bluuebunny/crossref_metadata_2025 huggingface dataset:
A Reappraisal of the Pathophysiology of Cushing Ulcer: A Narrative Review
Authors: Kumaria Ashwin , Kirkman Matthew A. , Scott Robert A. , Dow Graham R. , Leggate Alex J. , Macarthur Donald C. , Ingale Harshal A. , Smith Stuart J. , Basu Surajit
Published: May 2023

In 1932, Harvey Cushing described peptic ulceration secondary to raised intracranial pressure and attributed this to vagal overactivity, causing excess gastric acid secretion. Cushing ulcer remains a cause of morbidity in patients, albeit one that is preventable. This narrative review evaluates the evidence pertaining to the pathophysiology of neurogenic peptic ulceration. Review of the literature suggests that the pathophysiology of Cushing ulcer may extend beyond vagal mechanisms for several reasons: (1) clinical and experimental studies have shown only a modest increase in gastric acid secretion in head-injured patients; (2) increased vagal tone is found in only a minority of cases of intracranial hypertension, most of which are related to catastrophic, nonsurvivable brain injury; (3) direct stimulation of the vagus nerve does not cause peptic ulceration, and; (4) Cushing ulcer can occur after acute ischemic stroke, but only a minority of strokes are associated with raised intracranial pressure and/or increased vagal tone. The 2005 Nobel Prize in Medicine honored the discovery that bacteria play key roles in the pathogenesis of peptic ulcer disease. Brain injury results in widespread changes in the gut microbiome in addition to gastrointestinal inflammation, including systemic upregulation of proinflammatory cytokines. Alternations in the gut microbiome in patients with severe traumatic brain injury include colonization with commensal flora associated with peptic ulceration. The brain-gut-microbiome axis integrates the central nervous system, the enteric nervous system, and the immune system. Following the review of the literature, we propose a novel hypothesis that neurogenic peptic ulcer may be associated with alterations in the gut microbiome, resulting in gastrointestinal inflammation leading to ulceration.
Differences in Perioperative Management of Patients Undergoing Complex Spine Surgery: A Global Perspective
Authors: Blacker Samuel N. , Woody Nathan , Abate Shiferaw Ananya , Burbridge Mark , Bustillo Maria A. , Hazard Sprague W. , Heller Benjamin J. , Lamperti Massimo , Mejia-Mantilla Jorge , Nadler Jacob W. , Rath Girija Prasad , Robba Chiara , Vincent Anita , Admasu Azarias K. , Awraris Meron , Lele Abhijit V.
Published: May 2023

Background:

The aim of this survey was to understand institutional spine surgery practices and their concordance with published best practices/recommendations.

Methods:

Using a global internet-based survey examining perioperative spine surgery practice, reported institutional spine pathway elements (n=139) were compared with the level of evidence published in guideline recommendations. The concordance of clinical practice with guidelines was categorized as poor (≤20%), fair (21%–40%), moderate (41%–60%), good (61%–80%), or very good (81%–100%).

Results:

Seventy-two of 409 (17.6%) institutional contacts started the survey, of which 31 (7.6%) completed the survey. Six (19.4%) of the completed surveys were from respondents in low/middle-income countries, and 25 (80.6%) were from respondents in high-income countries. Forty-one incomplete surveys were not included in the final analysis, as most were less than 40% complete. Five of 139 (3.6%) reported elements had very good concordance for the entire cohort; hospitals with spine surgery pathways reported 18 elements with very good concordance, whereas institutions without spine surgery pathways reported only 1 element with very good concordance. Reported spine pathways included between 7 and 47 separate pathway elements. There were 87 unique elements in the reviewed pathways. Only 3 of 87 (3.4%) elements with high-quality evidence demonstrated very good practice concordance.

Conclusions:

This global survey-based study identified practice variation and low adoption rates of high-quality evidence in the care of patients undergoing complex spine surgery.
Use of the Strong Black Woman Construct in Research
Authors: Henry Carrie J. , Song Mi-Kyung
Published: May 2023

This was an integrative review of the literature on research using the strong Black woman (SBW) construct. We searched for data-based articles that mentioned SBW and examined topical areas of investigation, health outcomes and other constructs associated with SBW, and methods used to assess SBW. We found 47 articles. SBW was used to study coping with trauma (n = 11) or perceived offense (n = 10), or engaging in health-seeking behaviors (n = 10). Eighteen studies suggested that SBW was linked to several major health conditions (eg, hypertension, obesity, heart disease) and depressive and anxiety symptoms. SBW was positively correlated with undesirable coping behaviors (eg, self-silencing, maladaptive perfectionism) and negatively associated with self-compassion and help-seeking. The most common method of assessing SBW was using a structured questionnaire (n = 21). Longitudinal studies to examine the impact of SBW belief on Black women's coping with hardship were lacking.
Extracorporeal shockwaves therapy versus corticosteroid injection for the treatment of non-calcific rotator cuff tendinopathies: a randomized trial
Authors: Ebadi Safoora , Karimzad Yousef , Aflakian Negar , Forogh Bijan , Mansoori Korosh , Babaei-Ghazani Arash
Published: May 2023

Background:

Rotator cuff tendinopathy is the most common cause of painful shoulder. There is evidence supporting the use of extracorporeal shock wave therapy (ESWT) in the rotator cuff calcific tendinopathy, but evidence supporting its use in non-calcifying tendinopathy is lacking. The current study aimed to compare the clinical effectiveness of corticosteroid injections versus ESWT until 3 mo of follow-up for the management of painful non-calcific rotator cuff tendinopathies.

