos , Hernández Gabriela , Mendoza-Milla Criselda , Domínguez Andrea , Granados Julio , Mena-Hernández Lula , Pérez-Buenfil Luis Ángel , Domínguez-Cheritt Guillermo , Cabello-Gutiérrez Carlos , Luna Cesar , Salas-Hernández Jorge , Santillán-Doherty Patricio , Regalado Justino , Hernández-Martínez Angélica , Orozco Lorena , García-Latorre Ethel Awilda , Hernández-Cárdenas Carmen M. , Khader Shabaana A. , Zlotnik Albert , Zúñiga Joaquín
Published: August 2020

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a global health threat with the potential to cause severe disease manifestations in the lungs. Although clinical descriptions of COVID-19 are currently available, the factors distinguishing SARS-CoV-2 from other respiratory viruses are unknown. Here, we compared the clinical, histopathological, and immunological characteristics of patients with COVID-19 and pandemic influenza A(H1N1). We observed a higher frequency of respiratory symptoms, increased tissue injury markers, a histological pattern of alveolar pneumonia, and higher levels of IL-1RA, TNF-α, CCL3, G-CSF, APRIL, sTNF-R1, sTNF-R2, sCD30, and sCD163 in influenza patients. Conversely, dry cough, gastrointestinal symptoms, interstitial lung pathology, increased Th1 (IL-12, IFN-γ) and Th2 (IL-4, IL-5, IL-10, IL-13) cytokine levels, along with IL-1β, IL-6, CCL11, VEGF, TWEAK, TSLP, MMP-1, and MMP-3, were observed in COVID-19 cases. We demonstrated the diagnostic potential of some clinical and immune factors to differentiate COVID-19 from pandemic influenza A(H1N1). Our data suggest that SARS-CoV-2 induces a dysbalanced polyfunctional inflammatory response that is different from the immune response against influenza. These findings might be relevant for the upcoming 2020-2021 influenza season, which is projected to be historically unique due to its convergence with COVID-19.
Combining structured and unstructured data for predictive models: a deep learning approach
Authors: Zhang Dongdong , Yin Changchang , Zeng Jucheng , Yuan Xiaohui , Zhang Ping
Published: August 2020

Background

The broad adoption of Electronic Health Records (EHRs) provides great opportunities to conduct health care research and solve various clinical problems in medicine. With recent advances and success, methods based on machine learning and deep learning have become increasingly popular in medical informatics. However, while many research studies utilize temporal structured data on predictive modeling, they typically neglect potentially valuable information in unstructured clinical notes. Integrating heterogeneous data types across EHRs through deep learning techniques may help improve the performance of prediction models.

Methods

In this research, we proposed 2 general-purpose multi-modal neural network architectures to enhance patient representation learning by combining sequential unstructured notes with structured data. The proposed fusion models leverage document embeddings for the representation of long clinical note documents and either convolutional neural network or long short-term memory networks to model the sequential clinical notes and temporal signals, and one-hot encoding for static information representation. The concatenated representation is the final patient representation which is used to make predictions.

Results

We evaluate the performance of proposed models on 3 risk prediction tasks (i.e., in-hospital mortality, 30-day hospital readmission, and long length of stay prediction) using derived data from the publicly available Medical Information Mart for Intensive Care III dataset. Our results show that by combining unstructured clinical notes with structured data, the proposed models outperform other models that utilize either unstructured notes or structured data only.

Conclusions

The proposed fusion models learn better patient representation by combining structured and unstructured data. Integrating heterogeneous data types across EHRs helps improve the performance of prediction models and reduce errors.

Availability

The code for this paper is available at: https://github.com/onlyzdd/clinical-fusion.
Clinical and Epidemiological Characteristics of the First Month of the Covid-19 Pandemic in Chile
Authors: Vial Macarena R. , Peters Anne , Pérez Inia , Spencer María , Barbé Mario , Porte Lorena , Weitzel Thomas , Aylwin Mabel , Vial Pablo , Araos Rafael , Munita Jose M. ,   for the CAS-UDD Covid-19 Working Group
Published: August 2020

Introduction

Understanding the clinical course and outcomes of patients with Covid-19 in underrepresented populations like Latin America is paramount. In this study, we report the clinical characteristics of Covid-19 in Chile, with a focus on subjects requiring hospitalization during the initial phases of the SARS-CoV-2 pandemic.

Methods

This is a single center study including all consecutive patients diagnosed with Covid-19 during the first month of the pandemic. Demographics, clinical characteristics and laboratory data were collected within 24 hours of admission. The primary outcome was a composite of ICU admission or all-cause, in-hospital mortality.