Methods:

A total of 33 patients affected by painful rotator cuff tendinopathy were randomly divided into 2 groups of 16 and 17 cases. The first group received corticosteroid injection under ultrasound guidance and the second group received three sessions of shockwave within 3 consecutive weeks consisted of 2000 pulse energy, 5 Hz frequency, and pressure of 4 bar using a radial shock wave device. Two outcome measures of VAS and Quick-DASH were obtained to evaluate patients before treatment, and 2 and 12 wk after treatment.

Discussion:

Regarding both VAS and the score of the Quick-DASH questionnaire, no statistically significant difference was observed between these 2 therapeutic interventions (ultrasound-guided corticosteroid injection and shockwave). Both interventions reduced the patient’s pain to the same extent (P-value=0.955 for VAS, and P-value=0.865 for Quick DASH questionnaire score). Moreover, within-group changes showed that both groups’ improvements were significant in the time intervals of 1 to 2 and 1 to 3.

Conclusions:

Corticosteroid injection and radial shockwave, both can be effective to the same extent in reducing pain and improving function in non-calcific shoulder tendinopathy.

Level of Evidence:

Level I.
Association Between Vaccination Status and Outcomes in Patients Admitted to the ICU With COVID-19*
Authors: van Diepen Sean , McAlister Finlay A. , Chu Luan Manh , Youngson Erik , Kaul Padma , Kadri Sameer S.
Published: May 2023

OBJECTIVES:

Although COVID-19 vaccines can reduce the need for intensive care unit admission in COVID-19, their effect on outcomes in critical illness remains unclear. We evaluated outcomes in vaccinated patients admitted to the ICU with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the association between vaccination and booster status on clinical outcomes.

DESIGN:

Retrospective cohort.

SETTING AND PATIENTS:

All patients were admitted to an ICU between January 2021 (after vaccination was available) and July 2022 with a diagnosis of COVID-19 based on a SARS-CoV-2 polymerase chain reaction test in Alberta, Canada.

INTERVENTIONS:

None.

MEASUREMENT:

The propensity-matched primary outcome of all-cause in-hospital mortality was compared between vaccinated and unvaccinated patients, and vaccinated patients were stratified by booster dosing. Secondary outcomes were mechanical ventilation (MV) duration ICU length of stay (LOS).

MAIN RESULTS:

The study included 3,293 patients: 743 (22.6%) were fully vaccinated (54.6% with booster), 166 (5.0%) were partially vaccinated, and 2,384 (72.4%) were unvaccinated. Unvaccinated patients were more likely to require invasive MV (78.4% vs 68.2%), vasopressor use (71.1% vs 66.6%), and extracorporeal membrane oxygenation (2.1% vs 0.5%). In a propensity-matched analysis, in-hospital mortality was similar (31.8% vs 34.0%, adjusted odds ratio [OR], 1.25; 95% CI, 0.97–1.61), but median duration MV (7.6 vs 4.7 d;p< 0.001) and ICU LOS (6.6 vs 5.2 d;p< 0.001) were longer in unvaccinated compared to fully vaccinated patients. Among vaccinated patients, greater than or equal to 1 booster had lower in-hospital mortality (25.5% vs 40.9%; adjusted OR, 0.50; 95% CI, 0.0.36–0.68) and duration of MV (3.8 vs 5.6 d;p= 0.025).

CONCLUSIONS:

Nearly one in four patients admitted to the ICU with COVID-19 after widespread COVID-19 vaccine availability represented a vaccine-breakthrough case. Mortality risk remains substantial in vaccinated patients and similar between vaccinated and unvaccinated patients after the onset of critical illness. However, COVID-19 vaccination is associated with reduced ICU resource utilization and booster dosing may increase survivability from COVID-19-related critical illness.
Association Between eHealth Literacy and Health Education Experiences and Confidence Regarding Online Health Information Among Nurses
Authors: Tanaka Junichi , Ohnishi Mayumi , Hamasaki Miwa , Imoto Yui , Matsuno Arisa , Sakurai Takayoshi , Igawa Nana , Kuroda Hiromi
Published: May 2023

This cross-sectional study examined nurses' eHealth literacy, health education experiences, and confidence in health education regarding online health information and explored their association. A self-administered questionnaire was distributed among 442 nurses in Japan from September 2020 to March 2021. The survey items were the Japanese version of the eHealth Literacy Scale, health education experiences and confidence in health education regarding online health information, and sociodemographic variables. The final analysis comprised 263 responses. Nurses' mean eHealth literacy was 21.89. Most nurses had never received questions regarding online health information in search (66.9%), evaluation (85.2%), and utilization (81.0%) from their patients. Further, most nurses lacked experience (84.0%–89.7%) and confidence (94.7%–97.3%) in health education regarding online health information. The factor associated with having health education experience regarding online health information was eHealth literacy (adjusted odds ratio, 1.08; 95% confidence interval, 1.02–1.15). Factors associated with having confidence in health education regarding online health information were eHealth literacy (adjusted odds ratio, 1.10; 95% confidence interval, 1.10–1.43) and having learning experiences regarding eHealth literacy (adjusted odds ratio, 7.36; 95% confidence interval, 2.06–26.39). Our findings suggest the importance of enhancing eHealth literacy among nurses and a proactive approach by nurses to improve patients' eHealth literacy.
Development of the Scientific, Transparent and Applicable Rankings (STAR) tool for clinical practice guidelines
Authors: Yang Nan , Liu Hui , Zhao Wei , Pan Yang , Lyu Xiangzheng , Hao Xiuyuan , Liu Xiaoqing , Qi Wen’an , Chen Tong , Wang Xiaoqin , Zhang Boheng , Zhang Weishe , Li Qiu , Xu Dong , Gao Xinghua , Jin Yinghui , Sun Feng , Meng Wenbo , Li Guobao , Wu Qijun , Chen Ze , Wang Xu , Estill Janne , Norris Susan L. , Du Liang , Chen Yaolong , Wei Junmin
Published: May 2023

Background:

This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability.

Methods:

This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability.

Results:

STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min.

Conclusion:

The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.
Surgical Approaches to Orbital Fractures: A Practical and Systematic Review
Authors: Palavalli Manoj H. , Huayllani Maria T. , Gokun Yevgeniya , Lu Yurong , Janis Jeffrey E.
Published: May 2023

Background:

Orbital fractures constitute a significant percentage of all midface injuries. Here, we present a contemporary evidence-based review of the major surgical approaches for orbital wall fractures and analyze the literature to compare all major surgical procedures and their complication rates.

Method:

A systematic review was conducted to compare surgical approaches (subciliary, transcaruncular, transconjunctival, subtarsal, and endoscopic) and postoperative complications in patients who underwent surgical fixation of orbital wall fractures. A database search in PubMed (PubMed Central, MEDLINE and Bookshelf) was performed for all articles containing the terms “orbital,” “wall,” “fracture,” and “surgery” with different combinations.

Results:

A total of 950 articles were obtained and 25 articles were included, representing an analysis of 1137 fractures. The most frequent surgical approach was the endoscopic (33.3%) followed by the external surgical approaches, specifically transconjunctival (32.8%), subciliary (13.5%), subtarsal (11.5%), and transcaruncular (8.9%). The transconjunctival approach had a statistically significantly higher rate of complications (36.19%), followed by the subciliary (21.4%), and endoscopic approach (20.2%, P < 0.0001). The subtarsal approach had a statistically significantly lower rate of complications (8.2%) followed by the transcaruncular approach (14.0%, P < 0.0001).

Conclusion:

The subtarsal and transcaruncular approaches were observed to have the lowest rates of complications, whereas the transconjunctival, subciliary, and endoscopic approaches were reported to have higher rates of complications.
Etiological cure prevents further decompensation and mortality in patients with cirrhosis with ascites as the single first decompensating event
Authors: Tonon Marta , Balcar Lorenz , Semmler Georg , Calvino Valeria , Scheiner Bernhard , Incicco Simone , Barone Anna , Paternostro Rafael , Gambino Carmine G. , Bauer David Josef M. , Accetta Antonio , Hartl Lukas , Brocca Alessandra , Jachs Mathias , Trauner Michael , Mandorfer Mattias , Angeli Paolo , Reiberger Thomas , Piano Salvatore
Published: May 2023

Background and Aims:

Removal/suppression of the primary etiological factor reduces the risk of decompensation and mortality in compensated cirrhosis. However, in decompensated cirrhosis, the impact of etiologic treatment is less predictable. We aimed to evaluate the impact of etiological treatment in patients with cirrhosis who developed ascites as single index decompensating event.

Approach and Results:

Patients with cirrhosis and ascites as single first decompensation event were included and followed until death, liver transplantation, or Q3/2021. The etiology was considered “cured” (alcohol abstinence, hepatitis C cure, and hepatitis B suppression) versus “controlled” (partial removal of etiologic factors) versus “uncontrolled.” A total of 622 patients were included in the study. Etiology was “cured” in 146 patients (24%), “controlled” in 170 (27%), and “uncontrolled” in 306 (49%). During follow-up, 350 patients (56%) developed further decompensation. In multivariable analysis (adjusted for age, sex, varices, etiology, Child-Pugh class, creatinine, sodium, and era of decompensation), etiological cure was independently associated with a lower risk of further decompensation (HR: 0.46; p = 0.001). During follow-up, 250 patients (40.2%) died, while 104 (16.7%) underwent LT. In multivariable analysis, etiological cure was independently associated with a lower mortality risk (HR: 0.35, p < 0.001).

Conclusions:

In patients with cirrhosis and ascites as single first decompensating event, the cure of liver disease etiology represents a main treatment goal since this translates into considerably lower risks of further decompensation and mortality.
Association between modifiable vascular risk factors and rapid progression of postradiation carotid artery stenosis
Authors: Cheng Ya-Wen , Chen Chih-Hao , Yeh Shin-Joe , Tsai Li-Kai , Wang Chun-Wei , Tang Sung-Chun , Jeng Jiann-Shing
Published: May 2023

Background:

Postradiotherapy carotid vasculopathy is a clinically relevant complication in patients with head and neck cancer receiving radiotherapy. In this study, we investigated the factors associated with the development and progression of carotid artery stenosis (CAS) in such patients.

Methods:

Patients who received radiotherapy for head and neck cancers between October 2011 and May 2019 at a medical center in Taiwan were eligible for inclusion in this study. This study included patients who underwent two consecutive carotid duplex examinations within an interval of 1 to 3 years. The factors associated with ≥50% CAS at baseline and follow-up were analyzed.

Results:

In total, 694 patients (mean age, 57.8 ± 9.9 years; men, 75.2%; nasopharyngeal cancer, 73.3%) were included. The mean interval between radiotherapy and carotid duplex examination was 9.9 ± 5.9 years. At baseline, 103 patients had ≥50% CAS, which was significantly associated with tobacco smoking, hypercholesterolemia, and a prolonged interval between radiotherapy and carotid duplex examination. A total of 586 patients did not have CAS at baseline; of them, 68 developed ≥50% CAS during follow-up. Hypertension and hypercholesterolemia were identified as independent risk factors for CAS progression.