Results

During the first month of the pandemic, 381 patients were confirmed as positive for SARS-CoV-2 by molecular testing; 88 (23.1%) of them eventually required hospitalization. Median age of the cohort was 39 years (IQR 31-49). Overall mortality was 0.7% and 18 (3.7%) out of the 88 subjects who required hospitalization either died and/or required ICU. Increased body mass index (BMI), C-reactive protein levels (CRP) and the SaTO2/FiO2 index on admission were independently associated with a higher risk of ICU care or death.

Discussion

The lower mortality observed in our prospective cohort during the first month of SARS-Cov-2 pandemic was lower than previously reported. This finding could be due to a lower threshold for admission, a healthcare system not yet overburdened and a younger population, among other factors. BMI, CRP on admission were strong predictors for ICU care or all-cause, in-hospital mortality. Our data provide important information regarding the clinical course of Covid-19 in Latin America.
Protecting healthcare workers during the COVID-19 pandemic: Australian results from the PPE-SAFE survey
Authors: Ramanan Mahesh , Laupland Kevin B , Tabah Alexis
Published: August 2020

The COVID-19 pandemic has led to global shortages of personal protective equipment (PPE). Healthcare workers (HCW) have comprised a significant proportion of COVID-19 cases in many countries. The PPE-SAFE survey was conducted to study current practices, availability, shortages, training and confidence in PPE amongst intensive care HCWs around the world. Herein, we describe the results of the Australian respondents to the PPE-SAFE survey. 29% of respondents reported that at least one item of usually available PPE was missing, and 12% reported reuse of single-use items. Only 40% felt that the PPE available to them offered adequate protection. Fit-testing of respirators had never been performed for 47% of respondents, and 49% reported at least one adverse effect from the use of PPE.
A population scale analysis of rare SNCA variation in the UK Biobank
Authors: Blauwendraat Cornelis , Makarious Mary B. , Leonard Hampton L. , Bandres-Ciga Sara , Iwaki Hirotaka , Nalls Mike A. , Noyce Alastair J , Singleton Andrew B.
Published: August 2020

Parkinson’s disease (PD) is a complex neurodegenerative disease with a variety of genetic and environmental factors contributing to disease. The SNCA gene encodes for the alpha-synuclein protein which plays a central role in PD, where aggregates of this protein are one of pathological hallmarks of disease. Rare point mutations and copy number gains of the SNCA gene have been shown to cause autosomal dominant PD and common DNA variants identified using GWAS are a moderate risk factor for PD. The UK Biobank is a large prospective study including ~500,000 individuals and has revolutionized human genetics. Here we assessed the frequency of SNCA variation in this cohort and identified 26 subjects carrying variants of interest including duplications (n=6), deletions (n=6) and large complex likely mosaic events (n=14). No known pathogenic missense variants were identified. None of these subjects were reported to be a PD case, although it is possible that these individuals may develop PD at a later age, and whilst three had known prodromal features, these did not meet defined thresholds for being considered ‘prodromal’ cases. Four of the 14 large complex carriers showed a history of blood based cancer. Overall, we identified copy number variants in the SNCA region in a large population based cohort without reported PD phenotype and symptoms. Putative mosaicism of the SNCA gene was identified, however it is unclear whether it is associated with Parkinson's disease. These individuals are potential candidates for further investigation by performing SNCA RNA and protein expression studies, as well as promising clinical trial candidates to understand how duplication carriers potentially escape PD.
Towards safer risperidone prescribing in Alzheimer’s disease
Authors: Reeves Suzanne , Bertrand Julie , Uchida Hiroyuki , Yoshida Kazunari , Otani Yohei , Ozer Mikail , Liu Kathy Y , Bramon Elvira , Bies Robert , Pollock Bruce , Howard Robert
Published: August 2020

Background

In the treatment of psychosis, agitation and aggression in Alzheimer’s disease (AD), guidelines emphasise the need to ‘use the lowest possible dose’ of antipsychotic drugs, but provide no information on optimal dosing.

Aims

This analysis investigated the pharmacokinetic profiles of risperidone and active metabolite, 9-hydroxy (OH)-risperidone, and how this related to emergent extrapyramidal side effects (EPS), using data from The Clinical Antipsychotic Trials of Intervention Effectiveness-AD study.

Method

A statistical model, which described the concentration-time course of risperidone and 9-OH-risperidone, was used to predict peak, trough and average concentrations of risperidone, 9-OH-risperidone and ‘active moiety’ (combined concentrations) (108 CATIE-AD participants). Logistic regression was used to investigate the associations of pharmacokinetic biomarkers with EPS. Model based predictions were used to simulate the dose adjustments needed to avoid EPS.

Results

The model showed an age-related reduction in risperidone clearance (p<0.0001), and estimated that 22% of patients had slower active moiety clearance (concentration-to-dose ratio 20.2±7.2 versus 7.6±4.9 ng/mL per mg/day, Mann Whitney U,p<0.0001). Higher average and trough 9-OH-risperidone concentrations (p<0.0001), and lower Mini-Mental State Examination (MMSE) scores (p<0.0001), were associated with EPS. Model based predictions suggest the optimum dose ranged from 0.25mg/day in those aged 85 years with MMSEs of 5, to 1mg/day in those aged 75 years with MMSEs of 15, with alternate day dosing required for those with slower drug clearance.