Conclusion:

Modifiable vascular risk factors, such as hypertension and hypercholesterolemia, appear to be significantly associated with the rapid progression of postradiotherapy CAS in patients with head and neck cancer.
The clinical safety of generic and brand clopidogrel in patients undergoing carotid endarterectomy: a randomized controlled trial
Authors: Kakamad Fahmi H. , Baqi Dana H. , Hassan Marwan N. , Salih Karzan M. , Rahim Hawbash M. , Mohammed Shvan H. , Abdalla Berun A. , Salih Rawezh Q. , Ali Rebwar A. , Kakamad Suhaib H. , Abdullah Hiwa O.
Published: May 2023

Introduction:

Although some recent studies have found that original and generic clopidogrel brands are acceptable and have the same pharmacokinetic and pharmacodynamic properties, there is insufficient evidence to compare the clinical effectiveness and safety of brand and generic clopidogrel. The current study aims to evaluate the clinical safety of brand and generic clopidogrel by comparing clinical outcomes in patients undergoing carotid endarterectomy (CEA).

Method:

This was a single centre, parallel-arm, phase III, open-label, and randomized group sequential trial. It was conducted to compare the clinical safety of a brand and three generic clopidogrel forms in patients who have undergone CEA. All enrolled subjects were treated perioperatively with dual antiplatelet (aspirin and clopidogrel). The involved participants were assigned randomly into four groups based on the type of clopidogrel. Safety parameters were measured, including haematoma, blood draining from drainage, mouth deviation, tongue deviation, and stroke. SPSS software was used to perform the data analysis.

Results:

The trial included 80 patients in total (20 patients per group). Thirty-one (38.8%) patients were male. The mean age of patients was 65.6 years (49–79). Eighteen (22.5%) patients had a history of previous coronary intervention, and seventeen (21.3%) had symptomatic carotid artery stenosis. Overall, Plavix or Piax combined with aspirin were linked to better clinical safety than the other two generic clopidogrel, as the amount of bleeding was nearly two times lower in patients treated with Plavix or Piax (270±92.39 and 271.5±80.60, respectively) compared to PlavigrelAwa or Plavineer (505.7±169.1 and 496.5±174.6, respectively) (P≤0.001).

Conclusion:

The findings of the current study showed diversity in clinical safety of different clopidogrel formulations that were provided perioperatively in CEA patients.
Does Revision Carpal Tunnel Release Result in Long-term Outcomes Equivalent to Single Carpal Tunnel Release? A Matched Case-Control Analysis.
Authors: Westenberg Ritsaart F. , DiGiovanni Peter L. , Schep N.W.L. , Eberlin Kyle R. , Chen Neal C. , Coert J.H.
Published: May 2023

Aims:

The aims of this study are: (1) to evaluate the long-term patient reported outcomes (PROM’s) after revision CTR and compare these outcomes with patients who had a single CTR and a comparable age, sex, race, type of initial surgery and follow-up time, and (2) assess which factors are associated with worse PROM’s after revision CTR.

Methods:

We retrospectively identified 7351 patients who had a single CTR and 113 patients who had a revision CTR for CTS between 01/2002 and 12/2015 at five academic urban hospitals. Of these 113 revision CTR cases, there were 37 patients who completed a follow-up questionnaire including the BCTQ, the NRS Pain and Satisfaction. Those who completed the follow-up questionnaire were randomly matched to five controls (patients who had a single CTR) based on age, sex, race, type of initial surgery, and follow-up time. Of these 185 matched controls, 65 patients completed the follow-up questionnaire.

Results:

A linear mixed effects model using the matched sets as a random effect showed that patients who had a revision CTR had a higher total BCTQ score, NRS pain score, and a lower satisfaction score at time of follow-up than patients who only had a single CTR. Multivariable linear regression showed that thenar muscle atrophy prior to the revision surgery was independently associated with more pain after revision surgery.

Conclusion:

Patients improve after revision CTR, but generally have more pain, a higher BCTQ score, and are less satisfied at long-term follow-up compared to patient who had a single CTR.
Insurance Status Predicts Hand Therapy Adherence Following Flexor Tendon Repair: A Retrospective Cohort Study”
Authors: McLaughlin Matthew T. , Moura Steven P. , Edalatpour Armin , Seitz Allison J. , Michelotti Brett F.
Published: May 2023

Background:

Many patients are not adherent to hand therapy rehabilitation following surgical repair of traumatic flexor tendon injuries, which can negatively affect surgical outcomes and long-term hand function. We aimed to identify the factors that predict patient non-adherence to hand therapy following flexor tendon repair surgery.

Methods:

This retrospective cohort study included 154 patients who underwent surgical repair of flexor tendon injuries at a level I trauma center between January 2015 and January 2020. A manual chart review was performed to collect demographic data, insurance status, injury characteristics, and details of the postoperative course including health care utilization.

Results:

Factors significantly associated with occupational therapy no-shows included Medicaid insurance (OR, 8.35; 95% CI, 2.91 to 24.0; p < 0.001), self-identified Black race (OR, 7.28; 95% CI, 1.78 to 29.7; p = 0.006), and current cigarette smoker status (OR, 2.69; 95% CI, 1.18 to 6.15; p = 0.019). Patients without insurance attended 73.8% of their OT visits and patients with Medicaid attended 72.0% of their visits, which were significantly lower rates than those with private insurance 90.7% (p=0.026 and p=0.001, respectively). Patients with Medicaid were 8 times more likely to seek emergency department care postoperatively than patients with private insurance (p=0.002).

Conclusions:

Significant disparities in hand therapy adherence following flexor tendon repair surgery exist between patients with different insurance statuses, races, and tobacco use. Understanding these disparities can help providers identify at-risk patients to improve hand therapy utilization and postoperative outcomes.
Impact of Median MELD at Transplant Minus 3 National Policy on Quality of Transplanted Livers for Patients With and Without Hepatocellular Carcinoma
Authors: Mazur Rafal D. , Cron David C. , Chang David C. , Yeh Heidi , Dageforde Leigh Anne D.
Published: May 2023

Background.

Patients with hepatocellular carcinoma (HCC) have been overprioritized in the deceased donor liver allocation system. The United Network for Organ Sharing adopted a policy in May 2019 that limited HCC exception points to the median Model for End-Stage Liver Disease at transplant in the listing region minus 3. We hypothesized this policy change would increase the likelihood to transplant marginal quality livers into HCC patients.

Methods.

This was a retrospective cohort study of a national transplant registry, including adult deceased donor liver transplant recipients with and without HCC from May 18, 2017, to May 18, 2019 (prepolicy) to May 19, 2019, to March 1, 2021 (postpolicy). Transplanted livers were considered of marginal quality if they met ≥1 of the following: (1) donation after circulatory death, (2) donor age ≥70, (3) macrosteatosis ≥30% and (4) donor risk index ≥95th percentile. We compared characteristics across policy periods and by HCC status.

Results.

A total of 23 164 patients were included (11 339 prepolicy and 11 825 postpolicy), 22.7% of whom received HCC exception points (prepolicy versus postpolicy: 26.1% versus 19.4%; P = 0.03). The percentage of transplanted donor livers meeting marginal quality criteria decreased for non-HCC (17.3% versus 16.0%; P < 0.001) but increased for HCC (17.7% versus 19.4%; P < 0.001) prepolicy versus postpolicy. After adjusting for recipient characteristics, HCC recipients had 28% higher odds of being transplanted with marginal quality liver independent of policy period (odds ratio: 1.28; confidence interval, 1.09-1.50; P < 0.01).

Conclusions.

The median Model for End-Stage Liver Disease at transplant in the listing region minus 3 policy limited exception points and decreased the quality of livers received by HCC patients.
Middle-income country perspectives on global mental health
Authors: Adams Amy S. , Sibeko Goodman , Stein Dan J.
Published: May 2023

Purpose of review

Despite being a relatively new discipline, global mental health (GMH) has made substantial advances, paying particular attention to optimising the provision of mental health services in low- and middle-income countries (LMICs). Much of the work done in GMH has focused on low-income countries (LIC), but middle-income countries (MIC) such as Brazil, China, India, and South Africa, have particular characteristics that may impact the nature of this work. Here we examine key GMH issues, including mental health legislation, burden of disease, task-sharing, and mental health clinical and research capacity-building, in the MIC context.

Recent findings

In MICs there is particular concern about an increase in non-communicable diseases, including mental disorders. MICs have more resources than LICs, but the treatment gap in these settings remains significant. MICs are better equipped than LICs to mobilize task-sharing programs, and these can potentially include more highly educated community health workers. In MICs there have been important advances in mental health legislation, but more is needed regarding implementation and the promotion of human rights. Clinical and research capacity-building initiatives in MIC contexts are easier to establish and have potential to be more ambitious in scope.

GMH has developed important universal principles that apply across low-, middle-, and high-income countries. Nevertheless, particular issues in MICs may require moulding of more general GMH frameworks.
Seeking order in patterns of polysubstance use
Authors: Connor Jason P. , Leung Janni , Chan Gary C.K. , Stjepanović Daniel
Published: May 2023

Purpose of review

This review provides an overview of recent developments in understanding polysubstance use patterns across the lifespan, and advances made in the prevention and treatment of harm arising from polysubstance use.

Recent findings

A comprehensive understanding of the patterns of polysubstance use is hampered by heterogeneity across study methods and types of drugs measured. Use of statistical techniques such as latent class analysis has aided in overcoming this limitation, identifying common patterns or classes of polysubstance use. These typically include, with decreasing prevalence, (1) Alcohol use only; (2) Alcohol and Tobacco; (3) Alcohol, Tobacco, and Cannabis; and finally (4) a low prevalence, Extended Range cluster that includes other illicit drugs, New Psychoactive Substances (NPS), and nonmedical prescription medications.

Across studies, there are commonalities present in clusters of substances used. Future work that integrates novel measures of polysubstance use and leverages advances in drug monitoring, statistical analysis and neuroimaging will improve our understanding of how and why drugs are combined, and more rapidly identify emerging trends in multiple substance use. Polysubstance use is prevalent but there is a paucity of research exploring effective treatments and interventions.
7-Nitroindazole reduces L-DOPA-induced dyskinesias in non-human Parkinsonian primate
Authors: Herrero M. T. , Yuste J. E. , Cuenca-Bermejo L. , Almela P. , Arenas-Betancur L. , De Pablos V. , Gonzalez-Cuello A. , Del Bel E. , Navarro-Zaragoza J. , Fernández-Villalba E.
Published: May 2023