Conclusions

Our findings argue for age- and MMSE -related dose adjustments and suggest that a single plasma sample could be used to identify those with slower drug clearance.
Frontline healthcare workers’ knowledge and perception of COVID-19 and willingness to work during the pandemic in Nepal: a nationwide cross-sectional web-based study
Authors: Upadhyaya Dipak Prasad , Paudel Rajan , Bromberg Daniel J. , Acharya Dilaram , Khoshnood Kaveh , Lee Kwan , Park Ji-Huyuk , Yoo Seok-Ju , Shrestha Archana , Bom BC , Bhandari Sabin , Yadav Ramgyan , Timalsina Ashish , Wagle Chetan Nidhi , Das Brij Kumar , Kunwar Ramesh , Chalise Binaya , Bhatta Deepak Raj , Adhikari Mukesh
Published: August 2020

Background

The health sector’s effectiveness during a pandemic primarily depends on the availability, knowledge, skills, perceptions, and motivations of frontline healthcare workers. In this study, we aimed to investigate the contextual factors associated with the knowledge, perceptions, and the willingness of frontline healthcare workers to work during the COVID-19 pandemic in Nepal.

Methods

A total of 1051 frontline health-workers from all seven Nepalese provinces were included in this web-based cross-sectional study, which was conducted in May 2020. Using a 5-point Likert scale questionnaire, we collected information on knowledge, perceptions, and the willingness of frontline healthcare workers to work during the COVID-19 pandemic. Multivariable logistic regression was applied to identify independent associations between predictors and outcome variables.

Results

Of the 1051 frontline health-workers, 17.2% were found to have inadequate knowledge on COVID-19, 63.6% reported unsatisfactory perceptions of government response, and 35.9% showed an unwillingness to work during the pandemic. Health workers at local health facilities (AOR: 0.35; 95% CI: 0.17-0.68) and those with chronic diseases were less likely to have adequate knowledge of COVID-19. Nurses (AOR: 2.10; 95% CI: 1.38-3.18), health-workers from Karnali Province (AOR: 2.62; 95% CI: 1.52-4.53), and those who had adequate knowledge of COVID-19 (AOR: 3.86; 95% CI: 2.51-6.16) were more likely to have satisfactory perception towards government response to COVID-19. In addition, laboratory-workers, health workers from Karnali province, and those with adequate knowledge (AOR: 1.81; 95% CI: 1.27-2.58) were more likely to work during the COVID-19 pandemic.

Conclusions

We concluded that frontline healthcare workers have some gaps in knowledge-related to COVID-19; about two-thirds of them had a negative perception of government response, and nearly one-third of them were unwilling to work. These observations demonstrate that prompt actions are required to improve health-worker knowledge of COVID-19, address negative perceptions to government responses, and motivate them to provide healthcare services during the pandemic.
Double-zero-event studies matter: a re-evaluation of physical distancing, face masks, and eye protection for preventing person-to-person transmission of COVID-19 and its policy impact
Authors: Xiao Mengli , Lin Lifeng , Hodges James S. , Xu Chang , Chu Haitao
Published: August 2020

Objectives

High-quality meta-analyses on COVID-19 are in urgent demand for evidence-based decision making. However, conventional approaches exclude double-zero-event studies (DZS) from meta-analyses. We assessed whether including such studies impacts the conclusions in a recent systematic urgent review on prevention measures for preventing person-to-person transmission of COVID-19.

Study designs and settings

We extracted data for meta-analyses containing DZS from a recent review that assessed the effects of physical distancing, face masks, and eye protection for preventing person-to-person transmission. A bivariate generalized linear mixed model was used to re-do the meta-analyses with DZS included. We compared the synthesized relative risks (RRs) of the three prevention measures, their 95% confidence intervals (CI), and significance tests (at the level of 0.05) including and excluding DZS.

Results

The re-analyzed COVID-19 data containing DZS involved a total of 1,784 participants who were not considered in the original review. Including DZS noticeably changed the synthesized RRs and 95% CIs of several interventions. For the meta-analysis of the effect of physical distancing, the RR of COVID-19 decreased from 0.15 (95% CI, 0.03 to 0.73) to 0.07 (95% CI, 0.01 to 0.98). For several meta-analyses, the statistical significance of the synthesized RR was changed. The RR of eye protection with a physical distance of 2 m and the RR of physical distancing when using N95 respirators were no longer statistically significant after including DZS.

Conclusions

DZS may contain useful information. Sensitivity analyses that include DZS in meta-analysis are recommended.