Nitric oxide (NO) plays a pivotal role in integrating dopamine transmission in the basal ganglia and has been implicated in the pathogenesis of Parkinson disease (PD). The objective of this study was to ascertain whether the NO synthase inhibitor, 7-nitroindazole (7-NI), is able to reduce L-DOPA-induced dyskinesias (LIDs) in a non-human primate model of PD chronically intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Six Parkinsonian macaques were treated daily with L-DOPA for 3–4 months until they developed LIDs. Three animals were then co-treated with a single dose of 7-NI administered 45 min before each L-DOPA treatment. Dyskinetic MPTP-treated monkeys showed a significant decrease in LIDs compared with their scores without 7-NI treatment (
p
< 0.05). The anti-Parkinsonian effect of L-DOPA was similar in all three monkeys with and without 7-NI co-treatment. This improvement was significant with respect to the intensity and duration of LIDs while the beneficial effect of L-DOPA treatment was maintained and could represent a promising therapy to improve the quality of life of PD patients.
Clinical Knowledge and Reasoning Abilities of AI Large Language Models in Anesthesiology: A Comparative Study on the ABA Exam
Authors: Angel Mirana C. , Rinehart Joseph B. , Canneson Maxime P. , Baldi Pierre
Published: May 2023

Over the past decade, Artificial Intelligence (AI) has expanded significantly with increased adoption across various industries, including medicine. Recently, AI’s large language models such as GPT-3, Bard, and GPT-4 have demonstrated remarkable language capabilities. While previous studies have explored their potential in general medical knowledge tasks, here we assess their clinical knowledge and reasoning abilities in a specialized medical context. We study and compare their performances on both the written and oral portions of the comprehensive and challenging American Board of Anesthesiology (ABA) exam, which evaluates candidates’ knowledge and competence in anesthesia practice. In addition, we invited two board examiners to evaluate AI’s answers without disclosing to them the origin of those responses. Our results reveal that only GPT-4 successfully passed the written exam, achieving an accuracy of 78% on the basic section and 80% on the advanced section. In comparison, the less recent or smaller GPT-3 and Bard models scored 58% and 47% on the basic exam, and 50% and 46% on the advanced exam, respectively. Consequently, only GPT-4 was evaluated in the oral exam, with examiners concluding that it had a high likelihood of passing the actual ABA exam. Additionally, we observe that these models exhibit varying degrees of proficiency across distinct topics, which could serve as an indicator of the relative quality of information contained in the corresponding training datasets. This may also act as a predictor for determining which anesthesiology subspecialty is most likely to witness the earliest integration with AI.
Regularized COVID-19 Forecast Ensemble Methods
Authors: Stephens Alexandra , Mullany Luke C. , Kinsey Matt , Nicholas Paul , Freeman Jeffrey , Rainwater-Lovett Kaitlin
Published: May 2023

Forecasts of COVID-19 outcomes play an essential role in alerting public health and government officials to the trajectory of the pandemic. The sudden and critical need for these forecasts spurred both the proliferation of diverse epidemiological transmission models from academia and industry across the United States and efforts to standardize and curate these model outputs. In many scientific domains, ensemble models, where individual forecasts are aggregated into one, have demonstrated smaller forecasting error than the individual models from which they are constructed. Using COVID-19 deaths as an index outcome, we developed and evaluated several ensemble approaches where point forecast models were combined via weighted sums based on historical individual model or ensemble model performance. We found that a simple method that minimized the error of the past performance of individual models and used L2 regularization to encourage broader distribution of weights across models outperformed a baseline mean ensemble and all other tested methods across US states for both absolute error and weighted interval scores. This suggests that performance-based ensembles can produce accurate forecasts despite training on only point forecasts and recent historical data, provided that sufficient regularization and constraints are used to capture uncertainty. Availability of an accurate and explainable ensemble forecast model can increase trust among stakeholders and the general public, thus bettering preparedness and response efforts during the COVID-19 pandemic.
Effectiveness of Sotrovimab and Molnupiravir in community settings in England across the Omicron BA.1 and BA.2 sublineages: emulated target trials using the OpenSAFELY platform
Authors:   The OpenSAFELY collaborative, Tazare John , Nab Linda , Zheng Bang , Hulme William J , Green Amelia C A , Curtis Helen J , Mahalingasivam Viyaasan , Higgins Rose , Schultze Anna , Bhaskaran Krishnan , Mehrkar Amir , Schaffer Andrea , Smith Rebecca M , Bates Christopher , Cockburn Jonathan , Parry John , Hester Frank , Harper Sam , Eggo Rosalind M , Walker Alex J , Marks Michael , Brown Mike , Maringe Camille , Leyrat Clémence , Evans Stephen J W , Goldacre Ben , MacKenna Brian , Sterne Jonathan A C , Tomlinson Laurie A , Douglas Ian J
Published: May 2023

Background

The effectiveness of COVID-19 monoclonal antibody and antiviral therapies against severe COVID-19 outcomes is unclear. Initial benefit was shown in unvaccinated patients and before the Omicron variant emerged. We used the OpenSAFELY platform to emulate target trials to estimate the effectiveness of sotrovimab or molnupiravir, versus no treatment.

Methods

With the approval of NHS England, we derived population-based cohorts of non-hospitalised high-risk individuals in England testing positive for SARS-CoV-2 during periods of dominance of the BA.1 (16/12/2021-10/02/2022) and BA.2 (11/02/2022-21/05/2022) Omicron sublineages. We used the clone-censor-weight approach to estimate the effect of treatment with sotrovimab or molnupiravir initiated within 5 days after positive test versus no treatment. Hazard ratios (HR) for COVID-19 hospitalisation or death within 28 days were estimated using weighted Cox models.

Results

Of the 35,856 [BA.1 period] and 39,192 [BA.2 period] patients, 1,830 [BA.1] and 1,242 [BA.2] were treated with molnupiravir and 2,244 [BA.1] and 4,164 [BA.2] with sotrovimab. The estimated HRs for molnupiravir versus untreated were 1.00 (95%CI: 0.81;1.22) [BA.1] and 1.22 (0.96;1.56) [BA.2]; corresponding HRs for sotrovimab versus untreated were 0.76 (0.66;0.89) [BA.1] and 0.92 (0.79;1.06) [BA.2].

Interpretation

Compared with no treatment, sotrovimab was associated with reduced risk of adverse outcomes after COVID-19 in the BA.1 period, but there was weaker evidence of benefit in the BA2 period. Molnupiravir was not associated with reduced risk in either period.

Funding

UKRI, Wellcome Trust, MRC, NIHR and HDRUK.
DERIVED-BAND AUDITORY BRAINSTEM RESPONSES: COCHLEAR CONTRIBUTIONS DETERMINED BY NARROWBAND MASKERS
Authors: Stapells David R. , Fok Maxine R.
Published: May 2023

Objective

The present study sought to determine the cochlear frequency regions represented by Audtory Brainstem Responses (ABRs) obtained using the high-pass noise/derived response (HP/DR) technique.

Design

Broadband noise sufficient to mask the ABR to 50 dB nHL clicks was HP filtered (96 dB/oct) at 8000, 4000, 2000, 1000 and 500 Hz. Mixed with the clicks and high-pass noise masker was narrowband noise. Three DR bands, denoted by the upper and lower high-pass noise frequencies, were obtained: DR4000-2000, DR2000-1000, and DR1000-500.

Study sample

Ten adults with normal hearing, aged 19-27 years (mean age: 22.4 years), were recruited from the community.

Results

Frequencies contributing to each DR were determined from the wave V percent amplitude (or latency shift) vs narrowband masker frequency profiles (relative to a no-narrowband-noise condition). Overall, results indicate derived band center frequencies were closer to the lower HP cutoff frequencies for DR4000-2000 and DR2000-1000, and approximately halfway between the lower HP cutoff and the geometric mean of the two HP frequencies for DR1000-500, with bandwidths of 0.5-1 octave in width.

Conclusions

These results confirm the validity of the HP/DR technique for assessing narrow cochlear regions (≤1.0 octave wide), with center frequencies within ½-octave of the lower HP cutoff frequency.
Pulmonary Vascular Disease in Veterans with Post-Deployment Respiratory Syndrome
Authors: Gutor Sergey S. , Richmond Bradley W. , Agrawal Vineet , Brittain Evan L. , Mart Matthew F. , Shaver Ciara M. , Wu Pingsheng , Boyle Taryn K. , Mallugari Ravinder R. , Douglas Katrina , Piana Robert N. , Johnson Joyce E. , Miller Robert F. , Newman John H. , Blackwell Timothy S. , Polosukhin Vasiliy V.
Published: May 2023

Background

Increased frequency of exertional dyspnea has been documented in U.S. military personnel after deployment to Southwest Asia and Afghanistan. We studied whether continued exertional dyspnea in this patient population is associated with pulmonary vascular disease (PVD).

Methods

We recruited five Iraq and Afghanistan Veterans with post-deployment respiratory syndrome (PDRS) and continued exertional dyspnea to undergo a detailed clinical evaluation including symptom questionnaire, pulmonary function testing (PFT), surface echocardiography, and right heart catheterization (RHC) with exercise. We then performed detailed histomorphometry of blood vasculature in 52 Veterans with PDRS, 13 patients with advanced idiopathic pulmonary arterial hypertension (PAH) and 15 non-diseased (ND) control subjects.

Results

All five Veterans involved in clinical follow-up study had a continued dyspnea at exertion. On transthoracic echocardiography, we identified borderline or overt RV enlargement in three out of five Veterans. Right ventricle outflow tract (RVOT) acceleration time, a well-established surrogate measure of pulmonary pressure, was mildly reduced in three out of five Veterans. Of the five Veterans with PDRS who underwent RHC at exercise, we found that three had evidence of post-capillary PH at rest and one had PH at exercise. Morphometric evaluation of lung biopsy samples showed mild/moderate increase of fractional thicknesses of intima and media, and significant fibrosis of adventitia in pulmonary arteries in Veterans with PDRS compared to ND controls and PAH patients. Veterans with PDRS did not display plexiform or dilation/angiomatoid lesions, specific for PAH. Pulmonary veins showed similar levels of intima and adventitia fractional thickening in Veterans with PDRS and PAH patients compared to ND controls. In Veterans, IA veins were characterized by marked fibrous intima and adventitia thickening, usually with increased thickening and formation of multiple layers of elastic laminae, but without features of luminal occlusion, muscular hyperplasia or dilation/angiomatoid lesions seen in pulmonary veno-occlusive disease or chronic thromboembolic PH.

Conclusions

Our studies suggest that vasculopathy and PVD may explain exertional dyspnea and exercise limitation in some Veterans with PDRS. Evaluation for PVD should be considered in Iraq and Afghanistan Veterans with unexplained dyspnea.
Metabolic syndrome and hemorrhagic stroke among symptomatic CCMs in the Mexican Hispanic Population
Authors: Dwivedi Alok K. , Jang David , Belkin Ofek , Aickareth Justin , Renteria Mellisa , Hawwar Majd , Jacob Croft , Kalas M Ammar , Zuckerman Marc J. , Zhang Jun
Published: May 2023

Cerebral cavernous malformations (CCMs) are neurological disorders that make individuals more susceptible to hemorrhagic stroke. The Mexican-Hispanic population has a higher prevalence of both CCMs and metabolic syndrome (MetS), which is also associated with hemorrhagic stroke. A study was conducted with 184 Mexican-Hispanic CCM subjects and age- and sex-matched Hispanic and non-Hispanic white controls. The CCM cohort had a higher proportion of epilepsy and hemorrhagic stroke but a lower proportion of MetS. Higher blood pressure and fasting glucose levels were observed in the CCM cohort. MetS and epilepsy were associated with increased odds of hemorrhagic stroke among elderly CCM patients, and increased systolic blood pressure was significantly linked to increased odds of hemorrhagic stroke in the CCM cohort. To minimize the risk of hemorrhagic stroke, it is important to manage blood pressure and comorbidities like MetS and epilepsy in CCM patients, particularly those older than 50.

SUMMARUY

What is already known about this subject

Metabolic Syndrome (MetS) is widely associated with cardiovascular conditions, including stroke,

The association between MetS and ischemic stroke is well established

The relationship between MetS and hemorrhagic stroke remains unclear

Currently, one two studies explored the relationship between MetS and hemorrhagic stroke in CCM patients; one n sporadic CCM (sCCM) and one in familial CCM cases, with inconsistent results.

What are the new findings

In this study, a strong association was observed between systolic blood pressure (SBP) and hemorrhagic stroke in the CCM cohort, independent of obesity or fasting glucose levels.

This study also suggests that MetS is associated with hemorrhagic stroke among CCM patients, specifically in the older age group.

How might it impact on clinical practice in the foreseeable future

This study demonstrates many of the unique characteristics of symptomatic CCMs within the Mexican-Hispanic population

Our results suggests that of Mexican-Hispanic CCM subjects are at a greater risk for hemorrhagic stroke and epilepsy than other ethnic groups.

This study highlights the importance of reducing blood pressure and managing comorbidities such as MetS and epilepsy in CCM patients, especially those who are older than 50 years to minimize the risk of hemorrhagic stroke among CCM subjects
Deep-learning quantified cell-type-specific nuclear morphology predicts genomic instability and prognosis in multiple cancer types
Authors: Abel John , Jain Suyog , Rajan Deepta , Padigela Harshith , Leidal Kenneth , Prakash Aaditya , Conway Jake , Nercessian Michael , Kirkup Christian , Javed Syed Ashar , Biju Raymond , Harguindeguy Natalia , Shenker Daniel , Indorf Nicholas , Sanghavi Darpan , Egger Robert , Trotter Benjamin , Gerardin Ylaine , Brosnan-Cashman Jacqueline A. , Dhoot Aditya , Montalto Michael C. , Parmar Chintan , Wapinski Ilan , Khosla Archit , Drage Michael G. , Yu Limin , Taylor-Weiner Amaro
Published: May 2023

While alterations in nucleus size, shape, and color are ubiquitous in cancer, comprehensive quantification of nuclear morphology across a whole-slide histologic image remains a challenge. Here, we describe the development of a pan-tissue, deep learning-based digital pathology pipeline for exhaustive nucleus detection, segmentation, and classification and the utility of this pipeline for nuclear morphologic biomarker discovery. Manually-collected nucleus annotations were used to train an object detection and segmentation model for identifying nuclei, which was deployed to segment nuclei in H&E-stained slides from the BRCA, LUAD, and PRAD TCGA cohorts. Interpretable features describing the shape, size, color, and texture of each nucleus were extracted from segmented nuclei and compared to measurements of genomic instability, gene expression, and prognosis. The nuclear segmentation and classification model trained herein performed comparably to previously reported models. Features extracted from the model revealed differences sufficient to distinguish between BRCA, LUAD, and PRAD. Furthermore, cancer cell nuclear area was associated with increased aneuploidy score and homologous recombination deficiency. In BRCA, increased fibroblast nuclear area was indicative of poor progression-free and overall survival and was associated with gene expression signatures related to extracellular matrix remodeling and anti-tumor immunity. Thus, we developed a powerful pan-tissue approach for nucleus segmentation and featurization, enabling the construction of predictive models and the identification of features linking nuclear morphology with clinically-relevant prognostic biomarkers across multiple cancer types.
A Virus-like particle-based bivalent PCSK9 vaccine lowers LDL-cholesterol levels in Non-Human Primates
Authors: Fowler Alexandra , Van Rompay Koen K. A. , Sampson Maureen , Leo Javier , Watanabe Jennifer K. , Usachenko Jodie L. , Immareddy Ramya , Lovato Debbie M. , Schiller John T. , Remaley Alan T. , Chackerian Bryce
Published: May 2023

Elevated low-density lipoprotein cholesterol (LDL-C) is an important risk factor in the development of atherosclerotic cardiovascular disease (ASCVD). Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9), a negative regulator of LDL-C metabolism, have emerged as promising approaches for reducing elevated LDL-C levels. Here, we evaluated the cholesterol lowering efficacy of virus-like particle (VLP) based vaccines that target epitopes found within the LDL receptor (LDL-R) binding domain of PCSK9. In both mice and non-human primates, a bivalent VLP vaccine targeting two distinct epitopes on PCSK9 elicited strong and durable antibody responses and lowered cholesterol levels. In macaques, a VLP vaccine targeting a single PCSK9 epitope was only effective at lowering LDL-C levels in combination with statins, whereas immunization with the bivalent vaccine lowered LDL-C without requiring statin co-administration. These data highlight the efficacy of an alternative, vaccine-based approach for lowering LDL-C.